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Sample records for bla pharmacovigilance plan

  1. Risk management plans as a tool for proactive pharmacovigilance

    DEFF Research Database (Denmark)

    Vermeer, N S; Duijnhoven, R G; Straus, S M J M

    2014-01-01

    Risk Management Plans (RMPs) have become a cornerstone in the pharmacovigilance of new drugs in Europe. The RMP was introduced in 2005 to support a proactive approach in gaining knowledge on safety concerns through early planning of pharmacovigilance activities. However, the rate at which...... of uncertainties, suggests that opportunities for optimization exist while ensuring feasible and risk-proportionate pharmacovigilance planning....

  2. Strengthening pharmacovigilance in South Africa.

    Science.gov (United States)

    Mehta, U; Dheda, M; Steel, G; Blockman, M; Ntilivamunda, A; Maartens, G; Pillay, Y; Cohen, K

    2014-02-01

    This report outlines findings and recommendations of a national pharmacovigilance workshop held in August 2012 in South Africa (SA). A survey of current pharmacovigilance activities, conducted in preparation for the meeting, identified multiple programmes collecting drug safety data in SA, with limited co-ordination at national level. The meeting resolved that existing pharmacovigilance programmes need to be strengthened and consolidated to ensure that important local safety issues are addressed, data can be pooled and compared and outputs shared more widely. Pharmacovigilance activities should inform treatment guidelines with the goal of improving patient care. A variety of pharmaco-epidemiological approaches should be employed, including nesting drug safety studies within existing sentinel cohorts and the creation of a pregnancy exposure registry. The attendees agreed on key principles that will inform a national pharmacovigilance plan and compiled a list of priority pharmacovigilance issues facing public health programmes in SA.

  3. The role of systematic reviews in pharmacovigilance planning and Clinical Trials Authorisation application: example from the SLEEPS trial.

    Directory of Open Access Journals (Sweden)

    Carrol Gamble

    Full Text Available Adequate sedation is crucial to the management of children requiring assisted ventilation on Paediatric Intensive Care Units (PICU. The evidence-base of randomised controlled trials (RCTs in this area is small and a trial was planned to compare midazolam and clonidine, two sedatives widely used within PICUs neither of which being licensed for that use. The application to obtain a Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA required a dossier summarising the safety profiles of each drug and the pharmacovigilance plan for the trial needed to be determined by this information. A systematic review was undertaken to identify reports relating to the safety of each drug.The Summary of Product Characteristics (SmPC were obtained for each sedative. The MHRA were requested to provide reports relating to the use of each drug as a sedative in children under the age of 16. Medline was searched to identify RCTs, controlled clinical trials, observational studies, case reports and series. 288 abstracts were identified for midazolam and 16 for clonidine with full texts obtained for 80 and 6 articles respectively. Thirty-three studies provided data for midazolam and two for clonidine. The majority of data has come from observational studies and case reports. The MHRA provided details of 10 and 3 reports of suspected adverse drug reactions.No adverse reactions were identified in addition to those specified within the SmPC for the licensed use of the drugs. Based on this information and the wide spread use of both sedatives in routine practice the pharmacovigilance plan was restricted to adverse reactions. The Clinical Trials Authorisation was granted based on the data presented in the SmPC and the pharmacovigilance plan within the clinical trial protocol restricting collection and reporting to adverse reactions.

  4. Pharmacovigilance risk mitigation plans: action in public health to promote the safe use of medication.

    Science.gov (United States)

    Botelho, Stephanie Ferreira; Reis, Adriano Max Moreira

    2015-12-01

    Risk mitigation plans (RMP) are an innovative and important strategy for monitoring the sanitary risks of medication. The scope of the study was to identify RMPs for drugs registered with the Food and Drug Administration (FDA) and the actions to minimize risks established by the Brazilian Health Surveillance Agency (Anvisa) and the manufacturers of these drugs. This is a quantitative and descriptive study including a survey together with the pharmaceutical industries and research on sites and databases of Anvisa, the FDA and pharmaceutical industries. Forty drugs with RMPs filed with the FDA were also registered with Anvisa. Only 4 laboratories (10f%) reported RMPs developed in Brazil. Safety information for 15 drugs (37.5%) were located on the Anvisa site. In 91.4% of Brazilian user package leaflets there is safety information equivalent to actions to promote safe use described in RMPs available on the FDA website. The actions of communication on drug safety and sanitary risk of drugs needs to be expanded by Anvisa. The RMP is an important strategy in public health for managing new risks, monitoring known risks and, especially, for promoting the safe use of medication.

  5. Pharmacovigilance in Space: Stability Payload Compliance Procedures

    Science.gov (United States)

    Daniels, Vernie R.; Putcha, Lakshmi

    2007-01-01

    Pharmacovigilance is the science of, and activities relating to the detection, assessment, understanding, and prevention of drug-related problems. Over the lase decade, pharmacovigilance activities have contributed to the development of numerous technological and conventional advances focused on medication safety and regulatory intervention. The topics discussed include: 1) Proactive Pharmacovigilance; 2) A New Frontier; 3) Research Activities; 4) Project Purpose; 5) Methods; 6) Flight Stability Kit Components; 7) Experimental Conditions; 8) Research Project Logistics; 9) Research Plan; 10) Pharmaceutical Stability Research Project Pharmacovigilance Aspects; 11) Security / Control; 12) Packaging/Containment Actions; 13) Shelf-Life Assessments; 14) Stability Assessment Parameters; 15) Chemical Content Analysis; 16) Preliminary Results; 17) Temperature/Humidity; 18) Changes in PHysical and Chemical Assessment Parameters; 19) Observations; and 20) Conclusions.

  6. EU's new pharmacovigilance legislation: considerations for biosimilars.

    Science.gov (United States)

    Calvo, Begoña; Zuñiga, Leyre

    2014-01-01

    Biosimilars are biological medicines, the active substances of which are highly similar to those of biologics that have already been authorized. As for any other medicine, the applicant of the biosimilar marketing authorization must submit a risk-management plan (RMP)/pharmacovigilance plan. The pharmacovigilance plan should take into account risks identified during product development, the potential risks and how those risks will be addressed after authorization of the product.Recently, new European Pharmacovigilance legislation has been implemented, ensuring proper risk management through the recording of suspected adverse drug reactions and data collection from all stakeholders. The new regulation entails a reduction of the administrative burden on companies and regulatory agencies, as obligations of the responsible parties are clearly established and duplication of effort avoided.This article analyzes the new European Pharmacovigilance System requirements, with special focus on those medicines requiring additional monitoring, such as biosimilars, which are priorities for pharmacovigilance. Further, it provides the new obligations to marketing authorization holders, such as the continuous benefit-risk assessment.

  7. Forensic pharmacovigilance: Newer dimension of pharmacovigilance.

    Science.gov (United States)

    Sewal, Rakesh K; Saini, Vikas K; Medhi, Bikash

    2015-08-01

    Drug safety for the patients is of paramount importance for a medical professional. Pharmacovigilance attempts to ensure the safety of patients by keeping a close vigil on the pattern of adverse events secondary to drug use. Number of medicolegal cases is at rise since last few years. Forensic sciences and pharmacovigilance need to work hand in hand to unlock the mystery of many criminal and civil proceedings. Pharmacovigilance offers its wide scope in forensic sciences by putting forward its expertise on adverse profile of drugs which may be instrumental in solving the cases and bringing the justice forth. It may range from as simple affairs as defining the adverse drug reaction on one hand to putting expert advice in critical criminal cases on the other one. Pharmacovigilance experts have to abide by the ethics of the practice while executing their duties as expert else it may tarnish the justice and loosen its dependability. As a budding discipline of science, it is confronted with several hurdles and challenges which include reluctance of medical professionals for being involved in court proceedings, extrapolations of facts and data and variations in law across the globe etc. These challenges and hurdles call the medical fraternity come forward to work towards the momentous application of pharmacovigilance in the forensic sciences. Evidence based practice e.g. testing the biological samples for the presence of drugs may prove to be pivotal in the success of this collaboration of sciences. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  8. Past, Present and Future of Pharmacovigilance

    Directory of Open Access Journals (Sweden)

    Derya Kaya

    2016-06-01

    Full Text Available Pharmacovigilance, is a scientific study related to follow-up problems in drug administrations and identify, record, announce and take due precautions for these problems. Pharmacovigilance works on to increase safety and effectiveness of drugs and minimize the risks associated with drug use. It is significantly developed and continues to improve to satisfy the recent needs. While information spreads like wildfire in the world, there is a need for strategic planning which adopts an integrated approach to go through difficulties caused by increased transmission between borders, easy acceptance of medical product diversity and increased safety expectation of public. We will need dynamic improvement and continuation of pharmacovigilance in all its parts to improve public health and safety. [Archives Medical Review Journal 2016; 25(2.000: 129-139

  9. Training in post-authorization pharmacovigilance

    Directory of Open Access Journals (Sweden)

    Vivek Ahuja

    2010-01-01

    Full Text Available Post-authorization pharmacovigilance refers to all the activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems, from the time a product gets the authorization to be marketed in a territory. The ultimate objective of pharmacovigilance is patient safety. To ensure this, any responsible pharmaceutical company will readily vouch for the importance of all these activities, each requiring specific training for efficient and effective execution. Having a well planned job specific training curriculum can help the organization realize its goals and objectives by covering the gaps between current and desired job performance levels and existing competencies of its employees. Apart from this, trainings can help in problem solving, increasing productivity and prepare for and respond to future changes in the organization or job duties. As the pharmaceutical business continues to grow, increasing numbers of skilled people are required to manage resultant increase in pharmacovigilance activities to remain compliant. Thus, the need for training qualified resources to develop into highly skilled pharmacovigilance professionals is the need of the hour. Currently, the supply-demand situation for skilled manpower is highly skewed in favor of the demand, as this field is relatively new in India and elsewhere. It is interesting to note that not many resources, be it internet, literature or books, are available specifically addressing the need of the industry to guide them on training requirements to set up and maintain a competent pharmacovigilance department. This article aims to present a comprehensive perspective on the trainings required in the post authorization scenario pertaining to pharmacovigilance activities and suggest ways to manage these in an efficient way so as to be compliant with the global norms and best practices.

  10. Training in Post-authorization Pharmacovigilance

    Science.gov (United States)

    Ahuja, Vivek; Sharma, Varun

    2010-01-01

    Post-authorization pharmacovigilance refers to all the activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems, from the time a product gets the authorization to be marketed in a territory. The ultimate objective of pharmacovigilance is patient safety. To ensure this, any responsible pharmaceutical company will readily vouch for the importance of all these activities, each requiring specific training for efficient and effective execution. Having a well planned job specific training curriculum can help the organization realize its goals and objectives by covering the gaps between current and desired job performance levels and existing competencies of its employees. Apart from this, trainings can help in problem solving, increasing productivity and prepare for and respond to future changes in the organization or job duties. As the pharmaceutical business continues to grow, increasing numbers of skilled people are required to manage resultant increase in pharmacovigilance activities to remain compliant. Thus, the need for training qualified resources to develop into highly skilled pharmacovigilance professionals is the need of the hour. Currently, the supply-demand situation for skilled manpower is highly skewed in favor of the demand, as this field is relatively new in India and elsewhere. It is interesting to note that not many resources, be it internet, literature or books, are available specifically addressing the need of the industry to guide them on training requirements to set up and maintain a competent pharmacovigilance department. This article aims to present a comprehensive perspective on the trainings required in the post authorization scenario pertaining to pharmacovigilance activities and suggest ways to manage these in an efficient way so as to be compliant with the global norms and best practices. PMID:21829787

  11. The history of pharmacovigilance.

    Science.gov (United States)

    Caron, Jacques; Rochoy, Michaël; Gaboriau, Louise; Gautier, Sophie

    2016-04-01

    This article reviews the main historical events before the 21st century and explained their consequences in the current pharmacovigilance legislation. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  12. Pharmacovigilance in Europe: Place of the Pharmacovigilance Risk Assessment Committee (PRAC) in organisation and decisional processes.

    Science.gov (United States)

    Laroche, Marie-Laure; Batz, Arnaud; Géniaux, Hélène; Féchant, Corinne; Merle, Louis; Maison, Patrick

    2016-04-01

    The new European legislation that came into force in July 2012 reinforced the organisation of pharmacovigilance by setting up a committee in charge of risk assessment for medicines, the Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC has a remit covering the assessment of all aspects of the safety and the risk management of medicinal products for human use in the European Union. It deals with issues regarding pharmacovigilance signals, the periodic evaluation of benefit/risk reports from marketing authorization holders (MAH), risk management plans, post-marketing studies, variations or renewals of marketing authorisations, management of under surveillance drugs lists, inspections for pharmacovigilance reasons and audits of pharmacovigilance systems. The PRAC works with the pharmacovigilance systems of the European Member States, which draw up evaluation reports. These evaluations are circulated and discussed by Member States so as to issue recommendations, which serve as a basis for other European medicines committees, the Committee for Medicinal Products for Human Use (CHMP) or the Coordination Group for Mutual Recognition and Decentralised Procedures-Human (CMDh) which then give their opinion. The final decision, which applies to all Member States and to the concerned MAH, lies with the European Commission (EC). This decisional procedure thus rests on coordination involving the PRAC, the CHMP, the CMDh, the EC, the Member States and the pharmaceutical companies. In the 3 years from July 2012, the PRAC has processed nearly 4500 procedures and is still facing an increasing workload. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  13. Pharmacovigilance in Italy: An overview

    Science.gov (United States)

    Mazzitello, Carmela; Esposito, Stefania; De Francesco, Adele E.; Capuano, Annalisa; Russo, Emilio; De Sarro, Giovambattista

    2013-01-01

    Introduction: Spontaneous reporting of adverse drug reactions (ADRs) is the basis of pharmacovigilance. In fact, ADRs are associated with a high degree of morbidity and mortality. However, underreporting by all healthcare professionals remains the major problem in Italy and in the rest of the world. The dissemination of pharmacovigilance knowledge among Italian healthcare professionals, and the new pharmacovigilance regulations may promote the early detection and reporting of ADRs. This review examines the legislative framework concerning the pharmacovigilance in Italy. Materials and Methods: The information was collected from scientific articles and the websites of the Italian Ministry of Health and the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). Results: The pharmacovigilance system, both in Italy and Europe, has undergone profound changes. European legislation on pharmacovigilance has been changed in 2010 according to the EU Regulation 1235/2010 and Directive 2010/84/EU. Basically, the changes tend to increase the efficiency, speed and transparency of pharmacovigilance activities. The new Regulation (1235/2010) and the Directive (2010/84/EU) aim to strengthen the system of pharmacovigilance, establish more precisely who is obliged to do what, and allow faster and easier circulation and retrieval of information about ADRs. Conclusion: A greater knowledge on what is the Italian pharmacovigilance legislation will be useful to improve the status of ADRs reporting and spread the culture of spontaneous reporting. PMID:24347976

  14. French pharmacovigilance: Missions, organization and perspectives.

    Science.gov (United States)

    Vial, Thierry

    2016-04-01

    Pharmacovigilance aims to identify unknown adverse drug reactions once clinical development is complete, in order to promote improved use of drugs, and thus a reduction in risk for every exposed patient. We describe in this article the missions of French pharmacovigilance system, including French drug agency, Regional Centers of Pharmacovigilance, health professionals, pharmaceutical companies, patients and their associations. We also develop the French pharmacovigilance organization, its perspectives and challenges, both in French and European levels. Copyright © 2016. Published by Elsevier Masson SAS.

  15. [The European pharmacovigilance: regulatory aspects].

    Science.gov (United States)

    Dhanani, A; Castot, A

    2000-01-22

    ESTABLISHMENT: The European pharmacovigilance system has been operating since 1995 when the European Agency for the Evaluation of Medicinal Products as well as two new European registration procedures were established. This system is very similar to the French organization and is based on a decentralized collection and validation of safety data by member states and a centralized evaluation and decision making process at the European Agency for the Evaluation of Medicinal Products performed by the Committee for Proprietary Medicinal Products (CPMP) and its Pharmacovigilance Working Party. A EUROPEAN SYSTEM: In light of the experience gained, the European pharmacovigilance system moved to an interactive system which relies on a close cooperation between member states ensuring the common evaluation and management of safety concerns.

  16. Prevalence of bla NDM, bla PER, bla VEB, bla IMP, and bla VIM Genes among Acinetobacter baumannii Isolated from Two Hospitals of Tehran, Iran.

    Science.gov (United States)

    Fallah, Fatemeh; Noori, Maryam; Hashemi, Ali; Goudarzi, Hossein; Karimi, Abdollah; Erfanimanesh, Soroor; Alimehr, Shadi

    2014-01-01

    Background and Objectives. The aim of this study was to determine the frequency of bla NDM, bla PER, bla VEB, bla IMP, and bla VIM type genes among A. baumannii isolates from hospitalized patients in two hospitals in Tehran, Iran. Patients and Methods. Antibiotic susceptibility tests were performed by Kirby-Bauer disc diffusion and Broth microdilution methods. The frequency of MBL (metallo-beta-lactamase) and ESBL (extended-spectrum-beta-lactamase) producers was evaluated by CDDT. The β -lactamases genes were detected by PCR and sequencing methods. Results. The resistance of A. baumannii isolates against tested antibiotics was as follows: 103 (95.4%) to ceftazidime, 108 (100%) to cefotaxime, 105 (95.7%) to cefepime, 99 (91.7%) to imipenem, 99 (91.7%) to meropenem, 87 (80.6%) to amikacin, 105 (97.2%) to piperacillin, 100 (92.6%) to ciprofloxacin, 103 (95.4%) to piperacillin/tazobactam, 44 (40.7%) to gentamicin, 106 (98.1%) to ampicillin/sulbactam, 106 (98.1%) to co-trimoxazole, 87 (80.6%) to tetracycline, and 1 (1.8%) to colistin. Using combined disk diffusion test, 91 (84.2%) and 86 (86.86%) were ESBL and MBL producers, respectively. The prevalence of bla PER-1, bla VEB-1, bla IMP-1, and bla VIM-1 genes was 71 (78.03%), 36 (39.5%), 3 (3.48%), and 15 (17.44%), respectively. Conclusions. The prevalence of ESBLs and MBLs-producing A. baumannii strains detected in this study is a major concern and highlights the need of infection control measures.

  17. Detection of blaSPM-1, blaKPC, blaTEM and blaCTX-M genes in isolates of Pseudomonas aeruginosa, Acinetobacter spp. and Klebsiella spp. from cancer patients with healthcare-associated infections.

    Science.gov (United States)

    Jácome, Paula Regina Luna de Araújo; Alves, Lílian Rodrigues; Jácome-Júnior, Agenor Tavares; Silva, Maria Jesuíta Bezerra da; Lima, Jailton Lobo da Costa; Araújo, Paulo Sérgio Ramos; Lopes, Ana Catarina S; Maciel, Maria Amélia Vieira

    2016-07-01

    Pseudomonas aeruginosa, Acinetobacter spp. and Klebsiella spp. are three of the pathogens most frequently involved in infections of cancer patients, and the production of β -lactamases is a major mechanism of resistance due to its wide diversity of existing enzymes. Therefore, the aim of the present study was to investigate the microbiological profile and data related to patients and infections, and to search for β -lactamase genes in bacterial isolates from hospitalized cancer patients in a hospital in Recife, Pernambuco, Brazil. A total of 169 isolates were recovered between 2012 and 2014, of which 58 were P. aeruginosa, 36 were Acinetobacter spp. and 75 were Klebsiella spp. A high percentage of carbapenem resistance was observed in P. aeruginosa and Acinetobacter spp. Among the carbapenem-resistant bacteria, the blaSPM-1 gene was detected in P. aeruginosa (35.5 %) and Acinetobacter spp. (3.8 %), while blaKPC was detected in P. aeruginosa (25.8 %) only. Among the third- and fourth-generation cephalosporin-resistant strains, in Klebsiella spp. we detected the genes blaTEM (30.6 %), blaCTX-M (58.3 %) and blaKPC (5.6 %), and in Acinetobacter spp. only blaTEM (25.9 %). This the first report of an Acinetobacter baumannii blaSPM-1 gene carrier that has been isolated in Brazil. The most frequent cancer types were bowel tumour [14.8 %; 95 % confidence interval (CI95 %) 9.8-21.1 %], breast cancer (13.6 %; CI95 % 8.8-19.7 %) and prostate cancer (11.2%; CI95 % 6.9-17.0 %). These results therefore provide knowledge of susceptibility profile and resistance mechanisms and thus can contribute to the strategic formulation of hospital infection control plans and the rational use of antimicrobials, reducing mortality from infection levels in cancer patients.

  18. Pharmacovigilance activities in 55 low- and middle-income countries: a questionnaire-based analysis.

    Science.gov (United States)

    Olsson, Sten; Pal, Shanthi N; Stergachis, Andy; Couper, Mary

    2010-08-01

    The WHO Programme for International Drug Monitoring aims to develop a comprehensive global pharmacovigilance strategy that responds to the healthcare needs of low- and middle-income countries. However, first there is a need to measure and understand existing conditions and pharmacovigilance initiatives intended in these settings. Very few investigations have carried out such a systematic assessment of the pharmacovigilance landscape in recent years in low- and middle-income countries. To assess current and planned pharmacovigilance activities in low- and middle-income countries, identify gaps and the most urgent pharmacovigilance priorities at national and international levels, and define the elements of a sustainable global pharmacovigilance strategy. A standardized questionnaire was sent to 114 representatives of countries participating in the WHO Programme for International Drug Monitoring (but excluding Australia, Canada, New Zealand, Switzerland and the International Conference on Harmonization countries, i.e. countries in Europe, Japan and the US) and to a few other identified contacts from non-member countries. The questionnaire was sent out between March and July 2008 and was designed to collect information on the structure, resources, functions and achievements of pharmacovigilance systems in low- and middle-income countries, with a focus on pharmacovigilance activities supported by national health authorities including public health programmes. All questionnaires that were returned by the end of July 2008 were used in the analysis. Fifty-five completed questionnaires were received by July 2008, representing a response rate of 55.5%. Forty-five percent of the pharmacovigilance centres in the analysis were established during the 1990s and 49% were set up later; 69% were affiliated with their Drug Regulatory Agency, 20% with the Ministry of Health and 9% with a university or other scientific body. Few countries (23 of 55) have any budget allocated for

  19. Promoting and Protecting Public Health: How the European Union Pharmacovigilance System Works.

    Science.gov (United States)

    Santoro, Aniello; Genov, Georgy; Spooner, Almath; Raine, June; Arlett, Peter

    2017-10-01

    This article provides an overview of the European Union pharmacovigilance system resulting from the rationalisation and strengthening delivered through the implementation of the revised pharmacovigilance legislation. It outlines the system aims, underlying principles, components and drivers for future change. At its core, the Pharmacovigilance Risk Assessment Committee is responsible for assessing all aspects of the risk management of medicinal products, thus ensuring that medicines approved for the European Union market are optimally used by maximising their benefits and minimising risks. The main objectives of the system are to promote and protect public health by supporting the availability of medicines including those that fulfil previously unmet medical needs, and reducing the burden of adverse drug reactions. These are achieved through a proactive, risk proportionate and patient-centred approach, with high levels of transparency and engagement of civil society. In the European Union, pharmacovigilance is now fully integrated into the life cycle of medicinal products, with the planning of pharmacovigilance activities commencing before a medicine is placed on the market, and companies encouraged to start planning very early in development for high-innovation products. After authorisation, information on the safety of medicines continues to be obtained through a variety of sources, including spontaneous reports of adverse drug reactions or monitoring real-world data. Finally, the measurement of the impact of pharmacovigilance activities, auditing and inspections, as well as capacity building ensure that the system undergoes continuous improvement and can always rely on the best methodologies to safeguard public health.

  20. [The new pharmacovigilance legislation in practice].

    Science.gov (United States)

    Broekmans, André W; Mol, Peter G M

    2014-01-01

    Recent European legislation has provided new tools to enhance the overseeing of medicinal products in the postmarketing phase. Package leaflets of newly approved medicines contain a black inverted triangle as a signal for enhanced monitoring. The leaflets also have clear instructions on how to report possible adverse drug reactions. Databases of drug reactions are accessible by the public. The most important change is the establishment of the Pharmacovigilance Risk Assessment Committee (PRAC) within the European Medicines Agency (EMA). This Committee will review safety signals of medicinal products arising in the member states of the European Union. The Committee could recommend adaptation of the package leaflet, or suspension or revocation of the marketing authorisation. The PRAC is also involved in the assessment of risk management plans for medicinal products and post-authorisation efficacy and safety studies.

  1. [Pharmacovigilance of major parmaceutical innovation].

    Science.gov (United States)

    Xiang, Yongyang; Xie, Yanming; Yi, Danhui

    2011-10-01

    With the continuous improvement of international "pharmacovigilance" technology and methods,it becomes the key part of the post-marketing evaluation. This issue is based on this research background, and also means to find out the Chinese medicine safety monitor which consistents with the reality. A common problem is that those who choose a career in pharmacovigilance know how the complex data presented to us are a source of both fascination and frustration. In the 70's, for the first time data mining technology in the international pharmacovigilance turn up, we try to establish new signal detection method to make contributes to post-marketing evaluation of Chinese medicine and establishment of registration. Building the national adverse reaction reporting database is widely used in western country. Nature of the problem is that pharmacovigilance issues can come through a lot of assumptions into the statistical problems, different assumptions are for different statistical tests. Through the traditional imbalance between the proportion of fourfold table for other assumptions, few countries use in practice, this does not involve evidence, but this issue provides the introduce of the principle. Methods include the ratio of the report of the Netherlands (ROR), the proportion of reports than the UK ratio (PRR),WHO's information points (IC), the U.S. Food and Drug Administration empirical Bayes (EBS), etc. Because there is no international gold standard of the signal detection method, at first we use the simulation comparing these four methods of data mining, From the point of specificity, the sample size demand, this issue views the advantages and disadvantages of four methods and application conditions,and from a technical point of view and try to propose a new signal detection method, for example, Hierarchical Bayesian.

  2. The role of data mining in pharmacovigilance

    NARCIS (Netherlands)

    Hauben, Manfred; Madigan, David; Gerrits, Charles M; Walsh, Louisa; Van Puijenbroek, Eugene P

    A principle concern of pharmacovigilance is the timely detection of adverse drug reactions that are novel by virtue of their clinical nature, severity and/or frequency. The cornerstone of this process is the scientific acumen of the pharmacovigilance domain expert. There is understandably an

  3. [Pharmacovigilance in Portugal: Activity of the Central Pharmacovigilance Unit].

    Science.gov (United States)

    Batel-Marques, Francisco; Mendes, Diogo; Alves, Carlos; Penedones, Ana; Dias, Patricia; Martins, Angelina; Santiago, Luiz Miguel; Fontes-Ribeiro, Carlos; Caramona, Margarida; Macedo, Tice

    2015-01-01

    The aim of this study was to characterize the spontaneous reports of adverse events that were received by the Central Portugal Regional Pharmacovigilance Unit. Spontaneous reports received between 01/2001 and 12/2013 were considered. The annual reporting ratios were estimated. The cases were characterized according to their seriousness, previous description, causality assessment, origin and professional group of the reporter, type of adverse event and pharmacotherapeutic groups of the suspected drugs most frequently reported. The Pharmacovigilance Unit received 2408 reports that contained 5749 adverse events. In 2013, the reporting rate was estimated at 171 reports per million inhabitants. Fifty-five percent of the reports were assessed as serious. Ninety percent of the cases were assessed as being at least possibly related with the suspected drug. The suspected drugs most frequently reported were anti-infectives for systemic use (n = 809, 33%). The most frequently reported adverse events were "Skin and subcutaneous tissue disorders" (n = 1139, 20%). There were 154 (6.4%) reports resulting in life-threatening situations and/or death, and 88 (3.6%) containing at least one adverse event assessed as serious, unknown and certain or probable. The present results are in line with those found in other studies, namely the seriousness and type of the adverse events and the pharmacotherapeutic groups of the most frequently reported suspected drugs. In the last years, the Central Portugal Regional Pharmacovigilance Unit has registered a growth in the reporting rate in general, as well as an increase in the reporting of unknown and serious adverse drug reactions.

  4. Emergence of Klebsiella pneumoniae carrying bla(VIM) and bla(KPC) genes.

    Science.gov (United States)

    Meletis, G; Tzampaz, E; Protonotariou, E; Sofianou, D

    2010-04-01

    A Klebsiella pneumoniae clinical isolate resistant to imipenem was recovered from a wound sample. The patient, a 57-year-old man, underwent a surgical resection of small bowel and sigmoid colon and was treated with multiple courses of antimicrobials. PCR analysis revealed that the clinical isolate was carrying simultaneously bla(VIM-1), bla(KPC-2), bla(SHV) and bla(TEM) genes. The concomitant presence of these genes is alarming and poses therapeutic as well as infection control problems.

  5. Pharmacovigilance Discussion Forum--The European Generic Medicines Association's 8th Annual Meeting (January 21, 2015--London, UK).

    Science.gov (United States)

    Lam, S

    2015-01-01

    The practice and science of pharmacovigilance first emerged following the disaster caused by thalidomide in 1961, which led to the initiation of systemic international efforts to address drug safety issues spearheaded by the WHO. Systems were developed in member states of the WHO to analyze cases of adverse drug reactions (ADRs) and collate these data into a central database to aid national drug regulatory authorities in improving safety profiles of medicines. Pharmacovigilance is a key public health function for monitoring all medicinal products to assess their quality, efficacy and safety before and following authorization. These medicines are continually assessed to detect any aspect that could compromise their safety, and ensure that the necessary measures are taken. In July 2012, new legislation for pharmacovigilance in the E.U. came into effect as a result of the changes set out in the Directive 2010/84/EU and the European Commission (EC) implementing Regulation (EU) No 520/2012 to reduce the increasing number of ADRs. The latest developments in pharmacovigilance in Europe, including news on E.U. pharmacovigilance legislation, were discussed at the 8th European Generic Medicines Association (EGA) Pharmacovigilance Discussion Forum. The meeting facilitated constructive dialogue between regulators and industry on a range of topics including how to simplify pharmacovigilance activities and improve the processes of risk management plans, periodic safety update reports, signal detection, joint studies and inspections. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

  6. Pharmacovigilance and biosimilars: considerations, needs and challenges.

    Science.gov (United States)

    Casadevall, Nicole; Edwards, I Ralph; Felix, Thomas; Graze, Peter R; Litten, Jason B; Strober, Bruce E; Warnock, David G

    2013-07-01

    Biosimilars are biologic medicines that are highly similar to approved biologics, notwithstanding minor differences in clinically inactive components. Since 2007, biosimilars have been approved for use in patients in the European Union (EU) and other regions. European experience provides several lessons as the United States (US) healthcare system prepares for biosimilar approvals. These lessons emphasize the need for adequate efficacy and safety studies, post-marketing surveys and a robust pharmacovigilance system that can accurately track and trace biologics, including biosimilars and their reference products, from the patient to the manufacturer. We review the EU experience with biosimilar pharmacovigilance and discuss the implications for biosimilar pharmacovigilance in the USA. Furthermore, we review several aspects of biosimilar pharmacovigilance, including cohort event monitoring, traceability, biosimilar interchangeability, pharmacovigilance system development, nomenclature and counterfeit tracking. The availability of biosimilars as lower-cost biologics must carefully consider issues of safety, efficacy and traceability. Stringent pharmacovigilance procedures are required to detect potential differences in safety signals between biosimilars and their reference products. Pharmacovigilance of biologics should include processes that are easily used by prescribing practitioners to ensure that data are consistent and new safety signals are properly reported and assigned to the correct product.

  7. Pharmacovigilance: the devastating consequences of not thinking ...

    African Journals Online (AJOL)

    Pharmacovigilance: the devastating consequences of not thinking about adverse drug reactions: The burden of adverse drug reactions (ADRs) on patient care has been found to be high globally and is particularly high in South Africa.

  8. Patient-centered pharmacovigilance: A review

    African Journals Online (AJOL)

    html. 2. Smith MY, Benattia I. The Patient's Voice in. Pharmacovigilance: Pragmatic Approaches to Building a. Patient-Centric Drug Safety Organization. Drug Saf. 2016; 39(9): 779-785. 3. World Health Organization. Safety of Medicines - A Guide.

  9. Pharmacovigilance teaching in UK undergraduate pharmacy programmes.

    Science.gov (United States)

    Smith, Melvyn P; Webley, Sherael D

    2013-03-01

    Pharmacists in the UK are able to report spontaneous adverse drug reactions (ADRs) to the Medicines and Healthcare Products Regulatory Authority. The level of reporting by UK pharmacists remains low. This could be explained by poor knowledge of ADR reporting. The primary objective of this study was to investigate the level of pharmacovigilance education provided to pharmacy students on undergraduate pharmacy programmes in the UK. A cross-sectional survey was used to obtain data relating to the teaching of pharmacovigilance within schools of pharmacy. The survey was designed to reveal whether core elements pertinent to pharmacovigilance and specifically to spontaneous reporting were taught and to what extent. All of the respondents taught pharmacovigilance within an assessed compulsory module. A small number (23%) did not include pharmacovigilance law within their syllabus. In 54%, the amount of time devoted to teaching pharmacy students about their role in pharmacovigilance was less than 4 h in the 4-year course; only one respondent spent approximately 20 h, the remaining respondents (38%) spent between 4 and 8 h. The amount of time dedicated to the teaching of pharmacovigilance on pharmacy undergraduate degree programmes is low. Considering the importance of spontaneous reporting in drug safety and the shift in the role of the pharmacists, more time may need to be devoted to pharmacovigilance on pharmacy undergraduate courses. By doing so, new pharmacists would be more informed of the important role they play in drug safety and thereby potentially help enhance the level of ADR reporting. Copyright © 2012 John Wiley & Sons, Ltd.

  10. Multidrug resistance genes, including bla(KPC) and bla(CTX)-M-2, among Klebsiella pneumoniae isolated in Recife, Brazil.

    Science.gov (United States)

    Cabral, Adriane Borges; Melo, Rita de Cássia de Andrade; Maciel, Maria Amélia Vieira; Lopes, Ana Catarina Souza

    2012-10-01

    The prevalence of cephalosporins and carbapenem-resistant Klebsiella pneumoniae strains is rising in Brazil, with potential serious consequences in terms of patients' outcomes and general care. This study characterized 24 clinical isolates of K. pneumoniae from two hospitals in Recife, Brazil, through the antimicrobial susceptibility profile, analyses of β-lactamase genes (bla(TEM), bla(SHV),bla(CTX-M), bla(KPC), bla(VIM), bla(IMP), and bla(SPM), plasmidial profile and ERIC-PCR (Enterobacterial repetitive intergenic consensus-polymerase chain reaction). ERIC-PCR and plasmidial analysis grouped the isolates in 17 and 19 patterns, respectively. Six isolates from one hospital presented the same pattern by ERIC-PCR, indicating clonal dissemination. All isolates presented bla(SHV), 62.5% presented bla(CTX)-M-2, 29% bla(TEM), and 41.7% bla(KPC). Metallo-β-lactamase genes bla(VIM), bla(IMP), and bla(SPM) not detected. Eleven isolates were identified carrying at least 3 β-lactamase studied genes, and 2 isolates carried bla(SHV), bla(TEM), bla (CTX-M-2) and bla(KPC) simultaneously. The accumulation of resistance genes in some strains, observed in this study, imposes limitations in the therapeutic options available for the treatment of infections caused by K. pneumoniae in Recife, Brazil. These results should alert the Brazilian medical authorities to establish rigorous methods for more efficiently control the dissemination of antimicrobial resistance genes in the hospital environment.

  11. [Hospital pharmacists' perception of pharmacovigilance in Quebec].

    Science.gov (United States)

    Cerruti, L; Lebel, D; Bussières, J-F

    2016-03-01

    To assess the pharmacovigilance perception of Quebec's hospital pharmacists. Cross-sectional study. A questionnaire with 16 questions was developed in order to assess respondents' perception of their ability to practice pharmacovigilance, factors that can influence adverse drug reactions reporting and measures to increase reporting rate. The online questionnaire was sent to hospital pharmacist from Quebec in April 2014. The results were presented in the form of descriptive data. A total of 179/252 (71%) hospital pharmacists responded. More than 90% of respondents considered that they were able to practice all activities related to pharmacovigilance. During one year of practice, 98% of respondents faced at least one serious or unexpected adverse drug reaction and 77% notified at least one adverse drug reaction to Health Canada. The factors encouraging more than 89% of respondents to notify were: the severity, the rapidity of onset, the visibility of the reaction, the fact that the adverse drug reaction was unexpected or due to a recent marketed drug. More than 69% of respondents considered the overwork as the principal obstacle to the notification. The majority of respondents supported the implementation of 13/14 measures in order to increase reporting rate. Hospital pharmacists from Quebec presented a favorable ability to practice pharmacovigilance. Analysis of their perception of pharmacovigilance helped to identify improvements, such as the implementation of a pharmacovigilance coordinator in the health center. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

  12. Pharmacovigilance and the Italian Medicines Agency

    Science.gov (United States)

    Pimpinella, Giuseppe; Tartaglia, Loriana

    2013-01-01

    The new European Union (EU) regulations on pharmacovigilance require that the national systems are strengthened in order to fit the new requirements. The Italian Pharmacovigilance System, coordinated by the Italian Medicines Agency (AIFA), is made by local and regional structures. In 2007, a program for funding active pharmacovigilance projects in the Italian Regions was established by the National law. The AIFA is responsible for the preparation of guidelines aimed at the identification of research areas and for the approval of the projects submitted by the regions. In April 2012, the AIFA started a program of visits at the regional pharmacovigilance centers (RPCs), aimed at monitoring their performances, evaluating the quality of the activities in order to understand the main differences and discrepancies and with a view to start a program of harmonization of the procedures in place. The outcome of the visits program highlighted major differences among the quality management systems of the various centers; hence, AIFA has decided to launch an initiative to promote in the next months the harmonization of procedures. The synergy among AIFA, regional structures, RPCs, and local structure responsible for pharmacovigilance is needed in order to establish a robust pharmacovigilance system working in full compliance with the provisions of the new EU legislation. PMID:24347980

  13. Learning by doing in the student-run pharmacovigilance program

    NARCIS (Netherlands)

    Schutte, T.; Tichelaar, J.; Reumerman, M.O.; Van Eekeren, R.; Rolfes, L.; Richir, M.C.; Van Puijenbroek, E.; Van Agtmael, M.A.

    2015-01-01

    Background: Medication safety is an important topic in healthcare nowadays. Pharmacovigilance, the monitoring of drug safety after approval for marketing, depends mainly on the quality and quantity of reported adverse drug reactions (ADR). To increase pharmacovigilance awareness among medical

  14. Learning by doing in the student-run pharmacovigilance programme

    NARCIS (Netherlands)

    Schutte, T.; Tichelaar, J.; Reumerman, M.O.; Van Eekeren, R.; Rolfes, L.; Van Puijenbroek, E.P.; Richir, M.C.; Van Agtmael, M.A.

    2017-01-01

    Background: Pharmacovigilance, the monitoring of drug safety after marketing approval, depends highly on the adequate reporting of adverse drug reactions (ADRs). To improve pharmacovigilance awareness and future ADR reporting among medical students, we developed and evaluated a student-run

  15. [Pharmacovigilance in Germany : It is about time].

    Science.gov (United States)

    Douros, A; Schaefer, C; Kreutz, R; Garbe, E

    2016-06-01

    Pharmacovigilance is defined as the activities relating to the detection, assessment, and prevention of adverse drug reactions (ADRs). Although its beginnings in Germany date back more than 50 years, a stagnation in this field has been observed lately. Different tools of pharmacovigilance will be illustrated and the reasons for its stagnation in Germany will be elucidated. Spontaneous reporting systems are an important tool in pharmacovigilance and are based on reports of ADRs from treating physicians, other healthcare professionals, or patients. Due to several weaknesses of spontaneous reporting systems such as underreporting, media bias, confounding by comorbidity or comedication, and due to the limited quality of the reports, the development of electronic healthcare databases was publicly funded in recent years so that they can be used for pharmacovigilance research. In the US different electronic healthcare databases were merged in a project sponsored by public means resulting in more than 193 million individuals. In Germany the establishment of large longitudinal databases was never conceived as a public duty and has not been implemented so far. Further attempts to use administrative healthcare data for pharmacovigilance purposes are severely restricted by the Code of Social Law (Section 75, Book 10). This situation has led to a stagnation in pharmacovigilance research in Germany. Without publicly funded large longitudinal healthcare databases and an amendment of Section 75, Book 10, of the Code of Social Law, the use of healthcare data in pharmacovigilance research in Germany will remain a rarity. This could have negative effects on the medical care of the general population.

  16. Contribution of Latin America to pharmacovigilance.

    Science.gov (United States)

    González, Juan Camilo; Arango, Victoria E; Einarson, Thomas R

    2006-01-01

    Pharmacovigilance activities have been ongoing for 4 decades. However, little is known (especially outside of the area) about the contribution of Latin America to this field. To review and quantify the published literature on pharmacovigilance in Latin American countries. We searched electronic databases including MEDLINE (1966-2004), EMBASE (1980-2004), International Pharmaceutical Abstracts (1970-2004), Toxline (1992-2004), Literatura Latino-Americana e do Caribe em Ciências da Saúde (1982-2004), Sistema de Información Esencial en Terapéutica y Salud (1980-2004), and the Pan American Health Organization Web site (1970-2004) for articles on pharmacovigilance or adverse drug reactions in any of the 19 major Latin American countries. Papers were retrieved and categorized according to content and country of origin by 2 independent reviewers. There were 195 usable articles from 13 countries. Fifty-one of the papers retrieved dealt with pharmacovigilance centers (15 national centers, 10 hospitals, 26 other), 55 covered pharmacovigilance itself (21 theoretical papers, 9 with description of models, 25 educational papers), and 89 were pharmacoepidemiologic studies of adverse drug reactions (69 case reports, 13 observational cohorts, 2 cohort studies, 1 randomized clinical trial, 4 clinical papers on adverse reaction management). Studies have increased exponentially since 1980. Five countries (Argentina, Brazil, Chile, Costa Rica, Venezuela) published reports from national centers. No studies were found from 6 countries: Dominican Republic, El Salvador, Honduras, Nicaragua, Paraguay, or Uruguay. Most studied categories were antiinfectives and drugs affecting the central nervous system, cardiovascular system, and musculoskeletal system. Contributions of Latin American countries to the field of pharmacovigilence have been remarkable, considering the constraints on these countries. A need exists for an increased number of formal pharmacovigilance studies and research

  17. Detection of P. aeruginosa harboring bla CTX-M-2, bla GES-1 and bla GES-5, bla IMP-1 and bla SPM-1 causing infections in Brazilian tertiary-care hospital

    Directory of Open Access Journals (Sweden)

    Polotto Milena

    2012-08-01

    Full Text Available Abstract Background Nosocomial infections caused by Pseudomonas aeruginosa presenting resistance to beta-lactam drugs are one of the most challenging targets for antimicrobial therapy, leading to substantial increase in mortality rates in hospitals worldwide. In this context, P. aeruginosa harboring acquired mechanisms of resistance, such as production of metallo-beta-lactamase (MBLs and extended-spectrum beta-lactamases (ESBLs have the highest clinical impact. Hence, this study was designed to investigate the presence of genes codifying for MBLs and ESBLs among carbapenem resistant P. aeruginosa isolated in a Brazilian 720-bed teaching tertiary care hospital. Methods Fifty-six carbapenem-resistant P. aeruginosa strains were evaluated for the presence of MBL and ESBL genes. Strains presenting MBL and/or ESBL genes were submitted to pulsed-field gel electrophoresis for genetic similarity evaluation. Results Despite the carbapenem resistance, genes for MBLs (blaSPM-1 or blaIMP-1 were detected in only 26.7% of isolates. Genes encoding ESBLs were detected in 23.2% of isolates. The blaCTX-M-2 was the most prevalent ESBL gene (19.6%, followed by blaGES-1 and blaGES-5 detected in one isolate each. In all isolates presenting MBL phenotype by double-disc synergy test (DDST, the blaSPM-1 or blaIMP-1 genes were detected. In addition, blaIMP-1 was also detected in three isolates which did not display any MBL phenotype. These isolates also presented the blaCTX-M-2 gene. The co-existence of blaCTX-M-2 with blaIMP-1 is presently reported for the first time, as like as co-existence of blaGES-1 with blaIMP-1. Conclusions In this study MBLs production was not the major mechanism of resistance to carbapenems, suggesting the occurrence of multidrug efflux pumps, reduction in porin channels and production of other beta-lactamases. The detection of blaCTX-M-2,blaGES-1 and blaGES-5 reflects the recent emergence of ESBLs among antimicrobial resistant P. aeruginosa and

  18. Detection of P. aeruginosa harboring bla CTX-M-2, bla GES-1 and bla GES-5, bla IMP-1 and bla SPM-1 causing infections in Brazilian tertiary-care hospital

    Science.gov (United States)

    2012-01-01

    Background Nosocomial infections caused by Pseudomonas aeruginosa presenting resistance to beta-lactam drugs are one of the most challenging targets for antimicrobial therapy, leading to substantial increase in mortality rates in hospitals worldwide. In this context, P. aeruginosa harboring acquired mechanisms of resistance, such as production of metallo-beta-lactamase (MBLs) and extended-spectrum beta-lactamases (ESBLs) have the highest clinical impact. Hence, this study was designed to investigate the presence of genes codifying for MBLs and ESBLs among carbapenem resistant P. aeruginosa isolated in a Brazilian 720-bed teaching tertiary care hospital. Methods Fifty-six carbapenem-resistant P. aeruginosa strains were evaluated for the presence of MBL and ESBL genes. Strains presenting MBL and/or ESBL genes were submitted to pulsed-field gel electrophoresis for genetic similarity evaluation. Results Despite the carbapenem resistance, genes for MBLs (blaSPM-1 or blaIMP-1) were detected in only 26.7% of isolates. Genes encoding ESBLs were detected in 23.2% of isolates. The blaCTX-M-2 was the most prevalent ESBL gene (19.6%), followed by blaGES-1 and blaGES-5 detected in one isolate each. In all isolates presenting MBL phenotype by double-disc synergy test (DDST), the blaSPM-1 or blaIMP-1 genes were detected. In addition, blaIMP-1 was also detected in three isolates which did not display any MBL phenotype. These isolates also presented the blaCTX-M-2 gene. The co-existence of blaCTX-M-2 with blaIMP-1 is presently reported for the first time, as like as co-existence of blaGES-1 with blaIMP-1. Conclusions In this study MBLs production was not the major mechanism of resistance to carbapenems, suggesting the occurrence of multidrug efflux pumps, reduction in porin channels and production of other beta-lactamases. The detection of blaCTX-M-2,blaGES-1 and blaGES-5 reflects the recent emergence of ESBLs among antimicrobial resistant P. aeruginosa and the extraordinary

  19. Innovations for the future of pharmacovigilance.

    Science.gov (United States)

    Almenoff, June S

    2007-01-01

    Post-marketing pharmacovigilance involves the review and management of safety information from many sources. Among these sources, spontaneous adverse event reporting systems are among the most challenging and resource-intensive to manage. Traditionally, efforts to monitor spontaneous adverse event reporting systems have focused on review of individual case reports. The science of pharmacovigilance could be enhanced with the availability of systems-based tools that facilitate analysis of aggregate data for purposes of signal detection, signal evaluation and knowledge management. GlaxoSmithKline (GSK) recently implemented Online Signal Management (OSM) as a data-driven framework for managing the pharmacovigilance of marketed products. This pioneering work builds upon the strong history GSK has of innovation in this area. OSM is a software application co-developed by GSK and Lincoln Technologies that integrates traditional pharmacovigilance methods with modern quantitative statistical methods and data visualisation tools. OSM enables the rapid identification of trends from the individual adverse event reports received by GSK. OSM also provides knowledge-management tools to ensure the successful tracking of emerging safety issues. GSK has developed standard procedures and 'best practices' around the use of OSM to ensure the systematic evaluation of complex safety datasets. In summary, the implementation of OSM provides new tools and efficient processes to advance the science of pharmacovigilance.

  20. Advancing Drug Safety Through Prospective Pharmacovigilance.

    Science.gov (United States)

    Pitts, Peter J; Le Louet, Hervé

    2018-01-01

    Much has changed in a relatively short period of time. There is a raging debate over the level of evidence expected to first introduce a treatment to patients based on smaller, more adaptive data sets. Some argue for less data followed by postapproval follow-up, others for more adaptive clinical trial designs and end-point modification driven by patient-focused drug development and use of real-world evidence. The transition in both the review and postmarketing regulatory framework is happening in front of our eyes in real time. To improve the ability of patients to receive high-quality, safe, effective, and timely care, better information via pharmacovigilance must be a priority as the world's many regulatory systems build the capacity to harness electronic health information to improve health, care quality, and safety. Globally, the widely variable ability of nations to build reliable regulatory systems (from precise review to robust pharmacovigilance) is a dangerous source of health care inequality. Developing validated tools and techniques for "predictive pharmacovigilance" will assist all health systems in better understanding the risks and benefits of the medicines they regulate by understanding what should be happening once a new medicine moves from risk-benefit regulatory efficacy to real-world risk-effectiveness. This will be of particular utility for smaller regulatory agencies with fewer resources. By comparing preapproval predictive pharmacovigilance data, developing regulatory authorities will be able to better understand the potential gap between what was predicted and what was actually measured (via more traditional pharmacovigilance methodologies). Predictive pharmacovigilance recognizes the value of understanding the imperfect reporting of real-world clinical use and that the absence of reporting is, in itself, an important postmarketing signal.

  1. Detection of blaNDM, blaDIM, blaIMP, blaVIM and blaCTX-M-15 beta-lactamase Genes among Pseudomonas aeruginosa and Acinetobacter baumannii Strains Isolated from Two Hospitals of Tehran, Iran

    Directory of Open Access Journals (Sweden)

    Tahere Farajzadeh Alan

    2016-10-01

    Full Text Available Background: In this study, we evaluated the existence of blaNDM ,  blaDIM, blaIMP, blaVIM, blaCTX-M-15 beta-lactamase  genes among Pseudomonas aeruginosa and Acinetobacter baumannii strains isolated from hospitalized patients.Materials and Methods: From June 2013 to May 2014, thirty-four nonduplicate nonconsecutive isolates of A. baumannii and P. aeruginosa were isolated from blood, respiratory tract, wound, sputum and urine samples of patients from hospitalized in two hospitals in Tehran, Iran. Antibiotic susceptibility test was performed by Kirby-Bauer disc diffusion method according to CLSI guidelines. In this study, the frequency of MBL (metallo-beta-lactamase producers was evaluated by CDDT (Combined disk diffusion test and prevalence of blaNDM, blaDIM, blaIMP, blaVIM and blaCTX-M-15  genes were evaluated  by PCR and sequencing methods among P. aeruginosa and  A. baumannii strains isolated from  hospitalized patient of Tehran during 2013 -2014 years.Results: Of thirty-four non-fermenter isolates, 24 (70.58% P. aeruginosa and 10 (29.41% as A. baumannii were isolated and identified. High rate of resistance to common antibiotics were detected specially among A. baumannii isolates that showed 100% resistance to 4 of tested antibiotics. The CDDT results reveal that 4 (16.66% of the P. aeruginosa isolates and 1 (10% of the A.baumannii were positive for production of MBLs. The prevalence of blaCTX-M-15 gene among 10 A. baumannii isolates was 4 (40%, and for IMP-1, 2 (20%. The OXA-51 has been investigated and was detected in all A. baumannii isolates. Also the prevalence of blaCTX-M-15 gene among 24 P.aeruginosa isolates was 11 (45.83%, and for IMP-1, 3(12.5%. Fortunately, NDM, blaVIM, blaDIM gene was not detected in all isolates.Conclusion: The detection of MBL-producing A. baumannii and P. aeruginosa strains detected in this research is of great concern and highlights the need of infection control measures, including antimicrobial

  2. Occurrence of Enterobacter hormaechei carrying blaNDM-1 and blaKPC-2 in China.

    Science.gov (United States)

    Yang, Biwei; Feng, Yu; McNally, Alan; Zong, Zhiyong

    2018-02-01

    Three carbapenem-resistant clinical isolates of the Enterobacter cloacae complex (ECC) were recovered from different patients in a hospital. All 3 isolates carried 2 carbapenemase genes bla KPC-2 and bla NDM-1 . A study was performed to characterize their relatedness and to investigate possible links among the patients. Whole genome sequencing revealed that the isolates were Enterobacter hormaechei and belonged to ST177 of the ECC. There were 19-142 single nucleotide polymorphisms (SNPs) between the isolates, suggesting that the isolates were likely from a central reservoir, which might have existed for some time. bla KPC-2 and bla NDM-1 were carried on 2 different IncF-type plasmids in the isolates. The 3 bla NDM-1 -carrying plasmids were almost identical and were self-transmissible, while the bla KPC-2 -carrying plasmids were only transmissible in the presence of the bla NDM-1 -carrying plasmid. The source of and direct links among them were not identified, suggesting a hospital transmission of a common multidrug resistant strain. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Pharmacovigilance activities in ASEAN countries.

    Science.gov (United States)

    Suwankesawong, Wimon; Dhippayom, Teerapon; Tan-Koi, Wei-Chuen; Kongkaew, Chuenjid

    2016-09-01

    This study aimed to explore the current landscape and identify challenges of pharmacovigilance (PV) among Association of Southeast Asian Nations (ASEAN) countries. This cross-sectional survey collected data from May 2014 to December 2015. Questionnaires seeking to collect information on resources, processes, roles and responsibility, and functions of PV systems were sent to relevant persons in the ASEAN countries. Functions of PV centers were measured using the minimum World Health Organization requirements for a functional national PV system. Performances of PV centers were measured by the following: (1) the indicators related to the average number of individual case safety reports (ICSR); (2) presence of signal detection activities and subsequent action; and (3) contribution to the global vigilance database. Cambodia, Indonesia, Laos, Malaysia, the Philippines, Singapore, Thailand, and Vietnam completed the survey. PV systems in four surveyed countries (Indonesia, Malaysia, Singapore, and Thailand) achieved all aspects of the World Health Organization minimum requirement for a functional national PV system; the remaining countries were deemed to have unclear communication strategies and/or no official advisory committee. Average numbers of recent ICSR national returns ranged from 7 to 3817 reports/year/million population; three countries (Malaysia, Singapore, and Thailand) demonstrated good performance in reporting system and reported signal detection activities and subsequent actions. All participating countries had submitted ICSRs to the Uppsala Monitoring Center during the survey period (2013-2015). Four participating countries had functional PV systems. PV capacity, functionality, and legislative framework varied depending on local healthcare ecosystem networks. Implementing effective communication strategies and/or technical assistance from the advisory committee are needed to strengthen PV in ASEAN. Copyright © 2016 John Wiley & Sons, Ltd. Copyright

  4. Advances in pharmacovigilance initiatives surrounding antimicrobial resistance-Indian perspective.

    Science.gov (United States)

    Bairy, Laxminarayana Kurady; Nayak, Veena; A, Avinash; Kunder, Sushil Kiran

    2016-08-01

    In recent years the development of antimicrobial resistance has been accelerating, the discovery of new antimicrobial agents has slowed substantially in past decades. This review mainly focuses on the problem of antimicrobial resistance(AMR); the various contributor mechanisms, consequences and future of AMR. The review also highlights the irrational use of antimicrobials, improving their usage and problems associated with pharmacovigilance of antimicrobial resistance. Pharmacovigilance in the form of surveillance of antibiotic use is being done in 90% of the countries worldwide through the WHONET program developed by WHO. However, the data comes from a limited area of the globe. Data from every part of the world is required, so that there is geographical representation of every region. A major hurdle in quantifying the extent of antimicrobial resistance is the fact that there are several known microbes, that may turn out to be resistant to one or more of the several known antimicrobial agents. The global action plan initiated by WHO, if implemented successfully will definitely reduce AMR and will help in evaluating treatment interventions.

  5. Pharmacovigilance-related topics at the level of the International Conference on Harmonisation (ICH).

    Science.gov (United States)

    Bahri, Priya; Tsintis, Panos

    2005-06-01

    Marketing authorisations for medicines need to be based on the universal criteria quality, safety and efficacy, whilst taking into account local public health needs. With view to using resources efficiently and avoiding delay in access to medicines, scientific standards for investigating quality, safety and efficacy should be universal too. A major step to achieve this was taken in 1990 when the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) was established between authorities and industry in the European Union (EU), Japan and the United States. Since then more than 50 ICH Guidelines have been published, out of which six are specific to pharmacovigilance. They refer to management and expedited reporting of individual adverse drug reaction (ADR) cases, including electronic formats, periodic reporting of worldwide data and planning of pharmacovigilance. Their development has to be seen in the context of initiatives taken in the three ICH Regions to strengthen pharmacovigilance. Most recently this involves making use of risk management concepts, reflecting new thinking of proactivity in pharmacovigilance. Moreover, consideration is given to regional and international cooperation beyond the ICH Regions.

  6. Pharmacovigilance: Tiens Slimming Tea Causes Increased Blood ...

    African Journals Online (AJOL)

    ... possible link between the constituents of the slimming tea and increased blood pressure and also provide evidence of other possible harmful effects that may occur with the use of the slimming tea. Keywords: Pharmacovigilance, hypertension, slimming tea. West African Journal of Pharmacology and Drug Research Vol.

  7. Vaccine Pharmacovigilance: Adverse Effects Reported and the ...

    African Journals Online (AJOL)

    Routine utilization of vaccines during immunization in children is a tool in the reduction of childhood morbidity and mortality of infectious disease globally. This requires pharmacovigilance to ensure safety among the category of patients. Due to the exposure of new born to vaccine at birth, it became necessary to assess the ...

  8. Pharmacovigilance : methods, recent developments and future perspectives

    NARCIS (Netherlands)

    Harmark, L.; van Grootheest, A. C.

    Background Pharmacovigilance, defined by the World Health Organisation as 'the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem' plays a key role in ensuring that patients receive safe drugs. Our knowledge

  9. Pharmacovigilance Perceptions and Practice of Health Care ...

    African Journals Online (AJOL)

    This study aimed at documenting the perception and practice of pharmacovigilance amongst health workers in Lagos State. It also tried to identify the reasons for underreporting and steps that could be adapted to increase reporting rates in Nigeria. The study was a questionnaire based cross-sectional study. Multistage ...

  10. Past, present, and future of pharmacovigilance in Korea

    Science.gov (United States)

    Kang, Dong Yoon; Ahn, Kyung-Min; Kang, Hye-Ryun

    2017-01-01

    As an essential part of patient safety, pharmacovigilance is of worldwide interest and should expand its scope and focus on new emerging issues. South Korea has been making continuous efforts in the field of pharmacovigilance for the last 3 decades since voluntary adverse drug reaction (ADR) reporting system was first launched in 1988. Korea joined the World Health Organization Program for International Drug Monitoring in 1992, and the activities of Pharmacovigilance Research Network, Korean Society for Pharmacoepidemiology and Risk Management, and Regional Pharmacovigilance Center (RPVC) have contributed to the remarkable progress in the pharmacovigilance area and global status. RPVCs have played pivotal roles in establishment of pharmacovigilance system in Korea by monitoring voluntary ADR reports. RPVCs started with 3 hospitals in 2006 and have now expanded to 27 hospitals nationwide. The Korea Institute of Drug Safety & Risk Management was established in 2012 and in charge of operating the decentralized national pharmacovigilance system. The voluntary report of ADR, which is the basis of current pharmacovigilance system, has various limitations and an active surveillance system can be the overarching alternative. This change in pharmacovigilance paradigm is a global trend and Korea has excellent infrastructure such as broad distribution of electronic medical recording systems and a nationwide single healthcare insurance. As a result, the pharmacovigilance in Korea is now expected to progress to a new active surveillance system from traditional spontaneous reporting system. PMID:28765823

  11. Detection of multidrug-resistant Pseudomonas aeruginosa harboring bla GES-1 and bla GES-11 in Recife, Brazil

    Directory of Open Access Journals (Sweden)

    Valdemir Vicente da Silva Júnior

    Full Text Available Abstract INTRODUCTION: Pseudomonas aeruginosa, an important pathogen globally, presents several resistance mechanisms. This study aimed to investigate the presence of bla GES in clinical isolates of Pseudomonas aeruginosa obtained from various clinical specimens from patients admitted to three different hospitals in Recife, Brazil. The Guiana extended spectrum beta-lactamase (GES enzymes are responsible for conferring broad spectrum resistance to beta-lactam drugs, including the carbapenems. METHODS: A total of 100 carbapenem-resistant P. aeruginosa isolates underwent polymerase chain reaction (PCR testing to identify bla GES, bla KPC, bla SPM-1, bla IMP, and bla VIM. Additionally, PCR products positive for bla GES were sequenced. The clonal profiles of these same isolates were then determined by means of enterobacterial repetitive intergenic consensus (ERIC-PCR analysis. RESULTS: PCR analysis revealed that four isolates harbored bla GES; DNA sequencing showed that two harbored bla GES-1 and two bla GES-11. Beta-lactamase genes bla SPM-1, bla IMP, bla VIM, and bla KPC were investigated; none of these genes was detected. Automated susceptibility testing methods (Vitek®2, bioMérieux showed that the bla GES-1-positive isolates were only susceptible to polymyxin B. The patterns obtained with ERIC-PCR methods showed clonal relationship between the two isolates that harbored bla GES-11, whereas different clonal profiles were found in the isolates harboring bla GES-1. CONCLUSIONS: We detected the presence of bacterial isolates positive for two different variants of the enzyme GES in three different hospitals from Recife, Brazil. These enzymes have a great capacity for dissemination among Gram-negative bacteria and confer broad-spectrum resistance to beta-lactam antibiotics and to the carbapenems.

  12. Detection of multidrug-resistant Pseudomonas aeruginosa harboring bla GES-1 and bla GES-11 in Recife, Brazil.

    Science.gov (United States)

    Silva Júnior, Valdemir Vicente da; Ferreira, Laura Durão; Alves, Lílian Rodrigues; Cabral, Adriane Borges; Jácome, Paula Regina Luna de Araújo; Araújo, Paulo Sérgio Ramos de; Lopes, Ana Catarina de Souza; Maciel, Maria Amélia Vieira

    2017-01-01

    Pseudomonas aeruginosa, an important pathogen globally, presents several resistance mechanisms. This study aimed to investigate the presence of bla GES in clinical isolates of Pseudomonas aeruginosa obtained from various clinical specimens from patients admitted to three different hospitals in Recife, Brazil. The Guiana extended spectrum beta-lactamase (GES) enzymes are responsible for conferring broad spectrum resistance to beta-lactam drugs, including the carbapenems. A total of 100 carbapenem-resistant P. aeruginosa isolates underwent polymerase chain reaction (PCR) testing to identify bla GES, bla KPC, bla SPM-1, bla IMP, and bla VIM. Additionally, PCR products positive for bla GES were sequenced. The clonal profiles of these same isolates were then determined by means of enterobacterial repetitive intergenic consensus (ERIC)-PCR analysis. PCR analysis revealed that four isolates harbored bla GES; DNA sequencing showed that two harbored bla GES-1 and two bla GES-11. Beta-lactamase genes bla SPM-1, bla IMP, bla VIM, and bla KPC were investigated; none of these genes was detected. Automated susceptibility testing methods (Vitek®2, bioMérieux) showed that the bla GES-1-positive isolates were only susceptible to polymyxin B. The patterns obtained with ERIC-PCR methods showed clonal relationship between the two isolates that harbored bla GES-11, whereas different clonal profiles were found in the isolates harboring bla GES-1. We detected the presence of bacterial isolates positive for two different variants of the enzyme GES in three different hospitals from Recife, Brazil. These enzymes have a great capacity for dissemination among Gram-negative bacteria and confer broad-spectrum resistance to beta-lactam antibiotics and to the carbapenems.

  13. Rapid and simple identification of carbapenemase genes, blaNDM, blaOXA-48, blaVIM, blaIMP-14and blaKPCgroups, in Gram-negative bacilli by in-house loop-mediated isothermal amplification with hydroxynaphthol blue dye.

    Science.gov (United States)

    Srisrattakarn, Arpasiri; Lulitanond, Aroonlug; Wilailuckana, Chotechana; Charoensri, Nicha; Wonglakorn, Lumyai; Saenjamla, Pimjai; Chaimanee, Prajuab; Daduang, Jureerut; Chanawong, Aroonwadee

    2017-07-01

    Carbapenem-resistant Enterobacteriaceae isolates by carbapenemase production are being reported globally with increasing frequency, leading to limited therapeutic options. We therefore developed a loop-mediated isothermal amplification method with hydroxynaphthol blue dye (LAMP-HNB) for rapid confirmation of bla NDM , bla OXA-48 , bla VIM , bla IMP-14 and bla KPC groups. Sixty-two Enterobacteriaceae and Pseudomonas spp. isolates carrying various carbapenemase genes (28 bla NDM-1 , 9 bla IMP-14a , 2 bla IMP-48 , 1 bla IMP-1 , 1 bla IMP-4 , 1 bla IMP-9 , 1 bla IMP-15 , 4 bla VIM-2 , 1 bla VIM-1 , 1 bla IMP-14a & bla VIM-2 , 7 bla KPC-2 , 3 bla OXA-48 and 3 bla OXA-181 ) and 37 non-carbapenemase-producing Enterobacteriaceae isolates as confirmed by the PCR methods were included. Bacterial DNA was extracted by a simple boiling method. The LAMP-HNB method for each target gene was carried out using a set of six primers under isothermal condition at 65 °C in an ordinary water bath within 60 min and visual measurement of reaction by the change from violet to sky blue. This method had high efficiency (100% sensitivity and specificity) for identifying the bla NDM , bla OXA-48 , bla VIM , bla IMP-14 and bla KPC groups compared with the PCR method. The HNB is easy to prepare, inexpensive and provides reliable results. Therefore, this method could be used as a confirmatory carbapenemase test in routine laboratory or for epidemiological purposes.

  14. Dissemination of Pseudomonas aeruginosa producing bla IMP-1 and bla VIM-1 in Qazvin and Alborz educational hospitals, Iran.

    Science.gov (United States)

    Peymani, Amir; Naserpour Farivar, Taghi; Mohammadi Ghanbarlou, Mahdi; Najafipour, Reza

    2015-12-01

    Pseudomonas aeruginosa is a frequent opportunistic pathogen in health care associated infections that is highly resistant to the majority of β-lactams. The aims of this study were to access the antimicrobial susceptibility pattern of P. aeruginosa isolated from educational hospitals of Qazvin and Alborz provinces, to determine the prevalence of metallo-β-lactamase (MBL) among carbapenem non-susceptible isolates by combined disk (CD) method, and to detect the bla IMP, bla VIM, bla SIM, bla GIM, bla SPM and bla NDM-1-MBL genes. In this cross-sectional study, 300 P. aeruginosa isolates were collected from different clinical specimens in two provinces of Qazvin and Alborz hospitals, Iran. After identification of isolates by standard laboratory methods, antimicrobial susceptibility was done against 17 antibiotics according to clinical and laboratory standards institute (CLSI) guideline. CD method was carried out for detection of MBLs and the presence of bla IMP, bla VIM, bla SIM, bla GIM, bla NDM-1 and bla SPM-genes was further assessed by PCR and sequencing methods. In this study, 107 (35.66%) isolates were non-susceptible to imipenem and/or meropenem among those 56 (52.3%) isolates were metallo-β-lactamase producer. Twenty-four of 56 (42.85%) MBL-positive isolates were confirmed to be positive for MBL-encoding genes in which 14 (25%) and 10 (17.85%) isolates carried bla IMP-1 and bla VIM-1 genes either alone or in combination. Three (5.35%) isolates carried bla IMP and bla VIM genes, simultaneously. Considering the moderate prevalence and clinical importance of MBL-producing isolates, rapid identification and use of appropriate infection control (IC) measures are necessary to prevent further spread of infections by these resistant organisms.

  15. bla(IMP) and bla(VIM) mediated carbapenem resistance in Pseudomonas and Acinetobacter species in India.

    Science.gov (United States)

    Amudhan, M Shanthi; Sekar, Uma; Kamalanathan, Arunagiri; Balaraman, Sekar

    2012-11-26

    The emergence and rapid spread of blaIMP and blaVIM metallo-beta-lactamase (MBL) producing Gram-negative bacteria causing nosocomial infections are of concern worldwide due to limited treatment options. A total of 179 nonreplicate, consecutive, carbapenem resistant Pseudomonas aeruginosa (61), Acinetobacter baumannii (116), Acinetobacter lwoffii (1) and Pseudomonas stutzeri (1) isolated from patients hospitalized for 48 hours or more were included in the study. The minimum inhibitory concentrations (MIC) to imipenem and meropenem were determined and interpreted according to Clinical Laboratory Standards Institute guidelines. The Modified Hodge Test (MHT) and inhibitor potentiated disk diffusion tests with ethylenediaminetetraacetic acid (EDTA) were used for screening of carbapenamases and MBL production respectively. Polymerase chain reaction (PCR) was performed for the detection of MBL (blaVIM and blaIMP) genes. Gene sequencing was performed for representative isolates. MHT was positive in 94.4% (n = 169). MBL screening with EDTA was positive in 80.4% (n = 144). MBL genes bla VIM and bla IMP were detected in 92 (51.4%) isolates. Bla VIM alone was detected in 89 isolates while two isolates had bla IMP alone. One isolate had both bla VIM and bla IMP. Among the P. aeruginosa, 36 carried the MBL gene. In A. baumannii, 54 carried the MBL gene. Bla VIM was found in P. stutzeri and A. lwoffii isolates. Carbapenem resistance in P. aeruginosa and A. baumannii is chiefly mediated by MBL production. The common MBL gene is the blaVIM.

  16. European pharmacovigilance: increasingly outsourced to drug companies.

    Science.gov (United States)

    2014-12-01

    New regulations reorganising pharmacovigilance at the European level were adopted in late 2010, then revised in 2012 in the wake of the Mediator (benfluorex) disaster. The European Commission's original proposals, released in 2008, would have represented a major step backwards in the protection afforded to European citizens, in particular by facilitating earlier marketing authorisations. Thanks to the mobilisation of civil society, the Members of the European Parliament have improved these proposals, supported by EU health ministers. The role of the new European Pharmacovigilance Risk Assessment Committee (PRAC) has been strengthened. Patients in every Member State have the right to report adverse drug effects directly to health authorities. EU drug regulatory agencies are required to provide greater transparency, and public access to information about adverse effects has been improved. However, one major regression persists: the central role given to pharmaceutical companies in the collection and interpretation of reports of adverse drug effects, despite their conflicts of interest. Drug companies are asked to record the adverse effect reports of which they are aware in a vast European centralised database, Eudravigilance, without going through drug regulatory agencies. Pharmaceutical companies remain responsible for producing "a scientific evaluation of the risk-benefit balance" of their drug, as part of the periodic benefit-risk assessment reports they are required to submit to drug regulatory agencies. These reports are analysed for the entire EU by two Member States (one rapporteur and one co-rapporteur), so that harmonised decisions can be taken. But these decisions are based on data preanalysed by the drug companies. In addition, the independence of the European Medicines Agency is undermined by its financial reliance on the fees paid by pharmaceutical companies in exchange for these assessments. In 2012, following France's Mediator disaster, several modest

  17. Medication errors: pharmacovigilance centres in detection and prevention

    Science.gov (United States)

    Bencheikh, Rachida Soulaymani; Benabdallah, Ghita

    2009-01-01

    Detecting medication errors needs collaboration between various organizations, such as patient safety institutions, pharmacovigilance centres, and poison control centres. In order to evaluate the input of pharmacovigilance centres and poison control centres in detecting and evaluating medication errors a pilot project was initiated by the World Alliance for Patient Safety in collaboration with the Uppsala Monitoring Centre; the Moroccan pharmacovigilance centre acted as project coordinator. As part of this project, a questionnaire on detecting medication errors was circulated to pharmacovigilance centres and poison control centres around the world, in order to assess their ability to detect and analyse medication errors. The results showed that through their databases pharmacovigilance centres can detect, identify, analyse, and classify medication errors and carry out root cause analysis, which is an important tool in preventing medication errors. The duties of pharmacovigilance centres in preventing medication errors include informing health-care professionals about the importance of reporting such errors and creating a culture of patient safety. Pharmacovigilance centres aim to prevent medication errors in collaboration with poison control centres. Such collaboration allows improved detection and improved preventive strategies. In addition, collaboration with regulatory authorities is important in finalizing decisions. Collaboration between pharmacovigilance centres and poison control centres should be strengthened and bridges need to be built linking pharmacovigilance centres, poison control centres, and organizations dedicated to patient safety, in order to avoid duplication of workload. PMID:19594539

  18. Tamoxifen Pharmacovigilance: Implications for Safe Use in the Future.

    Science.gov (United States)

    Antimisiaris, Demetra; Bae, Ki-Hwan Gabriel; Morton, Laura; Gully, Zahara

    2017-09-01

    To survey the status of current tamoxifen pharmacovigilance documentation reflecting tamoxifen use in an academic outpatient multispecialty practice in older adults. This data will help provide information to develop improved pharmacovigilance for a growing cohort of older adult users. The data will be utilized by an interdisciplinary team developing new methods of identifying factors for individualized pharmacovigilance in older adults. Retrospective chart review to gather descriptive and quantitative data on tamoxifen pharmacovigilance. Multi-specialty clinic. Ninety-three patients 60 years of age and older. Quantitative report of tamoxifen monitoring as well as descriptive analysis of individual cases. We found 19 cases of serious adverse events possibly related to tamoxifen (thrombi, uterine malignancies). There were 15 cases with no documentation of pharmacovigilance. All cases had incomplete pharmacovigilance documented. There were two cases of hypercalcemia. There was one case of tamoxifen discontinuation resulting from muscle pain and with chronic muscle pain complaints while receiving tamoxifen. We observed a correlation in older age or high comorbidity burden patients and adverse events patients. Some studies direct the important pharmacovigilance toward prevention of thrombi, uterine malignancies, and hypercalcemia; however, it is not easy to identify recommendations for frequency or focus of monitoring to prevent adverse events for individual older adults based on existing recommendations. The data collected and presented in this study serve to heighten awareness of tamoxifen pharmacovigilance and as a starting point for the application of machine learning techniques and modeling to identify high-risk patients and individualized pharmacovigilance recommendations.

  19. Are we pharmacovigilant enough in ophthalmic practice?

    Directory of Open Access Journals (Sweden)

    Ashok Dubey

    2013-01-01

    Full Text Available No drug is absolutely safe. Pharmacovigilance is the science related to detection, assessment, understanding and prevention of adverse effects or any other possible drug-related problems. The ocular medications and devices can cause localized and systemic adverse effects. Not all adverse effects are known when a drug or device is launched in market because of limitations of clinical trials. Many adverse effects are recognized due to the spontaneous reporting of the vigilant doctors who observe and report such events encountered in their practice. Despite a large ophthalmic patient population base, India does not have robust adverse drug reaction (ADR database because of lack of reporting culture. Government of India recently launched the Pharmacovigilance Programme of India (PvPI to monitor ADRs and create awareness among the healthcare professionals about the importance of ADRs. Suspecting and reporting a possible drug reaction is very important in developing a safe and rational ophthalmic practice.

  20. A review of the National pharmacovigilance system in Malta - implementing and operating a pharmacovigilance management system.

    Science.gov (United States)

    Tanti, Amy; Micallef, Benjamin; Serracino-Inglott, Anthony; Borg, John-Joseph

    2017-01-01

    Regulatory authorities have a legal mandate to implement and maintain a Pharmacovigilance System designed to monitor the safety of authorised medicinal products and detect any change to their risk-benefit balance. Areas covered: This review maps the implementation of pharmacovigilance activities in Malta since accession in the EU in mid 2004 and discusses the challenges the Maltese Regulator encountered while setting up adequate and effective systems to fulfil its legal mandate. Areas reviewed are those around ADR reporting, promotion and safety communications including rapid alerts and recalls, direct healthcare professional communications, risk minimisation measures and safety circulars and quality systems. Expert opinion: Within a ten year period, 3 EU directives on pharmacovigilance were implemented by our agency. Despite limitations to resources, based on a prioritised implementation, the legislation provisions are now fully operational with a good level of sustainability. Lessons learnt from this process are discussed in this review. The coming years will involve strengthening and consolidation of existing processes.

  1. Pharmacoepidemiology and its input to pharmacovigilance.

    Science.gov (United States)

    Faillie, Jean-Luc; Montastruc, François; Montastruc, Jean-Louis; Pariente, Antoine

    2016-04-01

    The aim of this article is to discuss the contribution of pharmacoepidemiology to pharmacovigilance in the context of drug safety monitoring. Because this contribution requires a comparison of the approaches and a presentation of their respective merits, we have tried to show that this comparison did not necessarily mean opposing these methods, which would not serve any useful purpose. We wanted to underline the fact that the notion of contribution of one to the other implied a complementarity that we propose to demonstrate. Pharmacovigilance is essentially based on the study of spontaneous reports and the clinical and pharmaceutical analysis of the implication of given drugs in adverse drug reactions. It yields performances that are unequalled to this day when safety warning signs relate to rare adverse events or to drugs that are rarely used, or when the drug-related event has specificities that are not found for other aetiologies. Pharmacoepidemiology for its part, through its population-related studies and the possible use of a comparison group, enables a quantification of risks that is impossible to carry out using spontaneous reporting alone. It also enables the highlighting and quantification of safety signals for events that are frequent and multifactorial, where the role of a drug in individual cases can be difficult to detect, and therefore difficult to identify from spontaneous reporting. All in all, this is the major contribution of pharmacoepidemiology to pharmacovigilance, where it can be said that it complements pharmacovigilance in drug safety monitoring but in no way could replace it. Copyright © 2016. Published by Elsevier Masson SAS.

  2. ADVERSE DRUG REACTION (ADR) MONITORING AND PHARMACOVIGILANCE

    OpenAIRE

    D. KAVITHA

    2013-01-01

    The need for systematic follow up of medicines for adverse drug reactions once they are introduced into general use has been widely recognised today. Even in developing countries like India, national pharmacovigilance programme has been started for monitoring adverse drug reactions. In its first year this program mainly aimed to foster the culture of ADR notification among health care professionals. As a part of health care team every pharmacist must have knowledge about adverse drug reaction...

  3. Traceability of biologicals: present challenges in pharmacovigilance.

    Science.gov (United States)

    Vermeer, Niels S; Spierings, Irina; Mantel-Teeuwisse, Aukje K; Straus, Sabine M J M; Giezen, Thijs J; Leufkens, Hubert G M; Egberts, Toine C G; De Bruin, Marie L

    2015-01-01

    Traceability is important in the postmarketing surveillance of biologicals, since changes in the manufacturing process may give rise to product- or batch-specific risks. With the expected expansion of the biosimilar market, there have been concerns about the ability to trace individual products within pharmacovigilance databases. The authors discuss the present challenges in the traceability of biologicals in relation to pharmacovigilance, by exploring the processes involved in ensuring traceability. They explore both the existing systems that are in place for the recording of exposure information in clinical practice, as well as the critical steps involved in the transfer of exposure data to various pharmacovigilance databases. The existing systems ensure the traceability of biologicals down to the manufacturer within pharmacy records, but do not support the routine recording of batch information. Expected changes in supply chain standards provide opportunities to systematically record detailed exposure information. Spontaneous reporting systems are the most vulnerable link in ensuring traceability, due to the manual nature of data transfer. Efforts to improve the traceability should, in the short term, be focused toward encouraging health professionals and patients to systematically record and report detailed exposure information. Long-term solutions lie in expanding the accessibility to, and increasing the electronic exchange of exposure data.

  4. Pharmacovigilance of Biologics in a Multisource Environment.

    Science.gov (United States)

    Sagi, Sreedhar; Cohen, Hillel P; Woollett, Gillian R

    2017-12-01

    It is important that systems are in place to ensure that appropriate and comprehensive records are kept for use of all medications. It is fundamental to an effective pharmacovigilance system that patient medical records contain sufficient information to identify which medication has been prescribed, when it was administered, and at what dose. The availability of biologics from multiple sponsors has raised questions by some health care providers about the ability of current pharmacovigilance systems to trace specific biologics. In this article, periodic safety update reports were used to assess current postapproval safety monitoring for 3 biosimilars (epoetin alfa, somatropin, and filgrastim) that collectively represented nearly 350 million patient days of treatment worldwide. The reference products have each been marketed for over 10 years, forming a strong baseline of postmarketing safety data against which the safety of biosimilars can be compared. Published data from Denmark were also reviewed as additional evidence of how current pharmacovigilance systems are able to attribute adverse events to particular medicines. Collectively, the data show that spontaneous adverse drug reactions are reported by brand name in the majority of cases and are attributable to a specific medicine. Also discussed are the informational elements critical to monitoring biologics, or indeed any medicine, to ensure the availability of complete information so medicines that a patient has received can be quickly identified should a safety event occur. We support the addition of a single data element, the batch/lot number, to enhance the value of current pharmacovigilance systems. Adoption of 2-D barcodes in the European Union (EU) and standardized numerical identifiers in the United States addresses this need, since they include batch/lot numbers. These identifiers are already being implemented in the United States and the EU to improve patient safety, reduce medication errors, facilitate

  5. Patient-Reported Safety Information : A Renaissance of Pharmacovigilance?

    NARCIS (Netherlands)

    Härmark, Linda; Raine, June; Leufkens, Bert|info:eu-repo/dai/nl/075255049; Edwards, I Ralph; Moretti, Ugo; Sarinic, Viola Macolic; Kant, Agnes

    2016-01-01

    The role of patients as key contributors in pharmacovigilance was acknowledged in the new EU pharmacovigilance legislation. This contains several efforts to increase the involvement of the general public, including making patient adverse drug reaction (ADR) reporting systems mandatory. Three years

  6. [Interpretation of Guidelines on Good Pharmacovigilance Practices for European Union].

    Science.gov (United States)

    Xie, Yan-Ming; Tian, Feng

    2013-09-01

    Due to the limitations of pre-authorization clinical trials, the safety information obtained from them is relatively limited. Therefore, it is very necessary to carry out pharmacovigilance activities on drugs post-marketing. In order to promote the specific implementation of the new pharmacovigilance regulations, the European medicines agency (EMA) developed the Guideline on Good Pharmacovigilance Practices (GVP), as the new criteria for pharmacovigilance in the European Union (EU). Compared with the previously published, Guidelines on Pharmacovigilance for Medicinal Products for Human Use (2007), the GVP proposed more comprehensive and systematic provisions of pharmacovigilance systems, quality control systems, judgements, pharmacovigilance inspections and audits. In addition, it set more specific and comprehensive requirements on risk management systems, the management and reporting of adverse reactions to medicinal products, periodic safety update reports, post-authorization safety studies, signal management, and so on. Interpreting the basic principles, working mechanisms, key technologies and methods of the GVP provides a useful reference for us to carry out pharmacovigilance (especially regarding safety monitoring of parenterally administered Chinese medicine).

  7. Report processing and signal management at the netherlands pharmacovigilance centre

    NARCIS (Netherlands)

    Van Puijenbroek, E.P.; Harmark, L.; Van Grootheest, A.C.

    2009-01-01

    Introduction: The fast developments in pharmacovigilance in the past decades have had far-reaching consequences for the way of working in national pharmacovigilance centers. Firstly, processing and distribution of adverse drug reaction reports on both national and international levels became more

  8. Student views on the student-run pharmacovigilance program

    NARCIS (Netherlands)

    Schutte, T.; Tichelaar, J.; Reumerman, M.O.; Van Eekeren, R.; Groenland, S.; Rolfes, L.; Richir, M.C.; Van Puijenbroek, E.; Van Agtmael, M.A.

    2015-01-01

    Background: Pharmacovigilance centers play a vital role in the monitoring of drug safety after approval for marketing, and depend mainly on the quantity and quality of reported adverse drug reactions (ADRs). To ensure future ADR-reporting and increase pharmacovigilance awareness among medical

  9. Prevalence of blaTEM , blaSHV and blaCTX-M genes in clinical isolates of Escherichia coli and Klebsiella pneumoniae from Northeast India

    Directory of Open Access Journals (Sweden)

    Arijit Bora

    2014-01-01

    Full Text Available Aim: This study was carried out to determine the presence of blaTEM , blaSHV and blaCTX-M genes in extended-spectrum β-lactamase (ESBL producing Escherichia coli (E. coli and Klebsiella pneumoniae (K. pneumoniae at a tertiary care referral hospital in Northeast India. Materials and Methods: A total of 270 E. coli and 219 K. pneumoniae isolates were recovered during the period between August 2009 and July 2010. Kirby-Bauer disk diffusion method was performed to determine the antibiotic resistance pattern. Screening and phenotypic confirmatory test for ESBL production were performed using standard disc diffusion methods. Each of the initial ESBL screening test isolate was investigated for the presence of blaTEM , blaSHV and blaCTX-M genes via polymerase chain reaction (PCR using gene-specific primers. Results: Phenotypic confirmatory test able to detect ESBL production in 73.58% of E. coli and 67.24% of K. pneumoniae. However, PCR amplification showed the presence of one or more ESBL genes in each of the initial ESBL screening positive isolate. Among three ESBL genotypes, the most prevalent genotype was found to be blaCTX-M in E. coli (88.67% and blaTEM in K. pneumoniae (77.58% ESBL producing isolates. Majority of ESBL producing isolates possess more than one ESBL genes. Conclusion: This study constituted a primer report on high prevalence of blaTEM and blaCTX-M genes in ESBL producing isolates of E. coli and K. pneumoniae and denotes the need of more extensive studies on these antibiotic genes to determine the magnitude of the problem of antibiotic resistance exiting in this locality.

  10. Prevalence of blaTEM , blaSHV and blaCTX-M genes in clinical isolates of Escherichia coli and Klebsiella pneumoniae from Northeast India.

    Science.gov (United States)

    Bora, Arijit; Hazarika, Naba Kumar; Shukla, Sanket Kumar; Prasad, Kashi N; Sarma, Jayanta Biswa; Ahmed, Giasuddin

    2014-01-01

    This study was carried out to determine the presence of blaTEM , blaSHV and blaCTX-M genes in extended-spectrum β-lactamase (ESBL) producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) at a tertiary care referral hospital in Northeast India. A total of 270 E. coli and 219 K. pneumoniae isolates were recovered during the period between August 2009 and July 2010. Kirby-Bauer disk diffusion method was performed to determine the antibiotic resistance pattern. Screening and phenotypic confirmatory test for ESBL production were performed using standard disc diffusion methods. Each of the initial ESBL screening test isolate was investigated for the presence of blaTEM , blaSHV and blaCTX-M genes via polymerase chain reaction (PCR) using gene-specific primers. Phenotypic confirmatory test able to detect ESBL production in 73.58% of E. coli and 67.24% of K. pneumoniae. However, PCR amplification showed the presence of one or more ESBL genes in each of the initial ESBL screening positive isolate. Among three ESBL genotypes, the most prevalent genotype was found to be blaCTX-M in E. coli (88.67%) and blaTEM in K. pneumoniae (77.58%) ESBL producing isolates. Majority of ESBL producing isolates possess more than one ESBL genes. This study constituted a primer report on high prevalence of blaTEM and blaCTX-M genes in ESBL producing isolates of E. coli and K. pneumoniae and denotes the need of more extensive studies on these antibiotic genes to determine the magnitude of the problem of antibiotic resistance exiting in this locality.

  11. Pharmacovigilance and Biomedical Informatics: A Model for Future Development.

    Science.gov (United States)

    Beninger, Paul; Ibara, Michael A

    2016-12-01

    The discipline of pharmacovigilance is rooted in the aftermath of the thalidomide tragedy of 1961. It has evolved as a result of collaborative efforts by many individuals and organizations, including physicians, patients, Health Authorities, universities, industry, the World Health Organization, the Council for International Organizations of Medical Sciences, and the International Conference on Harmonisation. Biomedical informatics is rooted in technologically based methodologies and has evolved at the speed of computer technology. The purpose of this review is to bring a novel lens to pharmacovigilance, looking at the evolution and development of the field of pharmacovigilance from the perspective of biomedical informatics, with the explicit goal of providing a foundation for discussion of the future direction of pharmacovigilance as a discipline. For this review, we searched [publication trend for the log 10 value of the numbers of publications identified in PubMed] using the key words [informatics (INF), pharmacovigilance (PV), phar-macovigilance þ informatics (PV þ INF)], for [study types] articles published between [1994-2015]. We manually searched the reference lists of identified articles for additional information. Biomedical informatics has made significant contributions to the infrastructural development of pharmacovigilance. However, there has not otherwise been a systematic assessment of the role of biomedical informatics in enhancing the field of pharmacovigilance, and there has been little cross-discipline scholarship. Rapidly developing innovations in biomedical informatics pose a challenge to pharmacovigilance in finding ways to include new sources of safety information, including social media, massively linked databases, and mobile and wearable wellness applications and sensors. With biomedical informatics as a lens, it is evident that certain aspects of pharmacovigilance are evolving more slowly. However, the high levels of mutual interest in

  12. Pharmacoenvironmentology – a component of pharmacovigilance

    Directory of Open Access Journals (Sweden)

    Gupta Varun

    2007-07-01

    Full Text Available Abstract According to WHO, Pharmacovigilance activities are done to monitor detection, assessment, understanding and prevention of any obnoxious adverse reactions to drugs at therapeutic concentration on animal and human beings. However, there is also a growing focus among scientists and environmentalists about the impact of drugs on environment and surroundings. The existing term 'Ecopharmacology' is too broad and not even defined in a clear manner. The term 'Pharmacoenvironmentology' seeks to deal with the environmental impact of drugs given to humans and animals at therapeutic doses.

  13. Pharmacovigilance in developing countries (part I): importance and challenges.

    Science.gov (United States)

    Elshafie, Shaimaa; Zaghloul, Iman; Roberti, Anne Marie

    2017-12-16

    The thalidomide disaster was the significant historical event that acted as a catalyst for pharmacovigilance activity. Following this event developed countries initiated drug monitoring systems that evolved and now extend their scope to broader drug-related safety issues; however, this was not the case in developing countries. Pharmacovigilance is still a relatively new concept with low priority in developing countries although various issues are raising concerns that magnify the need for systems to monitor post marketing drug safety in these countries. This article analyzes the barriers to introducing robust pharmacovigilance systems in developing countries.

  14. Detection of bla KPC-2 in Proteus mirabilis in Brazil

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    Adriane Borges Cabral

    2015-02-01

    Full Text Available INTRODUCTION : Infections caused by Klebsiella pneumoniae carbapenemase (KPC-producing isolates pose a major worldwide public health problem today. METHODS : A carbapenem-resistant Proteus mirabilis clinical isolate was investigated for plasmid profiles and the occurrence of β-lactamase genes. RESULTS : The isolate exhibited resistance to ertapenem and imipenem and was susceptible to meropenem, polymyxin, and tigecycline. Five plasmids were identified in this isolate. DNA sequencing analysis revealed the presence of bla KPC-2 and bla TEM-1 genes. An additional PCR using plasmid DNA confirmed that bla KPC-2 was present in one of these plasmids. Conclusions: We report the detection of bla KPC-2 in P. mirabilis in Brazil for the first time. This finding highlights the continuous transfer of bla KPC between bacterial genera, which presents a serious challenge to the prevention of infection by multidrug-resistant bacteria.

  15. First Report of blaCTX-M-28 in Enterobacteriaceae Isolates in the United Arab Emirates

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    Mubarak Alfaresi

    2018-01-01

    Full Text Available Background. The CTX-M family of extended-spectrum beta lactamase (ESBL enzymes is comprised of over 60 blaCTX-M gene variants with the predominance of blaCTX-M-15 in many regions. In this report, we present the first description of blaCTX-M-28 in the United Arab Emirates. Methods. Forty-five non-duplicate ESBL producing isolates identified in a secondary care facility in the United Arab Emirates from June to July 2016 were studied. Gene sequencing was performed and DNA sequences were annotated using the BLAST program to identify the gene subtypes. Results. The majority of the ESBL positive isolates were E. coli (n/N=39/45; 86.6% followed by K. pneumoniae (n=5 and K. oxytoca (n=1. All isolates harboured blaCTX-M and blaTEM genes, 18 had blaSHV, and 2 were blaVIM positive. Thirty-seven isolates (82.2% were positive for blaCTX-M-28. Other blaCTX-M genes identified include blaCTX-M-167 (n=2; isolates #1 and 26 and one each for blaCTX-M-38, blaCTX-M-163, and blaCTX-M-198. No blaCTX-M-15 was identified. The predominant blaTEM subtype was blaTEM-171 (n=8 followed by one of each of blaTEM-120, blaTEM-163, and blaTEM-206. The blaSHV subtypes were blaSHV-148 and blaSHV-187. Conclusion. The findings indicate the first description of blaCTX-M-28 in a setting where blaCTX-M-15 was previously predominant.

  16. Abundance of carbapenemase genes (blaKPC, blaNDM and blaOXA-48) in wastewater effluents from Tunisian hospitals.

    Science.gov (United States)

    Nasri, Emna; Subirats, Jessica; Sànchez-Melsió, Alexandre; Mansour, Hedi Ben; Borrego, Carles M; Balcázar, José Luis

    2017-10-01

    Carbapenems are β-lactam antibiotics with a broad spectrum of activity and are usually considered the last resort for the treatment of severe infections caused by multidrug-resistant pathogens. The clinically most significant carbapenemases are KPC, NDM, and OXA-48-like enzymes, whose genes have been increasingly reported worldwide in members of the family Enterobacteriaceae. In this study, we quantified the abundance of these genes in wastewater effluents from different Tunisian hospitals. The bla NDM and bla OXA-48 -like genes were detected at similar concentrations in all hospital wastewater effluents. In contrast, the bla KPC gene was detected at lower concentration than other genes and it was only detected in three of the seven effluents analyzed. To the best of our knowledge, this study quantified for the first time the abundance of bla KPC , bla NDM , and bla OXA-48 -like genes in wastewater effluents from Tunisian hospitals, highlighting the widespread distribution of these carbapenemase genes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Statistical methods for active pharmacovigilance, with applications to diabetes drugs.

    Science.gov (United States)

    Zhuo, Lan; Farrell, Patrick J; McNair, Doug; Krewski, Daniel

    2014-01-01

    Pharmacovigilance aims to identify adverse drug reactions using postmarket surveillance data under real-world conditions of use. Unlike passive pharmacovigilance, which is based on largely voluntary (and hence incomplete) spontaneous reports of adverse drug reactions with limited information on patient characteristics, active pharmacovigilance is based on electronic health records containing detailed information about patient populations, thereby allowing consideration of modifying factors such as polypharmacy and comorbidity, as well as sociodemographic characteristics. With the present shift toward active pharmacovigilance, statistical methods capable of addressing the complexities of such data are needed. We describe four such methods here, and demonstrate their application in the analysis of a large retrospective cohort of diabetics taking anti-hyperglycemic medications that may increase the risk of adverse cardiovascular events.

  18. [blaTEM, blaSHV y blaCTX-M genes in extended-spectrum beta-lactamases producing enterobacterias isolated from patients with hospital-acquired infections].

    Science.gov (United States)

    Guzmán, Militza; Rodríguez, Eliosmar; Antón, Karen; Silva, Suyin; Navarro, Jhonilys; Lastra, Loriannys; Salazar, Elsa; Alonso, Guillermina

    2013-09-01

    The objective of the present investigation was to identify the blaTEM, blaSHV, and blaCTX-M genes on extended-spectrum beta-lactamases (ESBL) producing Enterobacteriaceae from clinical isolates, collected between September and November 2005. In addition to third-generation cephalosporin resistance, the isolates also showed resistance to chloramphenicol (59.2%), amikacin (37.0%) and gentamicin (40.7%), and demonstrated sensitivity to imipenem and meropenem. Nine strains were capable of transferring third-generation cephalosporin resistance, as well as the production of ESBL. In the clinical isolates, the genes blaSHV, blaTEM and blaCTX-M were detected, being more prevalent the types blaTEM-1, blaSHV-1, blaSHV-5 blaSHV-5-2a and blaCTX-M-1; while in the trans-conjugated only blaTEM-1, blaSHV-5 y blaSHV-5-2awere found. In total, seven types of genes were identified, five of which were codifying genes for ESBL-type enzymes. This demonstrates that in the hospital center, resistance to third-generation cephalosporin is mediated by several enzymes.

  19. State of knowledge of Cameroonian drug prescribers on pharmacovigilance.

    Science.gov (United States)

    Nde, Francis; Fah, Aimé Bernard Djitafo; Simo, Francis Ampère; Wouessidjewe, Denis

    2015-01-01

    The present study conducted in Cameroon from June 2013 to February 2014 aimed to estimating the level of pharmacovigilance knowledge and practice of health professionals in Cameroon. We conducted a descriptive cross-sectional survey on 149 health professionals in Cameroon from June to September 2013. Data were analyzed using software IBM SPSS 20.0. We calculated proportions and odd ratio, and confident interval of their values, keeping a threshold of p of 0.05 to determine the level of significance. Ninety percent (90%) of declaration of side effects were made to the medical representatives and 4% to the National Pharmacovigilance Centre. Fifty four percent (54%) of physicians were not aware of the existence of a National Pharmacovigilance system. Ten (10%) of prescribers had never heard of pharmacovigilance, however respondents answered unanimously that they need training on pharmacovigilance. A wrong definition was given by most of the nurses and dentists (61,1% and 58,3% respectively) as compared to physicians and pharmacists (respectively 15.2% and 26,5%). Given the results of this study, the establishment of a National Pharmacovigilance system based on a solid legal foundation is necessary in Cameroon. This implementation must go through the involvement of all stakeholders and their awareness raising on the importance of this activity and its positive impact on the health of populations. Pharmacovigilance is a public health problem in Cameroon, with due to lack of good knowledge and practice of prescribers, precisely physicians, pharmacists, nurses, and dentists who are not always aware of an existing pharmacovigilance system in Cameroon.

  20. Occurrence of co-existing bla VIM-2 and bla NDM-1 in clinical isolates of Pseudomonas aeruginosa from India.

    Science.gov (United States)

    Paul, Deepjyoti; Dhar, Debadatta; Maurya, Anand Prakash; Mishra, Shweta; Sharma, Gauri Dutt; Chakravarty, Atanu; Bhattacharjee, Amitabha

    2016-05-06

    bla VIM-2 harboring Pseudomonas aeruginosa has been reported worldwide and considered as the most prevalent metallo-β-lactamase after NDM which are found horizontally transferable and mostly associated with integron gene cassettes. The present study investigates the genetic background, transmission dynamics as well as stability of bla VIM-2 in clinical isolates of P. aeruginosa harbor bla NDM-1 as well which were collected from October 2012 to September 2013. Two P. aeruginosa strains harboring bla VIM-2 along with bla NDM-1 were isolated from Silchar Medical College and Hospital, India. Genetic environment of these resistance determinants was determined and transferability was checked by transformation and conjugation assay which was further confirmed by Southern hybridization. Replicon typing was performed to determine the incompatibility group of the resistant plasmid and their stability was checked by serial passage method. Antimicrobial susceptibility pattern of the isolates was determined and their clonal relatedness was checked by pulsed field gel electrophoresis. bla VIM-2 was found to be horizontally transferable through an Inc F type plasmid of approximately 30 kb in size. bla VIM-2 was found to be associated with integron gene cassette and was flanked by two different types of cassette arrays. Both the isolates were co-harboring bla NDM-1 which was carried within Inc N type of plasmid with an approximate 24 kb in size and associated with ISAba125 in their upstream region. Reduced susceptibility rate as well as high MIC range was observed in case of wild strains and transformants carrying bla VIM-2 and bla NDM-1. The detection of this co-existence of multiple carbapenem resistance genes in this part of world is worrisome and further investigation is required in order to trace the source and to initiate proper treatment option.

  1. Patient-Reported Safety Information: A Renaissance of Pharmacovigilance?

    Science.gov (United States)

    Härmark, Linda; Raine, June; Leufkens, Hubert; Edwards, I Ralph; Moretti, Ugo; Sarinic, Viola Macolic; Kant, Agnes

    2016-10-01

    The role of patients as key contributors in pharmacovigilance was acknowledged in the new EU pharmacovigilance legislation. This contains several efforts to increase the involvement of the general public, including making patient adverse drug reaction (ADR) reporting systems mandatory. Three years have passed since the legislation was introduced and the key question is: does pharmacovigilance yet make optimal use of patient-reported safety information? Independent research has shown beyond doubt that patients make an important contribution to pharmacovigilance signal detection. Patient reports provide first-hand information about the suspected ADR and the circumstances under which it occurred, including medication errors, quality failures, and 'near misses'. Patient-reported safety information leads to a better understanding of the patient's experiences of the ADR. Patients are better at explaining the nature, personal significance and consequences of ADRs than healthcare professionals' reports on similar associations and they give more detailed information regarding quality of life including psychological effects and effects on everyday tasks. Current methods used in pharmacovigilance need to optimise use of the information reported from patients. To make the most of information from patients, the systems we use for collecting, coding and recording patient-reported information and the methodologies applied for signal detection and assessment need to be further developed, such as a patient-specific form, development of a severity grading and evolution of the database structure and the signal detection methods applied. It is time for a renaissance of pharmacovigilance.

  2. Pharmacovigilance: Boon for the safety and efficacy of Ayuvedic formulations

    Science.gov (United States)

    Chaudhary, Anand; Singh, Neetu; Kumar, Neeraj

    2010-01-01

    Pharmacovigilance is a corrective process originating in pharmaco-epidemiology. The 1997 Erice Declaration, presented at the World Health Organisation, became the basis on which the concept was implemented internationally for conventional systems of medicine. The increasing international acceptance of Ayurveda, led regulators to implement a similar program for Ayurveda, particularly as some medical professionals, scientists and members of the public reported adverse reactions after taking Ayurvedic formulations. The World Health Organisation therefore persuaded the Department of AYUSH, Ministry of Health and Family Welfare, Government of India, to implement a pharmacovigilance program for Ayurveda, as a means to ensuring the safety and efficacy of Ayurvedic medicines. After a year of due diligence, the pharmacovigilance program was launched nationally on 29 September 2008. Since that time, Ayurveda, Siddha and Unani medicines have been monitored according to the provisions of a protocol prepared by the National Pharmacovigilance Resource Centre, IPGTRA, Jamnagar, and approved by Department of AYUSH. The program was reviewed, first, on 21st January 2009 by the National Pharmaco-vigilance Consultative Committee for ASU drugs (NPCC-ASU), and again, on 15 Feburary, 2010, when an evaluation meeting effectively rubber stamped the program. Among the outcomes of these meetings were several suggestions of measures to improve the program’s efficiency. Recent developments include the constitution of pharmacovigilance centers at all Ayurveda Teaching institutes and research centers. PMID:21731371

  3. Governance and pharmacovigilance in Brazil: a scoping review.

    Science.gov (United States)

    Moscou, Kathy; Kohler, Jillian C; MaGahan, Anita

    2016-01-01

    This scoping review investigates the relationship between governance, pharmacovigilance, and Agencia Nacional de Vigilancia Sanitaria (ANVISA) in Brazil, which has authority over Brazil's national pharmaceutical policy, drug registration and coordination of the national pharmacovigilance system. The purpose is to investigate opportunities for effective pharmacovigilance. Sixty-three terms pertaining to pharmacovigilance in Brazil and ANVISA, global institutions, pharmaceutical industry, and civil society were searched in thirteen relevant databases on November 17-18, 2013. Using a pharmacogovernance framework we analyzed ANVISA's pharmacogovernance: the manner in which governing structures, policy instruments, and institutional authority are managed to promote societal interests for patient safety due to medication use. The integration of transnational policy ideas for regulatory governance into pharmacogovernance in Brazil was also investigated. Brazil's policy, laws, and regulations support ANVISA's authority to ensure access to safe medicines and health products however ANVISA's broad mandate and gaps in pharmacogovernance account for regional disparities in monitoring and assessing drug safety. Gaps in pharmacogovernance include: equity and inclusiveness; stakeholder coordination; effectiveness and efficiency; responsiveness; and intelligence and information. Pharmacogovernance that addresses 1) regional resource disparities, 2) federal and state lack of coordination of pharmacovigilance regulations, 3) asymmetric representation in the pharmaceutical regulatory agenda and which 4) disaggregates regulatory authority over health and commercial sectors would strengthen pharmacovigilance in Brazil.

  4. Pharmacovigilance: Boon for the safety and efficacy of ayuvedic formulations

    Directory of Open Access Journals (Sweden)

    Anand Chaudhary

    2010-01-01

    Full Text Available Pharmacovigilance is a corrective process originating in pharmaco-epidemiology. The 1997 Erice Declaration, presented at the World Health Organisation, became the basis on which the concept was implemented internationally for conventional systems of medicine. The increasing international acceptance of Ayurveda, led regulators to implement a similar program for Ayurveda, particularly as some medical professionals, scientists and members of the public reported adverse reactions after taking Ayurvedic formulations. The World Health Organisation therefore persuaded the Department of AYUSH, Ministry of Health and Family Welfare, Government of India, to implement a pharmacovigilance program for Ayurveda, as a means to ensuring the safety and efficacy of Ayurvedic medicines. After a year of due diligence, the pharmacovigilance program was launched nationally on 29 September 2008. Since that time, Ayurveda, Siddha and Unani medicines have been monitored according to the provisions of a protocol prepared by the National Pharmacovigilance Resource Centre, IPGTRA, Jamnagar, and approved by Department of AYUSH. The program was reviewed, first, on 21st January 2009 by the National Pharmaco-vigilance Consultative Committee for ASU drugs (NPCC-ASU, and again, on 15 Feburary, 2010, when an evaluation meeting effectively rubber stamped the program. Among the outcomes of these meetings were several suggestions of measures to improve the program′s efficiency. Recent developments include the constitution of pharmacovigilance centers at all Ayurveda Teaching institutes and research centers.

  5. Pharmacovigilance in China: current situation, successes and challenges.

    Science.gov (United States)

    Zhang, Li; Wong, Lisa Y L; He, Ying; Wong, Ian C K

    2014-10-01

    With the integration of the global pharmaceutical economy and the gradual transformation of the healthcare insurance system in China, the legislative framework for a comprehensive regulatory system monitoring the whole process including drug development, manufacture, distribution and use has been established by the China Food and Drug Administration (CFDA) to ensure the safety and effectiveness of medication use. China has established a relatively comprehensive pharmacovigilance system covering regulation, organisation and technology from 1989 to 2014. As of 2013, one national centre, 34 provincial centres and more than 400 municipal centres for adverse drug reaction (ADR) monitoring were included in the four-level pharmacovigilance network (national, provincial, municipal and county) with more than 200,000 grassroot organisation users. The China Adverse Drug Reaction Monitoring System (CADRMS) is an online spontaneous reporting system which connects the four-level pharmacovigilance network. By 2013, CADRMS had received over 6.6 million ADR case reports. After integrating and analysing pharmacovigilance data, the National Centre for ADR Monitoring (NCADRM) publishes medication safety information by releasing ADR bulletins, National ADR Annual Reports and International Pharmacovigilance Newsletters. The NCADRM also routinely provides CADRMS data feedback to manufacturers. The CFDA implemented risk management through several approaches, including arranging 'manufacturer communication meetings', modification of medication package inserts, and restriction, suspension or withdrawal of marketing authorisations. Seamless information exchange with overseas regulatory authorities and organisations remains an area for improvement. Further development of the China pharmacovigilance system in terms of signal generation, post-marketing pharmacoepidemiology research and education is also needed.

  6. Rapid detection of Pseudomonas aeruginosa and Acinetobacter baumannii Harboring bla(VIM-2), bla(IMP-1) and bla(OXA-23) genes by using loop-mediated isothermal amplification methods.

    Science.gov (United States)

    Kim, Hye Jin; Kim, Hyung Sun; Lee, Jae Myun; Yoon, Sang Sun; Yong, Dongeun

    2016-01-01

    Carbapenem-resistant Pseudomonas aeruginosa (CRPA) and Acinetobacter baumannii (CRAB) are the leading causes of nosocomial infections. A rapid and sensitive test to detect CRPA and CRAB is required for appropriate antibiotic treatment. We optimized a loop-mediated isothermal amplification (LAMP) assay to detect the presence of bla(VIM-2), bla(IMP-1), and bla(OXA-23), which are critical components for carbapenem resistance. Two sets of primers, inner and outer primers, were manually designed as previously described. The LAMP buffer was optimized (at 2mM MgSO₄) by testing different concentrations of MgSO₄. The optimal reaction temperature and incubation time were determined by using a gradient thermocycler. Then, the optimized bla(VIM-2), bla(IMP-1), and bla(OXA-23) LAMP reactions were evaluated by using 120 P. aeruginosa and 99 A. baumannii clinical isolates. Only one strain of the 100 CRPA isolates harbored bla(IMP-1), whereas none of them harbored bla(VIM-2). These results indicate that the acquisition of bla(VIM-2) or bla(IMP-1) may not play a major role in carbapenem resistance in Korea. Fifty two strains of the 75 CRAB isolates contained bla(OXA-23), but none contained bla(VIM-2) and bla(IMP-1) alleles. Our results demonstrate the usefulness of LAMP for the diagnosis of CRPA and CRAB.

  7. Feasibility and Educational Value of a Student-Run Pharmacovigilance Programme : A Prospective Cohort Study

    NARCIS (Netherlands)

    Schutte, Tim; Tichelaar, Jelle; Reumerman, Michael O; van Eekeren, Rike; Rolfes, Leàn; van Puijenbroek, Eugène P; Richir, Milan C; van Agtmael, Michiel A

    2017-01-01

    INTRODUCTION: Pharmacovigilance, the monitoring of drug safety after marketing approval, highly depends on the adequate reporting of adverse drug reactions (ADRs). To improve pharmacovigilance awareness and future ADR reporting among medical students, we developed and evaluated a student-run

  8. Health professionals' knowledge, attitude and practices towards pharmacovigilance in Nepal

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    Palaian S

    2011-12-01

    Full Text Available Pharmacovigilance can be helpful in protecting consumers from harmful effects of medicines. Healthcare professionals should consider Adverse Drug Reaction (ADR reporting as their professional obligation and should be aware of the existing pharmacovigilance mechanisms in their countries. In Nepal, pharmacovigilance activities were initiated in 2004. Objectives: The present study evaluated the knowledge, attitude and practices (KAP of the healthcare professionals towards ADRs and pharmacovigilance in Manipal Teaching Hospital (MTH, a tertiary care teaching hospital attached to the regional pharmacovigilance center in western Nepal. Methods: A cross-sectional study was carried out in 2007 using a pretested (Cronbach alpha=0.72 questionnaire having 25 questions (15 questions on knowledge, 5 on attitude and 5 on practice. The correct/positive responses were given a score of ‘2’ and the wrong/negative responses ‘1’, maximum possible score of ‘50’. Results: A total of 131 responses were obtained among which 42 were incomplete and remaining 89 [females 49 (55.1%] were analyzed. Of the 89 professionals, 29 (32.6% were doctors, 46 (51.8 nurses and 14 (15.7% pharmacists. The mean age was 28.32 (SD=8.46 years and the median (interquartile range of duration of the service 14.5 (6-36 months. The total KAP scores was 40.06 (SD=3.51 for doctors, 38.92 (SD=4.83 for pharmacists, and 35.82 (SD=3.75 for nurses. Among the 89 professionals, 59 (62.3% had not reported even a single ADR to the pharmacovigilance center. Conclusion: The healthcare professionals at the MTH had a poor KAP towards ADRs and pharmacovigilance and there is a need for educational and awareness intervention for these professionals.

  9. Antigenic Determinants of the Bilobal Cockroach Allergen Bla g 2.

    Science.gov (United States)

    Woodfolk, Judith A; Glesner, Jill; Wright, Paul W; Kepley, Christopher L; Li, Mi; Himly, Martin; Muehling, Lyndsey M; Gustchina, Alla; Wlodawer, Alexander; Chapman, Martin D; Pomés, Anna

    2016-01-29

    Bla g 2 is a major indoor cockroach allergen associated with the development of asthma. Antigenic determinants on Bla g 2 were analyzed by mutagenesis based on the structure of the allergen alone and in complex with monoclonal antibodies that interfere with IgE antibody binding. The structural analysis revealed mechanisms of allergen-antibody recognition through cation-π interactions. Single and multiple Bla g 2 mutants were expressed in Pichia pastoris and purified. The triple mutant K132A/K251A/F162Y showed an ∼100-fold reduced capacity to bind IgE, while preserving the native molecular fold, as proven by x-ray crystallography. This mutant was still able to induce mast cell release. T-cell responses were assessed by analyzing Th1/Th2 cytokine production and the CD4(+) T-cell phenotype in peripheral blood mononuclear cell cultures. Although T-cell activating capacity was similar for the KKF mutant and Bla g 2 based on CD25 expression, the KKF mutant was a weaker inducer of the Th2 cytokine IL-13. Furthermore, this mutant induced IL-10 from a non-T-cell source at higher levels that those induced by Bla g 2. Our findings demonstrate that a rational design of site-directed mutagenesis was effective in producing a mutant with only 3 amino acid substitutions that maintained the same fold as wild type Bla g 2. These residues, which were involved in IgE antibody binding, endowed Bla g 2 with a T-cell modulatory capacity. The antigenic analysis of Bla g 2 will be useful for the subsequent development of recombinant allergen vaccines. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Antigenic Determinants of the Bilobal Cockroach Allergen Bla g 2*

    Science.gov (United States)

    Woodfolk, Judith A.; Glesner, Jill; Wright, Paul W.; Kepley, Christopher L.; Li, Mi; Himly, Martin; Muehling, Lyndsey M.; Gustchina, Alla; Wlodawer, Alexander; Chapman, Martin D.; Pomés, Anna

    2016-01-01

    Bla g 2 is a major indoor cockroach allergen associated with the development of asthma. Antigenic determinants on Bla g 2 were analyzed by mutagenesis based on the structure of the allergen alone and in complex with monoclonal antibodies that interfere with IgE antibody binding. The structural analysis revealed mechanisms of allergen-antibody recognition through cation-π interactions. Single and multiple Bla g 2 mutants were expressed in Pichia pastoris and purified. The triple mutant K132A/K251A/F162Y showed an ∼100-fold reduced capacity to bind IgE, while preserving the native molecular fold, as proven by x-ray crystallography. This mutant was still able to induce mast cell release. T-cell responses were assessed by analyzing Th1/Th2 cytokine production and the CD4+ T-cell phenotype in peripheral blood mononuclear cell cultures. Although T-cell activating capacity was similar for the KKF mutant and Bla g 2 based on CD25 expression, the KKF mutant was a weaker inducer of the Th2 cytokine IL-13. Furthermore, this mutant induced IL-10 from a non-T-cell source at higher levels that those induced by Bla g 2. Our findings demonstrate that a rational design of site-directed mutagenesis was effective in producing a mutant with only 3 amino acid substitutions that maintained the same fold as wild type Bla g 2. These residues, which were involved in IgE antibody binding, endowed Bla g 2 with a T-cell modulatory capacity. The antigenic analysis of Bla g 2 will be useful for the subsequent development of recombinant allergen vaccines. PMID:26644466

  11. Imipenem-resistant Acinetobacter baumannii carrying the ISAba1-bla OXA-23, 51 and ISAba1-bla ADC-7 genes in Monteria, Colombia

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    Pedro Martínez

    2012-12-01

    Full Text Available The purpose of this study was to identify the genes coding for resistance to ceftazidime and imipenem and describe the molecular epidemiology of A. baumannii strains isolated from a clinical center in Colombia. Twenty isolates of imipenem-resistant A. baumannii from an equal number of patients with nosocomial infections were obtained. Primers were used to amplify genes bla IMP, bla VIM, bla OXA-23, bla OXA-24, bla OXA-58, bla OXA-51 and bla ADC-7. To detect insertion sequences ISAba1/bla OXA-23, ISAba1/bla OXA-51 and ISAba1/bla ADC-7, mapping by PCR using combinations of reverse primers ISAba1 and reverse primers of bla OXA-23, bla OXA-51 and bla ADC-7 were used. The amplification products were purified and cloned into PCR 2.1-TOPO vector and transformed into chemically competent Escherichia coli TOP10. These amplicons were then sequenced. PFGE was performed on DNA of A. baumannii isolates digested with ApaI. Results. The DNA profiles obtained included 9 clusters with, four 2-7 isolates per profile, and 5 single-isolate profiles. Of the 20 isolates resistant to imipenem, 15 carried bla OXA-23 gene, 4 contained ISAba1 upstream of bla OXA-51 gene, and 6 contained ISAba1 upstream of bla OXA-23 gene. Eighteen of these isolates carried the bla ADC-7 gene, with 9 of the isolates having ISAba1 located upstream of this gene. This is the first report of the ISAba1 /ADC-7 associated with OXAs genes in A. baumannii isolates from Colombia.

  12. Imipenem-resistant Acinetobacter baumannii carrying the ISAba1-bla OXA-23,51 and ISAba1-bla ADC-7 genes in Monteria, Colombia.

    Science.gov (United States)

    Martínez, Pedro; Mattar, Salim

    2012-10-01

    The purpose of this study was to identify the genes coding for resistance to ceftazidime and imipenem and describe the molecular epidemiology of A. baumannii strains isolated from a clinical center in Colombia. Twenty isolates of imipenem-resistant A. baumannii from an equal number of patients with nosocomial infections were obtained. Primers were used to amplify genes bla IMP, bla VIM, bla OXA-23, bla OXA-24, bla OXA-58, bla OXA-51 and bla ADC-7. To detect insertion sequences ISAba1/bla OXA-23, ISAba1/bla OXA-51 and ISAba1/bla ADC-7, mapping by PCR using combinations of reverse primers ISAba1 and reverse primers of bla OXA-23, bla OXA-51 and bla ADC-7 were used. The amplification products were purified and cloned into PCR 2.1-TOPO vector and transformed into chemically competent Escherichia coli TOP10. These amplicons were then sequenced. PFGE was performed on DNA of A. baumannii isolates digested with ApaI. Results. The DNA profiles obtained included 9 clusters with, four 2-7 isolates per profile, and 5 single-isolate profiles. Of the 20 isolates resistant to imipenem, 15 carried bla OXA-23 gene, 4 contained ISAba1 upstream of bla OXA-51 gene, and 6 contained ISAba1 upstream of bla OXA-23 gene. Eighteen of these isolates carried the bla ADC-7 gene, with 9 of the isolates having ISAba1 located upstream of this gene. This is the first report of the ISAba1/ADC-7 associated with OXAs genes in A. baumannii isolates from Colombia.

  13. Obstacles to transparency over pharmacovigilance data within the EMA.

    Science.gov (United States)

    2015-11-01

    In July and August 2014, the European Medicines Agency (EMA) organised two public consultations concerning European pharmacovigilance. These two consultations reveal a number of EMA proposals that are counterproductive to the objective of improving transparency over pharmacovigilance data. The EMA's proposals offer pharmaceutical companies an opportunity to participate in public hearings held by the European Pharmacovigilance Risk Assessment Committee (PRAC), in order to defend their drug. They also provide for the possibility of holding non-public hearings to discuss public data. There is a great risk that the drug industry might use these provisions to influence the debate. The strings attached to the access that the EMA proposes to grant researchers to data contained in the centralised European pharmacovigilance database would allow the EMA to censor the publication of their findings. The EMA seems to regard pharmacovigilance data as commercially confidential information. Responding to these consultations provided an opportunity to remind the EMA that data about adverse effects are a public good, in the common interest, and that it is unacceptable to keep this information confidential.

  14. Pharmacovigilance: pharmacists’ perspective on spontaneous adverse drug reaction reporting

    Science.gov (United States)

    Hadi, Muhammad Abdul; Neoh, Chin Fen; Zin, Rosdi M; Elrggal, Mahmoud E; Cheema, Ejaz

    2017-01-01

    Globally, adverse drug reactions (ADRs), one of the leading causes of morbidity and mortality, will continue to pose a threat to public health as long as drugs are being used to treat various ailments. Prompt ADR reporting is crucial in ensuring drug safety. The aim of this narrative review was to highlight the role of pharmacists in pharmacovigilance and to identify barriers and facilitators toward ADR reporting documented in the literature. The perspective of pharmacy students on pharmacovigilance and ADR reporting has also been discussed with an aim to highlight the need to improve content related to ADR reporting and pharmacovigilance in undergraduate pharmacy curriculum. Globally, although the role of pharmacists within national pharmacovigilance systems varies, it is very well recognized. In general, pharmacists acknowledge that ADR reporting is part of their professional responsibility and have a positive attitude toward reporting ADRs. However, current research evidence suggests that there are still critical knowledge gaps with regard to ADR reporting among pharmacists, especially in countries where the role of pharmacists within the health care system is limited. These knowledge gaps can be fulfilled through continuous professional development programs and reinforcing theoretical and practical knowledge in undergraduate pharmacy curriculums. Without adequately identifying and fulfilling training needs of pharmacists and other health care professionals, the efficiency of national pharmacovigilance systems is unlikely to improve which may compromise patient’s safety. PMID:29354555

  15. What Can Big Data Offer the Pharmacovigilance of Orphan Drugs?

    Science.gov (United States)

    Price, John

    2016-12-01

    The pharmacovigilance of drugs for orphan diseases presents problems related to the small patient population. Obtaining high-quality information on individual reports of suspected adverse reactions is of particular importance for the pharmacovigilance of orphan drugs. The possibility of mining "big data" to detect suspected adverse reactions is being explored in pharmacovigilance generally but may have limited application to orphan drugs. Sources of big data such as social media may be infrequently used as communication channels by patients with rare disease or their caregivers or by health care providers; any adverse reactions identified are likely to reflect what is already known about the safety of the drug from the network of support that grows up around these patients. Opportunities related to potential future big data sources are discussed. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  16. Specific features of medicines safety and pharmacovigilance in Africa

    Science.gov (United States)

    Pal, Shanthi N.; Olsson, Sten; Dodoo, Alexander; Bencheikh, Rachida Soulayami

    2012-01-01

    The thalidomide tragedy in the late 1950s and early 1960s served as a wakeup call and raised questions about the safety of medicinal products. The developed countries rose to the challenge putting in place systems to ensure the safety of medicines. However, this was not the case for low-resource settings because of prevailing factors inherent in them. This paper reviews some of these features and the current status of pharmacovigilance in Africa. The health systems in most of the 54 countries of Africa are essentially weak, lacking in basic infrastructure, personnel, equipment and facilities. The recent mass deployment of medicines to address diseases of public health significance in Africa poses additional challenges to the health system with notable safety concerns. Other safety issues of note include substandard and counterfeit medicines, medication errors and quality of medicinal products. The first national pharmacovigilance centres established in Africa with membership of the World Health Organization (WHO) international drug monitoring programme were in Morocco and South Africa in 1992. Of the 104 full member countries in the programme, there are now 24 African countries with a further nine countries as associate members. The pharmacovigilance systems operational in African countries are based essentially on spontaneous reporting facilitated by the introduction of the new tool Vigiflow. The individual case safety reports committed to the WHO global database (Vigibase) attest to the growth of pharmacovigilance in Africa with the number of reports rising from 2695 in 2000 to over 25,000 in 2010. There is need to engage the various identified challenges of the weak pharmacovigilance systems in the African setting and to focus efforts on how to provide resources, infrastructure and expertise. Raising the level of awareness among healthcare providers, developing training curricula for healthcare professionals, provisions for paediatric and geriatric

  17. Pharmacovigilance Considerations for Biosimilars in the USA.

    Science.gov (United States)

    Grampp, Gustavo; Felix, Thomas

    2015-10-01

    In 2015, five or more biosimilars may be approved in the USA. Because no two biologic medicines are identical, postapproval safety monitoring will be critical to detect potential differences in safety signals between a biosimilar, its reference product, and other biosimilars. Postapproval safety monitoring in the USA uses two signal detection systems: spontaneous reporting systems (SRSs) and active surveillance (AS) systems. Both depend on accurate identification of the specific product(s) dispensed or administered to patients, which may be compromised when products from multiple manufacturers share common drug nomenclature or coding. Product identification can present challenges across different healthcare settings, including inpatient and ambulatory care. Common oral-dosage drugs are predominantly dispensed directly to patients by pharmacists, whereas most injectable drugs, including biologics, are administered to patients by healthcare professionals in outpatient clinics or hospitals. Thus, the effectiveness of SRS and AS mechanisms in both pharmacy and medical channels must be given greater consideration as biotechnology matures. In this article, we describe these systems and their limitations. We identify challenges and opportunities for product-specific safety surveillance of biologics in both the pharmacy and medical settings and provide recommendations to improve biologic safety surveillance under the current and future systems envisioned in the Drug Quality and Security Act. As biosimilars are integrated into existing pharmacovigilance systems, distinguishable nonproprietary names and codes for all biologics, as well as other opportunities to improve traceability (e.g., increased use of barcodes), must be considered to ensure patient safety and confidence in this new class of drugs.

  18. Identification and molecular characterization of Escherichia coli blaSHVgenes in a Chinese teaching hospital.

    Science.gov (United States)

    Zhu, Mei; Yang, Guangjian; Li, Ailing; Zong, Li; Dong, Zhaoguang; Lu, Junwan; Zhang, Kaibo; Cheng, Cong; Chang, Qingli; Wu, Xiuying; Ying, Jianchao; Li, Xianneng; Ding, Li; Zheng, Haixiao; Yu, Junping; Ying, Jun; Xu, Teng; Yi, Huiguang; Li, Peizhen; Li, Kewei; Wu, Songquan; Bao, Qiyu; Wang, Junrong

    2017-02-05

    Escherichia coli (E. coli) commonly reside in human intestine and most E. coli strains are harmless, but some serotypes cause serious food poisoning. This study identified and molecularly characterized bla SHV genes from 490 E. coli strains with multi-drug resistance in a hospital population. PCR and molecular cloning and southern blot were performed to assess functions and localizations of this resistant E. coli gene and the pulsed-field gel electrophoresis (PFGE) was utilized to demonstrate the clonal relatedness of the positive E. coli strains. The data showed that 4 of these 490 E. coli strains (4/499, 0.8%) carried bla SHV genes that included EC D2485 (bla SHV-5 ), EC D2487 (bla SHV-5 ), EC D2684 (bla SHV-11 ) and EC D2616 (bla SHV-195, a novel bla SHV ). Analysis of bla SHV open-reading frame showed that bla SHV-5 had a high hydrolysis activity to the broad-spectrum penicillin (ampicillin or piperacillin), ceftazidime, ceftriaxone, cefotaxime and aztreonam. bla SHV-195 and bla SHV-11 had similar resistant characteristics with high hydrolysis activities to ampicillin and piperacillin, but low activities to cephalosporins. Moreover, the two bla SHV-5 genes were located on a transferable plasmid (23kb), whereas the other two bla SHV variants (bla SHV-11 and bla SHV-195 ) seemed to be located in the chromosomal material. Both EC D2485 and EC D2487 clones isolated in 2010 had the same DNA finger printing profile and they might be the siblings of clonal dissemination. The data from the current study suggest that the novel bla SHV and clonal dissemination may be developed, although bla SHV genes were infrequently identified in this hospital population. The results of the work demonstrate the necessity for molecular surveillance in tracking bla SHV -producing strains in large teaching hospital settings and emphasize the need for epidemiological monitoring. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Emergence of blaCTX-M-15, blaTEM-169 and blaPER-1 extended-spectrum β-lactamase genes among different Salmonella enterica serovars from human faecal samples.

    Science.gov (United States)

    Tajbakhsh, Mercedeh; Avini, Mohammad Yaghoobi; Alikhajeh, Jahan; Tajeddin, Elahe; Rahbar, Mohammad; Eslami, Parisa; Alebouyeh, Masoud; Zali, Mohammad Reza

    2016-07-01

    Broad-spectrum β-lactams are used for empirical therapy of severe infections with non-typhoid Salmonella serotypes; however, activities of these drugs against the strains producing different β-lactamase is not so clear. This study investigated the prevalence of β-lactamase genes among isolates of S. enterica serovars from human faecal samples and determined their diversity in activity against different β-lactams. Antimicrobial resistance of faecal isolates of S. enterica to extended-spectrum cephalosporins was analysed and MIC values were determined for the strains presenting extended-spectrum β-lactamases (ESBLs) phenotypes. The β-lactamase genes were identified by PCR and sequencing. β-lactamase activity of the Salmonella strains exhibiting ESBL phenotype was detected by biological, iodometric, spectrophotometry and nitrocefin assays. Out of 202 S. enterica isolates, ESBLs phenotype was detected among 3.4% (7/202) of the strains. blaTEM-1 and blaCTX-M-15 were among the frequent β-lactamase genes. Detection of blaTEM-169 in S. enterica serovar Typhimurium and S. enterica serovar Bredeney and blaPER-1 in S. enterica serovar Infantis was a new finding in this experiment. Location of blaCTX-M-15/blaTEM-169/blaPER-1 genes on plasmid was confirmed in a transformation experiment. While crude extracts of the enzymes from each strain showed higher activity against cephalothin and cefotaxime, the lowest activity was detected against ceftazidime. The greatest synergistic activity was seen in a strain of S. enterica that carried blaCTX-M-15 and blaPER-1 genes compared with those presenting blaCTX-M-15/blaTEM-169 or blaCTX-M-15/blaTEM-1 genotypes. The results show dissemination of ESBLs encoding genes and their combined activity among different serovars of S. enterica that are a threat for future treatment options.

  20. Consumer adverse drug reaction reporting - A new step in pharmacovigilance?

    NARCIS (Netherlands)

    van Grootheest, K; de Graaf, L; de Jong-van den Berg, LTW

    2003-01-01

    The direct reporting of adverse drug reactions by patients is becoming an increasingly important topic for discussion in the world of pharmacovigilance. At this time, few countries accept consumer reports. We present an overview of experiences with consumer reporting in various countries of the

  1. 21st century pharmacovigilance: efforts, roles, and responsibilities.

    Science.gov (United States)

    Pitts, Peter J; Louet, Hervé Le; Moride, Yola; Conti, Rena M

    2016-11-01

    In an era when the number of expedited and conditional review pathways for newly available brand-name drugs and biosimilar medicines to treat serious and life-threatening diseases is increasing, defining pharmacovigilance has never been more crucial. 21st century pharmacovigilance is not merely about uncovering, reporting, and addressing adverse events associated with already approved and marketed agents, but can be described as the systematic monitoring of the process of pre-market review and post-market surveillance, which includes the use of medicines in everyday practice. Pharmacovigilance identifies previously unrecognised adverse events or changes in the patterns of these effects, the quality and adequacy of drug supply, and should ensure effective communication with the public, health-care professionals, and patients about the optimum safety and effective use of medicines. In this paper, the first in a Series of three about drug safety in oncology, we discuss evolving challenges in the purview, roles, and responsibilities of the US Food and Drug Administration and the European Medicines Agency with respect to pharmacovigilance efforts, with a special emphasis on oncology treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Sequence symmetry analysis in pharmacovigilance and pharmacoepidemiologic studies

    DEFF Research Database (Denmark)

    Lai, Edward Chia Cheng; Pratt, Nicole; Hsieh, Cheng Yang

    2017-01-01

    Sequence symmetry analysis (SSA) is a method for detecting adverse drug events by utilizing computerized claims data. The method has been increasingly used to investigate safety concerns of medications and as a pharmacovigilance tool to identify unsuspected side effects. Validation studies have i...

  3. [Pharmacovigilance center --internal medicine interactions: A useful diagnostic tool].

    Science.gov (United States)

    Rochoy, M; Gautier, S; Bordet, R; Caron, J; Launay, D; Hachulla, E; Hatron, P-Y; Lambert, M

    2015-08-01

    Patients hospitalized in internal medicine often have unexplained clinical symptoms for which a drug origin can be considered. The prevalence of patients hospitalized for iatrogenic is estimated between 4-22%. We wanted to evaluate the diagnostic value of the regional center of pharmacovigilance to identify or confirm an iatrogenic disease in the department of internal medicine of Lille and characterize factors associated with drug-related side effect. This is a single-center prospective diagnostic study. We included all subsequent requests from the department of internal medicine with the Nord-Pas-de-Calais regional pharmacovigilance center between 2010 and 2012. The opinion of the regional pharmacovigilance centre was held on the record of the adverse drug reaction in the national pharmacovigilance database and analyzed according to the conclusion of iatrogenic used by clinicians in internal medicine (reference diagnosis) with a follow-up to June 2013. The variables relating to the patient, medication and adverse events were analyzed by binary logistic regression. We analyzed 160 contacts: 118 concordant cases, 38 false-positives (drug-related side effect retained by the regional pharmacovigilance center only), 4 false negatives. Registration in the national pharmacovigilance database had a sensitivity of 96% (95% CI [0.92 to 0.99]), a specificity of 46% (95% CI [0.38 to 0.53]), a value positive predictive of 69% (95% CI [0.62 to 0.76]), a negative predictive value of 89% (95% CI [0.84 to 0.94]) and a negative likelihood ratio of 0.1. False-positive had chronological and semiological accountabilities questionable (adjusted RR=2.1, 95% CI [1.2 to 2.8]). In our study, the regional pharmacovigilance center confirms the clinician's suspicion of drug-related side effects and helps to exclude drug-induced with a high negative predictive value. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  4. Opportunities for Collaboration at the Interface of Pharmacovigilance and Manufacturing.

    Science.gov (United States)

    Beninger, Paul

    2017-04-01

    A case can be made that much common ground exists between pharmacovigilance and pharmaceutical manufacturing. Of the 8 major US statutes that shaped the pharmaceutical industry since early in the 20th Century, 7 followed fatally catastrophic events related to the use of a manufactured product, and 1 followed the discovery of a counterfeit product. To facilitate an understanding of the interplay between pharmacovigilance and manufacturing, it is convenient to divide manufacturing into 3 categories: (1) upstream sourcing of materials: pharmacovigilance plays an important role when adverse event clusters are seen during routine vigilance detection processes and the suspicion turns to possibly contaminated source material, (2) the manufacturing process itself: pharmacovigilance may be called on to conduct a health hazard evaluation if a manufacturing deviation is detected after product release (the assessment can inform the depth of a recall), and (3) downstream distribution and product use: there is only light regulation of the interval between product distribution after manufacturing release and just before administration to patients, a time during which product may be subject to an out-of-specification determination for environmental controls or subject to malfeasant activities, such as counterfeit substitution or product diversion. Recently introduced statutory remedies, including the FDA Safety and Innovation Act and the Drug Supply Chain Security Act in the United States and the Falsified Medicines Directive (directive 2011/62/EC) in the European Union, can provide capabilities to support pharmacovigilance signal management activities that have the potential to reduce the risk to patients of experiencing adverse events caused by counterfeit, diverted, or tampered product. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  5. Pharmacovigilance of herbal medicines in Africa: Questionnaire study.

    Science.gov (United States)

    Skalli, Souad; Bencheikh, Rachida Soulaymani

    2015-08-02

    In order to describe and evaluate Herbal Medicine (HM) pharmacovigilance in African countries who are members of the WHO International Programme for Drug Monitoring a survey questionnaire was sent to the national centres and national drug regulatory agencies of these countries. Data collection was carried out from October 1st to 31st December, 2014. Among the total of 39 African countries, 34 (87.2%) answered the questionnaire and 25 (64.1%) accepted to share their data in this publication. Spontaneous adverse reaction reporting for HM is voluntary in 7 (43.7%) countries. HM pharmacovigilance programmes covered suspected adverse HM reactions in 14 (87.5%) countries; HM information in 7 (43.7%) countries; HM dependence or abuse in 6 (37.5%) countries; medication errors in 5 (31.2%) countries; falsification and adulteration in 2 (each 12.5%) countries and HM-drug interactions in 1 (6.3%) country. Groups in countries encouraged to submit herbal reports were pharmacists and physicians (both n=15); nurses (n=13); herbal therapists (n=12); patients (n=11) and local manufacturers (n=8). The number of herbal reports received by most countries was very low or even insignificant. VigiFlow is used by 10 countries. Information from pharmacovigilance activities is disseminated using many means. Only five countries have regulatory status and quality control of their HM products. The participants identified a need for HM regulation, technical and training assistance, and funding as being major challenges to HM pharmacovigilance in countries. Particular attention to the development of pharmacovigilance of HM is required in Africa. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Role of Pharmacovigilance in India: An overview

    Science.gov (United States)

    Suke, Sanvidhan G; Kosta, Prabhat; Negi, Harsh

    2015-01-01

    Pharmacovigilance (PV) plays a key role in the healthcare system through assessment, monitoring and discovery of interactions amongst drugs and their effects in human. Pharmaceutical and biotechnological medicines are designed to cure, prevent or treat diseases; however, there are also risks particularly adverse drug reactions (ADRs) can cause serious harm to patients. Thus, for safety medication ADRs monitoring required for each medicine throughout its life cycle, during development of drug such as pre-marketing including early stages of drug design, clinical trials, and post-marketing surveillance. PV is concerns with the detection, assessment, understanding and prevention of ADRs. Pharmacogenetics and pharmacogenomics are an indispensable part of the clinical research. Variation in the human genome is a cause of variable response to drugs and susceptibility to diseases are determined, which is important for early drug discovery to PV. Moreover, PV has traditionally involved in mining spontaneous reports submitted to national surveillance systems. The research focus is shifting toward the use of data generated from platforms outside the conventional framework such as electronic medical records, biomedical literature, and patient-reported data in health forums. The emerging trend in PV is to link premarketing data with human safety information observed in the post-marketing phase. The PV system team obtains valuable additional information, building up the scientific data contained in the original report and making it more informative. This necessitates an utmost requirement for effective regulations of the drug approval process and conscious pre and post approval vigilance of the undesired effects, especially in India. Adverse events reported by PV system potentially benefit to the community due to their proximity to both population and public health practitioners, in terms of language and knowledge, enables easy contact with reporters by electronically. Hence, PV

  7. Prevalence of bla SHV genes in clinical isolates of Klebsiella ...

    African Journals Online (AJOL)

    Five bacterial strains (4 Klebsiella pneumoniae and 1 Escherichia coli) representative of pathogenic species and resistant to β-lactam antibiotics are investigated to isolate the genes responsible of β--lactamase activity. The use of engineering techniques enables us to show the widespread of blaSHV genes particularly in ...

  8. Rapid detection of blaVIM-1-37 and blaKPC1/2-12 alleles from clinical samples by multiplex PCR-based assays.

    Science.gov (United States)

    Frasson, Ilaria; Biasolo, Maria Angela; Bartolini, Andrea; Cavallaro, Antonietta; Richter, Sara N; Palù, Giorgio

    2013-07-01

    VIM and KPC are two major families of carbapenemases involved in nosocomial outbreaks of multidrug-resistant Gram-negative bacilli. To rapidly detect bla(VIM)- and bla(KPC)-encoding strains, three multiplex PCR-based methods were designed and validated: (i) a real-time PCR to detect all reported VIM alleles, namely bla(VIM-1-19, 23-37); (ii) a real-time PCR to identify bla(VIM)-type and bla(KPC) carbapenemases in an ultrarapid single reaction; and (iii) a standard PCR to amplify and sequence all VIM alleles. All three methods detected 33 VIM-positive samples among 107 Gram-negative isolates with imipenem and meropenem minimum inhibitory concentrations ≥1 mg/L. The three methods displayed 100% sensitivity, specificity and concordance. Sequencing of the bla(VIM) amplicons revealed that 30 samples encoded bla(VIM-1) and 3 samples encoded bla(VIM-2). The real-time assay, optimised for the simultaneous detection of bla(VIM) and bla(KPC), identified 3 and 12 isolates positive for both bla(VIM)/bla(KPC) and for bla(KPC), respectively. The analytical sensitivity of the real-time assays was linear over 6 log dilutions, with a reproducible detection limit of 1 CFU. No cross-reactivity was detected. The developed assays provide powerful tools for rapid identification of VIM and KPC carbapenemase producers, therefore contributing to the prevention and containment of resistance dissemination. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  9. Characteristics of β-lactamases and their genes (blaA and blaB in Yersinia intermedia and Y. frederiksenii

    Directory of Open Access Journals (Sweden)

    Sharma Sachin

    2007-04-01

    Full Text Available Abstract Background The presence of β-lactamases in Y. enterocolitica has been reported to vary with serovars, biovars and geographical origin of the isolates. An understanding of the β-lactamases in other related species is important for an overall perception of antibiotic resistance in yersiniae. The objective of this work was to study the characteristics of β-lactamases and their genes in strains of Y. intermedia and Y. frederiksenii, isolated from clinical and non-clinical sources in India. Results The enzymes, Bla-A (a constitutive class A penicillinase and Bla-B (an inducible class C cephalosporinase were found to be present in all the clinical and non-clinical strains of Y. intermedia and Y. frederiksenii by double disc diffusion method. The results showed differential expression of Bla-A as indicated by presence/absence of synergy whereas expression of Bla-B was quite consistent. The presence of these enzymes was also reflected in the high minimum inhibitory concentrations, MIC50 (126–1024 mg/L and MIC90 (256–1024 mg/L of β-lactam antibiotics against these species. Restriction fragment length polymorphism (RFLP revealed heterogeneity in both blaA and blaB genes of Y. intermedia and Y. frederiksenii. The blaA gene of Y. intermedia shared significant sequence identity (87–96% with blaA of Y. enterocolitica biovars 1A, 1B and 4. The sequence identity of blaA of Y. frederiksenii with these biovars was 77–79%. The sequence identity of blaB gene of Y. intermedia and Y. frederiksenii was more (85% with that of Y. enterocolitica biovars 1A, 1B and 2 compared to other species viz., Y. bercovieri, Y. aldovae and Y. ruckeri. Isoelectric focusing data further revealed that both Y. intermedia and Y. frederiksenii produced Bla-A (pI 8.7 and "Bla-B like" (pI 5.5–7.1 enzymes. Conclusion Both Y. intermedia and Y. frederiksenii showed presence of blaA and blaB genes and unequivocal expression of the two β-lactamases. Limited heterogeneity

  10. Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events

    DEFF Research Database (Denmark)

    Acquavella, John; Ehrenstein, Vera; Schiødt, Morten

    2016-01-01

    -authorization safety study of cancer patients treated with antiresorptive therapies. METHODS: As part of a comprehensive pharmacovigilance plan, developed with regulators' input, the study will estimate incidence of ONJ and of serious infections among adult cancer patients with bone metastases treated with denosumab...

  11. Characterization of a novel blaIMP gene, blaIMP-58, using whole genome sequencing in a Pseudomonas putida isolate detected in Denmark

    DEFF Research Database (Denmark)

    Holmgaard, Dennis Back; Hansen, Frank; Hasman, Henrik

    2017-01-01

    A multidrug-resistant strain of Pseudomonas putida was isolated from the urine of a 65-year-old women hospitalized for serious clinical conditions. Using whole genome sequencing a novel blaIMP gene, blaIMP-58 was discovered and characterized.......A multidrug-resistant strain of Pseudomonas putida was isolated from the urine of a 65-year-old women hospitalized for serious clinical conditions. Using whole genome sequencing a novel blaIMP gene, blaIMP-58 was discovered and characterized....

  12. Pharmacovigilance in Clinical Trials: Current Practice and Challenges.

    Science.gov (United States)

    Cheaib, N

    2016-01-01

    In view of the MENA increasing participation in multinational trials and the increasing number of national/regional trials, this article explores potential areas of pharmacovigilance, requiring reform and provides recommendations for building a robust safety reporting system. Regulatory silence on expedited reporting requirements creates confusion for local sites that are part of multinational trials. Not allowing waiver for serious adverse events that are protocol specified or are study endpoints, along with lack of emphasis on causality as reporting criteria, adds substantial burden of uninformative cases for regulatory review. Despite global focus on Development Safety Update Report, local regulators are not yet insistent on real-time update of a drug's cumulative safety profile. Issues like reporting requirements for generic trials, pregnancy reporting and lenient timeline for death/life-threatening events need attention. Finally, the need to formulate an all-encompassing local pharmacovigilance guideline, in sync with global practice cannot be overemphasized.

  13. Pharmacovigilance in Crisis: Drug Safety at a Crossroads.

    Science.gov (United States)

    Price, John

    2018-03-28

    Pharmacovigilance (PV) is under unprecedented stress from fundamental changes in a booming pharmaceutical industry, from the challenges of creating and maintaining an increasingly complex PV system in a globally diverse regulatory environment, and from unpredicted consequences of historical PV cost-reduction strategies. At the same time, talent availability lags demand, and many PV professionals may no longer be finding personal fulfillment in their careers. The situation creates risks for companies. Advantages and disadvantages of potential strategies to address this increasing problem at a corporate and industry level and in collaboration with regulatory agencies are discussed, as well as opportunities to adopt new technologies, including artificial intelligence and machine-learning to automate pharmacovigilance operations. These approaches would address burdensome and wasteful effort assuring regulatory compliance and free up resources to support the original mission of PV as an important public health activity and to reinvest in the development of new drugs. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  14. Biologics, Pharmacovigilance, and Patient Safety: It's All in the Name.

    Science.gov (United States)

    Stevenson, James G; Green, Larry

    2016-08-01

    The most appropriate naming convention for biologics and biosimilars has been an area of significant debate. The ultimate decision will have an impact on patient safety, pharmacovigilance program effectiveness, and, potentially, the overall adoption of biosimilars in the United States. This article reviews some of the advantages and disadvantages of various naming approaches. For clarity in communication, optimal pharmacovigilance, and patient safety, it is recommended that biosimilars be named with a common USAN (United States Adopted Name) with the reference product, along with a suffix that is memorable, such as one associated with the original manufacturer of the product. This approach supports the FDA's mission of protecting patient safety and public health, while minimizing the possibility of inadvertent switching of products and facilitating effective pharmacovigilance. No funding supported the writing of this article. Stevenson reports consulting fees from Amgen, Inc., AbbVie, and Pfizer and is employed by Visante. Green is employed by and owns stock in Amgen, Inc. Article concept was contributed primarily by Stevenson, along with Green. The manuscript was written and revised primarily by Stevenson, along with Green. Both authors contributed equally to data interpretation.

  15. Genetic characterization of blaNDM-harboring plasmids in carbapenem-resistant Escherichia coli from Myanmar.

    Directory of Open Access Journals (Sweden)

    Yo Sugawara

    Full Text Available The bacterial enzyme New Delhi metallo-β-lactamase hydrolyzes almost all β-lactam antibiotics, including carbapenems, which are drugs of last resort for severe bacterial infections. The spread of carbapenem-resistant Enterobacteriaceae that carry the New Delhi metallo-β-lactamase gene, blaNDM, poses a serious threat to public health. In this study, we genetically characterized eight carbapenem-resistant Escherichia coli isolates from a tertiary care hospital in Yangon, Myanmar. The eight isolates belonged to five multilocus-sequence types and harbored multiple antimicrobial-resistance genes, resulting in resistance against nearly all of the antimicrobial agents tested, except colistin and fosfomycin. Nine plasmids harboring blaNDM genes were identified from these isolates. Multiple blaNDM genes were found in the distinct Inc-replicon types of the following plasmids: an IncA/C2 plasmid harboring blaNDM-1 (n = 1, IncX3 plasmids harboring blaNDM-4 (n = 2 or blaNDM-7 (n = 1, IncFII plasmids harboring blaNDM-4 (n = 1 or blaNDM-5 (n = 3, and a multireplicon F plasmid harboring blaNDM-5 (n = 1. Comparative analysis highlighted the diversity of the blaNDM-harboring plasmids and their distinct characteristics, which depended on plasmid replicon types. The results indicate circulation of phylogenetically distinct strains of carbapenem-resistant E. coli with various plasmids harboring blaNDM genes in the hospital.

  16. Genetic characterization of blaNDM-harboring plasmids in carbapenem-resistant Escherichia coli from Myanmar.

    Science.gov (United States)

    Sugawara, Yo; Akeda, Yukihiro; Sakamoto, Noriko; Takeuchi, Dan; Motooka, Daisuke; Nakamura, Shota; Hagiya, Hideharu; Yamamoto, Norihisa; Nishi, Isao; Yoshida, Hisao; Okada, Kazuhisa; Zin, Khwar Nyo; Aye, Mya Mya; Tomono, Kazunori; Hamada, Shigeyuki

    2017-01-01

    The bacterial enzyme New Delhi metallo-β-lactamase hydrolyzes almost all β-lactam antibiotics, including carbapenems, which are drugs of last resort for severe bacterial infections. The spread of carbapenem-resistant Enterobacteriaceae that carry the New Delhi metallo-β-lactamase gene, blaNDM, poses a serious threat to public health. In this study, we genetically characterized eight carbapenem-resistant Escherichia coli isolates from a tertiary care hospital in Yangon, Myanmar. The eight isolates belonged to five multilocus-sequence types and harbored multiple antimicrobial-resistance genes, resulting in resistance against nearly all of the antimicrobial agents tested, except colistin and fosfomycin. Nine plasmids harboring blaNDM genes were identified from these isolates. Multiple blaNDM genes were found in the distinct Inc-replicon types of the following plasmids: an IncA/C2 plasmid harboring blaNDM-1 (n = 1), IncX3 plasmids harboring blaNDM-4 (n = 2) or blaNDM-7 (n = 1), IncFII plasmids harboring blaNDM-4 (n = 1) or blaNDM-5 (n = 3), and a multireplicon F plasmid harboring blaNDM-5 (n = 1). Comparative analysis highlighted the diversity of the blaNDM-harboring plasmids and their distinct characteristics, which depended on plasmid replicon types. The results indicate circulation of phylogenetically distinct strains of carbapenem-resistant E. coli with various plasmids harboring blaNDM genes in the hospital.

  17. Successful treatment of a Carbapenem-resistant Klebsiella pneumoniae carrying bla OXA-48 , bla VIM-2 , bla CMY-2 and bla SHV- with high dose combination of imipenem and amikacin.

    Science.gov (United States)

    Hajjej, Zied; Gharsallah, Hedi; Naija, Habiba; Boutiba, Ilhem; Labbene, Iheb; Ferjani, Mustapha

    2016-01-01

    We describe a case of 58-year-old man with septic shock due to Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) bloodstream infections (BSI) who was successfully treated with a high dose association of amikacin and imipenem combined with continuous venovenous hemodiafiltration (CVVHDF). A Klebsiella pneumoniae (Kp) was isolated from the catheter culture and from two blood samples, drawn from the catheter before removal and from a peripheral vein. The Kp was intermediate to Amikacin (MIC = 16 μg/ml) and was resistant to all other antibiotics including Imipenem (MIC = 4 μg/ml), Colistin (MIC = 16 μg/ml) and Tigecycline (MIC = 4 μg/ml) according to the Clinical and Laboratory Standards Institute (CLSI) published in 2011. PCR amplification and sequencing verified the presence of blaOXA-48, blaVIM-2, blaCMY-2 and blaSHV-1 genes. Amikacin was given at a dose of 30 mg/kg (2.5 g) in a 30 min infusion and the dose of imipenem was increased to 1 g every 6 h despite patient's altered renal function (Creatinine Clearance = 25 ml/min). To avoid amikacin nephrotoxicity and to allow the use of high doses of imipenem, continuous venovenous hemodiafiltration (CVVHDF) (blood flow, 200 ml/h; dialysate, 1000 ml/h; ultrafiltrate, 2000 ml/h) was initiated 1 h after the start of the amikacin infusion and continued thereafter. The patient improved hemodynamically and norepinephrine was stopped five days after antibiotherapy adaptation.

  18. Co-existence of bla OXA-23 and bla NDM-1 genes of Acinetobacter baumannii isolated from Nepal: antimicrobial resistance and clinical significance

    Directory of Open Access Journals (Sweden)

    Prabhu Raj Joshi

    2017-02-01

    Full Text Available Abstract Background Molecular analysis of carbapenem-resistant genes in Acinetobacter baumannii, an emerging pathogen, is less commonly reported from Nepal. In this study we determined the antibiotic susceptibility profile and genetic mechanism of carbapenem resistance in clinical isolates of A. baumannii. Methods A. baumannii were isolated from various clinical specimens and identified based on Gram staining, biochemical tests, and PCR amplification of organism specific 16S rRNA and bla OXA-51 genes. The antibiotic susceptibility testing was performed using disc diffusion and E-test method. Multiplex PCR assays were used to detect the following β-lactamase genes: four class D carbapenem hydrolyzing oxacillinases (bla OXA-51, bla OXA-23, bla OXA-24 and bla OXA-58. Uniplex PCRs were used to detect three class B metallo-β-lactamases genes (bla IMP, bla VIM and bla NDM-1, class C cephalosporin resistance genes (bla ADC, aminoglycoside resistance gene (aphA6, and ISAba1 of all isolates. Insertion sequence ISAba125 among NDM-1 positive strains was detected. Clonal relatedness of all isolates were analyzed using repetitive sequence-based PCR (rep-PCR. Results Of total 44 analyzed isolates, 97.7% (n = 43 were carbapenem-resistant A. baumannii (CR-AB and 97.7% (n = 43 were multidrug resistant A. baumannii (MDR-AB. One isolate was detected to be extremely drug resistant A. baumannii (XDR-AB. All the isolates were fully susceptible to colistin (MICs < 2 μg/ml. The bla OXA-23 gene was detected in all isolates, while bla NDM-1 was detected in 6 isolates (13.6%. Insertion sequence, ISAba1 was detected in all of bla OXA-23 positive isolates. ISAba125 was detected in all bla NDM-1 positive strains. The bla ADC and aphA6 genes were detected in 90.1 and 40.1%, respectively. The rep-PCR of all isolates represented 7 different genotypes. Conclusion We found high prevalence of CR-AB and MDR-AB with bla OXA-23 gene in a tertiary care hospital in

  19. Detection of bla(IMP) and bla(VIM) metallo-β-lactamases genes among Pseudomonas aeruginosa strains.

    Science.gov (United States)

    Fallah, Fatemeh; Borhan, Rebwar Shams; Hashemi, Ali

    2013-01-01

    Acquired Metallo-β-Lactamases (MBLs) are emerging resistance determinants in Pseudomonas aeruginosa and other gram-negative bacteria.Using Combination Disk Diffusion test, it was found that among 83 imipenem non-susceptible P. aeruginosa strains, 48 (57.9%) were MBL producers. PCR and Sequencing methods proved that these isolates were positive for blaIMP-1 genes, whereas none were positive for bla(VIM) genes. The mortality rate due to MBL-producing Pseudomonas infection was 4 (8.3%) among the hospitalized patients. Therefore, identification of drug resistance patterns in P. aeruginosa and detection of MBLs producing isolates are of great importance in the prevention and control of infections.

  20. Developing a Crowdsourcing Approach and Tool for Pharmacovigilance Education Material Delivery

    NARCIS (Netherlands)

    Bate, Andrew; Beckmann, Juergen; Dodoo, Alexander; Härmark, Linda; Hartigan-Go, Kenneth; Hegerius, Anna; Lindquist, Marie; van Puijenbroek, Eugene; Tuccori, Marco; Hagemann, Ulrich

    The number of pharmacovigilance professionals worldwide is increasing with a high staff turnover. There is a constant stream of new colleagues with an interest or need to learn about the discipline. Consequently, there is an increasing need for training in pharmacovigilance. An important step

  1. Developing a Crowdsourcing Approach and Tool for Pharmacovigilance Education Material Delivery.

    Science.gov (United States)

    Bate, Andrew; Beckmann, Jürgen; Dodoo, Alexander; Härmark, Linda; Hartigan-Go, Kenneth; Hegerius, Anna; Lindquist, Marie; van Puijenbroek, Eugène; Tuccori, Marco; Hagemann, Ulrich

    2017-03-01

    The number of pharmacovigilance professionals worldwide is increasing with a high staff turnover. There is a constant stream of new colleagues with an interest or need to learn about the discipline. Consequently, there is an increasing need for training in pharmacovigilance. An important step towards this has been made through developing and publishing the World Health Organization (WHO)-International Society of Pharmacovigilance (ISoP) Pharmacovigilance Curriculum. Using the Pharmacovigilance Curriculum effectively, it should be supplemented by providing comprehensive training material from various sources, and making the Pharmacovigilance Curriculum attractive and a high-utility product. We describe a pilot of the development and initial evaluation of a crowdsourcing tool for the provision of pharmacovigilance education material. Pharmacovigilance experts shared links to their material to sections of relevance in the hierarchy and a small group of organisations conducted an initial testing. In this pilot, we have shown the usability of such a web-based tool. The strengths of this approach include the potential for a routine 'democratic' approach to sharing educational material to a wider community and an openness for access.

  2. Characterization of a novel blaIMPgene, blaIMP-58, using whole genome sequencing in a Pseudomonas putida isolate detected in Denmark.

    Science.gov (United States)

    Holmgaard, Dennis Back; Hansen, Frank; Hasman, Henrik; Justesen, Ulrik S; Hammerum, Anette M

    2017-01-01

    A multidrug-resistant strain of Pseudomonas putida was isolated from the urine of a 65-year-old women hospitalized for serious clinical conditions. Using whole genome sequencing a novel blaIMP gene, blaIMP-58 was discovered and characterized. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Pharmacovigilance systems in developing countries: an evaluative case study in Burkina Faso.

    Science.gov (United States)

    Kabore, Lassane; Millet, Pascal; Fofana, Souleymane; Berdai, Driss; Adam, Caroline; Haramburu, Françoise

    2013-05-01

    Burkina Faso, like other Sub-Saharan African countries, has recently experienced a large-scale deployment of new medicines for the prevention and treatment of notable diseases of public health interest, including malaria, HIV/AIDS and meningitis. This new context rendered the implementation of pharmacovigilance necessary in order to monitor and establish the safety and effectiveness of these medicines. In 2008, the Ministry of Health of Burkina Faso, West Africa, launched a formal pharmacovigilance system to respond to this need. The aim of this study was to evaluate the early-stage pharmacovigilance system of Burkina Faso through a comprehensive and system-based approach with the prospect of identifying areas for improvements. We conducted a descriptive cross-sectional study in Burkina Faso. Sixteen key informants from the National Drug Authority (NDA), public health programmes (PHPs) and hospitals were interviewed. Study participants were selected based on a convenience sampling in the NDA, three teaching hospitals, two regional hospitals and six PHPs. Data were collected using the Indicator-based Pharmacovigilance Assessment Tool (IPAT), a metric instrument recently designed and validated by 'Management Sciences for Health', a US non-profit organization. The evaluation also involved the collection and review of relevant pharmacovigilance-related documentation in the institutions assessed. A scoring system was used for the quantification of assessment results. The NDA of Burkina Faso, the institution statutorily in charge of pharmacovigilance, achieved a performance score of 70 %. The basic structures for pharmacovigilance activities were in place; however, the lack of specific laws dedicated to pharmacovigilance, the lack of national guidelines and standard operating procedures on pharmacovigilance, and the insufficient coordination of pharmacovigilance stakeholders in the country were identified as the main weaknesses. Safety data collected thus far have not

  4. Molecular characterisation and diversity in Enterobacter cloacae from Edinburgh and Egypt carrying bla(CTX-M-14) and bla(VIM-4) β-lactamase genes.

    Science.gov (United States)

    Dimude, J U; Amyes, S G B

    2013-06-01

    The purpose of this study was to compare the carbapenemases and extended-spectrum β-lactamases (ESBLs) associated with resistance, the genetic environment of these genes, and their location on plasmids among Enterobacter cloacae isolates from Edinburgh (UK) and Egypt. Nine E. cloacae isolates were obtained from Egypt (n=3) and Edinburgh (n=6). Antimicrobial susceptibility testing was performed by agar dilution. Molecular detection of carbapenemase genes, blaCTX-M-14 and the presence of integron structures was done by PCR and sequencing. Genotyping of the strains was performed by pulsed-field gel electrophoresis (PFGE) with XbaI restriction. Plasmids were extracted to determine the location of the resistance genes. PCR sequencing revealed that all of the isolates carried the blaCTX-M-14 ESBL gene, whilst two isolates also carried the blaVIM-4 metallo-β-lactamase gene. The blaCTX-M-14 genes in two isolates were associated with the ISEcp1 transposase. Analysis of the integrons found an intI1 integron associated with the complex ISCR1. The blaVIM-4 gene was identified in the form of a gene cassette within the class 1 integron, followed downstream by the resistance genes aacA7, dfrA1 and aadA2. PFGE revealed genetic relatedness among six isolates, whereas the others were diverse although related. Plasmid analysis revealed a single plasmid carrying both blaVIM-4 and blaCTX-M-14. In conclusion, the presence of insertion sequence ISEcp1 upstream of blaCTX-M-14 suggests its involvement in the expression and mobilisation of this gene. Linked carriage of blaVIM-4 and blaCTX-M-14 on the same plasmid in E. cloacae results in resistance to all β-lactams and limits antibiotic treatment options. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  5. Impact of training on Nigerian healthcare professionals' knowledge and practice of pharmacovigilance.

    Science.gov (United States)

    Osakwe, Adeline; Oreagba, Ibrahim; Adewunmi, Adebowale J; Adekoya, Abisola; Fajolu, Iretiola

    2013-01-01

    Pharmacovigilance is the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug related problem.. The effectiveness of this system revolves on the active participation of the healthcare practitioners. Poor knowledge and practice of pharmacovigilance has necessitated training of healthcare professionals in different parts of Nigeria. The objectives of this study are to determine the knowledge and practice of pharmacovigilance amongst health professionals in Nigeria and the impact of previous training in pharmacovigilance on their knowledge and practice. In this descriptive cross sectional study, purposive and systematic random sampling method was used in selecting health facilities and health care practitioners respectively. Data were collected using a three-part peer-reviewed structured questionnaire administered through electronic mail (25) and self administration by healthcare professionals (316). Respondents who had received training on pharmacovigilance had better knowledge of correct definition of pharmacovigilance (P = 0.001) and better theoretical knowledge and practice scores of pharmacovigilance (P = 0.001). Receiving quarterly newsletters was not significantly associated (p = 0.220) with improved knowledge of pharmacovigilance. Overall, knowledge and practice of pharmacovigilance in Nigeria was still below average. The main challenges faced in the reporting and detecting of ADR were lack of awareness, poor communication, lack of continuity in training and poor funding. Although training was associated with improved knowledge and practice of pharmacovigilance amongst the health care providers studied, its overall impact was mild. Strengthened awareness creation and innovations in PV training methods are necessary to improve the efficiency of the program.

  6. Feasibility and Educational Value of a Student-Run Pharmacovigilance Programme: A Prospective Cohort Study.

    Science.gov (United States)

    Schutte, Tim; Tichelaar, Jelle; Reumerman, Michael O; van Eekeren, Rike; Rolfes, Leàn; van Puijenbroek, Eugène P; Richir, Milan C; van Agtmael, Michiel A

    2017-05-01

    Pharmacovigilance, the monitoring of drug safety after marketing approval, highly depends on the adequate reporting of adverse drug reactions (ADRs). To improve pharmacovigilance awareness and future ADR reporting among medical students, we developed and evaluated a student-run pharmacovigilance programme. In this project, teams of medical students (first- to fifth-year) assessed real ADR reports, as submitted to the national pharmacovigilance centre. After assessment of causality, including identification of a potential pharmacological explanation for the ADR, the students wrote a personalized feedback letter to the reporter, as well as a summary for the European Medicines Agency (EMA) and World Health Organization (WHO) pharmacovigilance databases. This student assessment was then verified and evaluated by staff from The Netherlands Pharmacovigilance Centre Lareb (Lareb), using an e-questionnaire. Student attitudes, intentions, skills, and knowledge of ADR reporting were evaluated using the e-questionnaire, before and after participation in the programme. From May 2014 to January 2015, a total of 43 students assessed 100 different ADR reports selected by Lareb staff (n = 3). Student assessments were rated as useful (93%), scientifically substantiated (90%), accurate (92%), and complete (92%), and, on average, did not cost Lareb staff extra time. Medical students were positive about ADR reporting, and their awareness of ADR reporting increased significantly following participation in the programme (p < 0.05). After participation in the programme, the students intended to report serious ADRs in their future practice, and their knowledge of pharmacovigilance and ADR reporting showed they had a high overall level of pharmacological understanding. The student-run pharmacovigilance programme is a win-win venture. It offers students a valuable 'pharmacovigilance experience', creates awareness in future doctors, and has the potential to increase pharmacovigilance

  7. Predominance of carbapenem-resistant Pseudomonas aeruginosa isolates carrying blaIMP and blaVIM metallo-β-lactamases in a major hospital in Costa Rica.

    Science.gov (United States)

    Toval, Francisco; Guzmán-Marte, Anel; Madriz, Vivian; Somogyi, Teresita; Rodríguez, César; García, Fernando

    2015-01-01

    This study aimed to assess the molecular basis of the resistance to carbapenems in clinical isolates of Pseudomonas aeruginosa recovered from a tertiary-level health facility in San José, Costa Rica. A total of 198 non-duplicated isolates were evaluated for their susceptibility to β-lactams, aminoglycosides and fluoroquinolones. The production of metallo-β-lactamases (MBLs), the presence of MBL encoding genes (blaIMP, blaVIM and blaGIM-1) and the occurrence of these genes within class 1 integrons were investigated. In addition, an ERIC2 PCR fingerprinting method was used to elucidate the distribution of the detected MBL genes within the strain collection. Of the 198 isolates tested, 125 (63.1 %) were categorized as carbapenem-resistant. The majority (88.8 %) of the carbapemen-resistant isolates also showed resistance to ceftazidime, cefepime, aztreonam, ticarcillin/clavulanic acid, amikacin, gentamicin, tobramycin, ciprofloxacin and gatifloxacin. Among the carbapenem-resistant isolates, 102 (81.6 %) showed MBL activity. Strikingly, both blaIMP and blaVIM genes were simultaneously detected in most (94.1 %) of the 102 MBL producers. Five carbapenem-resistant MBL producers were positive only for blaIMP genes. Almost 70 % of the isolates examined harboured the intI1 gene, accompanied by the sul1 and qacEΔ1 genes in 136 (99 %) and 122 (89 %) isolates, respectively. The majority (94.4 %) of the carbapenem-resistant isolates carried the intI1 gene, in contrast to 26 % of the carbapenem-susceptible isolates. Ninety-three out of 96 (96.9 %) isolates carrying both blaIMP and blaVIM genes also harboured the intI1, sul1 and qacEΔ1 genes. Gene cassettes from carbapenem-susceptible and MBL-negative carbapenem-resistant isolates encoded aminoglycoside-resistance enzymes (aadA2, aadA4 and aadA6) as well as orfD and qacF genes. RAPD analysis distributed 126 of the isolates in 29 clusters. Eighty of the 90 blaIMP (+) blaVIM (+) isolates were sorted into 16

  8. The EU-ADR Web Platform: delivering advanced pharmacovigilance tools.

    Science.gov (United States)

    Oliveira, José Luis; Lopes, Pedro; Nunes, Tiago; Campos, David; Boyer, Scott; Ahlberg, Ernst; van Mulligen, Erik M; Kors, Jan A; Singh, Bharat; Furlong, Laura I; Sanz, Ferran; Bauer-Mehren, Anna; Carrascosa, Maria C; Mestres, Jordi; Avillach, Paul; Diallo, Gayo; Díaz Acedo, Carlos; van der Lei, Johan

    2013-05-01

    Pharmacovigilance methods have advanced greatly during the last decades, making post-market drug assessment an essential drug evaluation component. These methods mainly rely on the use of spontaneous reporting systems and health information databases to collect expertise from huge amounts of real-world reports. The EU-ADR Web Platform was built to further facilitate accessing, monitoring and exploring these data, enabling an in-depth analysis of adverse drug reactions risks. The EU-ADR Web Platform exploits the wealth of data collected within a large-scale European initiative, the EU-ADR project. Millions of electronic health records, provided by national health agencies, are mined for specific drug events, which are correlated with literature, protein and pathway data, resulting in a rich drug-event dataset. Next, advanced distributed computing methods are tailored to coordinate the execution of data-mining and statistical analysis tasks. This permits obtaining a ranked drug-event list, removing spurious entries and highlighting relationships with high risk potential. The EU-ADR Web Platform is an open workspace for the integrated analysis of pharmacovigilance datasets. Using this software, researchers can access a variety of tools provided by distinct partners in a single centralized environment. Besides performing standalone drug-event assessments, they can also control the pipeline for an improved batch analysis of custom datasets. Drug-event pairs can be substantiated and statistically analysed within the platform's innovative working environment. A pioneering workspace that helps in explaining the biological path of adverse drug reactions was developed within the EU-ADR project consortium. This tool, targeted at the pharmacovigilance community, is available online at https://bioinformatics.ua.pt/euadr/. Copyright © 2012 John Wiley & Sons, Ltd.

  9. Therapeutic drug monitoring in pharmacovigilance and pharmacotherapy safety.

    Science.gov (United States)

    Haen, E

    2011-09-01

    Quantification of serum or plasma concentrations of medications is essential to find out if an adverse drug effect (ADE) is associated with an elevated drug concentration. In former years TDM was therefore often used in pharmacovigilance just to confirm that an ADE that had already occurred was due to an elevated drug plasma concentration without identifying the underlying cause for the surprising high concentration. This old approach of Therapeutic Drug Monitoring (TDM) in pharmacovigilance needs to be revised due to new developments in information technology, new analytical procedures and due to the inclusion of clinical pharmacological expert opinions in the presentation of laboratory medicine results. Today, TDM may be used to prevent ADE, rather than just confirming a suggested cause of an ADE that has happened in the past. This approach means that blood should be drawn for TDM analysis after the pharmacokinetic steady state has been reached (5 times of the elimination half life of the drug) with low to moderate dosages under the intended (poly)medication if the patient is clinically regarded as not belonging to the "normal" patient population. With the availability of reliable automated analytical methods this can be performed at a reasonable price. Funds may be saved to the health care system, because hospitalization will be thereby shortened and expensive diagnoses and treatment of ADE will be avoided. However, this has still to be proven in cross-system studies: Budget will be saved in 2 areas of the health system (hospital stay and drug costs), whereas a much smaller amount of money has to be invested for laboratory analyses in another area. TDM may thus change pharmacovigilance as a tool for monitoring and documentation of ADE to a safety tool in drug therapy for prevention of ADE. Georg Thieme Verlag KG Stuttgart · New York.

  10. Leveraging MEDLINE indexing for pharmacovigilance - Inherent limitations and mitigation strategies.

    Science.gov (United States)

    Winnenburg, Rainer; Sorbello, Alfred; Ripple, Anna; Harpaz, Rave; Tonning, Joseph; Szarfman, Ana; Francis, Henry; Bodenreider, Olivier

    2015-10-01

    Traditional approaches to pharmacovigilance center on the signal detection from spontaneous reports, e.g., the U.S. Food and Drug Administration (FDA) adverse event reporting system (FAERS). In order to enrich the scientific evidence and enhance the detection of emerging adverse drug events that can lead to unintended harmful outcomes, pharmacovigilance activities need to evolve to encompass novel complementary data streams, for example the biomedical literature available through MEDLINE. (1) To review how the characteristics of MEDLINE indexing influence the identification of adverse drug events (ADEs); (2) to leverage this knowledge to inform the design of a system for extracting ADEs from MEDLINE indexing; and (3) to assess the specific contribution of some characteristics of MEDLINE indexing to the performance of this system. We analyze the characteristics of MEDLINE indexing. We integrate three specific characteristics into the design of a system for extracting ADEs from MEDLINE indexing. We experimentally assess the specific contribution of these characteristics over a baseline system based on co-occurrence between drug descriptors qualified by adverse effects and disease descriptors qualified by chemically induced. Our system extracted 405,300 ADEs from 366,120 MEDLINE articles. The baseline system accounts for 297,093 ADEs (73%). 85,318 ADEs (21%) can be extracted only after integrating specific pre-coordinated MeSH descriptors and additional qualifiers. 22,889 ADEs (6%) can be extracted only after considering indirect links between the drug of interest and the descriptor that bears the ADE context. In this paper, we demonstrate significant improvement over a baseline approach to identifying ADEs from MEDLINE indexing, which mitigates some of the inherent limitations of MEDLINE indexing for pharmacovigilance. ADEs extracted from MEDLINE indexing are complementary to, not a replacement for, other sources. Published by Elsevier Inc.

  11. Clinical Performance of Check-Direct CPE, a Multiplex PCR for Direct Detection of bla(KPC), bla(NDM) and/or bla(VIM), and bla(OXA)-48 from Perirectal Swabs.

    Science.gov (United States)

    Lau, Anna F; Fahle, Gary A; Kemp, Margaret A; Jassem, Agatha N; Dekker, John P; Frank, Karen M

    2015-12-01

    We evaluated the clinical performance of Check-Direct CPE for carbapenemase detection directly from 301 perirectal swabs (258 patients) in a nonoutbreak setting. Culture of a PCR-confirmed, carbapenemase-containing organism, or history of colonization with such organism within the previous 2 weeks, was used as the reference standard. Check-Direct CPE demonstrated a sensitivity value, specificity value, positive predictive value (PPV), and negative predictive value (NPV) of 100% (all bla(KPC)), 88%, 21%, and 100%, respectively. False positives accounted for 79% (n = 34) of samples for which a cycle threshold (C(T)) value was reached. Simulated studies to evaluate specimen pooling as an approach to minimize costs showed no difference in C(T) values for pooled groups of three or five that each contained a single specimen spiked with ∼1,500 CFU bla(KPC) Klebsiella pneumoniae; however, the detection rate dropped to 60% at a seeded concentration of ∼150 CFU. When data were pooled, C(T) values for bla(KPC) were higher for heavy-feces-containing than for light-feces-containing liquid-suspended specimens. Furthermore, C(T) values for liquid-suspended specimens were 4 to 5 C(T) values lower (i.e., represented greater sensitivity) than those seen in direct swab analysis. Culture was equivalent to or better than Check-Direct CPE for 13/15 (87%) isolates tested in a limit-of-detection analysis. Detection of a carbapenemase gene at a C(T) cutoff value of ≤35 was culture confirmed in 23/24 (96%) of cases; however, C(T) values of >35 overlapped broadly between culture-positive (n = 21) and culture-negative (n = 36) specimens. Check-Direct CPE will likely prove most useful in high-prevalence areas or in outbreak settings where rapid carbapenemase detection is critical for infection control management. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Veterinary pharmacovigilance in India: A need of hour.

    Science.gov (United States)

    Kumar, Rishi; Kalaiselvan, Vivekanandan; Verma, Ravendra; Kaur, Ismeet; Kumar, Pranay; Singh, G N

    2017-01-01

    Veterinary pharmacovigilance (PV) is important for the Medicine which are used for treating disease in animals. It becomes more important when these animals are further used for producing food. Adverse drug reactions (ADRs) have a direct impact on animals and indirect impact on human beings, for example, through milk products, other animal producing food products. Currently, PV program of India is playing a vital role in assessing the safety of medicines in Indian Population. The safety of medicine in animals can be assessed by veterinary PV. The research institutes involved in animal research and veterinary hospitals can be considered as ADR monitoring centers to assess the safety of medicines on animals.

  13. Pharmacovigilance in Russia: current state of affairs, challenges, and prospects.

    Science.gov (United States)

    Gildeeva, Geliya; Belostotsky, Andrey

    2017-12-01

    This review outlines current issues of the pharmacovigilance (PV) system in the Russian Federation, namely the present state of regulatory aspects, regulatory requirements in both Russia and the Eurasian Economic Union, and review of causes of under-reporting of adverse drug reactions. Specific attention will be focused on how the system is designed to monitor drug safety functions, reporting and accountability of pharmaceutical products, their manufacturers and medical staff, the role played by regional centers for drug-safety monitoring, and insufficient understanding of the part taken by patients in the system of PV. The prospects of the Russian PV system and its harmonization with global practice will also be discussed.

  14. Adolescent Alcohol Drinking Renders Adult Drinking BLA-Dependent: BLA Hyper-Activity as Contributor to Comorbid Alcohol Use Disorder and Anxiety Disorders.

    Science.gov (United States)

    Moaddab, Mahsa; Mangone, Elizabeth; Ray, Madelyn H; McDannald, Michael A

    2017-11-14

    Adolescent alcohol drinking increases the risk for alcohol-use disorder in adulthood. Yet, the changes in adult neural function resulting from adolescent alcohol drinking remain poorly understood. We hypothesized that adolescent alcohol drinking alters basolateral amygdala (BLA) function, making alcohol drinking BLA-dependent in adulthood. Male, Long Evans rats were given voluntary, intermittent access to alcohol (20% ethanol) or a bitter, isocaloric control solution, across adolescence. Half of the rats in each group received neurotoxic BLA lesions. In adulthood, all rats were given voluntary, intermittent access to alcohol. BLA lesions reduced adult alcohol drinking in rats receiving adolescent access to alcohol, but not in rats receiving adolescent access to the control solution. The effect of the BLA lesion was most apparent in high alcohol drinking adolescent rats. The BLA is essential for fear learning and is hyper-active in anxiety disorders. The results are consistent with adolescent heavy alcohol drinking inducing BLA hyper-activity, providing a neural mechanism for comorbid alcohol use disorder and anxiety disorders.

  15. Emergence of Klebsiella pneumoniae ST273 Carrying blaNDM-7and ST656 Carrying blaNDM-1in Manila, Philippines.

    Science.gov (United States)

    Chou, Andrew; Roa, Marylette; Evangelista, Michael A; Sulit, Arielle Kae; Lagamayo, Evelina; Torres, Brian C; Klinzing, David C; Daroy, Maria Luisa G; Navoa-Ng, Josephine; Sucgang, Richard; Zechiedrich, Lynn

    2016-10-01

    We sought to determine the epidemiology of carbapenem-resistant Enterobacteriaceae and to investigate the emergence of carbapenem-resistant Klebsiella pneumoniae in two teaching hospitals in Manila, Philippines. We screened 364 Enterobacteriaceae for carbapenem resistance between 2012 and 2013 and detected four carbapenem-resistant K. pneumoniae isolates from three different patients. We used whole genome sequencing to determine the antibiotic resistance profiles and confirmed the presence of carbapenemase genes by multiplex PCR. We used multilocus sequence typing and PCR-based replicon typing to genetically characterize the carbapenem-resistant isolates. The carbapenemase gene bla NDM was detected in K. pneumoniae isolates from two patients. The first patient had ventilator-associated pneumonia and lumbar shunt infection from K. pneumoniae ST273 carrying bla NDM-7 . The second patient had asymptomatic genitourinary colonization with K. pneumoniae ST656 carrying bla NDM-1 . The third patient had a gluteal abscess with K. pneumoniae ST1 that did not carry a carbapenemase gene, but did carry bla DHA-1 , bla OXA-1 , and bla SHV-1 . In this study, we report the first cases of bla NDM -carrying pathogens in the Philippines and add to the growing evidence of the worldwide spread of ST273 and NDM-7, a more efficient carbapenem hydrolyzer than NDM-1.

  16. High prevalence of multidrug-resistance in Acinetobacter baumannii and dissemination of carbapenemase-encoding genes blaOXA-23-like, blaOXA-24-like and blaNDM-1 in Algiers hospitals.

    Science.gov (United States)

    Khorsi, Khadidja; Messai, Yamina; Hamidi, Moufida; Ammari, Houria; Bakour, Rabah

    2015-06-01

    To assess and characterize antibiotic resistance in Acinetobacter baumannii strains recovered from 5 health-care facilities in Algiers. Antibiotic susceptibility testing was performed by agar diffusion and agar dilution methods, resistance genes were identified by PCR and sequencing, and molecular typing of isolates was carried out by enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR). Among 125 tested isolates, 117 (93.6%) were multidrug-resistant, of which 94 (75.2%) were imipenem resistant. The blaADC and blaOXA-51-like genes were detected in all isolates, in association with ISAba1 sequence in 84% and 8% (imipenem resistant) of isolates, respectively. The blaOXA-23-like and blaOXA-24-like carbapenemase genes were detected in 67.02% and 20.21% of imipenem-resistant isolates, respectively. The blaOXA-23-like gene is linked to ISAba1 or ISAba4 elements. The metallo-β-lactamase NDM-1 gene was found in 10 (10.6%) imipenem-resistant strains from three hospitals, it is linked to ISAba125 element in nine strains. Extended spectrum β-lactamases production was not detected. Imipenem and cefotaxime resistance phenotypes could not be transferred to Escherichia coli by conjugation. Outer membrane protein CarO gene was not detected in four imipenem-resistant isolates. The aac(6')-Ib, sul1, sul2, tetA and tetB genes were present in 5.31%, 36.17%, 77.65%, 1.06% and 65.92% of strains, respectively. Class 1 integrons were detected in 23.4% strains. ERIC-PCR typing showed a genetic diversity among blaOXA-23-like and blaOXA-24-like positive strains, while clonality was observed among blaNDM-1 positives. This study highlighted the high prevalence of imipenem resistance in Acinetobacter baumannii in Algiers hospitals mediated mainly by blaOXA-23-like, blaOXA-24-like, and blaNDM-1 genes. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  17. A qualitative exploration of the major challenges facing pharmacovigilance in Saudi Arabia.

    Science.gov (United States)

    Aljadhey, Hisham; Mahmoud, Mansour A; Alshammari, Thamir M; Al-Dhaeefi, Mohammed; Le Louet, Herve; Perez-Gutthann, Susana; Pitts, Peter J

    2015-09-01

    To explore the challenges facing pharmacovigilance in Saudi Arabia and formulate recommendations to improve it from the perspective of healthcare professionals in Saudi Arabia. This was a qualitative study of 4 focus group discussions with pharmacists, physicians, and academicians held under the auspices of the King Saud University School of Pharmacy and the Center for Medicine in the Public Interest, Riyadh, Saudi Arabia. A total of 29 eligible healthcare professionals were invited to participate in the discussion. The predefined themes of the study were the current practice and major challenges facing pharmacovigilance in regulatory bodies, hospitals, the community, and academia, as well as recommendations to improve pharmacovigilance practice.  Of the 29 participants invited, 27 attended the discussion. Challenges facing regulatory bodies included complicated adverse drug reactions (ADR) reporting forms, lack of feedback on ADRs submitted to the Saudi Food and Drug Authority, lack of decisions from the local authority to withdraw medications, and lack of data on pharmacovigilance. The challenges to pharmacovigilance in hospitals included the lack of knowledge of the significance of ADR reporting, workload, blaming culture, and lack of collaboration between regulatory bodies and hospitals. However, challenges facing pharmaceutical industries included the lack of drug manufacturers in Saudi Arabia and lack of interest in pharmacovigilance. Recommendations to improve pharmacovigilance included the need for communication, stronger regulatory requirements, the need for research, the need for unified ADRs reporting, and continuous education and training.  The study has identified the challenges facing pharmacovigilance in Saudi Arabia and made certain recommendations to overcome them. These recommendations might be helpful for regulatory bodies to enhance spontaneous reporting and promote pharmacovigilance.

  18. Modern Approaches to Continuous Audit in the Pharmacovigilance System Vinnytsia region: the Results of 2016

    Directory of Open Access Journals (Sweden)

    Fedir Hladkykh

    2017-12-01

    Full Text Available The results of the pharmacovigilance system operation in Vinnytsia region during 2016 are presented based on the data of the electronic online system "Pharmacovigilance-2016", which was first introduced by us on the basis of the table editor Microsoft Excel of the file-hosting system Google Drive. The formula for calculating the efficiency of the pharmacovigilance implementation as an integral assessment of the safety oversight of medical devices in their use in Vinnytsia region during 2016 is proposed, taking into account the capacity of health facilities at the local level.

  19. Performance assessment of the Thai National Center for Pharmacovigilance.

    Science.gov (United States)

    Kaewpanukrungsi, Wanida; Anantachoti, Puree

    2015-01-01

    The Thai National Pharmacovigilance Center (NPVC) has operated since 1983, but its performance has never been formally assessed. The paper aimed to present the main findings of performance assessment of the Thai NPVC. A survey was conducted. Data from January 2011-December 2013 were collected. The performance was assessed through four indicator domains. The NPVC has a clear mission to guide its roles and responsibilities. The center has a well-established structure, adequate budget, qualified personnel, and good IT infrastructure, but it has no in-house IT personnel.Safety surveillance function was considered excellent. The Thai adverse drug reaction database accumulate a number of quality reports. Typically, new signals of traditional or herbal medicines could be generated from the database.The risk management process was well established and carried out. The National Drug Safety Advisory Sub-Committee was composed of qualified representatives from related disciplines. Not only do these committee members make safety decisions, but they also provide key safety messages and communicate these to their member audiences.The risk communication function was evaluated to be unsatisfactory. It was not effectively distributed to individual health care professionals. The overall performance of the Thai NPVC was considerably good. The findings suggested that risk communication should be improved. Moreover, organizational performance should be routinely evaluated. If possible, benchmarking with international pharmacovigilance centers should also be performed.

  20. Pharmacovigilance in veterinary medicine in Chile: a pilot study.

    Science.gov (United States)

    Iragüen, D; Urcelay, S; San Martín, B

    2011-04-01

    Iragüen, D., Urcelay, S., San Martín, B. Pharmacovigilance in veterinary medicine in Chile: a pilot study. J. vet. Pharmacol. Therap.34, 108-115. In Chile, there is no present government policy to survey and analyse adverse drug reactions (ADRs) in the field of veterinary medicine. The intent of this study is to assess, for the first time, ADR frequency in treated animals. To this purpose, a 6-month period pilot study based on WHO recommendations was conducted to monitor ADRs in cats and dogs for frequently used drugs and common labelled signs. Of a total of 149 detected ADRs, 29 (6 in cats and 23 in dogs) were notified by means of ADR report forms, while the rest was identified after reviewing patient clinical records, thus evidencing strong under-reporting problems. More than 70% of ADRs were related to antimicrobials, vaccines and tranquilizers. In dogs, there was a significant effect on ADRs' presentation when acepromazine, amoxicillin, carprofen, ivermectin, sextuple vaccine (polyvalent vaccine that confers immunity against canine distemper virus, canine parvovirus, Leptospira canicola, L. icterohemmoragiae, canine adenovirus type 2 and canine parainfluenza virus) and phytomenadione (subcutaneous injection) were administered. In the case of cats, a significant influence on ADRs was detected when acepromazine, amoxicillin or vitamin K was administered. Present results suggest the need for a pharmacovigilance programme in veterinary medicine for timely ADR-presenting drug detection and drug safety improvement. © 2010 Blackwell Publishing Ltd.

  1. Pharmacovigilance Mobile Tool Design in the Field of Arhroplasty.

    Science.gov (United States)

    Åserød, Hanne; Babic, Ankica

    2017-01-01

    Pharmacovigilance is an important part of the patient safety and it has a great appeal to physicians. It is concerned with the safety of medical devices and treatments in the light of understanding the risks and dangers based on the already reported safety issues. Internet resources such as the Manufacturer And User Facility Device Experience (MAUDE) web-site are often retrieved due to the lack of internal, local safety databases. The research looked at how Human Computer Interaction could improve user experience. We have designed data entry for safety reporting and pharmacovigilance based on the web-bases system called WebBISS (Web-based implant search system). The expectation is not only to improve usability, but also to stimulate physicians to enter their safety data and become also contributors, and not only users of information. The expert evaluation has been generally positive and encouraged stronger help and error reporting functions. The high fidelity design has given a good impression of the future mobile solution.

  2. A day in the life of a pharmacovigilance case processor.

    Science.gov (United States)

    Bhangale, Ritesh; Vaity, Sayali; Kulkarni, Niranjan

    2017-01-01

    Pharmacovigilance (PV) has grown significantly in India in the last couple of decades. The etymological roots for the word "pharmacovigilance" are "Pharmakon" (Greek for drug) and "Vigilare" (Latin for to keep watch). It relies on information gathered from the collection of individual case safety reports and other pharmacoepidemiological data. The PV data processing cycle starts with data collection in computerized systems followed by complete data entry which includes adverse event coding, drug coding, causality and expectedness assessment, narrative writing, quality control, and report submissions followed by data storage and maintenance. A case processor plays an important role in conducting these various tasks. The case processor should also manage drug safety information, possess updated knowledge about global drug safety regulations, summarize clinical safety data, participate in meetings, write narratives with medical input from a physician, report serious adverse events to the regulatory authorities, participate in the training of operational staff on drug safety issues, quality control work of other staff in the department, and take on any other task as assigned by the manager or medical director within the capabilities of the drug safety associate. There can be challenges while handling all these tasks at a time, hence the associate will have to maintain a balance to overcome them and keep on updating their knowledge on drug safety regulations, which in turn, would help in increasing their learning curve.

  3. Dissemination of blaOXA-370gene among several Enterobacteriaceae species in Brazil.

    Science.gov (United States)

    Magagnin, C M; Rozales, F P; Antochevis, L; Nunes, L S; Martins, A S; Barth, A L; Sampaio, J M; Zavascki, A P

    2017-10-01

    OXA-370 is a recently described OXA-48 variant that has only been described in a few Enterobacter spp. and Klebsiella pneumoniae isolates. The purpose of this study is to assess the prevalence of OXA-370-producing isolates in carbapenem-nonsusceptible Enterobacteriaceae recovered from 28 hospitals from Brazil. Real-time PCR was used to determine the presence of bla NDM-1 , bla KPC-2 , bla VIM-type , bla GES-type , bla OXA-48-like , and bla IMP-type genes. A total of 4,451 Enterobacteriaceae were screened. The gene bla OXA-48-like was detected in 74 (2.5%) isolates, mostly of Enterobacter spp. (44.6% E. cloacae and 2.7% E. aerogenes) and Klebsiella spp. (31.1% K. pneumoniae and 6.7% K. oxytoca), followed by Escherichia coli, (6.7%), Morganella morganii, (2.7%), Citrobacter freundii (1.3%), Proteus mirabilis (1.3%), Providencia stuartii (1.3%), and Serratia spp. (1.3%). These isolates were from five hospitals, 67 (90.5%) from the hospital where the bla OXA-370 was first described. Sequencing of bla OXA-48-like was performed in 52 isolates, including E. cloacae, E. aerogenes, K. pneumoniae, K. oxytoca, E. coli, and C. freundii; all presenting 100% identity with bla OXA-370 . PFGE revealed the presence of distinct clones among K. pneumoniae, E. cloacae, K. oxytoca, and E. coli. Susceptibility rates to meropenem, imipenem, and ertapenem among OXA-370-producing isolates were 92.3%, 78.8%, 7.7% respectively; the MIC 50 /MIC 90 were 0.38/2 mg/L and 1/3 mg/L for meropenem and imipenem respectively. Overall, antimicrobial susceptibility analysis suggests that OXA-370 lacks carbapenemase activity. Our study demonstrated that the bla OXA-370 gene is disseminated among several Enterobacteriaceae species and clones, indicating a high potential for dissemination.

  4. Short communication: Extended-spectrum cephalosporin-resistant Escherichia coli in colostrum from New Brunswick, Canada, dairy cows harbor blaCMY-2and blaTEMresistance genes.

    Science.gov (United States)

    Awosile, B B; McClure, J T; Sanchez, J; VanLeeuwen, J; Rodriguez-Lecompte, J C; Keefe, G; Heider, L C

    2017-10-01

    Dairy calves are colonized shortly after birth by multidrug resistant (MDR) bacteria, including Escherichia coli. The role of dairy colostrum fed to calves as a potential source of MDR bacteria resistance genes has not been investigated. This study determined the recovery rate of extended-spectrum cephalosporin-resistant (ESC-R) E. coli in colostrum from cows. The ESC-R E. coli isolates were further investigated to determine their phenotypic antimicrobial resistance pattern and the genes conferring ESC-R. Fresh colostrum was collected from 452 cows from 8 dairy herds in New Brunswick, Canada. The ESC-R E. coli was isolated from the colostrum by using the VACC agar, a selective media for extended-spectrum β-lactamase producing Enterobacteriaceae. Minimum inhibitory concentration was determined for all the suspected ESC-R E. coli isolates using a commercial gram-negative broth microdilution method. Two multiplex PCR were conducted on all the suspected ESC-R E. coli isolates to determine the presence of the bla CTX-M (groups 1, 2, 9, and 8/25) bla CMY-2 , bla SHV , and bla TEM resistance genes. The ESC-R E. coli were detected in 20 (4.43%) of the colostrum samples. At least 1 ESC-R E. coli isolate was detected in 6 (75%) of the dairy herds. All ESC-R E. coli had MDR profiles based on minimum inhibitory concentration testing. No bla CTX-M groups genes were detected; however, the bla CMY-2 gene was detected in 9 or 20 (45%) and bla TEM was detected in 7 of 20 (35%) of the ESC-R E. coli. No ESC-R E. coli had both bla CMY-2 and bla TEM resistance genes. This is the first report of bla CMY-2 and bla TEM genes found in E. coli isolates cultured from dairy colostrum to our knowledge. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Novel variant (bla(VIM-4)) of the metallo-beta-lactamase gene bla(VIM-1) in a clinical strain of Pseudomonas aeruginosa.

    Science.gov (United States)

    Pournaras, Spyros; Tsakris, Athanassios; Maniati, Maria; Tzouvelekis, Leonidas S; Maniatis, Antonios N

    2002-12-01

    A Pseudomonas aeruginosa isolate highly resistant to carbapenems was collected from a patient with postsurgical cerebrospinal infection in Greece. The isolate carried a class 1 integron that contained as a sole cassette the gene bla(VIM-4), a novel variant of bla(VIM-1), with one nucleotide difference resulting in a Ser-to-Arg change at amino acid position 175 of the VIM-1 enzyme. This is the first detection of a VIM-1 variant after its appearance in Italy.

  6. Enterobacter cloacae Complex Isolates Harboring blaNMC-A or blaIMI-Type Class A Carbapenemase Genes on Novel Chromosomal Integrative Elements and Plasmids.

    Science.gov (United States)

    Boyd, David A; Mataseje, Laura F; Davidson, Ross; Delport, Johannes A; Fuller, Jeff; Hoang, Linda; Lefebvre, Brigitte; Levett, Paul N; Roscoe, Diane L; Willey, Barbara M; Mulvey, Michael R

    2017-05-01

    Carbapenem-resistant Enterobacter cloacae complex isolates submitted to a reference laboratory from 2010 to 2015 were screened by PCR for seven common carbapenemase gene groups, namely, KPC, NDM, OXA-48, VIM, IMP, GES, and NMC-A/IMI. Nineteen of the submitted isolates (1.7%) were found to harbor Ambler class A bla NMC-A or bla IMI -type carbapenemases. All 19 isolates were resistant to at least one carbapenem but susceptible to aminoglycosides, trimethoprim-sulfamethoxazole, tigecycline, and ciprofloxacin. Most isolates (17/19) gave positive results with the Carba-NP test for phenotypic carbapenemase detection. Isolates were genetically diverse by pulsed-field gel electrophoresis macrorestriction analysis, multilocus sequence typing, and hsp60 gene analysis. The genes were found in various Enterobacter cloacae complex species; however, bla NMC-A was highly associated with Enterobacter ludwigii Whole-genome sequencing and bioinformatics analysis revealed that all NMC-A ( n = 10), IMI-1 ( n = 5), and IMI-9 ( n = 2) producers harbored the carbapenemase gene on EludIMEX-1-like integrative mobile elements (EcloIMEXs) located in the identical chromosomal locus. Two novel genes, bla IMI-5 and bla IMI-6 , were harbored on different IncFII-type plasmids. Enterobacter cloacae complex isolates harboring bla NMC-A/IMI -type carbapenemases are relatively rare in Canada. Though mostly found integrated into the chromosome, some variants are located on plasmids that may enhance their mobility potential. © Crown copyright 2017.

  7. Detection of blaOXA-23-like and blaNDM-1 in Acinetobacter baumannii from the Eastern Region, Saudi Arabia.

    Science.gov (United States)

    El-Mahdy, Taghrid S; Al-Agamy, Mohamed H; Al-Qahtani, Ahmed A; Shibl, Atef M

    2017-01-01

    Acinetobacter baumannii is currently considered as one of the most common successful pathogens in the healthcare system due to its ability to quickly develop resistance. Ten carbapenem-resistant A. calcoaceticus-baumannii complex were isolated from the eastern region, Saudi Arabia in 2014. All isolates were resistant to ciprofloxacin, however, 8 of 10 isolates were tigecycline resistant. Susceptibility test was also carried out for three aminoglycosides, resistance to gentamicin was 80%, amikacin was 90%, and tobramycin was 50%. Colistin susceptibility was seen in all isolates. The 10 isolates harbored bla OXA-23-like and ISAba1 and 9 of them also carried bla ADC . Three isolates of 10 harbored bla NDM-1 coding for NDM metallo-β-lactamase (MBL) with coexistence of bla ADC together with either bla GES or bla TEM or both. Those three isolates exhibited negative Etest MBL screening test. Pulsed-field gel electrophoresis revealed the high clonal variability of the isolates, although two isolates were indistinguishable. The risk of dissemination of carbapenem resistance through presence of ISAba1 upstream of OXA-23-like in all isolates raises the concern about emergence of higher carbapenem prevalence rates in the future in our region. This study also demonstrated the importance of molecular surveillance to provide accurate and reliable data about the resistance rates of A. baumannii. Finally, the high incidence of NDM-1 among our isolates requires a routine surveillance to monitor the future prevalence of this enzyme in the region.

  8. Antibiotic Resistance Pattern and Evaluation of Metallo-Beta Lactamase Genes Including bla- IMP and bla- VIM Types in Pseudomonas aeruginosa Isolated from Patients in Tehran Hospitals.

    Science.gov (United States)

    Aghamiri, Samira; Amirmozafari, Nour; Fallah Mehrabadi, Jalil; Fouladtan, Babak; Samadi Kafil, Hossein

    2014-01-01

    Beta-lactamase producing strains of Pseudomonas aeruginosa are important etiological agents of hospital infections. Carbapenems are among the most effective antibiotics used against Pseudomonas infections, but they can be rendered infective by group B β -lactamase, commonly called metallo-beta lactamase. In this study, the antimicrobial sensitivity patterns of P. aeruginosa strains isolated from 9 different hospitals in Tehran, Iran, as well as the prevalence of MBLs genes (bla- VIM and bla- IMP ) were determined. A total of 212 strains of P. aeruginosa recovered from patients in hospitals in Tehran were confirmed by both biochemical methods and PCR. Their antimicrobial sensitivity patterns were determined by Kirby-Bauer disk diffusion method. Following MIC determination, imipenem resistant strains were selected by DDST method which was followed by PCR tests for determination of MBLs genes: bla- IMP and bla- VIM . The results indicated that, in the DDST phenotypic method, among the 100 imipenem resistant isolates, 75 strains were MBLs positive. The PCR test indicated that 70 strains (33%) carried bla- VIM gene and 20 strains (9%) harbored bla- IMP . The results indicated that the extent of antibiotic resistance among Pseudomonas aeruginosa is on the rise. This may be due to production of MBLs enzymes. Therefore, determination of antibiotic sensitivity patterns and MBLs production by these bacteria, can be important in control of clinical Pseudomonas infection.

  9. Evolution of IncA/C blaCMY-₂-carrying plasmids by acquisition of the blaNDM-₁ carbapenemase gene.

    Science.gov (United States)

    Carattoli, Alessandra; Villa, Laura; Poirel, Laurent; Bonnin, Rémy A; Nordmann, Patrice

    2012-02-01

    The bla(NDM-1) gene has been reported to be often located on broad-host-range plasmids of the IncA/C type in clinical but also environmental bacteria recovered from the New Delhi, India, area. IncA/C-type plasmids are the main vehicles for the spread of the cephalosporinase gene bla(CMY-2), frequently identified in the United States, Canada, and Europe. In this study, we completed the sequence of IncA/C plasmid pNDM-KN carrying the bla(NDM-1) gene, recovered from a Klebsiella pneumoniae isolate from Kenya. This sequence was compared with those of three IncA/C-type reference plasmids from Escherichia coli, Yersinia ruckeri, and Photobacterium damselae. Comparative analysis showed that the bla(NDM-1) gene was located on a widely diffused plasmid scaffold known to be responsible for the spread of bla(CMY-2)-like genes and consequently for resistance to broad-spectrum cephalosporins. Considering that IncA/C plasmids possess a broad host range, this scaffold might support a large-scale diffusion of the bla(NDM-1) gene among Gram-negative rods.

  10. Investigation of diversity of plasmids carrying the blaTEM-52 gene

    DEFF Research Database (Denmark)

    Bielak, Eliza Maria; Bergenholtz, Rikke D.; Jørgensen, Mikael Skaanning

    2011-01-01

    OBJECTIVES: To investigate the diversity of plasmids that carry blaTEM-52 genes among Escherichia coli and Salmonella enterica originating from animals, meat products and humans. METHODS: A collection of 22 blaTEM-52-encoding plasmids was characterized by restriction fragment length polymorphism...... of self-transfer to a plasmid-free E. coli recipient. CONCLUSIONS: The blaTEM-52 gene found in humans could have been transmitted on transferable plasmids originating from animal sources. Some of the blaTEM-52 plasmids carry replicons that differ from the classical ones. Two novel replicons were detected...... (RFLP), replicon typing (by PCR or replicon sequencing), susceptibility testing, assessment of plasmid ability to self-transfer by conjugation and typing of the genetic environment of the blaTEM-52 gene. Detected IncI1 plasmids underwent further plasmid multilocus sequence typing. RESULTS: RFLP profiles...

  11. Nurses' self-reported medication competence in relation to their pharmacovigilant activities in clinical practice.

    Science.gov (United States)

    Johansson-Pajala, Rose-Marie; Martin, Lene; Fastbom, Johan; Jorsäter Blomgren, Kerstin

    2015-02-01

    Adverse drug reactions (ADRs) represent a major health problem and previous studies show that nurses can have an active role in promoting medication safety. The aim of this study was to describe and evaluate nurses' self-reported competence and pharmacovigilant activities in clinical practice and also to explore the impact of age, education, workplace and nursing experience on these matters. This cross-sectional study was based on a questionnaire covering areas related to nurses' medication competence, including knowledge, assessment and information retrieval, and pharmacovigilant activities within these areas, for example, the detection and assessment of ADRs. A 45-item questionnaire was 2013 sent out to 296 nurses in different settings and counties in Sweden. They were selected on the basis of having applied to a university course including pharmacovigilance during 2008-2011. One hundred twenty-four had participated in the courses (exposed) and 172 had applied to the courses but not participated (unexposed). Completed questionnaires were obtained from 75 exposed (60%) and 93 unexposed (54%) nurses. Overall nurses rated themselves high in medication competence but low in pharmacovigilant activities. Significant (P ≤ 0.001) differences between groups were observed regarding medication competence. The exposure of completed dedicated courses in pharmacovigilance was the strongest factor for self-reported medication competence when adjusted for age, other education, workplace and experience. No significant differences between the groups were found regarding the number of pharmacovigilant activities during the 6 months prior to answering the questionnaire. Dedicated university courses improved nurses' self-reported competence in pharmacovigilance but did not increase the number of related activities. Education per se seems to be not sufficient to generate pharmacovigilant activities among nurses. © 2014 John Wiley & Sons, Ltd.

  12. Pharmacovigilance Skills, Knowledge and Attitudes in our Future Doctors - A Nationwide Study in the Netherlands.

    Science.gov (United States)

    Schutte, Tim; Tichelaar, Jelle; Reumerman, Michael O; van Eekeren, Rike; Rissmann, Robert; Kramers, Cornelis; Richir, Milan C; van Puijenbroek, Eugène P; van Agtmael, Michiel A

    2017-05-01

    Pharmacovigilance centres monitor the safety of drugs, based on adverse drug reactions (ADRs) reported by doctors, pharmacists and pharmaceutical companies. However, the under-reporting of ADRs remains a major problem. Our aim was to investigate preparedness of future doctors for their role in pharmacovigilance, by assessing their pharmacovigilance awareness, skills and knowledge. The study was a nationwide e-survey among medical students (third to sixth year) of all eight medical schools in the Netherlands. The survey consisted of questions regarding pharmacovigilance awareness, skills and knowledge. Overall, 874 students provided informed consent and participated (response 12%). Almost all students (96%) intended to report serious ADRs in their future practice. Almost half (44%) of the students did not know where to report an ADR, and 78% did not know which items were necessary for a good-quality ADR report. While more than 78% of the students agreed that pharmacovigilance is an important topic in their medical education, only 26% found that their current curriculum covered pharmacovigilance adequately. Although ADR reporting is considered relevant and important among future doctors, many do not know where and what to report. This is highly undesirable and should have consequences for pharmacotherapy teaching. © 2016 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  13. Healthcare professionals’ awareness and knowledge of adverse drug reactions and pharmacovigilance

    Science.gov (United States)

    Almandil, Noor B.

    2016-01-01

    Objectives To document the knowledge of, attitudes toward, and practices of adverse drug reaction (ADR) reporting and pharmacovigilance systems among healthcare professionals. Methods This descriptive cross-sectional study was conducted using a questionnaire. This study took place at King Fahd Hospital of the University (KFHU), Khobar, Kingdom of Saudi Arabia, between April 2015 and April 2016. Healthcare professionals, including physicians, pharmacists, pharmacy technicians, and nurses, were considered eligible and invited to take part in the study. A link to the online questionnaire was sent to each participant via E-mail, and a hard copy was circulated at the hospital after the objectives of the study were explained. The questionnaire comprised items regarding knowledge/awareness of pharmacovigilance and ADRs, perception/attitude towards pharmacovigilance and ADR reporting, and practices of ADR reporting. Descriptive statistics were used to analyze the data. Results A total of 400 questionnaires were distributed to the healthcare professionals and 331 participants responded, providing a response rate of 82.75%. The healthcare professionals comprised 161 physicians, 39 pharmacists, 21 pharmacist technicians, and 110 nurses. Most of the participants were female (n=198) and Saudi (61.9%). Most healthcare professionals (62.5%) were unaware of the term pharmacovigilance; the pharmacists and pharmacist technicians had the highest rate of pharmacovigilance awareness (60.5% of the pharmacists and 40% of pharmacist technicians). Conclusion There is a lack of awareness and knowledge of pharmacovigilance and ADR reporting among healthcare professionals working at KFHU. PMID:27874152

  14. Perception of pharmacovigilance among doctors in a tertiary care hospital: influence of an interventional lecture.

    Science.gov (United States)

    Sanghavi, Dhara R; Dhande, Priti P; Pandit, Vijaya A

    2013-01-01

    One of the important pillars of an efficient pharmacovigilance system is contribution by healthcare professionals in the form of spontaneous reporting. This study was aimed at investigating the knowledge, attitude and practice of spontaneous ADR reporting among doctors in a teaching hospital in Pune, and to analyze the effect of an informative lecture about Pharmacovigilance on the same. This was an interventional study conducted among 220 doctors at a tertiary care teaching hospital, Pune. Each participant was explained the purpose of study and asked to fill in a questionnaire about their knowledge, attitude and practice of pharmacovigilance. Only 80 of them attended the interventional lecture on Pharmacovigilance and again filled up the questionnaire after a period of one month from this intervention. Merely 7.5% of the participants knew ADR reporting system in India. Majority of the respondents (95%) knew that, as doctors, they could report ADRs but were unaware about the methodology to report (92.5%) which affected their practice of Pharmacovigilance. All (100%) the participants expressed that proper training should be provided to clinicians for ADR reporting & 81% felt ADR reporting should be made mandatory. Only 80 participants (36.4%) attended the interventional lecture which reflected a poor response. Intervention improved their (96%) knowledge about ADR reporting system and now majority of them (92%) agreed that all sort of ADRs should be reported (p pharmacovigilance.

  15. The spread of bla OXA-48 and bla OXA-244 carbapenemase genes among Klebsiella pneumoniae, Proteus mirabilis and Enterobacter spp. isolated in Moscow, Russia.

    Science.gov (United States)

    Fursova, Nadezhda K; Astashkin, Eugeny I; Knyazeva, Anastasia I; Kartsev, Nikolay N; Leonova, Ekaterina S; Ershova, Olga N; Alexandrova, Irina A; Kurdyumova, Natalia V; Sazikina, Svetlana Yu; Volozhantsev, Nikolay V; Svetoch, Edward A; Dyatlov, Ivan A

    2015-11-02

    The spread of carbapenemase-producing Enterobacteriaceae (CPE) is a great problem of healthcare worldwide. Study of the spread for bla OXA-48-like genes coding epidemically significant carbapenemases among hospital pathogens is important for the regional and global epidemiology of antimicrobial resistance. Antibacterial resistant isolates of Klebsiella pneumoniae (n = 95) from 54 patients, P. mirabilis (n = 32) from 20 patients, Enterobacter aerogenes (n = 6) from four patients, and Enterobacter cloacae (n = 4) from four patients were collected from January, 2013 to October, 2014 in neurosurgical intensive care unit (ICU) of the Burdenko Neurosurgery Institute, Moscow. Characteristics of the isolates were done using susceptibility tests, PCR detection of the resistance genes, genotyping, conjugation, DNA sequencing, and bioinformatic analysis. Major strains under study were multi drug resistant (MDR), resistant to three or more functional classes of drugs simultaneously-98.9 % K. pneumoniae, 100 % P. mirabilis, one E. aerogenes isolate, and one E. cloacae isolate. Molecular-genetic mechanism of MDR in K. pneumoniae and P. mirabilis isolates were based on carrying of epidemic extended-spectrum beta-lactamase bla CTX-M-15 gene (87.2 and 90.6 % accordingly), carbapenemase bla OXA-48-like gene (55.3 and 23.3 % accordingly), and class 1 (54.8 and 31.3 % accordingly) and class 2 (90.6 % P. mirabilis) integrons. The bla OXA-48-like-positive K. pneumoniae were collected during whole two-year surveillance period, while P. mirabilis and Enterobacter spp. carrying bla OXA-48-like genes were detected only after four and 18 months after the research start, respectively. The bla OXA-48-like gene acquisition was shown for P. mirabilis isolates collected from five patients and for E. cloacae isolate collected from one patient during their stay in the ICU, presumably from bla OXA-48-like-positive K. pneumoniae. The source of the bla OXA-244 gene acquired by E

  16. Molecular detection of metallo-β-lactamase genes, bla IMP-1, bla VIM-2 and bla SPM-1 in imipenem resistant Pseudomonas aeruginosa isolated from clinical specimens in teaching hospitals of Ahvaz, Iran.

    Science.gov (United States)

    Moosavian, Mojtaba; Rahimzadeh, Mohammad

    2015-02-01

    Carbapenem resistant Pseudomonas aeruginosa is a serious cause of nosocomial infections. The main purpose of the study is to determine the prevalence rate of imipenem resistant Pseudomonas aeruginosa carrying metallo-ß-lactamase (MBL) genes. 236 Pseudomonas aeruginosa isolates were collected from teaching hospitals of Ahvaz University of Medical Sciences during a period of 9 months in 2012. These strains were identified using conventional microbiological tests. The susceptibility of isolates to antibiotics were assessed using disk diffusion test. The IMP-EDTA combination disk phenotypic test was performed for detection of MBL producing strains. Finally, polymerase chain reaction (PCR) was performed to detect MBL genes, bla IMP-1, bla VIM-2 and bla SPM-1 in imipenem resistant strains. Out of 236 examined isolates, 122 isolates (51.4%) were resistant to imipenem. The IMP-EDTA combination test showed that among 122 imipenem resistant strains, 110 strains (90%) were phenotipically MBL producers. Additionally, the results of PCR method showed that 2 strains (1.6%) and 67strains (55%) of imipenem resistant Pseudomonas aeruginosa isolates contained bla VIM-2 and bla IMP-1 genes respectively. No SPM-1gene was found in the examined samples. Resistance of P. aeruginosa isolates to imipenem due to MBL enzymes is increasing in Ahavaz. Because of clinical significance of this kind of resistance, rapid detection of MBL producing strains and followed by appropriate treatment is necessary to prevent the spreading of these organisms.

  17. Yersinia enterocolitica and Photorhabdus asymbiotica β-lactamases BlaA are exported by the twin-arginine translocation pathway.

    Science.gov (United States)

    Schriefer, Eva-Maria; Hoffmann-Thoms, Stephanie; Schmid, Franz X; Schmid, Annika; Heesemann, Jürgen

    2013-01-01

    In general, β-lactamases of medically important Gram-negative bacteria are Sec-dependently translocated into the periplasm. In contrast, β-lactamases of Mycobacteria spp. (BlaC, BlaS) and the Gram-negative environmental bacteria Stenotrophomonas maltophilia (L2) and Xanthomonas campestris (Bla(XCC-1)) have been reported to be secreted by the twin-arginine translocation (Tat) system. Yersinia enterocolitica carries 2 distinct β-lactamase genes (blaA and blaB) encoding BlaA(Ye) and the AmpC-like β-lactamase BlaB, respectively. By using the software PRED-TAT for prediction and discrimination of Sec from Tat signal peptides, we identified a functional Tat signal sequence for Yersinia BlaA(Ye). The Tat-dependent translocation of BlaA(Ye) could be clearly demonstrated by using a Y. enterocolitica tatC-mutant and cell fractionation. Moreover, we could demonstrate a unique unusual temperature-dependent activity profile of BlaA(Ye) ranging from 15 to 60 °C and a high 'melting temperature' (T(M)=44.3°) in comparison to the related Sec-dependent β-lactamase TEM-1 (20-50°C, T(M)=34.9 °C). Strikingly, the blaA gene of Y. enterocolitica is present in diverse environmental Yersinia spp. and a blaA homolog gene could be identified in the closely related Photorhabdus asymbiotica (BlaA(Pa); 69% identity to BlaA(Ye)). For BlaA(Pa) of P. asymbiotica, we could also demonstrate Tat-dependent secretion. These results suggest that Yersinia BlaA-related β-lactamases may be the prototype of a large Tat-dependent β-lactamase family, which originated from environmental bacteria. Copyright © 2012 Elsevier GmbH. All rights reserved.

  18. Pharmacovigilance Programme of India: Recent developments and future perspectives.

    Science.gov (United States)

    Kalaiselvan, Vivekanandan; Thota, Prasad; Singh, Gyanendra Nath

    2016-01-01

    Promoting safe use of medicines is a priority of Indian Pharmacopoeia Commission that functions as the National Coordination Center (NCC) for Pharmacovigilance Programme of India (PvPI). One hundred and seventy-nine adverse drug reactions (ADRs) monitoring centers currently report ADRs to NCC. Current India contribution to global safety database reaches 3% and the completeness score is 0.93 out of 1. NCC is taking several measures to enhance patient safety including capacity building for monitoring, surveillance, collaboration with national health programs and other organizations to increase ADR reporting and to ensure that PvPI is a vital knowledge database for Indian regulators. The Central Drugs Standard Control Organization has notified important safety label changes on drugs such as carbamazepine and piperacillin + tazobactam in the year 2015, other drugs are under monitoring for regulatory interventions.

  19. Diversity and evolution of blaZ from Staphylococcus aureus and coagulase-negative staphylococci

    DEFF Research Database (Denmark)

    Olsen, John E.; Christensen, Henrik; Aarestrup, Frank Møller

    2006-01-01

    NS) and Staphylococcus aureus of bovine origin. Methods: blaZ was detected in 143 strains of penicillin-resistant S. aureus and CoNS from five Danish cattle herds (n = 25/23), random CoNS isolates from Denmark (n = 37), a collection of S. aureus from six different countries (n = 52), humans in Denmark (n = 3) and beta...... types. The major types all contained strains of both human and bovine origin, and more than one Staphylococcus species, demonstrating a shared gene pool. In a comparison of S. aureus and CoNS obtained from five Danish cattle herds, the same type of blaZ was only detected in one case. Conclusions....... The localization of blaZ was determined by Southern blotting in 108 isolates. Results: All penicillin-resistant strains carried blaZ and showed a similar organization of blaR1 and blaZ. The blaZ gene was localized to a plasmid in only 16 of the resistant strains. Sixty-nine sequences representing 105 isolates...

  20. Transcriptional analysis of bla NDM-1 and copy number alteration under carbapenem stress

    Directory of Open Access Journals (Sweden)

    Deepjyoti Paul

    2017-02-01

    Full Text Available Abstract Background New Delhi metallo beta-lactamase is known to compromise carbapenem therapy and leading to treatment failure. However, their response to carbapenem stress is not clearly known. Here, we have investigated the transcriptional response of bla NDM-1 and plasmid copy number alteration under carbapenem exposure. Methods Three bla NDM-1 harboring plasmids representing three incompatibility types (IncFIC, IncA/C and IncK were inoculated in LB broth with and without imipenem, meropenem and ertapenem. After each 1 h total RNA was isolated, immediately reverse transcribed into cDNA and quantitative real time PCR was used for transcriptional expression of bla NDM-1. Horizontal transferability and stability of the plasmids encoding bla NDM-1 were also determined. Changes in copy number of bla NDM-1 harboring plasmids under the exposure of different carbapenems were determined by real time PCR. Clonal relatedness among the isolates was determined by pulsed field gel electrophoresis. Results Under carbapenem stress over an interval of time there was a sharp variation in the transcriptional expression of bla NDM-1 although it did not follow a specific pattern. All bla NDM-1 carrying plasmids were transferable by conjugation. These plasmids were highly stable and complete loss was observed between 92nd to 96th serial passages when antibiotic pressure was withdrawn. High copy number of bla NDM-1 was found for IncF type plasmids compared to the other replicon types. Conclusion This study suggests that the single dose of carbapenem pressure does not significantly influence the expression of bla NDM-1 and also focus on the stability of this gene as well as the change in copy number with respect to the incompatible type of plasmid harboring resistance determinant.

  1. Decreased Fitness and Virulence in ST10 Escherichia coli Harboring blaNDM-5 and mcr-1 against a ST4981 Strain with blaNDM-5

    Directory of Open Access Journals (Sweden)

    Yawei Zhang

    2017-06-01

    Full Text Available Although coexistence of blaNDM-5 and mcr-1 in Escherichia coli has been reported, little is known about the fitness and virulence of such strains. Three carbapenem-resistant Escherichia coli (GZ1, GZ2, and GZ3 successively isolated from one patient in 2015 were investigated for microbiological fitness and virulence. GZ1 and GZ2 were also resistant to colistin. To verify the association between plasmids and fitness, growth kinetics of the transconjugants were performed. We also analyzed genomic sequences of GZ2 and GZ3 using PacBio sequencing. GZ1 and GZ2 (ST10 co-harbored blaNDM-5 and mcr-1, while GZ3 (ST4981 carried only blaNDM-5. GZ3 demonstrated significantly more rapid growth (P < 0.001 and overgrew GZ2 with a competitive index of 1.0157 (4 h and 2.5207 (24 h. Increased resistance to serum killing and mice mortality was also identified in GZ3. While GZ2 had four plasmids (IncI2, IncX3, IncHI2, IncFII, GZ3 possessed one plasmid (IncFII. The genetic contexts of blaNDM-5 in GZ2 and GZ3 were identical but inserted into different backbones, IncX3 (102,512 bp and IncFII (91,451 bp, respectively. The growth was not statistically different between the transconjugants with mcr-1 or blaNDM-5 plasmid and recipient (P = 0.6238. Whole genome sequence analysis revealed that 28 virulence genes were specific to GZ3, potentially contributing to increased virulence of GZ3. Decreased fitness and virulence in a mcr-1 and blaNDM-5 co-harboring ST10 E. coli was found alongside a ST4981 strain with only blaNDM-5. Acquisition of mcr-1 or blaNDM-5 plasmid did not lead to considerable fitness costs, indicating the potential for dissemination of mcr-1 and blaNDM-5 in Enterobacteriaceae.

  2. Multidrug-resistant Acinetobacter baumannii strains carrying the bla(OxA-23) and the bla(GES-11) genes in a neonatology center in Tunisia.

    Science.gov (United States)

    Charfi-Kessis, Karama; Mansour, Wejdene; Ben Haj Khalifa, Anis; Mastouri, Maha; Nordmann, Patrice; Aouni, Mahjoub; Poirel, Laurent

    2014-09-01

    Multidrug-resistant and difficult-to-treat Acinetobacter baumannii may be responsible for nosocomial infections. The production of carbapenem-hydrolyzing class D β-lactamases (CHDLs) and extended-spectrum β-lactamase (ESBLs) of the GES type possessing a carbapenemase activity has been increasingly reported worldwide in A. baumannii. The aim of this study was to analyze the resistance mechanisms of two carbapenem resistant A. baumannii clinical isolates recovered in a neonatology center in the center-east of Tunisia. Two carbapenem resistant A. baumannii isolates were recovered. The first isolate co-harbored the blaGES-11 ESBL gene and the blaOxA-23 CHDL gene. Analyses of the genetic location indicated that the blaGES-11 gene was plasmid located (Gr6). However, the blaOxA-23 gene was located on the chromosome. The second strain had only the blaOxA-23 CHDL gene, which was plasmid located. This study showed the first description of the GES-type β-lactamase in A. baumannii in Tunisia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Rapid Detection of blaKPC Carbapenemase Genes by Real-Time PCR▿

    OpenAIRE

    Hindiyeh, Musa; Smollen, Gill; Grossman, Zehava; Ram, Daniela; Davidson, Yehudit; Mileguir, Fernando; Vax, Marina; Ben David, Debbie; Tal, Ilana; Rahav, Galia; Shamiss, Ari; Mendelson, Ella; Keller, Nathan

    2008-01-01

    Carbapenem resistance among Enterobacteriaceae is an emerging problem worldwide. Klebsiella pneumoniae carbapenemase (blaKPC) enzymes are among the most common β-lactamases described. In this study, we report the development and validation of a real-time PCR (q-PCR) assay for the detection of blaKPC genes using TaqMan chemistry. The q-PCR amplification of blaKPC DNA was linear over 7 log dilutions (r2 = 0.999; slope, 3.54), and the amplification efficiency was 91.6%. The q-PCR detection limit...

  4. Prospects of consumer-initiated adverse drug reaction reporting in cardiovascular pharmacovigilance

    Directory of Open Access Journals (Sweden)

    Vinu Wilson

    2015-01-01

    Full Text Available Drugs used for the treatment of cardiovascular disorders are frequently reported to cause adverse drug reactions (ADRs, second only to antimicrobials. ADRs strain the patients′ health and finances further and could prove fatal too. Pharmacovigilance programs aim to detect, monitor and understand ADRs in order to prevent them. Pharmacovigilance provides vital input to drug regulatory agencies to monitor safety of new as well as old drugs. Spontaneous reporting of suspected ADRs by healthcare professionals forms the backbone of pharmacovigilance programs worldwide including the Pharmacovigilance Program of India (PvPI launched in 2010. The PvPI has significantly contributed to strengthening pharmacovigilance in India but suffers from under-reporting of ADRs like similar programs worldwide. Consumer-initiated reporting of ADRs incorporated in pharmacovigilance programs of several countries has been found to decrease under-reporting rates besides supplementing traditional pharmacovigilance information. The PvPI has recently introduced the facility for consumers to report ADRs by contacting a hotline (1800-180-3024, through e-mail (pvpi.compat@gmail.com or by filling specifically designed ADR reporting forms, either in English language or vernacular translations, and submitting them to the nearest ADR monitoring centre. This is a welcome step in empowering patients as consumers of drugs with the mechanism to monitor their safety. It could potentially fill the huge gap in spontaneous ADR reporting and supplement the indigenous drug safety database with patients′ perspectives regarding ADRs e.g. effect on their quality of life. Whether it encourages rational prescription practices by doctors or enhances transparency regarding safety of investigational drugs in clinical trials needs to be seen.

  5. Non-medical prescribers and pharmacovigilance: participation, competence and future needs.

    Science.gov (United States)

    Stewart, Derek; MacLure, Katie; Paudyal, Vibhu; Hughes, Carmel; Courtenay, Molly; McLay, James

    2013-04-01

    To determine UK non-medical prescribers' (NMPs) (supplementary or independent) current participation and self-reported competence in pharmacovigilance, and their perceptions of training and future needs. Non-medical prescribers in health care in the United Kingdom. Awareness of and participation in the Yellow Card Scheme (YCS); attitudes towards ADR reporting; strategies to encourage reporting; pharmacovigilance training; and demographics. The sample comprised nurse (n = 912) and pharmacist (n = 2,439) NMPs in the UK. Self-reported competence in pharmacovigilance, knowledge of and participation in the YCS, attitudes towards ADR reporting; strategies to encourage ADR reporting; pharmacovigilance training during NMP training. Six hundred and thirteen responses were received giving an overall response rate of 20.4 %. Response rates for nurse and pharmacist prescribers were 32.2 % (n = 293) and 13.1 % (n = 320) respectively. Three hundred and fifty-nine respondents (58.6 %) had submitted a Yellow Card. Although the majority of respondents (70.4 %) felt competent in pharmacovigilance, a third (34.2 %) said they needed further training. Respondents reported a positive attitude towards ADR reporting, yet only a minority (22.9 %) correctly answered factual questions about the YCS. Approximately a third of respondents (35.6 %) "couldn't remember" if pharmacovigilance was covered in their prescribing training. Publicity and education were commonly suggested measures to enhance contribution to the YCS. While NMPs report participation and competence in ADR reporting, there are several key issues to consider including the need for further training and support to optimise their role in pharmacovigilance.

  6. Enterobacteriaceae Harboring AmpC (blaCMY) and ESBL (blaCTX-M) in Migratory and Nonmigratory Wild Songbird Populations on Ohio Dairies.

    Science.gov (United States)

    Mathys, Dimitria A; Mathys, Blake A; Mollenkopf, Dixie F; Daniels, Joshua B; Wittum, Thomas E

    2017-04-01

    Extended-spectrum β-lactamases (ESBLs) confer bacterial resistance to critically important antimicrobials, including extended-spectrum cephalosporins (ESCs). Livestock are important reservoirs for the zoonotic food-borne transmission of ESC-resistant enteric bacteria. Our aim is to describe the potential role of migratory and resident wild birds in the epidemiology of ESBL-mediated bacterial resistance on dairy farms. Using mist nets, we sampled wild migratory and resident birds either immediately adjacent to or 600 ft away from free-stall barns on three Ohio dairy farms during the 2014 and 2015 spring migrations. Individual swabs were used to obtain both a cloacal and external surface swab from each bird. Samples were inoculated into MacConkey broth containing cefotaxime then inoculated onto MacConkey agar with cefoxitin, cefepime, or meropenem to identify the bla CMY, bla CTX-M, and carbapenemase phenotypes, respectively. Six hundred twenty-three birds were sampled, 19 (3.0%) of which harbored bacteria with bla CMY and 32 (5.1%) harbored bacteria with bla CTX-M from either their cloacal sample or from their external swab. There was no difference in the prevalence of either gene between migratory and resident birds. Prevalence of bla CMY and bla CTX-M was higher among birds sampled immediately outside the barns compared with those sampled 600 ft away. Our results suggest that wild birds can serve as mechanical and/or biological vectors for Enterobacteriaceae with resistance to ESCs. Birds live in close contact with dairy cows and their feed, therefore, transmission locally between farms is possible. Finding a similar prevalence in migratory and nonmigratory birds suggests the potential for regional and intercontinental movement of these resistance genes via birds.

  7. Detection of bla-IMP-1 and bla-IMP-2 Genes Among Metallo-β-lactamase-Producing Pseudomonas Aeruginosa Isolated from Burn Patients in Isfahan

    Directory of Open Access Journals (Sweden)

    M. Pourbabaee

    2016-02-01

    Full Text Available Background: Pseudomonas aeruginosa is a nosocomial pathogen which especially causes infections among burn patients. Carbapenems are extensively used for the treatment of infections caused by multidrug-resistant P. aeruginosa isolates. The emergence of carbapenemases producing isolates is an outcome of increased utilization of carbapenems. The aim of this study was to determine the bla-IMP-1 and bla-IMP-2 genes in metallo-β-lactamase (MBL -producing Pseudomonas aeruginosa isolated from burn patients in Isfahan. Material and Methods: A total of 150 P. aeruginosa were isolated from burn patients hospitalized in Imam-Mousakazem hospital in Isfahan. Antimicrobial susceptibility was determined using disk diffusion method according to the Clinical and Laboratory Standards Institute (CLSI guidelines. Double Disk Synergy Test (DDST was carried out for screening of MBL production in imipenem-resistant strains. PCR assays were used for detection of bla-IMP-1 and bla-IMP-2 genes among metallo-β-lactamase-producing Pseudomonas aeruginosa isolates. The purified PCR products were sequenced. Results: Of 150 Pseudomonas aeruginosa isolates, %100 identified as multi-drug resistant strains. The most resistance rates were seen against ciprofloxacin, tobromycin, meropenem and imipenem. All of 144 imipenem-resistant Pseudomonas aeruginosa isolates were MBL producing by DDST test. Twenty-nine (19.3% and 8(5.3% MBL producing Pseudomonas aeruginosa isolates harbored bla-IMP-1 and bla-IMP-2 genes respectively. Conclusions: According to results of this study high level resistance to imipenem and MBl genes carriage was seen among Pseudomonas aeruginosa isolated from burn patient infections in our region.

  8. First detection of bla TEM, SHV and CTX-M among Gram negative ...

    African Journals Online (AJOL)

    First detection of bla TEM, SHV and CTX-M among Gram negative bacilli exhibiting extended spectrum β- lactamase phenotype isolated at University Hospital Center, Yalgado Ouedraogo, Ouagadougou, Burkina Faso.

  9. Providencia isolates carrying bla (PER-1) and bla (VIM-2) genes: biofilm-forming capacity and biofilm inhibitory concentrations for carbapenem antibiotics.

    Science.gov (United States)

    Kim, Jungmin; Kim, Shukho; Lee, Hee Woo; Kim, Sung Min; Seol, Sung Yong

    2011-06-01

    Multidrug-resistant clinical isolates of Providentia carrying bla (PER-1) and bla (VIM-2) were evaluated for the abilities to form biofilm and high biofilm forming capacity was demonstrated in them. Minimum biofilm inhibitory concentrations (MBICs), minimum biofilm eradication concentrations (MBECs), and minimum inhibitory concentrations (MICs) for imipenem and meropenem were also determined. In all tested strains, the MBICs were higher than the MICs for both drugs. Interestingly, the MBICs and the MBEC(50) for meropenem were lower than those for imipenem in the isolates producing high amounts of biofilm, suggesting that meropenem is superior to imipenem in the growth inhibition and eradication of biofilm forming Providentia strains.

  10. Occurrence of blaNDM-1 & absence of blaKPC genes encoding carbapenem resistance in uropathogens from a tertiary care centre from north India

    Directory of Open Access Journals (Sweden)

    Balvinder Mohan

    2015-01-01

    Interpretation & conclusions: The bla NDM-1 gene was absent in our isolates obtained during 2008 but was present amongst Enterobacteriaceae isolated in 2012. The bla KPC gene was also not found. Nine isolates obtained during the two years had multiple genes encoding carbapenemases confirming the previous reports of emergence of GNB containing genes encoding multiple carbapenemases. Typing using BOX-PCR indicated that this emergence was not because of clonal expansion of a single strain, and multiple strains were circulating at a single point of time.

  11. Effect of an educational intervention on knowledge and attitude regarding pharmacovigilance and consumer pharmacovigilance among community pharmacists in Lalitpur district, Nepal.

    Science.gov (United States)

    Jha, Nisha; Rathore, Devendra Singh; Shankar, Pathiyil Ravi; Bhandary, Shital; Pandit, Rabi Bushan; Gyawali, Sudesh; Alshakka, Mohamed

    2017-01-03

    Pharmacovigilance activities are in a developing stage in Nepal. ADR reporting is mainly confined to healthcare professionals working in institutions recognized as regional pharmacovigilance centers. Community pharmacists could play an important role in pharmacovigilance. This study was conducted among community pharmacists in Lalitpur district to examine their knowledge and attitude about pharmacovigilance before and after an educational intervention. Knowledge and attitude was studied before, immediately after and 6 weeks following the intervention among 75 community pharmacists. Responses were analysed using descriptive and inferential statistics. A pretested questionnaire having twelve and nine statements for assessing knowledge and attitude were used. The overall scores were obtained by adding the 'knowledge' and 'attitude' scores and 'overall' scores were summarized using median and interquartile range. Wilcoxon signed-rank test for repeated samples was used to compare the differences between knowledge and attitude of the pharmacists before and after the educational program. Knowledge scores [median (interquartile range)] improved significantly between pre-test [39 (44-46)], post-test [44 (44-44)] and retention period of 6 weeks after the intervention [46 (43-46)]. Knowledge score improved immediately post-intervention among both males [44 (41-47)] and females [44 (43-45)] but the retention scores (after 6 weeks) were higher [46 (42-48)] among males. Attitude scores improved significantly among females [46 (44-48)]. The overall scores were higher among pharmacists from rural areas. Knowledge and attitude scores improved after the educational intervention. Further studies in other regions of the country are required. The national pharmacovigilance center should promote awareness about ADR reporting among community pharmacists.

  12. Implementing a centralised pharmacovigilance service in a non-commercial setting in the United Kingdom

    Science.gov (United States)

    2013-01-01

    The implementation of a pharmacovigilance service compliant with the legal and regulatory responsibilities of clinical trial sponsors presents particular challenges for sponsors in a non-commercial setting. In this paper we examine these challenges in detail. We identify and discuss the key steps in the development of a pharmacovigilance service within a public health service and university setting in the United Kingdom. We describe how we have established a central Pharmacovigilance Office with dedicated staff and resources within our organisation. This office is supported by an electronic pharmacovigilance reporting infrastructure developed to facilitate the receipt and processing of safety information, the onward reporting in compliance with legislation and the provision of sponsor institution oversight of clinical trial participant safety. An education and training programme has also been set up to ensure that all relevant staff in the organisation are fully aware of the pharmacovigilance service and are appropriately trained in its use. We discuss possible alternatives to this approach and why we consider our solution to be the most appropriate to ensure that a non-commercial sponsor organisation and investigators are operating in a fully compliant way. PMID:23758677

  13. A study on pharmacovigilance of herbal medicines in Lagos West Senatorial District, Nigeria.

    Science.gov (United States)

    Awodele, O; Daniel, A; Popoola, T D; Salami, E F

    2013-01-01

    There is an increasing use of herbal products and herbal medicines globally with the belief that herbal medicines are always 'safe' and carry no risk because they are from natural sources. However, there are concerns regarding medicinal plants and their ability to produce adverse effects. The growing herbal medicine usage has increased the need to monitor the safety of herbal medicines. Thus, the recommended approach by the World Health Organization (WHO) is to include herbal medicines in existing national pharmacovigilance systems. This study aimed to determine the knowledge of pharmacovigilance of herbal medicines amongst herbal medicine practitioners. The study was carried out in Lagos West Senatorial District of Lagos State, Nigeria. Three categories of practitioners (378 respondents) were engaged and they include Traditional Herbal Sellers, Natural Health Practitioners and Pharmacists. The results showed that herbal medicines are commonly recommended for malaria, typhoid, diabetes and fever. 281 (74.3%) of the respondents claimed that herbal medicines have no adverse effects and only 91 (24.1%) of the respondents said there were some adverse effects reported by the users. Adverse effects reported include nausea, diarrhoea and weight loss. Amongst those that received reports of adverse effects, only 19 (20.9%) documented these reported adverse effects; none of these documentations were forwarded to the regulatory bodies or national pharmacovigilance centre in Nigeria. These results showed inadequate adverse effects monitoring (Pharmacovigilance) amongst the practitioners and underscore the necessity to educate and enlighten herbal medicine practitioners on the need for pharmacovigilance activity of herbal products.

  14. Molecular characterization of intestinal carriage of carbapenem-resistant Enterobacteriaceae among inpatients at two Iranian university hospitals: first report of co-production of blaNDM-7and blaOXA-48.

    Science.gov (United States)

    Solgi, H; Badmasti, F; Aminzadeh, Z; Giske, C G; Pourahmad, M; Vaziri, F; Havaei, S A; Shahcheraghi, F

    2017-11-01

    Gastrointestinal colonization of carbapenem-resistant Enterobacteriaceae (CRE) could serve as a reservoir for the transmission of these pathogens in the clinical setting. The aim of this study was to investigate the intestinal carriage of CRE and to analyze risk factors for CRE carriage. Rectal swabs were collected from 95 patients at two Iranian university hospitals. CRE screening was performed using selective media (CHROMagar and MacConkey agar). Polymerase chain reaction (PCR) was used to detect carbapenemase-encoding genes. Clonal relatedness was investigated by pulsed-field gel electrophoresis (PFGE). The rate of carriage of CRE in hospitalized patients was 37.9%. Overall, 54 CRE isolates were identified, of which 47 were carbapenemase-producers. All of the 54 CRE were detected using CHROMagar compared with 52 CRE detected using MacConkey agar. Fifteen patients were colonized by multiple CRE isolates. Three significant risk factors for CRE carriage were detected: intensive care unit (ICU) hospitalization, antibiotic exposure, and mechanical ventilation. bla OXA-48 was the most frequent carbapenemase detected, followed by bla NDM-1 and bla NDM-7 . Eleven carbapenemase-producing Enterobacteriaceae (CPE) isolates co-harbored bla NDM-1 and bla OXA-48 . Also, six CPE isolates co-harbored bla NDM-7 and bla OXA-48 . We did not detect bla KPC , bla GES , bla IMP , or bla VIM . PFGE analysis showed that Escherichia coli clones were diverse, while Klebsiella pneumoniae isolates were divided into four clusters. Cluster I was the major clone carrying bla OXA-48 and bla CTX-M-15 genes. In our study, the carriage rate of CRE was high and the emergence of CPE isolates among patients is alarming. The implementation of adequate preventive measures such as active surveillance is urgently needed to control the spread of CPE in the healthcare setting.

  15. Hospital medication errors in a pharmacovigilance system in Colombia

    Directory of Open Access Journals (Sweden)

    Jorge Enrique Machado-Alba

    2015-11-01

    Full Text Available Objective: this study analyzes the medication errors reported to a pharmacovigilance system by 26 hospitals for patients in the healthcare system of Colombia. Methods: this retrospective study analyzed the medication errors reported to a systematized database between 1 January 2008 and 12 September 2013. The medication is dispensed by the company Audifarma S.A. to hospitals and clinics around Colombia. Data were classified according to the taxonomy of the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP. The data analysis was performed using SPSS 22.0 for Windows, considering p-values < 0.05 significant. Results: there were 9 062 medication errors in 45 hospital pharmacies. Real errors accounted for 51.9% (n = 4 707, of which 12.0% (n = 567 reached the patient (Categories C to I and caused harm (Categories E to I to 17 subjects (0.36%. The main process involved in errors that occurred (categories B to I was prescription (n = 1 758, 37.3%, followed by dispensation (n = 1 737, 36.9%, transcription (n = 970, 20.6% and administration (n = 242, 5.1%. The errors in the administration process were 45.2 times more likely to reach the patient (CI 95%: 20.2–100.9. Conclusions: medication error reporting systems and prevention strategies should be widespread in hospital settings, prioritizing efforts to address the administration process.

  16. Pharmacovigilance, risks and adverse effects of self-medication.

    Science.gov (United States)

    Montastruc, Jean-Louis; Bondon-Guitton, Emmanuelle; Abadie, Delphine; Lacroix, Isabelle; Berreni, Aurélia; Pugnet, Grégory; Durrieu, Geneviève; Sailler, Laurent; Giroud, Jean-Paul; Damase-Michel, Christine; Montastruc, François

    2016-04-01

    Self-medication means resorting to one or more drugs in order to treat oneself without the help of a doctor. This phenomenon is developing fast. In this review, we will discuss the main definitions of self-medication; we will then present a few important characteristics of this therapeutic practice: prevalence, reasons, populations involved and drugs used. Whilst the theoretical risks of self-medication have been abundantly discussed in the literature (adverse effects, interactions, product, dosage or treatment duration errors, difficulty in self-diagnosis, risk of addiction or abuse…), there is in fact very little detailed pharmacovigilance data concerning the characteristics and the consequences of this usage in real life. This study therefore describes the all too rare data that is available: patients, clinical characteristics, "seriousness" and drugs involved in the adverse effects of self-medication. It also discusses leads to be followed in order to minimize medication risks, which are obviously not well known and clearly not sufficiently notified. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  17. A day in the life of a pharmacovigilance case processor

    Directory of Open Access Journals (Sweden)

    Ritesh Bhangale

    2017-01-01

    Full Text Available Pharmacovigilance (PV has grown significantly in India in the last couple of decades. The etymological roots for the word “pharmacovigilance” are “Pharmakon” (Greek for drug and “Vigilare” (Latin for to keep watch. It relies on information gathered from the collection of individual case safety reports and other pharmacoepidemiological data. The PV data processing cycle starts with data collection in computerized systems followed by complete data entry which includes adverse event coding, drug coding, causality and expectedness assessment, narrative writing, quality control, and report submissions followed by data storage and maintenance. A case processor plays an important role in conducting these various tasks. The case processor should also manage drug safety information, possess updated knowledge about global drug safety regulations, summarize clinical safety data, participate in meetings, write narratives with medical input from a physician, report serious adverse events to the regulatory authorities, participate in the training of operational staff on drug safety issues, quality control work of other staff in the department, and take on any other task as assigned by the manager or medical director within the capabilities of the drug safety associate. There can be challenges while handling all these tasks at a time, hence the associate will have to maintain a balance to overcome them and keep on updating their knowledge on drug safety regulations, which in turn, would help in increasing their learning curve.

  18. Differential Binding of Co(II) and Zn(II) to Metallo-beta-Lactamase Bla2 from Bacillus anthracis

    Energy Technology Data Exchange (ETDEWEB)

    Hawk, M.; Breece, R; Hajdin, C; Bender, K; Hu, Z; Costello, A; Bennett, B; Tierney, D; Crowder, M

    2009-01-01

    In an effort to probe the structure, mechanism, and biochemical properties of metallo-{beta}-lactamase Bla2 from Bacillus anthracis, the enzyme was overexpressed, purified, and characterized. Metal analyses demonstrated that recombinant Bla2 tightly binds 1 equiv of Zn(II). Steady-state kinetic studies showed that mono-Zn(II) Bla2 (1Zn-Bla2) is active, while di-Zn(II) Bla2 (ZnZn-Bla2) was unstable. Catalytically, 1Zn-Bla2 behaves like the related enzymes CcrA and L1. In contrast, di-Co(II) Bla2 (CoCo-Bla2) is substantially more active than the mono-Co(II) analogue. Rapid kinetics and UV-vis, 1H NMR, EPR, and EXAFS spectroscopic studies show that Co(II) binding to Bla2 is distributed, while EXAFS shows that Zn(II) binding is sequential. To our knowledge, this is the first documented example of a Zn enzyme that binds Co(II) and Zn(II) via distinct mechanisms, underscoring the need to demonstrate transferability when extrapolating results on Co(II)-substituted proteins to the native Zn(II)-containing forms.

  19. First report of blaNDM-1-producing Acinetobacter baumannii isolated in Lebanon from civilians wounded during the Syrian war.

    Science.gov (United States)

    Rafei, Rayane; Dabboussi, Fouad; Hamze, Monzer; Eveillard, Matthieu; Lemarié, Carole; Mallat, Hassan; Rolain, Jean-Marc; Joly-Guillou, Marie-Laure; Kempf, Marie

    2014-04-01

    The emergence of carbapenem-resistant Acinetobacter baumannii has been observed worldwide. We describe the first detection of A. baumannii carrying the blaNDM-1 gene in Lebanon, isolated from Syrian patients wounded during the civil war. Four carbapenem-resistant A. baumannii strains isolated in 2012 in the Tripoli Government Hospital, Lebanon, from civilians wounded during the Syrian war, were analysed. Susceptibility was determined by disk diffusion testing, and resistance to carbapenems was confirmed by Etest. The presence of blaOXA-23-like, blaOXA-24-like, blaOXA-58-like, blaOXA-143-like, and blaNDM was investigated by PCR. Clonal relationships were studied by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and blaOXA-51 sequence-based typing. All isolates harboured the blaNDM-1 gene and were negative for other tested carbapenemases. They all belonged to the sequence type 85 and formed a single cluster by PFGE. Finally, blaOXA-51-like gene sequencing revealed the presence of the blaOXA-94 variant in all four isolates. These findings show that Syria constitutes a reservoir for NDM-1-producing bacteria. These results also highlight the need for effective measures to stop the threatening spread of such strains. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Zoo or savannah? Choice of training ground for evidence-based pharmacovigilance.

    Science.gov (United States)

    Norén, G Niklas; Caster, Ola; Juhlin, Kristina; Lindquist, Marie

    2014-09-01

    Pharmacovigilance seeks to detect and describe adverse drug reactions early. Ideally, we would like to see objective evidence that a chosen signal detection approach can be expected to be effective. The development and evaluation of evidence-based methods require benchmarks for signal detection performance, and recent years have seen unprecedented efforts to build such reference sets. Here, we argue that evaluation should be made against emerging and not established adverse drug reactions, and we present real-world examples that illustrate the relevance of this to pharmacovigilance methods development for both individual case reports and longitudinal health records. The establishment of broader reference sets of emerging safety signals must be made a top priority to achieve more effective pharmacovigilance methods development and evaluation.

  1. [Development and evaluation of novel loop-mediated isothermal amplification for rapid detection of bla(IMP-1) and bla(VIM-2) genes].

    Science.gov (United States)

    Kojima, Tadashi; Shibata, Naohiro; Ikedo, Masanari; Arakawa, Yoshichika

    2006-07-01

    Loop-mediated isothermal amplification (LAMP) amplifies a target gene with high specificity and rapidity under isothermal conditions. LAMP assays were developed for the rapid detection of metallo-beta-lactamase (MBL) genes such as bla(IMP-1)) and bla(VIM-2). We initially designed specific primers to detect MBL genes for LAMP assays and evaluated the specificity and sensitivity of these assays. LAMP assays amplified MBL genes under a constant temperature of 63 degrees C within 1 hour, and were compared to PCR in MBL-producing strains. The results of MBL genes typing by LAMP assays agree completely with PCR results. The lower detection limits of bla(IMP-1)- and bla(VIM-2)-LAMP assays using real-time turbidimeters were 30cfu/test and 3cfu/test. After amplification, products were directly observed by the naked eye with a fluorescent detection reagent. In conclusion, LAMP assays are convenient, rapid, and fully feasible for detecting MBL genes in ordinary clinical microbiology laboratories without special apparatus.

  2. Healthcare professionals' awareness and knowledge of adverse drug reactions and pharmacovigilance.

    Science.gov (United States)

    Almandil, Noor B

    2016-12-01

    To document the knowledge of, attitudes toward, and practices of adverse drug reaction (ADR) reporting and pharmacovigilance systems among healthcare professionals. Methods: This descriptive cross-sectional study was conducted using a questionnaire. This study took place at King Fahd Hospital of the University (KFHU), Khobar, Kingdom of Saudi Arabia,  between  April 2015 and  April 2016. Healthcare professionals, including physicians, pharmacists, pharmacy technicians, and nurses, were considered eligible and invited to take part in the study. A link to the online questionnaire was sent to each participant via E-mail, and a hard copy was circulated at the hospital after the objectives of the study were explained. The questionnaire comprised items regarding knowledge/awareness of pharmacovigilance and ADRs, perception/attitude towards pharmacovigilance and ADR reporting, and practices of ADR reporting. Descriptive statistics were used to analyze the data. Results: A total of 400 questionnaires were distributed to the healthcare professionals and 331 participants responded, providing a response rate of 82.75%. The healthcare professionals comprised 161 physicians, 39 pharmacists, 21 pharmacist technicians, and 110 nurses. Most of the participants were female (n=198) and Saudi (61.9%). Most healthcare professionals (62.5%) were unaware of the term pharmacovigilance; the pharmacists and pharmacist technicians had the highest rate of pharmacovigilance awareness (60.5% of the pharmacists and 40% of pharmacist technicians). Conclusion: There is a lack of awareness and knowledge of pharmacovigilance and ADR reporting among healthcare professionals working at KFHU.

  3. [Post-marketing drug safety-risk management plan(RMP)].

    Science.gov (United States)

    Ezaki, Asami; Hori, Akiko

    2013-03-01

    The Guidance for Risk Management Plan(RMP)was released by the Ministry of Health, Labour and Welfare in April 2012. The RMP consists of safety specifications, pharmacovigilance plans and risk minimization action plans. In this paper, we outline post-marketing drug safety operations in PMDA and the RMP, with examples of some anticancer drugs.

  4. Spread of plasmids containing the bla(VIM-1) and bla(CTX-M) genes and the qnr determinant in Enterobacter cloacae, Klebsiella pneumoniae and Klebsiella oxytoca isolates.

    Science.gov (United States)

    Miró, Elisenda; Segura, Concha; Navarro, Ferran; Sorlí, Lluisa; Coll, Pere; Horcajada, Juan P; Alvarez-Lerma, Francisco; Salvadó, Margarita

    2010-04-01

    We describe 12 VIM-1-producing strains (7 Enterobacter cloacae, 2 Klebsiella pneumoniae and 3 clonal Klebsiella oxytoca strains) detected among clinically relevant Enterobacteriaceae isolates from routine cultures at the Hospital del Mar (Barcelona, Spain) from December 2006 to May 2007. Susceptibility to carbapenems was evaluated with the MicroScan system. beta-Lactamases were identified by PCR and sequencing. Clonal relationships between the isolates were analysed by PFGE. Transferability of the enzymes was tested by conjugation. Plasmid characterization was performed by PCR-based replicon typing and PFGE with S1 nuclease digestion of whole genomic DNA. The PFGE gels were then transferred and hybridized. The disc diffusion method correctly identified five of the seven E. cloacae isolates as intermediate or resistant strains. All isolates produced the VIM-1 enzyme. Three E. cloacae and three K. oxytoca strains were also CTX-M-9-producing strains, and one E. cloacae was also a CTX-M-3-producing strain. The plasmids carrying the bla(VIM) gene, of unknown incompatibility group, had a size of approximately 75 kb (eight strains) or 40 kb (three strains) and also contained the qnrS and the aac(6')-Ib-cr genes. In the remaining strain the bla(VIM-1) gene was found in an HI2 plasmid of 290 kb together with bla(CTX-M-9), qnrA, qnrS and the aac(6')-Ib-cr genes. The results showed a linkage between the bla(VIM-1) and the qnrS and the aac(6')-Ib-cr genes, and between the bla(CTX-M-9) and the qnrA genes.

  5. A novel transposon, Tn6306, mediates the spread of blaIMI in Enterobacteriaceae in hospitals

    Directory of Open Access Journals (Sweden)

    Fangfang Zhang

    2017-12-01

    Full Text Available The increasing incidence of carbapenem-resistant Enterobacteriaceae has become a challenge for clinical therapy. In our study, we analysed the molecular characteristics of imipenem-hydrolyzing β-lactamase (IMI in Enterobacteriaceae isolates. Two reported clinical isolates, the IMI-3-producing Raoultella ornithinolytica RJ46C and the IMI-2-producing Escherichia coli RJ18 were identified in our retrospective review of isolates collected from June 2010 to June 2013, both isolates were resistant to carbapenem but sensitive to expanded-spectrum cephalosporins. The blaIMI gene was located on different ∼170-kb plasmids in both isolates. The blaIMI-3 gene was carried by the plasmid pRJ46C, which was extracted from the transconjugant and identified to be a 166,620-bp conjugative IncFIIY plasmid that contained 193 open reading frames, including replication-, plasmid conjugal transfer-, partitioning-, and mobilization-associated structures. The blaIMI-3 gene was located on a 15-kb region with a completely inverted sequence relative to that of plasmid pGA45, two ISEcl1-like elements containing two 33-bp complete inverted repeats were in an inverted orientation on both sides of the 15-kb region. We identified this typical structure as a novel composite transposon named Tn6306, indicating the occurrence of transposition. In addition, the blaIMI-2-carrying pRJ18 was an IncFIB plasmid, and a similar ISEcl1-like element was identified in an inverted direction upstream of IMI-2 in pRJ18. The identification of blaIMI in R. ornithinolytica and E. coli highlights the diversity of spreading carbapenemases in Enterobacteriaceae between hospitals and the environment in China. The novel transposon Tn6306, and other insert sequences, may play important roles in blaIMI mobilization. Keywords: blaIMI in Enterobacteriaceae, Genetic environment, Plasmids, Novel transposon structure Tn6306, ISEcl1-like element

  6. Incidence of blaNDM-1 gene in Escherichia coli isolates at a tertiary care referral hospital in Northeast India

    Directory of Open Access Journals (Sweden)

    A Bora

    2013-01-01

    Full Text Available Purpose: Increasing reports on New Delhi metallo-β-lactamase-1 (NDM-1 producing Escherichia coli constitute a serious threat to global health since it is found to be highly resistant to most of the currently available antibiotics including carbapenems. This study has been performed to find out the incidence blaNDM-1 in E. coli isolates recovered from the various clinical samples at a tertiary care referral hospital in Northeast India. Materials and Methods: A total of 270 non-duplicated E. coli isolates were recovered from the various clinical samples at a tertiary care referral hospital in Northeast India. All isolates with reduced susceptibility to meropenem or ertapenem (diameter of zones of inhibition, ≤21 mm were further phenotypically confirmed for carbapenemase production by modified Hodge test. All screened isolates were also subjected to the polymerase chain reaction detection of blaNDM-1 gene and additional bla genes coding for transmission electron microscopy, SHV, CTX-M, and AmpC. Results: Out of 270 E. coli isolates, 14 were screened for carbapenemase production on the basis of their reduced susceptibility to meropenem or ertapenem. All screened isolates were found to be positive for blaNDM-1 . Each of the blaNDM-1 possessing isolate was also positive for two or more additional bla genes, such as blaTEM , blaCTX-M and blaAmpC . Phylogenetic analysis showed very less variation in blaNDM-1 gene with respect to blaNDM-1 possessing E. coli isolates from other parts of India and abroad. Conclusions: Our findings highlight the incidence of blaNDM-1 in E. coli isolates with a reduced susceptibility to meropenem or ertapenem.

  7. Safety profile of etifoxine: A French pharmacovigilance survey.

    Science.gov (United States)

    Cottin, Judith; Gouraud, Aurore; Jean-Pastor, Marie-Josèphe; Dautriche, Anne Disson-; Boulay, Charlène; Geniaux, Hélène; Auffret, Marine; Bernard, Nathalie; Descotes, Jacques; Vial, Thierry

    2016-04-01

    Etifoxine chlorhydrate is a benzoxazine derivative approved for the treatment of psychosomatic manifestations of anxiety since 1979. Previously labeled adverse drug reactions (ADRs) only include drowsiness, benign cutaneous reactions, and acute hypersensitivity reactions. The objectives were to examine recent data on etifoxine-related ADR by reviewing Individual Case Safety Reports (ICSRs) recorded in France especially unexpected ADRs. Etifoxine-related ICSRs were extracted from the French Pharmacovigilance database from 1 January 2000 to 30 April 2012 and data from the marketing authorization holder up to 31 December 2011 were also obtained. Of the 350 cases retained for analysis, 123 (35%) were considered serious. Dermatological or acute hypersensitivity reactions were the most frequent ADRs (59%) mainly isolated cutaneous eruptions. However, there were 24 cases of severe toxidermia (DRESS in 5, erythema multiforme in 10 and Stevens-Johnson syndrome in 5) with etifoxine as the most suspected drug in 11 patients, and seven cases of vasculitis or serum sickness-like reaction. Liver disorders were reported in 34 patients of whom 25 developed acute hepatitis with a cytolytic biological pattern in 16. Other unexpected ADRs included 16 reversible cases of metrorrhagia with positive rechallenge in 5, and three cases of biopsy-proven microscopic colitis of which one recurred after etifoxine re-administration. Although etifoxine has been marketed for more than 30 years, this survey identified a number of unexpected and sometimes serious ADRs, in particularly severe toxidermia and acute cytolytic hepatitis. A recent update of the French etifoxine summary of the product characteristics (SPC) was based on these findings. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  8. Gentamicin nephrotoxicity: Animal experimental correlate with human pharmacovigilance outcome

    Directory of Open Access Journals (Sweden)

    Olufunsho Awodele

    2015-04-01

    Full Text Available Background: National Agency for Food and Drugs Administration and Control (NAFDAC, which is responsible for pharmacovigilance activity in Nigeria, recently withdrew injection gentamicin 280 mg, used in the management of life-threatening and multidrug-resistant infections from circulation, due to reported toxicity. Thus, this study aimed to investigate the toxicity profile of the commonly used strengths (80 mg and 280 mg of gentamicin on kidney using animal models. Methods: Animals were divided into five groups of 16 rats each. For rats of groups 1 and 2, gentamicin (1.14 mg/kg each group was administered intramuscularly twice daily for 7 and 14 days, respectively, after which eight of them were sacrificed by cervical dislocation. Blood was collected via cardiac puncture and the kidneys were carefully removed and weighed immediately. The remaining eight animals were kept for reversibility study for another 7 and 14 days, respectively. For groups 3 and 4, gentamicin (4 mg/kg each group was administered as a single daily dose for 7 and 14 days, respectively, and eight animals from the groups were subjected to reversibility study for 7 and 14 days, respectively. Group 5, the control group animals, were given 10 ml/kg distilled water for 14 days. Histopathology of the kidneys, serum creatinine levels, and antioxidant enzyme activities were investigated. Results: Significant increase (p ≤ 0.001 in the level of creatinine of rats administered 4.0 mg/kg for 14 days was observed compared with all other groups. Significant (p ≤ 0.001 elevations in the lipid peroxidation in all gentamicin-administered animals and acute tubular necrosis in most of the gentamicin-administered animals were observed. Conclusion: Toxicity profile of gentamicin on the kidneys is dependent on both dose and duration of administration. The findings justify the decision made by NAFDAC to ban the use of high-dose inj. gentamicin 280 mg in Nigeria.

  9. Clinical pharmacology: special safety considerations in drug development and pharmacovigilance.

    Science.gov (United States)

    Atuah, Kwame N; Hughes, Dyfrig; Pirmohamed, Munir

    2004-01-01

    The dose of a drug is a major determinant of its safety, and establishing a safe dose of a novel drug is a prime objective during clinical development. The design of pre-marketing clinical trials precludes the representation of important subpopulations such as children, the elderly and people with co-morbidities. Therefore, postmarketing surveillance (PMS) activities are required to monitor the safety profile of drugs in real clinical practice. Furthermore, individual variations in pharmacogenetic profiles, the immune system, drug metabolic pathways and drug-drug interactions are also important factors in the occurrence of adverse drug reactions. Thus, the safety of a drug is a major clinical consideration before and after it is marketed. A multidisciplinary approach is required to enhance the safety profile of drugs at all stages of development, including PMS activities. Clinical pharmacology encompasses a range of disciplines and forms the backbone of drug safety consideration during clinical drug development. In this review we give an overview of the clinical drug development process and consider its limitations. We present a discussion of several aspects of clinical pharmacology and their application to enhancing drug safety. Pharmacokinetic-pharmacodynamic modelling provides a method of predicting a clinically safe dose; consideration of drug pharmacokinetics in special populations may enhance safe therapeutics in a wider spectrum of patients, while pharmacogenetics provides the possibility of genotype-specific therapeutics. Pharmacovigilance activities are also discussed. Given the complex nature and unpredictability of type B reactions, PMS activities are crucial in managing the risks drugs pose to the general population. The various aspects of clinical pharmacology discussed make a strong case for this field as the backbone of optimising and promoting safe development and use of drugs.

  10. Post-marketing drug withdrawals: Pharmacovigilance success, regulatory problems.

    Science.gov (United States)

    Aronson, Jeffrey K

    2017-10-01

    Modern pharmacovigilance began in the 1960s, since when the subject has grown markedly, interest having particularly increased since 2010. One index of its success is the increasing speed with which serious adverse drug reactions are discovered after marketing of a medicinal product. However, the speed with which products have subsequently been withdrawn as a result of the discovery of serious adverse reactions has not consistently changed. This highlights problems that regulators and manufacturers face when serious reactions are discovered, with difficulties in deciding which of several consequent actions to take: to add specific warnings (cautions) or contraindications to the product label; to issue a Direct Healthcare Professional Communication; to allow informed patients to decide whether they will take the drug; or, in the most serious cases, to withdraw the product or revoke the licence. Conflicts of interest may inhibit decision-making. Recommendations that arise from these observations are that: health professionals and patients should be more vigorously encouraged to report suspected adverse drug reactions; regulatory authorities and drug manufacturers should take quicker confirmatory action when serious suspected adverse drug reactions are reported, even anecdotally, with formal studies to test for causality conducted sooner rather than later, applying lower than usual thresholds for suspicion; temporary suspensions or restrictions could be considered during such assessments; universal guidelines are needed for determining when a drug should be withdrawn if serious adverse drug reactions are suspected; there should be more rigorous monitoring and verification of deaths and reporting of reasons for drop-outs during clinical trials, with more transparency in reporting adverse events and ready access to premarketing clinical study reports; post-marketing drug monitoring systems and medicines regulation in low-to-middle income economies, especially in Africa

  11. The impact of exposure model misspecification on signal detection in prospective pharmacovigilance.

    Science.gov (United States)

    van Gaalen, Rolina D; Abrahamowicz, Michal; Buckeridge, David L

    2015-05-01

    Pharmacovigilance monitors the safety of drugs after their approval and marketing. Timely detection of adverse effects is important. The true relationship between time-varying drug use and the adverse event risk is typically unknown. Yet, most current pharmacovigilance studies rely on arbitrarily chosen exposure metrics such as current exposure or use in the past 3 months. The authors used simulations to assess the impact of a misspecified exposure model on the timeliness of adverse effect detection. Prospective pharmacovigilance studies were simulated assuming different true relationships between time-varying drug use and the adverse event hazard. Simulated data were analyzed by fitting conventional parametric and more complex spline-based estimation models at multiple, pre-specified testing times. The 'signal' was generated on the basis of the corrected model-specific p-value selected to ensure a 5% probability of incorrectly rejecting the null hypothesis of no association. Results indicated that use of an estimation model that diverged substantially from the true underlying association-reduced sensitivity and increased the time to detection of a clinically important association. Time to signal detection in pharmacovigilance may depend strongly on the method chosen to model the exposure. No single estimation model performed optimally across different simulated scenarios, suggesting the need for data-dependent criteria to select the model most appropriate for a given study. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Pharmacovigilance Skills, Knowledge and Attitudes in our Future Doctors - A Nationwide Study in the Netherlands

    NARCIS (Netherlands)

    Schutte, Tim; Tichelaar, Jelle; Reumerman, Michael O; van Eekeren, Rike; Rissmann, Robert; Kramers, Cornelis; Richir, Milan C; van Puijenbroek, Eugène P; van Agtmael, Michiel A

    2016-01-01

    Pharmacovigilance centres monitor the safety of drugs, based on adverse drug reactions (ADRs) reported by doctors, pharmacists and pharmaceutical companies. However, the underreporting of ADRs remains a major problem. Our aim was to investigate preparedness of future doctors for their role in

  13. Pharmacovigilance Skills, Knowledge and Attitudes in our Future Doctors - A Nationwide Study in the Netherlands

    NARCIS (Netherlands)

    Schutte, T.; Tichelaar, J.; Reumerman, M.O.; Eekeren, R. van; Rissmann, R.; Kramers, C.; Richir, M.C.; Puijenbroek, E.P. van; Agtmael, M.A. van

    2017-01-01

    Pharmacovigilance centres monitor the safety of drugs, based on adverse drug reactions (ADRs) reported by doctors, pharmacists and pharmaceutical companies. However, the under-reporting of ADRs remains a major problem. Our aim was to investigate preparedness of future doctors for their role in

  14. Pharmacovigilance implemented by patients: A necessity in the 21st century.

    Science.gov (United States)

    Lafond, Jean

    2016-04-01

    Pharmacovigilance should become a well-thought-out reflex for each of us, for any drugs taken on prescription or by self-medication. The issue of pharmacovigilance should naturally take its place in the dialogue between patients and health professionals, through advice given before medication is taken. Patients need to be told the importance of notifying any adverse drug reactions (ADRs). Pharmacovigilance would then become a post-hoc way of protecting patients. The importance of using pharmacovigilance should be promoted by emphasizing the fact that the life of a drug really starts after its marketing. This state of mind could be reinforced by a wider advertising campaign on the possibility of notifying the relevant authorities of any ADRs. Patient associations should encourage and help their members to do this. Notifying any ADRs should become a concern for all medical and paramedical staff: those who prescribe drugs, those who dispense them (pharmacists or pharmacy assistants), those who administer them (nurses), but also the consumers (patients) whose place is becoming more and more prominent. Copyright © 2016. Published by Elsevier Masson SAS.

  15. 3D Pharmacophoric Similarity improves Multi Adverse Drug Event Identification in Pharmacovigilance

    Science.gov (United States)

    Vilar, Santiago; Tatonetti, Nicholas P.; Hripcsak, George

    2015-03-01

    Adverse drugs events (ADEs) detection constitutes a considerable concern in patient safety and public health care. For this reason, it is important to develop methods that improve ADE signal detection in pharmacovigilance databases. Our objective is to apply 3D pharmacophoric similarity models to enhance ADE recognition in Offsides, a pharmacovigilance resource with drug-ADE associations extracted from the FDA Adverse Event Reporting System (FAERS). We developed a multi-ADE predictor implementing 3D drug similarity based on a pharmacophoric approach, with an ADE reference standard extracted from the SIDER database. The results showed that the application of our 3D multi-type ADE predictor to the pharmacovigilance data in Offsides improved ADE identification and generated enriched sets of drug-ADE signals. The global ROC curve for the Offsides ADE candidates ranked with the 3D similarity score showed an area of 0.7. The 3D predictor also allows the identification of the most similar drug that causes the ADE under study, which could provide hypotheses about mechanisms of action and ADE etiology. Our method is useful in drug development, screening potential adverse effects in experimental drugs, and in drug safety, applicable to the evaluation of ADE signals selected through pharmacovigilance data mining.

  16. An evaluation of the knowledge and perceptions of pharmacy students on pharmacovigilance activities in Nigeria.

    Science.gov (United States)

    Osemene, Kanayo P; Afolabi, Margaret O

    2017-07-12

    The use of the modified-prescription event monitoring technique has facilitated the understanding and reporting of pharmacovigilance (PV). However, in Nigeria, PV activities are largely misunderstood. Furthermore, there is a dearth of information on the knowledge and perceptions of pharmacy students on PV activities in relation to demographics. This study investigated and assessed the knowledge and perceptions of pharmacy students about pharmacovigilance as well as the demographic factors that are related to pharmacovigilance activities. A cross-sectional survey was conducted among final year pharmacy students in three universities in months of January and February, 2016 with permission from the institutions and with written consents from 342 respondents. Pre-tested questionnaire was used to elicit information on the study objectives. Data were analysed using appropriate descriptive and inferential statistical techniques. The study revealed that the mean score on knowledge of pharmacy students on pharmacovigilance activities was 4.3 ± 0.18 which was significant according to gender (P marketing phase of drug assessment. About 204 (59.7%) of the respondents erroneously believed that adverse reactions caused by cosmetics should not be reported. Respondents have inadequate knowledge of PV activities. Therefore, pharmacy student educators should enhance students' knowledge about PV through training, during clerkship, and lay more emphasis on relevant PV courses in the Pharmacy Curriculum.

  17. Validation of signal impact assessment tool in order to explore pharmacovigilance signals' follow-up actions

    NARCIS (Netherlands)

    Rolfes, Leàn; Kolfschoten, Judith; Van Hunsel, Florence; Van Puijenbroek, Eugene; van Grootheest, Kees

    2014-01-01

    Background: To determine which actions are advisable for signals arising from a spontaneous reporting system, the Netherlands Pharmacovigilance Centre Lareb uses a Signal Impact Assessment Tool (SIAT). It categorizes signals into one of four categories: strong/moderate signal strength and similarly

  18. Natural Language Processing for EHR-Based Pharmacovigilance: A Structured Review.

    Science.gov (United States)

    Luo, Yuan; Thompson, William K; Herr, Timothy M; Zeng, Zexian; Berendsen, Mark A; Jonnalagadda, Siddhartha R; Carson, Matthew B; Starren, Justin

    2017-11-01

    The goal of pharmacovigilance is to detect, monitor, characterize and prevent adverse drug events (ADEs) with pharmaceutical products. This article is a comprehensive structured review of recent advances in applying natural language processing (NLP) to electronic health record (EHR) narratives for pharmacovigilance. We review methods of varying complexity and problem focus, summarize the current state-of-the-art in methodology advancement, discuss limitations and point out several promising future directions. The ability to accurately capture both semantic and syntactic structures in clinical narratives becomes increasingly critical to enable efficient and accurate ADE detection. Significant progress has been made in algorithm development and resource construction since 2000. Since 2012, statistical analysis and machine learning methods have gained traction in automation of ADE mining from EHR narratives. Current state-of-the-art methods for NLP-based ADE detection from EHRs show promise regarding their integration into production pharmacovigilance systems. In addition, integrating multifaceted, heterogeneous data sources has shown promise in improving ADE detection and has become increasingly adopted. On the other hand, challenges and opportunities remain across the frontier of NLP application to EHR-based pharmacovigilance, including proper characterization of ADE context, differentiation between off- and on-label drug-use ADEs, recognition of the importance of polypharmacy-induced ADEs, better integration of heterogeneous data sources, creation of shared corpora, and organization of shared-task challenges to advance the state-of-the-art.

  19. Pharmacovigilance training for specialist oncology nurses-a two way evaluation

    NARCIS (Netherlands)

    Schutte, T.; Van Eekeren, R.; Richir, M.; Van Staveren, J.; Van Puijenbroek, E.P.; Tichelaar, J.; Van Agtmael, M.A.

    2017-01-01

    Background: In a new prescribing qualifcation course for specialist oncology nurses, we thought it important to emphasize pharma-covigilance and adverse drug reaction (ADR)-reporting. To this end, our aim was to develop and evaluate an ADR reporting assignment for specialist oncology nurses.

  20. Pharmaco-epidemiology as a Tool in Pharmacovigilance: Studying cancer as adverse drug reaction

    NARCIS (Netherlands)

    T.R. Ruiter (Tanneke Rikje)

    2012-01-01

    textabstractPharmacovigilance is defined by the World Health Organization (WHO) as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug-related problem. There has been concern about the safety of medicines

  1. Quality management system as a tool for improvement of the dutch pharmacovigilance system

    NARCIS (Netherlands)

    Zweers, P.G.M.A.; Van Puijenbroek, E.P.; Van Grootheest, A.C.

    2009-01-01

    Introduction: The Netherlands Pharmacovigilance centre Lareb started as a regional organization in 1985. In 1995 it was appointed by the Health Authorities as the national centre for collection and analysis for reports of adverse drug reactions. Since then, Lareb has become a solid, professional

  2. First Identification of a Patient Colonized With Klebsiella pneumoniae Carrying blaNDM-1 in Taiwan

    Directory of Open Access Journals (Sweden)

    Hua-Shin Wu

    2010-11-01

    Full Text Available New Delhi metallo-β-lactamase 1 (NDM-1 is a novel type of metallo-β-lactamase (MBL. Enterobacteriaceae carrying this NDM-1 encoding gene, blaNDM-1, have been identified worldwide. Bacteria carrying blaNDM-1 are not only resistant to carbapenem, but also highly resistant to many classes of antibiotics, which indicate the importance of prompt identification of these bacteria and implementation of strict infection control measures to prevent their transmission. Here, we report the first identification and management of a patient colonized with Klebsiella pneumoniae carrying blaNDM-1 in Taiwan, who returned from New Delhi where he had been hospitalized for a gun-shot injury.

  3. BlaSTorage: a fast package to parse, manage and store BLAST results.

    Science.gov (United States)

    Orsini, Massimiliano; Carcangiu, Simone

    2013-01-30

    Large-scale sequence studies requiring BLAST-based analysis produce huge amounts of data to be parsed. BLAST parsers are available, but they are often missing some important features, such as keeping all information from the raw BLAST output, allowing direct access to single results, and performing logical operations over them. We implemented BlaSTorage, a Python package that parses multi BLAST results and returns them in a purpose-built object-database format. Unlike other BLAST parsers, BlaSTorage retains and stores all parts of BLAST results, including alignments, without loss of information; a complete API allows access to all the data components. BlaSTorage shows comparable speed of more basic parser written in compiled languages as C++ and can be easily integrated into web applications or software pipelines.

  4. BlaSTorage: a fast package to parse, manage and store BLAST results

    Directory of Open Access Journals (Sweden)

    Orsini Massimiliano

    2013-01-01

    Full Text Available Abstract Background Large-scale sequence studies requiring BLAST-based analysis produce huge amounts of data to be parsed. BLAST parsers are available, but they are often missing some important features, such as keeping all information from the raw BLAST output, allowing direct access to single results, and performing logical operations over them. Findings We implemented BlaSTorage, a Python package that parses multi BLAST results and returns them in a purpose-built object-database format. Unlike other BLAST parsers, BlaSTorage retains and stores all parts of BLAST results, including alignments, without loss of information; a complete API allows access to all the data components. Conclusions BlaSTorage shows comparable speed of more basic parser written in compiled languages as C++ and can be easily integrated into web applications or software pipelines.

  5. Crystal Structure of a Dimerized Cockroach Allergen Bla g 2 Complexed with a Monoclonal Antibody

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mi; Gustchina, Alla; Alexandratos, Jerry; Wlodawer, Alexander; Wünschmann, Sabina; Kepley, Christopher L.; Chapman, Martin D.; Pomes, Anna (INDOOR Bio.); (VCU); (NIH)

    2008-09-03

    The crystal structure of a 1:1 complex between the German cockroach allergen Bla g 2 and the Fab' fragment of a monoclonal antibody 7C11 was solved at 2.8-{angstrom} resolution. Bla g 2 binds to the antibody through four loops that include residues 60-70, 83-86, 98-100, and 129-132. Cation-{pi} interactions exist between Lys-65, Arg-83, and Lys-132 in Bla g 2 and several tyrosines in 7C11. In the complex with Fab', Bla g 2 forms a dimer, which is stabilized by a quasi-four-helix bundle comprised of an {alpha}-helix and a helical turn from each allergen monomer, exhibiting a novel dimerization mode for an aspartic protease. A disulfide bridge between C51a and C113, unique to the aspartic protease family, connects the two helical elements within each Bla g 2 monomer, thus facilitating formation of the bundle. Mutation of these cysteines, as well as the residues Asn-52, Gln-110, and Ile-114, involved in hydrophobic interactions within the bundle, resulted in a protein that did not dimerize. The mutant proteins induced less {beta}-hexosaminidase release from mast cells than the wild-type Bla g 2, suggesting a functional role of dimerization in allergenicity. Because 7C11 shares a binding epitope with IgE, the information gained by analysis of the crystal structure of its complex provided guidance for site-directed mutagenesis of the allergen epitope. We have now identified key residues involved in IgE antibody binding; this information will be useful for the design of vaccines for immunotherapy.

  6. Acinetobacter baumannii transfers the blaNDM-1 gene via outer membrane vesicles.

    Science.gov (United States)

    Chatterjee, Somdatta; Mondal, Ayan; Mitra, Shravani; Basu, Sulagna

    2017-08-01

    To investigate the transmission of the gene encoding New Delhi metallo-β-lactamase-1 ( bla NDM-1 ) through outer membrane vesicles (OMVs) released from an Acinetobacter baumannii strain (A_115). Isolation and purification of OMVs by density gradient from a carbapenem-resistant clinical strain of A. baumannii harbouring plasmid-mediated bla NDM-1 and aac(6')-Ib-cr genes was performed. DNA was purified from the OMVs and used for PCR and dot-blot analysis. Vesicles treated with DNase I and proteinase K were used to transform A. baumannii ATCC 19606 and Escherichia coli JM109 strains. MIC values for the transformants were determined, followed by PCR and restriction digestion of plasmids. PFGE was done for A_115 and transformants of ATCC 19606 and JM109. The A. baumannii strain (ST 1462) released vesicles (25-100 nm) during in vitro growth at late log phase. PCR and dot-blot analysis confirmed the presence of bla NDM-1 and aac(6')-Ib-cr genes in intravesicular DNA. bla NDM-1 and aac(6')-Ib-cr genes were transferred to both the A. baumannii ATCC 19606 and E. coli JM109 recipient cells. The transformation frequency of the purified OMVs was in the range of 10 -5 -10 -6 and gradually reduced with storage of OMVs. The sizes of the plasmids in the transformants and their restriction digestion patterns were identical to the plasmid in A_115. The transformants showed elevated MIC values of the β-lactam group of antibiotics, which confirmed the presence of a bla NDM-1 -harbouring plasmid. This is the first experimental evidence of intra- and inter-species transfer of a plasmid harbouring a bla NDM-1 gene in A. baumannii via OMVs with high transformation frequency. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Occurrence of blaNDM-7within IncX3-type plasmid of Escherichia coli from India.

    Science.gov (United States)

    Paul, Deepjyoti; Bhattacharjee, Amitabha; Ingti, Birson; Choudhury, Nargis Alom; Maurya, Anand Prakash; Dhar, Debadatta; Chakravarty, Atanu

    2017-04-01

    New-Delhi metallo-β-lactamase-7 with higher hydrolytic activity than its ancestor NDM-1 is emerging across the globe including India. In this study, we have investigated the genetic context of bla NDM-7 and alteration in plasmid copy number under concentration gradient carbapenem stress. Six bla NDM-7 producing Escherichia coli isolates were obtained from Silchar Medical College and Hospital and the co-existence of other β-lactamases and transferability of this resistant determinant was determined by transformation and conjugation assay followed by typing of the plasmid by PBRT method. Genetic context and plasmid stability of bla NDM-7 was also determined. The change in copy number of transconjugable plasmid carrying bla NDM-7 under exposure of different carbapenem antibiotics was determined by quantitative Real Time PCR. All the six isolates carrying bla NDM-7 were conjugatively transferable through an IncX3-type plasmid and were also found to co-harbor bla CTX-M-15 . Genetic analysis of bla NDM-7 showed an association of ISAba125, IS5 and a truncated portion of ISAba125 in the upstream region and ble MBL gene in the downstream region of bla NDM-7 . Complete loss of the plasmids carrying bla NDM-7 was observed between 85th to 90th serial passages when antibiotic pressure was withdrawn. After analyzing the relative copy number it was observed that the copy number of the bla NDM-7 encoding plasmid was highly affected by the concentration of ertapenem. The present study has first demonstrated presence of IncX3-type plasmid encoding bla NDM-7 within nosocomial isolates of E. coli. Measures must be taken to prevent or atleast slowdown the emergence of this resistance determinant in this country. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  8. Knowledge and attitude of health-care professionals in hospitals towards pharmacovigilance in Saudi Arabia.

    Science.gov (United States)

    Alshammari, Thamir M; Alamri, Khaled K; Ghawa, Yazeed A; Alohali, Noura F; Abualkol, Shaza A; Aljadhey, Hisham S

    2015-12-01

    Drug safety has major implications for patients' lives. However, this concept is still considered new to some healthcare professionals. This study aims to investigate the knowledge and awareness of Saudi healthcare professionals to pharmacovigilance (PV). Setting Governmental and private hospitals at three main cities in Saudi Arabia (Riyadh, Jeddah, and Dammam). A cross-sectional survey among healthcare professionals (pharmacists, physicians, and nurses) within 12 Saudi hospitals was conducted between November and December 2012. The questionnaire consisted of 18 questions assessing the knowledge, awareness, and attitude of healthcare professionals (HCPs) towards science and the concept of PV. Descriptive statistics were used to analyze the data. The data were analyzed using Statistical Analysis Software (SAS 9.3). Main outcome measure Knowledge, attitude and practice of HCPs toward pharmacovigilance. Three-hundred and thirty-two healthcare professionals completed the survey (response rate 72 %), 110 (34 %) physicians, 106 (33 %) pharmacists, and 104 (32 %) nurses. More than half of the participants (55 %) did not know the correct definition of PV. Two-thirds of the respondents, 207 (65.5 %), had knowledge of the aim of post-marketing surveillance, yet only 113 (36.9 %) were aware that the National Pharmacovigilance and Drug Safety Center is the official body for monitoring adverse drug reaction in Saudi Arabia. In addition, 34.7 % agreed that lack of time could be a major barrier for reporting. The majority of the respondents (78.4 %) believed that reporting was a professional obligation and hospitals should have a drug safety department. There was a limited knowledge of pharmacovigilance that could have affected reporting incidence. Educational intervention and a practical training program need to be applied by the drug regulatory body as well as health authorities to enhance the pharmacovigilance and drug safety culture in Saudi Arabia.

  9. Non-O1/Non-O139 Vibrio cholerae Avian Isolate from France Cocarrying the bla(VIM-1) and bla(VIM-4) Genes.

    Science.gov (United States)

    Aberkane, Salim; Compain, Fabrice; Barraud, Olivier; Ouédraogo, Abdoul-Salam; Bouzinbi, Nicolas; Vittecoq, Marion; Jean-Pierre, Hélène; Decré, Dominique; Godreuil, Sylvain

    2015-10-01

    We describe here a non-O1/non-O139 Vibrio cholerae isolate producing both VIM-1 and VIM-4 carbapenemases. It was isolated from a yellow-legged gull in southern France. The blaVIM genes were part of a class 1 integron structure located in an IncA/C plasmid. This study emphasizes the presence of carbapenemase genes in wildlife microbiota. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Prevalencia de bacterias Gram negativas portadoras del gen blaKPC en hospitales de Colombia

    Directory of Open Access Journals (Sweden)

    Robinson Pacheco

    2014-04-01

    Full Text Available Introducción. Las enzimas carbapenemasas de tipo KPC tienen gran capacidad de diseminación, son causantes de epidemias y se asocian a mayor mortalidad y estancia hospitalaria. En Colombia se han venido reportando cada vez más desde 2007, pero se desconoce la prevalencia hospitalaria. Objetivo. Estimar la prevalencia hospitalaria del gen blaKPC. Materiales y métodos. Se evaluó la presencia del gen blaKPC y su ‘clonalidad’ en aislamientos de enterobacterias y Pseudomonas aeruginosa de pacientes hospitalizados. Resultados. De los 424 aislamientos evaluados durante el periodo de estudio, 273 cumplieron con criterios de elegibilidad, 31,1 % fue positivo para el gen blaKPC y, al ajustar por ‘clonalidad’, la positividad fue de 12,8 %. El gen blaKPC se encontró con mayor frecuencia en Klebsiella pneumoniae seguido de P. aeruginosa y otras enterobacterias. A pesar de que la unidad de cuidados intensivos aportó el mayor número de aislamientos, no se encontró un patrón más prevalente del gen blaKPC en las ellas que en las otras salas. El aparato respiratorio fue el sitio anatómico de origen con la mayor prevalencia. No se presentó estacionalidad en la frecuencia de los aislamientos portadores del gen blaKPC. Conclusión. Este estudio reveló la alta prevalencia del gen blaKPC en diferentes microorganismos aislados en varias instituciones hospitalarias del país. La extraordinaria capacidad de propagación del gen blaKPC, las dificultades del diagnóstico y la limitada disponibilidad de antibióticos plantean la apremiante necesidad de fortalecer los sistemas de vigilancia epidemiológica y ajustar oportunamente las políticas institucionales de uso racional de antibióticos con el fin de contener su diseminación a otras instituciones de salud del país.

  11. Utilizing social media data for pharmacovigilance: A review.

    Science.gov (United States)

    Sarker, Abeed; Ginn, Rachel; Nikfarjam, Azadeh; O'Connor, Karen; Smith, Karen; Jayaraman, Swetha; Upadhaya, Tejaswi; Gonzalez, Graciela

    2015-04-01

    Automatic monitoring of Adverse Drug Reactions (ADRs), defined as adverse patient outcomes caused by medications, is a challenging research problem that is currently receiving significant attention from the medical informatics community. In recent years, user-posted data on social media, primarily due to its sheer volume, has become a useful resource for ADR monitoring. Research using social media data has progressed using various data sources and techniques, making it difficult to compare distinct systems and their performances. In this paper, we perform a methodical review to characterize the different approaches to ADR detection/extraction from social media, and their applicability to pharmacovigilance. In addition, we present a potential systematic pathway to ADR monitoring from social media. We identified studies describing approaches for ADR detection from social media from the Medline, Embase, Scopus and Web of Science databases, and the Google Scholar search engine. Studies that met our inclusion criteria were those that attempted to extract ADR information posted by users on any publicly available social media platform. We categorized the studies according to different characteristics such as primary ADR detection approach, size of corpus, data source(s), availability, and evaluation criteria. Twenty-two studies met our inclusion criteria, with fifteen (68%) published within the last two years. However, publicly available annotated data is still scarce, and we found only six studies that made the annotations used publicly available, making system performance comparisons difficult. In terms of algorithms, supervised classification techniques to detect posts containing ADR mentions, and lexicon-based approaches for extraction of ADR mentions from texts have been the most popular. Our review suggests that interest in the utilization of the vast amounts of available social media data for ADR monitoring is increasing. In terms of sources, both health

  12. Utilizing Social Media Data for Pharmacovigilance: A Review

    Science.gov (United States)

    Sarker, Abeed; Ginn, Rachel; Nikfarjam, Azadeh; O’Connor, Karen; Smith, Karen; Jayaraman, Swetha; Upadhaya, Tejaswi; Gonzalez, Graciela

    2015-01-01

    Objective Automatic monitoring of Adverse Drug Reactions (ADRs), defined as adverse patient outcomes caused by medications, is a challenging research problem that is currently receiving significant attention from the medical informatics community. In recent years, user-posted data on social media, primarily due to its sheer volume, has become a useful resource for ADR monitoring. Research using social media data has progressed using various data sources and techniques, making it difficult to compare distinct systems and their performances. In this paper, we perform a methodical review to characterize the different approaches to ADR detection/extraction from social media, and their applicability to pharmacovigilance. In addition, we present a potential systematic pathway to ADR monitoring from social media. Methods We identified studies, describing approaches for ADR detection from social media from the Medline, Embase, Scopus and Web of Science databases, and the Google Scholar search engine. Studies that met our inclusion criteria were those that attempted to utilize ADR information posted by users on any publicly available social media platform. We categorized the studies into various dimensions such as primary ADR detection approach, size of data, source(s), availability, evaluation criteria, and so on. Results Twenty-two studies met our inclusion criteria, with fifteen (68.2%) published within the last two years. The survey revealed a clear trend towards the usage of annotated data with eleven of the fifteen (73.3%) studies published in the last two years relying on expert annotations. However, publicly available annotated data is still scarce, and we found only six (27.3%) studies that made the annotations used publicly available, making system performance comparisons difficult. In terms of algorithms, supervised classification techniques to detect posts containing ADR mentions, and lexicon-based approaches for extraction of ADR mentions from texts have been

  13. Emergence of carbapenem resistant Escherichia coli isolates producing blaNDM and blaOXA-48-like carried on IncA/C and IncL/M plasmids at two Iranian university hospitals.

    Science.gov (United States)

    Solgi, Hamid; Giske, Christian G; Badmasti, Farzad; Aghamohammad, Shadi; Havaei, Seyed Asghar; Sabeti, Shahram; Mostafavizadeh, Kamyar; Shahcheraghi, Fereshteh

    2017-11-01

    The emergence of carbapenem resistance among Escherichia coli is a serious threat to public health. The objective of this study was to investigate resistance genes and clonality of carbapenem resistant E. coli in Iran. Between February 2015 and July 2016, a total of 32 non-duplicate E. coli isolates that were ertapenem resistant or intermediate (R/I-ETP) were collected from patient clinical or surveillance cultures (rectal swabs) at two university hospitals. Resistance genes were identified by PCR and sequencing. Conjugation experiments, PCR-based replicon typing, PFGE and multilocus sequence typing (MLST) were performed. PCR assays showed, among the 32 isolates, twenty-nine strains produced carbapenemase genes. The predominant carbapenemase was bla OXA-48 (82.8%), followed by bla NDM-1 (31%), bla NDM-7 (6.9%) and bla OXA-181 (3.4%). Seven of the bla NDM positive isolates co-harbored bla OXA-48 carbapenemases. The bla NDM and bla OXA-48 were found in IncA/C and IncL/M conjugative plasmids, respectively. The bla CTX-M-15 , qnrA and intI1 genes were also present in most isolates. The PFGE revealed genetic diversity among the 28 E. coli isolates, which belonged to six minor PFGE clusters and 14 isolates were singletons. The 26 isolates were distributed into 18 STs, of which two were dominant (ST648 and ST167). We identified one bla NDM-1 -positive ST131 E. coli isolates that harbor the bla CTX-M-15 and bla TEM genes. Horizontal transfer of IncA/C and IncL/M plasmids has likely facilitated the spread of the bla OXA-48 and bla NDM genes among E. coli. Their clonal diversity and the presence of faecal carriers in isolates suggest an endemic spread of OXA-48 and NDM. Therefore, it emphasizes the critical importance of monitoring and controlling the spread of carbapenem resistant E. coli. Copyright © 2017. Published by Elsevier B.V.

  14. Effectiveness of Pharmacovigilance Training of General Practitioners A Retrospective Cohort Study in the Netherlands Comparing Two Methods

    NARCIS (Netherlands)

    Gerritsen, Roald; Faddegon, Hans; Dijkers, Fred; van Grootheest, Kees; van Puijenbroek, Eugene

    2011-01-01

    Background: Spontaneous reporting is a cornerstone of pharmacovigilance. Unfamiliarity with the reporting of suspected adverse drug reactions (ADRs) is a major factor leading to not reporting these events. Medical education may promote more effective reporting. Numerous changes have been implemented

  15. Uterine Perforation with the Levonorgestrel-Releasing Intrauterine Device Analysis of Reports from Four National Pharmacovigilance Centres

    NARCIS (Netherlands)

    van Grootheest, Kees; Sachs, Bernhardt; Harrison-Woolrych, Mira; Caduff-Janosa, Pia; van Puijenbroek, Eugene

    2011-01-01

    Background: Levonorgestrel-releasing intrauterine devices (LNG-IUD) are commonly used for contraception and other indications in many countries. National pharmacovigilance centres have been receiving reports from healthcare professionals and patients of uterine perforation associated with the use of

  16. Functional blaKPC-2 sequences are present in United States beef cattle feces regardless of antibiotic use

    Science.gov (United States)

    Recently, using quantitative PCR (qPCR) we detected blaKPC-2 in metagenomic DNA (mgDNA) prepared from the feces of 36 lots beef cattle "raised without antibiotics" (RWA) and 36 lots raised "conventionally" (CONV). Since a small internal fragment of the blaKPC-2 gene was targeted we sought to confirm...

  17. Detection of New Delhi Metallo-Beta-Lactamase (Encoded by blaNDM-1 ) in Enterobacter aerogenes in China.

    Science.gov (United States)

    Shen, Yong; Xiao, Wei-Qiang; Gong, Jiao-Mei; Pan, Jun; Xu, Qing-Xia

    2017-03-01

    The increase in bla NDM -1 in Enterobacteriaceae has become a major concern worldwide. In previous study, we investigated clonal dissemination and mechanisms of resistance to carbapenem in China. We carried out retrospective surveillance for bla NDM -1 among carbapenem-resistant enterobacter strains, which were isolated from patients at our hospital by bacterial strains selection, antimicrobial susceptibility testing, species identification, and molecular detection of resistance gene. We found three bla NDM -1 -positive isolates which were identified as Enterobacter aerogenes in clinical patients in China. The bla NDM -1 -positive Enterobacter aerogenes isolates were first found. It is important to mandate prudent usage of antibiotics and implement infection control measures to control the spread of these resistant bla NDM -1 -positive strains. © 2016 Wiley Periodicals, Inc.

  18. OpenVigil FDA - Inspection of U.S. American Adverse Drug Events Pharmacovigilance Data and Novel Clinical Applications.

    Science.gov (United States)

    Böhm, Ruwen; von Hehn, Leocadie; Herdegen, Thomas; Klein, Hans-Joachim; Bruhn, Oliver; Petri, Holger; Höcker, Jan

    2016-01-01

    Pharmacovigilance contributes to health care. However, direct access to the underlying data for academic institutions and individual physicians or pharmacists is intricate, and easily employable analysis modes for everyday clinical situations are missing. This underlines the need for a tool to bring pharmacovigilance to the clinics. To address these issues, we have developed OpenVigil FDA, a novel web-based pharmacovigilance analysis tool which uses the openFDA online interface of the Food and Drug Administration (FDA) to access U.S. American and international pharmacovigilance data from the Adverse Event Reporting System (AERS). OpenVigil FDA provides disproportionality analyses to (i) identify the drug most likely evoking a new adverse event, (ii) compare two drugs concerning their safety profile, (iii) check arbitrary combinations of two drugs for unknown drug-drug interactions and (iv) enhance the relevance of results by identifying confounding factors and eliminating them using background correction. We present examples for these applications and discuss the promises and limits of pharmacovigilance, openFDA and OpenVigil FDA. OpenVigil FDA is the first public available tool to apply pharmacovigilance findings directly to real-life clinical problems. OpenVigil FDA does not require special licenses or statistical programs.

  19. Prevalence of blaSHV genes in clinical isolates of Klebsiella ...

    African Journals Online (AJOL)

    Owner

    Five bacterial strains (4 Klebsiella pneumoniae and 1 Escherichia coli ) representative of pathogenic species and ... Keys words: β-Lactamases, Klebsiella pneuminiae, blaSHV gene, Saint Camille medical centre, Ouagadougou. INTRODUCTION .... recombinant plasmids from strain 1004 DNA with this approach failed.

  20. DHPG Activation of Group 1 mGluRs in BLA Enhances Fear Conditioning

    Science.gov (United States)

    Rudy, Jerry W.; Matus-Amat, Patricia

    2009-01-01

    Group 1 metabotropic glutamate receptors are known to play an important role in both synaptic plasticity and memory. We show that activating these receptors prior to fear conditioning by infusing the group 1 mGluR agonist, (R.S.)-3,5-dihydroxyphenylglycine (DHPG), into the basolateral region of the amygdala (BLA) of adult Sprague-Dawley rats…

  1. Detecting medication errors in the New Zealand pharmacovigilance database: a retrospective analysis.

    Science.gov (United States)

    Kunac, Desireé L; Tatley, Michael V

    2011-01-01

    Despite the traditional focus being adverse drug reactions (ADRs), pharmacovigilance centres have recently been identified as a potentially rich and important source of medication error data. To identify medication errors in the New Zealand Pharmacovigilance database (Centre for Adverse Reactions Monitoring [CARM]), and to describe the frequency and characteristics of these events. A retrospective analysis of the CARM pharmacovigilance database operated by the New Zealand Pharmacovigilance Centre was undertaken for the year 1 January-31 December 2007. All reports, excluding those relating to vaccines, clinical trials and pharmaceutical company reports, underwent a preventability assessment using predetermined criteria. Those events deemed preventable were subsequently classified to identify the degree of patient harm, type of error, stage of medication use process where the error occurred and origin of the error. A total of 1412 reports met the inclusion criteria and were reviewed, of which 4.3% (61/1412) were deemed preventable. Not all errors resulted in patient harm: 29.5% (18/61) were 'no harm' errors but 65.5% (40/61) of errors were deemed to have been associated with some degree of patient harm (preventable adverse drug events [ADEs]). For 5.0% (3/61) of events, the degree of patient harm was unable to be determined as the patient outcome was unknown. The majority of preventable ADEs (62.5% [25/40]) occurred in adults aged 65 years and older. The medication classes most involved in preventable ADEs were antibacterials for systemic use and anti-inflammatory agents, with gastrointestinal and respiratory system disorders the most common adverse events reported. For both preventable ADEs and 'no harm' events, most errors were incorrect dose and drug therapy monitoring problems consisting of failures in detection of significant drug interactions, past allergies or lack of necessary clinical monitoring. Preventable events were mostly related to the prescribing and

  2. Early detection of pharmacovigilance signals with automated methods based on false discovery rates: a comparative study.

    Science.gov (United States)

    Ahmed, Ismaïl; Thiessard, Frantz; Miremont-Salamé, Ghada; Haramburu, Françoise; Kreft-Jais, Carmen; Bégaud, Bernard; Tubert-Bitter, Pascale

    2012-06-01

    Improving the detection of drug safety signals has led several pharmacovigilance regulatory agencies to incorporate automated quantitative methods into their spontaneous reporting management systems. The three largest worldwide pharmacovigilance databases are routinely screened by the lower bound of the 95% confidence interval of proportional reporting ratio (PRR₀₂.₅), the 2.5% quantile of the Information Component (IC₀₂.₅) or the 5% quantile of the Gamma Poisson Shrinker (GPS₀₅). More recently, Bayesian and non-Bayesian False Discovery Rate (FDR)-based methods were proposed that address the arbitrariness of thresholds and allow for a built-in estimate of the FDR. These methods were also shown through simulation studies to be interesting alternatives to the currently used methods. The objective of this work was twofold. Based on an extensive retrospective study, we compared PRR₀₂.₅, GPS₀₅ and IC₀₂.₅ with two FDR-based methods derived from the Fisher's exact test and the GPS model (GPS(pH0) [posterior probability of the null hypothesis H₀ calculated from the Gamma Poisson Shrinker model]). Secondly, restricting the analysis to GPS(pH0), we aimed to evaluate the added value of using automated signal detection tools compared with 'traditional' methods, i.e. non-automated surveillance operated by pharmacovigilance experts. The analysis was performed sequentially, i.e. every month, and retrospectively on the whole French pharmacovigilance database over the period 1 January 1996-1 July 2002. Evaluation was based on a list of 243 reference signals (RSs) corresponding to investigations launched by the French Pharmacovigilance Technical Committee (PhVTC) during the same period. The comparison of detection methods was made on the basis of the number of RSs detected as well as the time to detection. Results comparing the five automated quantitative methods were in favour of GPS(pH0) in terms of both number of detections of true signals and

  3. Class 1 Integron Containing Metallo-β-Lactamase Gene blaVIM-2 in Pseudomonas aeruginosa Clinical Strains Isolated in Japan

    OpenAIRE

    Yatsuyanagi, Jun; Saito, Shioko; Harata, Seizaburo; Suzuki, Noriyuki; Ito, Yuko; Amano, Ken-ichi; Enomoto, Katsuhiko

    2004-01-01

    Four blaVIM-2 gene-harboring Pseudomonas aeruginosa strains were identified. These strains possessed a class 1 integron harboring ORF1, blaVIM-2, and aacA4 gene cassettes. The transposon-mediated horizontal spread of the blaVIM-2 gene among these strains was suggested, which increases the threat that the blaVIM-2 gene will disseminate among diverse genera of bacteria.

  4. National strategy for the integration of pharmacovigilance in the Moroccan TB Control Program.

    Science.gov (United States)

    Tanani, Driss Soussi; Serragui, Samira; Hammi, Sanae; Moussa, Latifa Ait; Soulaymani, Abdelmajid; Soulaymani, Rachida; Cherrah, Yahia

    2017-01-01

    The objective of this work is to demonstrate the interest of integration of pharmacovigilance in Moroccan Tuberculosis Control Program (MTCP). The integration of pharmacovigilance in MTCP was conducted in October 2012with the Global Fund support. We compared the reports notified before and after this integration (period 1: January 2010-October2012; period 2: October 2012-December 2013). The detection of signals was based on the Information Component available inVigiMine. We used the SPSS version 10.0 and Med Calc version 7.3 for data analysis. The average number of spontaneous reports increased from 3.6 to 37.4 cases/month (Ppharmacovigilance in Moroccan Tuberculosis Control Program improved the management of ADRs and detected new signals of antituberculosis drugs.

  5. The reorganisation of European pharmacovigilance. Part 2. From spontaneous reports to agency reviews and decisions.

    Science.gov (United States)

    2015-02-01

    Despite the fact that adverse effects are vastly under-reported, spontaneous reporting remains the foundation of pharmacovigilance. A small series of properly documented cases, when very specific, can suffice to constitute a signal. In France, reporting adverse effects to Regional Pharmacovigilance Centres (CRPVs) permits high-quality analysis of pharmacovigilance signals, so that they can be brought to the attention of the national agency responsible for making decisions about drugs, the French Health Products Agency (ANSM). The ANSM can use this information to protect patients by implementing the measures within its power or by initiating a European referral. When a decision taken at the national level concerns a drug marketed in several Member States of the European Union, a "harmonisation" procedure results in a decision taken at community level, applicable in all Member States. This means that a safety issue raised by a single Member State sometimes leads to a decision that protects the population of the entire European Union. But it also means that other European decisions can compel national agencies to allow back onto the market a drug that they sought to withdraw in order to protect their citizens. Negotiations with other Member States, the European Medicines Agency (EMA) and the European Commission must be supported by robust data: this is yet another reason for each country to have its own effective national pharmacovigilance database, the contents of which should be publicly accessible. This is unfortunately not yet the case in France in 2014. It also provides another good reason for healthcare professionals and patients to report adverse effects, so that the details can be recorded in national and European databases.

  6. Safety of fibrinogen concentrate: analysis of more than 27 years of pharmacovigilance data.

    Science.gov (United States)

    Solomon, C; Gröner, A; Ye, J; Pendrak, I

    2015-04-01

    Fibrinogen concentrate use as a haemostatic agent has been increasingly explored. This study evaluates spontaneous reports of potential adverse drug reactions (ADRs) that occurred during postmarketing pharmacovigilance of Haemocomplettan P/RiaSTAP, and reviews published safety data. This descriptive study analysed postmarketing safety reports recorded in the CSL Behring pharmacovigilance database from January 1986 to December 2013. A literature review of clinical studies published during the same period was performed. Commercial data indicated that 2,611,294 g of fibrinogen concentrate were distributed over the pharmacovigilance period, corresponding to 652,824 standard doses of 4 g each, across a range of clinical settings and indications. A total of 383 ADRs in 106 cases were reported (approximately 1 per 24,600 g or 6,200 standard doses). Events of special interest included possible hypersensitivity reactions in 20 cases (1 per 130,600 g or 32,600 doses), possible thromboembolic events in 28 cases (1 per 93,300 g or 23,300 doses), and suspected virus transmission in 21 cases (1 per 124,300 g or 31,000 doses). One virus transmission case could not be analysed due to insufficient data; for all other cases, a causal relationship was assessed as unlikely due to negative polymerase chain reaction tests and/or alternative explanations. The published literature revealed a similar safety profile. In conclusion, underreporting of ADRs is a known limitation of pharmacovigilance. However, the present assessment indicates that fibrinogen concentrate is administered across a range of indications, with few ADRs and a low thromboembolic event rate. Overall, fibrinogen concentrate showed a promising safety profile.

  7. The value of patient reporting to the pharmacovigilance system: a systematic review.

    Science.gov (United States)

    Inácio, Pedro; Cavaco, Afonso; Airaksinen, Marja

    2017-02-01

    Current trends in pharmacovigilance systems are veering towards patient involvement in spontaneous reporting of adverse drug reactions (ADRs). The aim of the current systematic review was to identify what is known and what remains unknown with respect to patient reporting to pharmacovigilance systems. A systematic literature search was conducted in PubMed, CINAHL, Journals@Ovid and the Cochrane Library. Studies were included if they contained: (i) reviews about patient reporting; (ii) evaluation of patient reports to national or supranational pharmacovigilance authorities; (iii) a comparison between patient and healthcare professional (HCP) reports submitted to pharmacovigilance authorities; and (iv) surveys of patient experiences, opinions and awareness about reporting ADRs. The methodological quality of the studies was assessed according to principles of Grading of Recommendations, Assessment, Development and Evaluations (GRADE). A total of thirty four studies were included. Five of the studies were reviews (two of which systematic reviews), fourteen retrospective observational studies, nine surveys and six applied mixed research methods. Patient reporting has the advantages of bringing novel information about ADRs. It provides a more detailed description of ADRs, and reports about different drugs and system organ classes when compared with HCP reporting. In addition, patients describe the severity and impact of ADRs on daily life, complementing information derived from HCPs. Patient reporting is relatively rare in most countries. Patient reporting adds new information, and perspective about ADRs in a way otherwise unavailable. This can contribute to better decision-making processes in regulatory activities. The present review identified gaps in knowledge that should be addressed to improve our understanding of the full potential and drawbacks of patient reporting. © 2016 The British Pharmacological Society.

  8. Hydrolysis of clavulanate by Mycobacterium tuberculosis β-lactamase BlaC harboring a canonical SDN motif.

    Science.gov (United States)

    Soroka, Daria; Li de la Sierra-Gallay, Inès; Dubée, Vincent; Triboulet, Sébastien; van Tilbeurgh, Herman; Compain, Fabrice; Ballell, Lluis; Barros, David; Mainardi, Jean-Luc; Hugonnet, Jean-Emmanuel; Arthur, Michel

    2015-09-01

    Combinations of β-lactams with clavulanate are currently being investigated for tuberculosis treatment. Since Mycobacterium tuberculosis produces a broad spectrum β-lactamase, BlaC, the success of this approach could be compromised by the emergence of clavulanate-resistant variants, as observed for inhibitor-resistant TEM variants in enterobacteria. Previous analyses based on site-directed mutagenesis of BlaC have led to the conclusion that this risk was limited. Here, we used a different approach based on determination of the crystal structure of β-lactamase BlaMAb of Mycobacterium abscessus, which efficiently hydrolyzes clavulanate. Comparison of BlaMAb and BlaC allowed for structure-assisted site-directed mutagenesis of BlaC and identification of the G(132)N substitution that was sufficient to switch the interaction of BlaC with clavulanate from irreversible inactivation to efficient hydrolysis. The substitution, which restored the canonical SDN motif (SDG→SDN), allowed for efficient hydrolysis of clavulanate, with a more than 10(4)-fold increase in k cat (0.41 s(-1)), without affecting the hydrolysis of other β-lactams. Mass spectrometry revealed that acylation of BlaC and of its G(132)N variant by clavulanate follows similar paths, involving sequential formation of two acylenzymes. Decarboxylation of the first acylenzyme results in a stable secondary acylenzyme in BlaC, whereas hydrolysis occurs in the G(132)N variant. The SDN/SDG polymorphism defines two mycobacterial lineages comprising rapidly and slowly growing species, respectively. Together, these results suggest that the efficacy of β-lactam-clavulanate combinations may be limited by the emergence of resistance. β-Lactams active without clavulanate, such as faropenem, should be prioritized for the development of new therapies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Mechanisms Involved in Acquisition of blaNDM Genes by IncA/C2 and IncFIIY Plasmids.

    Science.gov (United States)

    Wailan, Alexander M; Sidjabat, Hanna E; Yam, Wan Keat; Alikhan, Nabil-Fareed; Petty, Nicola K; Sartor, Anna L; Williamson, Deborah A; Forde, Brian M; Schembri, Mark A; Beatson, Scott A; Paterson, David L; Walsh, Timothy R; Partridge, Sally R

    2016-07-01

    blaNDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a blaNDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the blaNDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C2 plasmids with almost identical backbones. Different regions carrying blaNDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of blaNDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFIIY backbones, but different regions carrying blaNDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of blaNDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFIIY plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired blaNDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of blaNDM genes among species of the Enterobacteriaceae family. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. Multiplication of blaOXA-23 is common in clinical Acinetobacter baumannii, but does not enhance carbapenem resistance.

    Science.gov (United States)

    Hua, Xiaoting; Shu, Jianfeng; Ruan, Zhi; Yu, Yunsong; Feng, Ye

    2016-12-01

    To investigate the copy number of bla OXA-23 and its correlation with carbapenem resistance in carbapenem-resistant Acinetobacter baumannii (CRAB). A total of 113 bla OXA-23 -positive clinical CRAB isolates were collected from two hospitals in Zhejiang province, China. Their genetic relatedness was determined by MLST. The MIC of imipenem was determined using the agar diffusion method and the copy number of bla OXA-23 was measured using quantitative real-time PCR (qRT-PCR). The complete genomes of five clinical CRAB strains were sequenced using PacBio technology to investigate the multiplication mechanism of bla OXA-23 . Most of the isolates (100/113) belonged to global clone II and the MIC of imipenem ranged from 16 to 96 mg/L. The gene bla OXA-23 resided exclusively in Tn2006 or Tn2009. Approximately 38% of the isolates carried two or more copies of bla OXA-23 . The copy number of bla OXA-23 was not correlated with the MIC of imipenem. Within the five sequenced strains, multiple copies of bla OXA-23 were either tandemly clustered or independently inserted at different genomic sites. Multiplication of bla OXA-23 is common in CRAB, but does not enhance carbapenem resistance. Multiplication can be present in the form of either tandem amplifications or independent insertions at different sites. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. [Cyamemazine (Tercian®): Exploration of extrapyramidal syndrome cases contained in the French pharmacovigilance database].

    Science.gov (United States)

    Khouri, Charles; Lepelley, Marion; Villier, Céline; Bougerol, Thierry; Mallaret, Michel

    2017-06-01

    Cyamemazine (Tercian ® ) is currently the most widely prescribed neuroleptic in France. This widespread use is due to its anxiolytics properties and to a claimed good safety profile. Although, prescription of cyamemazine is not devoid of the risks associated with the use of neuroleptics: extrapyramidal syndromes. This study aims at describing extrapyramidal syndromes induced by cyamemazine registered in the French pharmacovigilance database. All spontaneous reports of extrapyramidal syndromes in the French pharmacovigilance database between 1st January 1985 and 31th December 2015 were described and analyzed. During this period 132 cases following cyamemazine intake were reported in the French pharmacovigilance database. The extrapyramidal syndromes were considered as "serious" in 77% of cases. More than 80% of the cases were described with a dosage of cyamemazine under 100mg/day and no correlation between drug dose and seriousness of the cases were found. Thirty-six cases were described with a monotherapy of cyamemazine. We should keep in mind that despite its widespread use in various indications (e.g. anxiolytic) cyamemazine remains a neuroleptic and could induce extrapyramidal syndromes even with low dosage. Careful monitoring should be performed when introducing and with long-term use of cyamemazine, mostly in elderly patients or patient already being treated with neuroleptics. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  12. [Adverse drug reactions in pediatrics: Experience of a regional pharmacovigilance center].

    Science.gov (United States)

    Saint-Martin, Caroline; Kanagaratnam, Lukshe; de Boissieu, Paul; Azzouz, Brahim; Abou Taam, Malak; Trenque, Thierry

    2016-10-01

    To describe the adverse drug reactions (ADR) and the drugs involved in pediatrics. An observational study on all ADR notifications recorded in the French pharmacovigilance database by the Regional Pharmacovigilance Center of Champagne-Ardenne between 1 January 1985 and 31 December 2014 involving children from 0 to 17 years inclusive was performed. For all notifications, we studied the patient and the ADR characteristics. During the study period, 632 notifications were collected. The most frequently reported ATC (anatomical, therapeutic and chemical) classes were vaccines (15.9%), antineoplastics (12%) and antibiotics (11.1%). Forty-six percent of the notifications were serious. For serious ADRs, the most involved drugs were paracetamol, asparaginase and ibuprofen. Skin reactions were the most often reported ADRs. The most common lowest level terms (LLT) were urticaria (4.9%), hypersensitivity (4.1%), fever (2.9%) and vomiting (2.8%). ADR reporting to the pharmacovigilance system, in particular pediatric ADRs, should be encouraged. Information on the use of medicinal products, especially on self-medication use, need to be improve. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  13. [Pharmacovigilance implementation and operational conditions in the pharmaceutical industry in São Paulo State, Brazil].

    Science.gov (United States)

    Freitas, Márcia Sayuri Takamatsu; Romano-Lieber, Nicolina Silvana

    2007-01-01

    The development of new drugs and limitations of clinical trials have increased the likelihood of adverse drug events. Pharmacovigilance is essential to detect and evaluate adverse drug events, thereby reducing risks and avoiding excessive public health costs. This study focused on the pharmacovigilance programs in the pharmaceutical industry in São Paulo State, Brazil. Data were collected through questionnaires sent electronically to 105 companies, 41.9% of which responded. The main reason for implementing pharmacovigilance programs was to comply with legal requirements, while the main justification for its absence was production limited to herbal remedies, officinal products, and supplements. The article discusses the obstacles to program implementation, resources used, and characteristics of several such programs. (a) standardization is the reason for the increasing number of programs and reports, but more specific guidelines are needed; (b) results depend on multi-sector involvement; (c) customer service centers are an important source of reports; and (d) operation of the service requires only modest human and material resources.

  14. Pharmacovigilance and drug safety 2011 in Calabria (Italy: Adverse events analysis

    Directory of Open Access Journals (Sweden)

    Francesca Scicchitano

    2012-01-01

    Full Text Available Background : Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs. The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. Materials and Methods: We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Results : Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100 in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %. Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%. There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it, and there is a strong interest in participating to training courses in the field (95% are interested. Conclusions : Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

  15. Knowledge and Perception about Pharmacovigilance among Pharmacy Students of Universities in Sana'a Yemen.

    Science.gov (United States)

    Othman, Gamil Qasem; Ibrahim, Mohamed Izham Mohamed; Alshakka, Mohammed; Ansari, Mukhtar; Al-Qadasi, Farouk; Halboup, Abdulsalam M

    2017-06-01

    Pharmacists in community or hospital setting play a key role in reporting Adverse Drug Reaction (ADRs) during practice. Under reporting is considered as a profession malpractice worldwide. To determine the level of knowledge and perception about phramacovigilance and ADRs reporting among final year pharmacy students of Universities in Sana'a Yemen. A cross-sectional study design was conducted among 385 final year pharmacy students. One public and four private universities were selected randomly using a validated self-administered questionnaire. The questionnaire contained data about student demographic data, knowledge and perception about the ADRs. The data was analysed by SPSS program and Chi-square tests were used to assess the significance of association. The male students were more knowledgeable than female (p=0.035), as well as private university students had better ideas on how to report ADRs than public university students (p=0.009). Private university students reported that pharmacovigilance topic is well covered in their curriculum compared to public university students (p≤0.001). A significant difference was seen amongst the students of public and private universities when asked about reporting ADRs in future, former found more confident (p≤0.001). Furthermore, the private university students also had more command on the concept of post-marketing surveillance than public university students (p≤0.001). The private university students in Yemen were more known to causality assessment of ADRs as compared to the students of public universities (p≤0.001). The results of perception revealed regarding perception toward ADRs and pharmacovigilance. Female students (p≤0.018) and private universities students (p≤0.001) had positive perception than male and public university students respectively. The findings showed poor knowledge among students in Sana'a Universities and positive perception towards pharmacovigilance and ADRs reporting. A poor knowledge

  16. Collaboration in pharmacovigilance: lamotrigine and fatal severe cutaneous adverse reactions – a review of spontaneous reports

    Directory of Open Access Journals (Sweden)

    Brickel N

    2017-07-01

    Full Text Available Neil Brickel,1 Haris Shaikh,1 Andrew Kirkham,2 Greg Davies,1 Michelle Chalker,1 Pascal Yoshida3 1Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Uxbridge, Middlesex, UK; 2Classic and Established Products, GlaxoSmithKline, Brentford, Middlesex, UK; 3Clinical Safety and Post-marketing Surveillance, GlaxoSmithKline KK, Tokyo, Japan Abstract: Pharmacovigilance presents many challenges, particularly when managing unpredictable, rare conditions, eg, severe cutaneous adverse reactions (SCARs. Such rare events are often only detected from spontaneous reports, which present their own limitations, particularly during a prolonged global launch schedule. GlaxoSmithKline’s routine pharmacovigilance includes regular reviews of global adverse event (AE reports and aggregate data from a central safety database. Lamotrigine is one of the several antiepileptic drugs associated with SCARs. After identification of increased rates of fatal SCAR cases with lamotrigine in Japan between September and December 2014, this analysis investigated the global incidence of fatal SCARs with lamotrigine and explored whether known risk factors may have contributed to these cases. Global fatal SCAR cases reported with lamotrigine administration from launch until January 2015 were reviewed for evidence of temporal association with dosing and the presence of risk factors, including comorbidities, concomitant medications, and noncompliance with the prescribing information (PI. Worldwide, the estimated cumulative exposure to lamotrigine was >8.4 million patient-years. Globally, there were 54,513 AE reports for lamotrigine, of which 3,454 (6.3% concerned SCARs. Of these, 122 (3.5% had a fatal outcome (attributable and nonattributable to lamotrigine, equating to 0.01 fatal SCARs per 1,000 patient-years. In Japan (estimated cumulative exposure 141,000 patient-years, 17 fatal SCARs were reported (attributable and nonattributable, equating to 0.12 per 1,000 patient

  17. blaCTX-M-2 and blaCTX-M-28 extended-spectrum β-lactamase genes and class 1 integrons in clinical isolates of Klebsiella pneumoniae from Brazil

    Directory of Open Access Journals (Sweden)

    Ana Catarina S Lopes

    2010-03-01

    Full Text Available Twenty-eight Klebsiella pneumoniae clinical isolates that exhibited an extended-spectrum cephalosporin-resistance profile from a city in the Northeast of Brazil were analysed by PCR and DNA sequencing in order to determine the occurrence of blaCTX-M genes and class 1 integrons. We determined the occurrence of the blaCTX-M-2 gene in six K. pneumoniae isolates and describe the first detection of the blaCTX-M-28 gene in South America. Seven isolates carried class 1 integrons. Partial sequencing analysis of the 5'-3'CS variable region in the class 1 integrons of three isolates revealed the presence of aadA1, blaOXA-2 and dfr22 gene cassettes.

  18. Isolation of Enterobacter aerogenes carrying blaTEM-1 and blaKPC-3 genes recovered from a hospital Intensive Care Unit.

    Science.gov (United States)

    Pulcrano, Giovanna; Pignanelli, Salvatore; Vollaro, Adriana; Esposito, Matilde; Iula, Vita Dora; Roscetto, Emanuela; Soriano, Amata Amy; Catania, Maria Rosaria

    2016-06-01

    Enterobacter aerogenes has recently emerged as an important hospital pathogen. In this study, we showed the emergence of E. aerogenes isolates carrying the blaKPC gene in patients colonized by carbapenem-resistant Klebsiella pneumoniae strains. Two multiresistant E. aerogenes isolates were recovered from bronchial aspirates of two patients hospitalized in the Intensive Care Unit at the "Santa Maria della Scaletta" Hospital, Imola. The antimicrobial susceptibility test showed the high resistance to carbapenems and double-disk synergy test confirmed the phenotype of KPC and AmpC production. Other investigation revealed that ESBL and blaKPC genes were carried on the conjugative pKpQIL plasmid. This is a relevant report in Italy that describes a nosocomial infection due to the production of KPC beta-lactamases by an E. aerogenes isolate in patients previously colonized by K. pneumoniae carbapenem-resistant. In conclusion, it's necessary a continuous monitoring of multidrug-resistant strains for the detection of any KPC-producing bacteria that could expand the circulation of carbapenem-resistant pathogens. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  19. blaGES carrying Pseudomonas aeruginosa isolates from a public hospital in Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    Flávia L. P. C. Pellegrino

    Full Text Available Previous analysis of Pseudomonas aeruginosa class-1 integrons from Rio de Janeiro, Brazil, revealed the blaGES gene in one isolate. We screened isolates of two widespread PFGE genotypes, A and B, at a public hospital in Rio, for the presence of blaGES. The gene was detected in all seven P. aeruginosa isolates belonging to genotype B. Three of the seven genotype-B isolates were resistant to amikacin, aztreonam, ceftazidime, cefepime, ciprofloxacin, gentamicin, imipenem, meropenem, piperacillin-tazobactam and ticarcillin-clavulanic acid. The other four isolates were resistant to all these agents, except gentamicin, imipenem, meropenem and piperacillin-tazobactam. A synergistic effect between ceftazidime and imipenem or clavulanic acid suggested the production of GES-type ESBL.

  20. Clonal spread of blaOXA-72-carrying Acinetobacter baumannii sequence type 512 in Taiwan.

    Science.gov (United States)

    Kuo, Han-Yueh; Hsu, Po-Jui; Chen, Jiann-Yuan; Liao, Po-Cheng; Lu, Chia-Wei; Chen, Chang-Hua; Liou, Ming-Li

    2016-07-01

    This is the first report to show an insidious outbreak of armA- and blaOXA-72-carrying Acinetobacter baumannii sequence type 512 (ST512) at a study hospital in northern Taiwan. Multilocus sequence typing revealed that this was a ST512 clone. All of the isolates with ST512 carried a novel 12,056-bp repGR2 in combination with a repGR12-type plasmid. This plasmid, designated pAB-ML, had one copy of the blaOXA-72 gene that was flanked by XerC/XerD-like sites and conferred resistance to carbapenems. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  1. Sources of diversity of carbapenem resistance levels in Klebsiella pneumoniae carrying blaVIM-1.

    Science.gov (United States)

    Loli, A; Tzouvelekis, L S; Tzelepi, E; Carattoli, A; Vatopoulos, A C; Tassios, P T; Miriagou, V

    2006-09-01

    To elucidate the mechanisms responsible for the diversity of beta-lactam resistance phenotypes among isolates of a VIM-1-producing Klebsiella pneumoniae (VPKP) strain that is endemic in Greek hospitals. Five VPKP clinical isolates were studied. MICs of beta-lactams were determined by agar dilution. PFGE of XbaI-digested genomic DNA was used for typing. Profiles of outer membrane proteins (OMPs) were determined by SDS-PAGE. Selected isolates were transformed with a plasmid encoding the Omp36K porin. beta-Lactamase activities were analysed by IEF and imipenem hydrolysis was assessed by spectrophotometry. VIM-1-encoding, self-transmissible plasmids were characterized by replicon typing, RFLP and hybridization with bla(VIM)- and IS26-specific probes. Characterization of integrons was performed by PCR, cloning and sequencing. Isolates exhibited highly similar PFGE patterns. Imipenem MICs were 2, 4, 16, 32 and 64 mg/L. The isolate with the highest imipenem MIC (Vipm-64) lacked a 36 kDa OMP. Expression of a cloned OmpK36 in this isolate reduced the imipenem MIC to susceptibility levels. Imipenem-hydrolysing activity was significantly higher in Vipm-16 as compared with the other isolates that expressed similar amounts of VIM-1. All isolates transferred beta-lactam resistance to Escherichia coli through conjugative, IncN plasmids that exhibited differences in the RFLP and hybridization patterns with bla(VIM)- and IS26-specific probes. The Vipm-16 plasmid, mediating the higher imipenem MICs among transconjugants, carried two copies of bla(VIM-1). Cloning and sequencing showed In-e541-like integrons truncated at the 5'CS by insertion of IS26 elements at two different positions. A VIM-1-producing strain of K. pneumoniae has evolved through OMP alterations and rearrangements in the bla(VIM-1)-carrying plasmid probably mediated by IS26, generating isolates with imipenem MICs ranging from susceptibility to resistance.

  2. Adverse Drug Reaction Reporting Pattern in Turkey: Analysis of the National Database in the Context of the First Pharmacovigilance Legislation.

    Science.gov (United States)

    Ozcan, Gulnihal; Aykac, Emel; Kasap, Yelda; Nemutlu, Nergiz T; Sen, Ebru; Aydinkarahaliloglu, N Demet

    2016-03-01

    In Turkey, pharmacovigilance began in 1985. A fully structured adverse drug reaction (ADR)-reporting system was established with the publication of the first pharmacovigilance regulation in 2005. Subsequent regulation published in 2014 brought further improvements to the system. In this study, we aimed to analyse the ADR-reporting pattern in the context of the first pharmacovigilance legislation in Turkey. We analysed ADR reports submitted to the Turkish Pharmacovigilance Center (TUFAM) from 2005 to 2014 with respect to reporting rate (RR), patient characteristics, type of the ADRs, suspected drugs, source of the report and the profession of the reporter. The annual RR increased gradually over the study period. RRs for females were greater than those for males. RRs were highly correlated with age. Most commonly reported ADRs were skin and subcutaneous tissue disorders. Most commonly suspected drugs were antineoplastic and immunomodulating agents. There was no remarkable change in reporting pattern of ADRs, patient characteristics or classes of suspected drugs over the years. The most common source of reports was spontaneous reporting. Contribution of the reports from studies increased gradually. Most of the reports were reported by physicians. RRs by pharmacists increased substantially over the years. This study showed that the annual RR increased gradually over the 9-year study period. This increase was neither due to an increased reporting of a specific group of ADRs or drugs, nor to an increased reporting in a specific group of patients. There was a general increase in RR in parallel to pharmacovigilance activities.

  3. FarmaREL: An Italian pharmacovigilance project to monitor and evaluate adverse drug reactions in haematologic patients.

    Science.gov (United States)

    Fracchiolla, Nicola S; Artuso, Silvia; Cortelezzi, Agostino; Pelizzari, Anna M; Tozzi, Paola; Bonfichi, Maurizio; Bocchio, Federica; Gargantini, Livio; De Rosa, Elisa; Vighi, Giuseppe D; Prestini, Lucia; Sammassimo, Simona; Frungillo, Niccolò; Pasquini, Maria C; Ragazzi, Alessandra; Boghi, Daniele; Pastore, Alessia; Lanzi, Eraldo; Gritti, Giuseppe; Quaresmini, Giulia; Voltolini, Simone; Gaiardoni, Roberta; Corti, Consuelo; Vilardo, Maria C; La Targia, Maria L; Berini, Giacomo; Magagnoli, Massimo; Bacci, Claudia; Consonni, Dario; Rivolta, Alma L; Muti, Giuliana

    2018-02-01

    Adverse drug reactions (ADRs) reduce patients' quality of life, increase mortality and morbidity, and have a negative economic impact on healthcare systems. Nevertheless, the importance of ADR reporting is often underestimated. The project "FarmaREL" has been developed to monitor and evaluate ADRs in haematological patients and to increase pharmacovigilance culture among haematology specialists. In 13 haematology units, based in Lombardy, Italy, a dedicated specialist with the task of encouraging ADRs reporting and sensitizing healthcare professionals to pharmacovigilance has been assigned. The ADRs occurring in haematological patients were collected electronically and then analysed with multiple logistic regression. Between January 2009 and December 2011, 887 reports were collected. The number of ADRs was higher in older adults (528; 59%), in male (490; 55%), and in non-Hodgkin lymphoma patients (343; 39%). Most reactions were severe (45% required or prolonged hospitalization), but in most cases, they were fully resolved at the time of reporting. According to Schumock and Thornton criteria, a percentage of ADRs as high as 7% was found to be preventable versus 2% according to reporter opinion. Patients' haematological diagnosis, not age or gender, resulted to be the variable that most influenced ADR, in particular severity and outcome. The employment of personnel specifically dedicated to pharmacovigilance is a successful strategy to improve the number and quality of ADR reports. "FarmaREL", the first programme of active pharmacovigilance in oncohaematologic patients, significantly contributed to reach the WHO "Gold Standard" for pharmacovigilance in Lombardy, Italy. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Tn5090-like class 1 integron carrying bla(VIM-2) in a Pseudomonas putida strain from Portugal.

    Science.gov (United States)

    Santos, C; Caetano, T; Ferreira, S; Mendo, S

    2010-10-01

    Three Pseudomonas putida strains containing bla(VIM-2) were isolated from an inanimate surface of a female ward sanitary facility in the Hospital Infante D. Pedro, Aveiro. A novel class 1 integron was found in strain Pp2 (aacA4/bla(VIM-2)/aac6'-IIc disrupted by an insertion sequence IS1382), and strain Pp1 was found to carry a class 1 integron (aacA7/bla(VIM-2)/aacC1/aacA4), which is described for the first time in this species. Strain PF1 carries a class 1 integron associated with a Tn5090-like transposon, constituting the first finding of this type of arrangement in a strain from Portugal. This association highlights further dissemination of bla(VIM-2) in environmental hospital isolates. © 2010 The Authors. Journal Compilation © 2010 European Society of Clinical Microbiology and Infectious Diseases.

  5. Assessment of antibiotic resistance pattern in Acinetobacter bumannii carrying bla oxA type genes isolated from hospitalized patients

    Directory of Open Access Journals (Sweden)

    Hossein Goudarzi

    2013-11-01

    Full Text Available AbstractPlease cite this article as: Goudarzi H, Douraghi M, Ghalavand Z, Goudarzi M. Assessment of antibiotic resistance pattern in Acinetobacter baumannii carrying bla oxA type genes isolated from hospitalized patients. Novel Biomed 2013;1(2:54-61.Introduction: Acinetobacter baumannii is a Gram-negative coccobacillus and one of the most opportunistic pathogens responsible for serious infections in hospitalized patients.Methods: During a 12 month study, 221 clinical isolates and 22 environmental Acinetobacter baumannii isolates were collected. In vitro susceptibility of Acinetobacter baumannii isolates to 13 antimicrobial agents amikacin; cefepime; ceftazidime; ciprofloxacin; meropenem; piperacillin/tazobactam; sulfamethoxazole/ trimethoprim; imipenem; tigecycline; colistin; gentamycin; ceftriaxone; levofloxacin was performed by the disk diffusion method and Minimum Inhibitory Concentration(MICs of imipenem; levofloxacin and cefepime.was done by the E-test according to Clinical and Laboratory Standards Institute (CLSI criteria. blaOXA-23, blaOXA-24, blaOXA-58, blaOXA-51genes were detected by polymerase chain reaction and sequencing.Results: The result of antimicrobial susceptibility test of clinical isolates by the disk diffusion method revealed that that all strains of Acinetobacter baumannii were resistant to piperacillin/tazobactam. The rates of resistance to the majority of antibiotics tested varied between 69% and 100 %, with the exception of tigecycline and colistin. Of 221 isolates tested 99(44.8% were XDR. All strains carry a blaOXA-51-like gene. blaOXA-23gene was the most prevalence among blaOXA-types.Conclusion: colistin and tigecycline can be effective drugs for treatment of Acinetobacter baumannii infections. Continuous Surveillance for Acinetobacter baumannii multidrug-resistant strains is necessary to prevent the further spread of resistant isolates.

  6. Acinetobacter calcoaceticus from a fatal case of pneumonia harboring bla(NDM-1) on a widely distributed plasmid.

    Science.gov (United States)

    Li, Peng; Yang, Chaojie; Xie, Jing; Liu, Nan; Wang, Houzhao; Zhang, Ling; Wang, Xu; Wang, Yong; Qiu, Shaofu; Song, Hongbin

    2015-03-18

    We have recovered one bla(NDM-1)-harboring bacterial strain, designated as XM1570, from a sputum sample obtained from a fatal case of pneumonia in China. Biochemical profiling, 16S rRNA sequencing and antimicrobial susceptibility testing were performed. Conjugation experiments were conducted to determine transmissibility of resistance. Pulsed-field gel electrophoresis and whole genome sequencing were performed to identify strain-specific features. The isolate XM1570 was identified as Acinetobacter calcoaceticus. Whole genome sequencing identified two plasmids, pXM1 and pXM2. Comparative analysis showed >99% similarity between XM1570 and A. calcoaceticus PHEA-2. Plasmid pXM1 carried the carbapenemase gene bla(NDM-1) and displayed high homology with previously described plasmids isolated from different Acinetobacter spp., which were collected from human or livestock distributed in China and worldwide. The bla(NDM-1) gene was located on this conjugative plasmid in a transposon-like region flanked by two copies of the insertion sequence ISAba125; and resistance to all tested β-lactams was observed. Transferability of resistance from pXM1 to the transconjugants was identified. Plasmid pXM2 had an insertion sequence ISAba125 and a -35 region of the bla NDM-1 gene promoter but the bla NDM-1 gene was not present. A chromosomally located carbapenemase-encoding gene bla OXA-75 was detected; however, this gene was interrupted by an insertion sequence ISAba22 belonging to IS3 family. Location of bla(NDM-1) on different self-transmissible plasmids could facilitate geographically broad dissemination and host range expansion of the bla(NDM-1) gene via horizontal gene transfer. Our findings of this normally environmental species A. calcoaceticus XM1570 further underline the significant clinical challenge and the essential need for surveillance including molecular methods and plasmid analyses.

  7. Human β-defensin HBD3 binds to immobilized Bla g2 from the German cockroach (Blattella germanica).

    Science.gov (United States)

    Dietrich, Deborah E; Martin, Aaron D; Brogden, Kim A

    2014-03-01

    Human β-defensin 3 (HBD3) is a small, well-characterized peptide in mucosal secretions with broad antimicrobial activities and diverse innate immune functions. Among these functions is the ability of HBD3 to bind to antigens. In this study, we hypothesize that HBD3 binds to the allergen Bla g2 from the German cockroach (Blattella germanica). The ability of HBD1 (used as a control β-defensin) and HBD3 to bind to Bla g2 and human serum albumin (HSA, used as a control ligand) was assessed using the SensíQ Pioneer surface plasmon resonance (SPR) spectroscopy biosensor system. HBD1 was observed to bind weakly to Bla g2, while HBD3 demonstrated a stronger affinity for the allergen. HBD3 was assessed under two buffer conditions using 0.15 M and 0.3 M NaCl to control the electrostatic attraction of the peptide to the chip surface. The apparent K(D) of HBD3 binding Bla g2 was 5.9±2.1 μM and for binding HSA was 4.2±0.7 μM, respectively. Thus, HBD3, found in mucosal secretions has the ability to bind to allergens like Bla g2 possibly by electrostatic interaction, and may alter the ability of Bla g2 to induce localized allergic and/or inflammatory mucosal responses. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Molecular epidemiology of an outbreak of imipenem-resistant Acinetobacter baumannii carrying the ISAba1-bla(OXA-51-like) genes in a Korean hospital.

    Science.gov (United States)

    Chaulagain, Bidur Prasad; Jang, Sook Jin; Ahn, Gyuu Yeol; Ryu, So Yeon; Kim, Dong Min; Park, Geon; Kim, Won Yong; Shin, Jong Hee; Kook, Joong Ki; Kang, Seong-Ho; Moon, Dae Soo; Park, Young Jin

    2012-01-01

    Between January 2004 and December 2004, an outbreak of imipenem-resistant Acinetobacter baumannii (IRAB) in 2 intensive care units (ICU) of Chosun University Hospital, Korea affected 77 patients. A case-control study revealed that the time spent in the hospital and mechanical ventilation practices were risk factors. IRAB was isolated from the hands of 4% (5/124) of healthcare workers; 27.3% (21/77) of the samples obtained from the ICU environment. A pulsed-field gel electrophoresis analysis showed that 82.1% (23/28) of clinical IRAB isolates and 85.7% (6/7) of environmental IRAB isolates were type A. The ISAba1F/OXA-51-likeR PCR showed that 93.7% (30/32) of IRAB strains had the ISAba1 gene upstream of the bla(OXA-51-like) gene. Two ISAba1F/OXA-51-likeR PCR-negative IRAB strains were bla(IMP-1) positive. All of the IRAB strains tested by PCR were negative for bla(VIM), bla(SIM), bla(GIM-1), bla(SPM-1), bla(GES), bla(OXA-23-like), bla(OXA-24-like), and bla(OXA-58-like) carbapenemase genes. After implementing an infection control strategy, a steady reduction in the attack rate of IRAB infection was observed.

  9. Complémentarité des méthodes numériques et symboliques en pharmacovigilance

    OpenAIRE

    Villerd, Jean; Toussaint, Yannick; Lillo-Le Louet, Agnès

    2010-01-01

    National audience; La pharmacovigilance a pour objet la surveillance du risque d'effet indésirable résultant de l'utilisation des médicaments et produits à usage humain. Elle consiste à détecter des « signaux » correspondant à des corrélations suspectes entre la prise d'un médicament et l'observation d'un effet indésirable. Les professionnels de santé sont tenus de signaler tout effet indésirable inattendu en envoyant un rapport a leur centre régional de pharmacovigilance, alimentant ainsi un...

  10. Delayed identification of Acinetobacter baumannii during an outbreak owing to disrupted blaOXA-51-like by ISAba19.

    Science.gov (United States)

    Ahmadi, Amjad; Salimizand, Himen

    2017-07-01

    Early detection of Acinetobacter baumannii, an emerging pathogen in hospital settings, is of interest. The bla OXA-51-like family had been used as a marker to detect A. baumannii. During an infection outbreak, 14 isolates produced a 1.7-kb PCR band instead of 353 bp for this marker. This work sought the reasons behind the increased marker size. Characterisation of isolates was done by API-20NE, gyrB multiplex PCR and 16S-23S rRNA ITS sequencing. The 1.7-kb band generated and the complete bla OXA-51-like variant were sequenced to find the probable integrated element. Susceptibility testing to various antimicrobials was performed by microdilution. bla OXA-like , metallo-β-lactamases (MBLs), the ISAba1 element and the presence of ISAba1 adjacent to bla OXA-like were sought. rep-PCR, global clonal (GC) lineage determination and multilocus sequence typing (MLST) were performed to analyse the relationship among isolates. Isolates were characterised as Acinetobacter baumannii-calcoaceticus complex by API-20NE. gyrB multiplex PCR and 16S-23S ITS sequencing verified the isolates as A. baumannii. Sequencing of the 1.7-kb band revealed ISAba19 as the disrupting element. The bla OXA-51 variant was bla OXA-66 , which was elongated to 2.2 kb due to ISAba19. The bla OXA-23-like family was found in 67% of isolates. MBL genes were not detected; however, ISAba1-bla OXA-23-like was characterised in carbapenem-resistant isolates (53%; 8/15). Isolates were divided into three clusters by rep-PCR. All strains were ST2 and all but one belonged to GC II. Identification of A. baumannii based only on bla OXA-51-like is not reliable. Besides bla OXA-51-like , multiplex PCR of gyrB and rpoB could provide rapid and cost-effective results. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  11. Was the thrombotic risk of rofecoxib predictable from the French Pharmacovigilance Database before 30 September 2004?

    Science.gov (United States)

    Sommet, A; Grolleau, S; Bagheri, H; Lapeyre-Mestre, M; Montastruc, J L

    2008-08-01

    Rofecoxib was withdrawn from the market on 30 September 2004 following the results of a randomized controlled trial. Following this sudden decision, several controversies occurred in the literature to determine whether this adverse drug reaction (ADR) could have been detected earlier. The aim of this study was to investigate whether this kind of signal could have been seen using the French Pharmacovigilance Database before this date of rofecoxib withdrawal. Using cases registered in the French Pharmacovigilance Database from May 2000 to December 2006, we applied the case-noncase method to "serious" thrombotic ADRs reported with oral formulations of rofecoxib or celecoxib in patients older than 15 years. Cases were all notifications of thrombotic ADRs [World Health Organization Adverse Reaction Terminology (WHO-ART) codes 1300] occurred under coxib (rofecoxib, celecoxib) and noncases all other reports registered in the database (whatever the drug). We calculated a cumulative odds ratio (OR) from 20 May 2000 to 31 December 2006, with a special interest for the period before the 30 September 2004. Among the 50,087 "serious" ADRs registered in the database during this period, 1,127 were thrombotic ones. Rofecoxib exposure was significantly associated with high values of odds ratio (OR) [4.2 (95% CI 1.97-8.61)] for thrombotic ADRs as early as the end of 2001. The values of ADR reporting ORs remained high (3.0-3.5) until 2006. For celecoxib, a significant trend occurred only from September 2004. Despite the compulsory limits of the case/noncase methodology, this study found an association between rofecoxib exposure and the occurrence of "serious" thrombotic ADRs as early as the end of the first year of rofecoxib marketing in France. The association between celecoxib and the occurrence of such ADRs appears less clear. Our work also shows the potential use of careful analysis of pharmacovigilance databases (investigating, for example, cumulative values of risk) in the

  12. Extent of pharmacovigilance among resident doctors in Edo and Lagos states of Nigeria.

    Science.gov (United States)

    Ohaju-Obodo, J O; Iribhogbe, O I

    2010-02-01

    Systematic attention to adverse drug reactions (ADRs) started with the thalidomide disaster in the early 60s of the 20(th) century. In 1968 ten countries supported a spontaneous reporting system for ADR and collaborated with the WHO pilot research project for international drug monitoring. This survey was conducted to determine the level of awareness of resident doctors about ADRs reporting, the extent of their involvement in pharmacovigilance activities and to build a useful data base that will improve the quality of health care in Nigeria. This cross-sectional observational survey was conducted in University of Benin Teaching Hospital (UBTH) and Irrua Specialist Teaching Hospital (ISTH), Lagos University Teaching Hospital (LUTH) and Lagos State University Teaching Hospital (LASUTH) in Edo and Lagos states, Nigeria, respectively. STUDY DESIGN / METHODS: A cross-sectional observational survey was used in this study. Total population under survey being 971 residents with the sample size of 350 statistically determined. The survey conducted revealed that 78.1% (258) of the respondents had inadequate knowledge about pharmacovigilance with 71.2% (235) unaware of the yellow forms for ADR reporting distributed by the National Agency for Food and Drug Administration and Control (NAFDAC). The respondents (92.4%) have observed ADRs in the course of their training and practice, yet only 25.5% of cases were reported. The reported cases (7.3%) were to the National Agency for Food and Drug Administration and Control. The study showed a statistically significant difference between the institution of respondents, knowledge and experience about pharmacovigilance (p Edo and Lagos states. This may be what obtains in other states in Nigeria.

  13. Information technology in pharmacovigilance: Benefits, challenges, and future directions from industry perspectives

    Directory of Open Access Journals (Sweden)

    Zhengwu Lu

    2009-10-01

    Full Text Available Zhengwu LuClinical Research Department, Abbott Vascular, Santa Clara, CA, USAAbstract: Risk assessment during clinical product development needs to be conducted in a thorough and rigorous manner. However, it is impossible to identify all safety concerns during controlled clinical trials. Once a product is marketed, there is generally a large increase in the number of patients exposed, including those with comorbid conditions and those being treated with concomitant medications. Therefore, postmarketing safety data collection and clinical risk assessment based on observational data are critical for evaluating and characterizing a product’s risk profile and for making informed decisions on risk minimization. Information science promises to deliver effective e-clinical or e-health solutions to realize several core benefits: time savings, high quality, cost reductions, and increased efficiencies with safer and more efficacious medicines. The development and use of standard-based pharmacovigilance system with integration connection to electronic medical records, electronic health records, and clinical data management system holds promise as a tool for enabling early drug safety detections, data mining, results interpretation, assisting in safety decision making, and clinical collaborations among clinical partners or different functional groups. The availability of a publicly accessible global safety database updated on a frequent basis would further enhance detection and communication about safety issues. Due to recent high-profile drug safety problems, the pharmaceutical industry is faced with greater regulatory enforcement and increased accountability demands for the protection and welfare of patients. This changing climate requires biopharmaceutical companies to take a more proactive approach in dealing with drug safety and pharmacovigilance.Keywords: information technology, pharmacovigilance, safety, standard, risk management, adverse event

  14. The Patient's Voice in Pharmacovigilance: Pragmatic Approaches to Building a Patient-Centric Drug Safety Organization.

    Science.gov (United States)

    Smith, Meredith Y; Benattia, Isma

    2016-09-01

    Patient-centeredness has become an acknowledged hallmark of not only high-quality health care but also high-quality drug development. Biopharmaceutical companies are actively seeking to be more patient-centric in drug research and development by involving patients in identifying target disease conditions, participating in the design of, and recruitment for, clinical trials, and disseminating study results. Drug safety departments within the biopharmaceutical industry are at a similar inflection point. Rising rates of per capita prescription drug use underscore the importance of having robust pharmacovigilance systems in place to detect and assess adverse drug reactions (ADRs). At the same time, the practice of pharmacovigilance is being transformed by a host of recent regulatory guidances and related initiatives which emphasize the importance of the patient's perspective in drug safety. Collectively, these initiatives impact the full range of activities that fall within the remit of pharmacovigilance, including ADR reporting, signal detection and evaluation, risk management, medication error assessment, benefit-risk assessment and risk communication. Examples include the fact that manufacturing authorization holders are now expected to monitor all digital sources under their control for potential reports of ADRs, and the emergence of new methods for collecting, analysing and reporting patient-generated ADR reports for signal detection and evaluation purposes. A drug safety department's ability to transition successfully into a more patient-centric organization will depend on three defining attributes: (1) a patient-centered culture; (2) deployment of a framework to guide patient engagement activities; and (3) demonstrated proficiency in patient-centered competencies, including patient engagement, risk communication and patient preference assessment. Whether, and to what extent, drug safety departments embrace the new patient-centric imperative, and the methods and

  15. Awareness among tertiary care doctors about Pharmacovigilance Programme of India: Do endocrinologists differ from others?

    Directory of Open Access Journals (Sweden)

    Pramod Kumar Sharma

    2016-01-01

    Full Text Available Background and Objectives: Reporting adverse drug reactions (ADRs associated with drug use is an important factor in patient safety. Majority of ADRs are preventable through improved prescribing and monitoring. Endocrinologists prescribe drugs with actions on almost all organs and for relatively longer durations. ADR are expected following the use of these drugs. Pharmacovigilance is the study of drug-related adverse effects aimed at protecting patients and public from drug-related harms. The concept of pharmacovigilance is relatively new in India, and this survey is an attempt to explore awareness among doctors of an establishing institution of national importance. Materials and Methods: The survey was conducted on faculty and resident doctors by administering a written structured questionnaire in a voluntary manner. The questionnaire contained questions meant to evaluate their awareness, understanding, and misconception about ADR reporting. Identity of the responder was kept confidential. Results: A total of 106 (faculty = 56; residents = 50 participated in survey. The most common cause cited for not reporting an ADR was “do not know how to report” by 64.15%. Majority of them (64% had no information about the Pharmacovigilance Programme of India (PvPI, and only few (8.5% had actually reported or published an ADR. Interpretation and Conclusions: ADRs are major public health problem that needs to be addressed at all levels of health care. High index of clinical suspicion are crucial for their timely detection and management. Various educational interventions have shown to improve medical professionals' awareness, understanding about ADRs and in their reporting behavior. PvPI is an important initiative toward ensuring patient safety.

  16. Targeted Spontaneous Reporting: Assessing Opportunities to Conduct Routine Pharmacovigilance for Antiretroviral Treatment on an International Scale.

    Science.gov (United States)

    Rachlis, Beth; Karwa, Rakhi; Chema, Celia; Pastakia, Sonak; Olsson, Sten; Wools-Kaloustian, Kara; Jakait, Beatrice; Maina, Mercy; Yotebieng, Marcel; Kumarasamy, Nagalingeswaran; Freeman, Aimee; de Rekeneire, Nathalie; Duda, Stephany N; Davies, Mary-Ann; Braitstein, Paula

    2016-10-01

    Targeted spontaneous reporting (TSR) is a pharmacovigilance method that can enhance reporting of adverse drug reactions related to antiretroviral therapy (ART). Minimal data exist on the needs or capacity of facilities to conduct TSR. Using data from the International epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium, the present study had two objectives: (1) to develop a list of facility characteristics that could constitute key assets in the conduct of TSR; (2) to use this list as a starting point to describe the existing capacity of IeDEA-participating facilities to conduct pharmacovigilance through TSR. We generated our facility characteristics list using an iterative approach, through a review of relevant World Health Organization (WHO) and Uppsala Monitoring Centre documents focused on pharmacovigilance activities related to HIV and ART and consultation with expert stakeholders. IeDEA facility data were drawn from a 2009/2010 IeDEA site assessment that included reported characteristics of adult and pediatric HIV care programs, including outreach, staffing, laboratory capacity, adverse event monitoring, and non-HIV care. A total of 137 facilities were included: East Africa (43); Asia-Pacific (28); West Africa (21); Southern Africa (19); Central Africa (12); Caribbean, Central, and South America (7); and North America (7). Key facility characteristics were grouped as follows: outcome ascertainment and follow-up; laboratory monitoring; documentation-sources and management of data; and human resources. Facility characteristics ranged by facility and region. The majority of facilities reported that patients were assigned a unique identification number (n = 114; 83.2 %) and most sites recorded adverse drug reactions (n = 101; 73.7 %), while 82 facilities (59.9 %) reported having an electronic database on site. We found minimal information is available about facility characteristics that may contribute to pharmacovigilance activities. Our findings

  17. Pharmacovigilance: What to do if you see an adverse reaction and the consequences

    Energy Technology Data Exchange (ETDEWEB)

    Stenver, Doris I. [Danish Medicines Agency, 1 Axel Heides Gade, DK-2300 Copenhagen S (Denmark)], E-mail: dis@dkma.dk

    2008-05-15

    With outset in a recently identified safety signal - the association between gadolinium and nephrogenic systemic fibrosis - the article highlights the aim of pharmacovigilance and provides an overview of the European regulatory drug safety network. The main objective of the article is to provide appropriate information concerning the regulatory environment to health care professionals working in a clinical setting. The important role played by health care professionals in drug safety surveillance, as well as examples of how the regulatory decision making is functioning in practice, are described and exemplified by means of the gadolinium case.

  18. The Internet and drug safety: what are the implications for pharmacovigilance?

    Science.gov (United States)

    Cobert, B; Silvey, J

    1999-02-01

    Use of the Internet is becoming widespread throughout the world. Its use in the domain of drug safety and pharmacovigilance is spreading rapidly. Governments and industry have taken the lead in developing extensive web sites. The US Food and Drug Administration (FDA), the European Agency for the Evaluation of Medicinal Products (EMEA) and other agencies have developed sites containing enormous amounts of information both on pharmacovigilance in general and on specific drugs in particular. Under the US 'Freedom of Information Act' the FDA has put major parts of its adverse event database on line. Regulatory documents are also available from the FDA site or from hyperlinks described in the site. The US Center for Drug Evaluation and Research updates its site most days and maintains a free automated e-mail announcement service of these updates. Similarly, the EMEA updates its site frequently and publishes extensive material including regulatory documents, guidelines, European Public Assessment Reports on newly approved medications and other useful information. A free update service by e-mail is also available. Although English is the primary language used on the EMEA site, some of the information is available in other languages. Pharmaceutical companies are not using the Internet for pharmacovigilance yet. Rather, the Internet is being used for promotion of their products and for informing consumers on general information on diseases, for financial and investor data and for employment opportunities, etc. Other organisations such as lobbies, consumer groups and medical journals are also beginning to use the Internet. The electronic transmission of safety information, using the standards developed by the International Conference on Harmonization, is currently being tested for the transmission of individual patient adverse event information between companies and governments. In addition, the FDA has begun to accept adverse events from healthcare providers and consumers

  19. Characterization of blaCTX-M IncFII plasmids and clones of Escherichia coli from pets in France.

    Science.gov (United States)

    Dahmen, Safia; Haenni, Marisa; Châtre, Pierre; Madec, Jean-Yves

    2013-12-01

    To characterize bla(CTX-M) IncFII plasmids and clones of Escherichia coli from cats and dogs and to compare them with bla(CTX-M) IncFII plasmids reported in humans. From December 2006 to April 2010, 518 E. coli isolates from clinical infections in cats and dogs were screened for extended-spectrum β-lactamase (ESBL) production. Antimicrobial susceptibility was performed by disc diffusion and resistance genes were identified by PCR and sequencing. Plasmids were characterized using PCR-based replicon typing and sub-typing schemes, restriction fragment length polymorphism analysis, S1-PFGE and Southern hybridization. Isolates were characterized by PFGE, phylogenetic grouping, O25b typing and multilocus sequence typing. Nineteen E. coli isolates (3.7%) produced ESBLs, of which 14 (74%) carried bla(CTX-M) IncFII plasmids. The bla(CTX-M) gene was predominant and located on F31:A4:B1, F36:A4:B1 or F36:A1:B20 plasmids, abundantly reported in humans. The bla(CTX-M) F22:A1:B20 or F2:A2:B20 plasmids were also found. Different sequence types (STs) were identified, such as ST10, ST410, ST359, ST617 and ST224. Only one E. coli isolate belonged to the ST131 E. coli clone and carried a bla(CTX-M) F2:A2:B20 plasmid. This is the first known extensive study on ESBL-producing E. coli isolates from pets in France. The ST131 clone was rare. However, the predominance of human-like bla(CTX-M) IncFII plasmids suggests exchanges of these plasmids with the human reservoir.

  20. Chromosomal Integration of the Klebsiella pneumoniae Carbapenemase Gene,blaKPC, in Klebsiella Species Is Elusive but Not Rare.

    Science.gov (United States)

    Mathers, Amy J; Stoesser, Nicole; Chai, Weidong; Carroll, Joanne; Barry, Katie; Cherunvanky, Anita; Sebra, Robert; Kasarskis, Andrew; Peto, Tim E; Walker, A Sarah; Sifri, Costi D; Crook, Derrick W; Sheppard, Anna E

    2017-03-01

    Carbapenemase genes in Enterobacteriaceae are mostly described as being plasmid associated. However, the genetic context of carbapenemase genes is not always confirmed in epidemiological surveys, and the frequency of their chromosomal integration therefore is unknown. A previously sequenced collection of bla KPC -positive Enterobacteriaceae from a single U.S. institution (2007 to 2012; n = 281 isolates from 182 patients) was analyzed to identify chromosomal insertions of Tn 4401 , the transposon most frequently harboring bla KPC Using a combination of short- and long-read sequencing, we confirmed five independent chromosomal integration events from 6/182 (3%) patients, corresponding to 15/281 (5%) isolates. Three patients had isolates identified by perirectal screening, and three had infections which were all successfully treated. When a single copy of bla KPC was in the chromosome, one or both of the phenotypic carbapenemase tests were negative. All chromosomally integrated bla KPC genes were from Klebsiella spp., predominantly K. pneumoniae clonal group 258 (CG258), even though these represented only a small proportion of the isolates. Integration occurred via IS 15 -ΔI-mediated transposition of a larger, composite region encompassing Tn 4401 at one locus of chromosomal integration, seen in the same strain ( K. pneumoniae ST340) in two patients. In summary, we identified five independent chromosomal integrations of bla KPC in a large outbreak, demonstrating that this is not a rare event. bla KPC was more frequently integrated into the chromosome of epidemic CG258 K. pneumoniae lineages (ST11, ST258, and ST340) and was more difficult to detect by routine phenotypic methods in this context. The presence of chromosomally integrated bla KPC within successful, globally disseminated K. pneumoniae strains therefore is likely underestimated. Copyright © 2017 Mathers et al.

  1. First report on blaNDM-1-producing Acinetobacter baumannii in three clinical isolates from Ethiopia.

    Science.gov (United States)

    Pritsch, Michael; Zeynudin, Ahmed; Messerer, Maxim; Baumer, Simon; Liegl, Gabriele; Schubert, Soeren; Löscher, Thomas; Hoelscher, Michael; Belachew, Tefara; Rachow, Andrea; Wieser, Andreas

    2017-03-01

    Multidrug-resistant Gram-negative bacterial infections are recognized as one of the major threats to global health. In this study, we describe for the first time bla NDM-1 gene carrying organisms from Ethiopia consisting of three Acinetobacter baumannii isolates from patients in Jimma. Besides phenotypic antimicrobial susceptibility testing, molecular strain typing and sequencing was performed to describe the phylogenetic relation of the Ethiopian isolates in detail in relation to published isolates from all over the globe. Three multi-resistant, bla NDM-1 -positive Acinetobacter baumannii isolates, most likely a local clonal diffusion, were isolated. Two of the three isolates described within this study were untreatable with the locally available antimicrobials and were only susceptible to polymyxin B and amikacin. The genome sequences confirmed the isolates to be distinct from the outbreak strains reported from Kenya, the only other characterized bla NDM-1 positive Acinetobacter baumannii strains in East Africa so far. Up to date, no other bacterial species were found to harbour the gene cassette in Jimma and conjugation to E. coli was not successful under laboratory conditions. However, natural transmission to other bacteria seems likely, given the evident lack of hygienic precautions due to limited resource settings. The detected isolates could solely be the tip of the iceberg regarding the presence of NDM-1 producing organisms in the region, as only a limited number of bacterial isolates were evaluated so far and until recently, susceptibility testing and isolation of bacteria could hardly be performed in clinical patient care. These multi-drug resistant organisms pose a serious threat to antimicrobial treatments in Jimma, Ethiopia.

  2. Susceptibility Pattern and Distribution of Oxacillinases and blaPER-1 Genes among Multidrug Resistant Acinetobacter baumannii in a Teaching Hospital in Iran

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    Sareh Bagheri Josheghani

    2015-01-01

    Full Text Available Acinetobacter baumannii (A. baumannii is an important nosocomial pathogen in healthcare institutions. β-Lactamase-mediated resistance is the most common mechanism for carbapenem resistance in A. baumannii. The aim of this study was to determine the antibiotic resistance pattern, to detect OXA encoding genes, class A, blaPER-1, and to detect the presence of ISAba1. A total of 124 A. baumannii isolates were collected from hospitalized patients in a teaching hospital in Kashan, Iran. The susceptibility of isolates to different antibiotics was determined by disk-diffusion method. PCR was used to detect blaPER-1, blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, and ISAba1 genes. All isolates were resistant to ceftazidime, ceftriaxone, and cefotaxime. All of the isolates revealed susceptibility to polymyxin B and colistin. Ninety-six percent of the isolates were extensive drug resistance (XDR, 5.6% extended spectrum beta-lactamase (ESBL, and 54.8% metallo-beta-lactamase (MBL. All isolates were positive for blaOXA-51 and ISAba1. blaOXA-23,  blaOXA-24, and blaOXA-58 were found in 79.8%, 25%, and 3.2%, respectively. The frequency rate of blaPER-1 gene was 52.4%. Multidrug resistant A. baumannii isolates are increasing in our setting and extensively limit therapeutic options. The high rate presence of class D carbapenemase-encoding genes, mainly blaOXA-23 carbapenemases, is worrying and alarming as an emerging threat in our hospital.

  3. The complex genetic context of blaPER-1 flanked by miniature inverted-repeat transposable elements in Acinetobacter johnsonii.

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    Zhiyong Zong

    Full Text Available On a large plasmid of Acinetobacter johnsonii strain XBB1 from hospital sewage, blaPER-1 and ISCR1 were found in a complex Tn402-like integron carrying an arr3-aacA4 cassette array. The integron was truncated by the same 439-bp miniature inverted-repeat transposable element (MITE at both ends. blaPER-1 and its complex surroundings might have been mobilized by the MITEst into an orf of unknown function, evidenced by the presence of the characteristic 5-bp direct target repeats. The same 439-bp MITEs have also been found flanking class 1 integrons carrying metallo-β-lactamases genes bla IMP-1, bla IMP-5 and bla VIM-2 before but without ISCR1. Although the cassette arrays are different, integrons have always been truncated by the 439-bp MITEs at the exact same locations. The results suggested that MITEs might be able to mobilize class 1 integrons via transposition or homologous recombination and therefore represent a possible common mechanism for mobilizing antimicrobial resistance determinants.

  4. IncFII Conjugative Plasmid-Mediated Transmission of blaNDM-1 Elements among Animal-Borne Escherichia coli Strains.

    Science.gov (United States)

    Lin, Dachuan; Xie, Miaomiao; Li, Ruichao; Chen, Kaichao; Chan, Edward Wai-Chi; Chen, Sheng

    2017-01-01

    This study aims to investigate the prevalence and transmission dynamics of the bla NDM-1 gene in animal Escherichia coli strains. Two IncFII bla NDM-1 -encoding plasmids with only minor structural variation in the MDR region, pHNEC46-NDM and pHNEC55-NDM, were found to be responsible for the transmission of bla NDM-1 in these strains. The bla NDM-1 gene can be incorporated into plasmids and stably inherited in animal-borne E. coli strains that can be maintained in animal gut microflora even without carbapenem selection pressure. Copyright © 2016 American Society for Microbiology.

  5. Characterization of a novel plasmid type and various genetic contexts of bla OXA-58 in Acinetobacter spp. from multiple cities in China.

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    Yiqi Fu

    Full Text Available BACKGROUND/OBJECTIVE: Several studies have described the epidemiological distribution of blaOXA-58-harboring Acinetobacter baumannii in China. However, there is limited data concerning the replicon types of blaOXA-58-carrying plasmids and the genetic context surrounding blaOXA-58 in Acinetobacter spp. in China. METHODOLOGY/PRINCIPAL FINDINGS: Twelve non-duplicated blaOXA-58-harboring Acinetobacter spp. isolates were collected from six hospitals in five different cities between 2005 and 2010. The molecular epidemiology of the isolates was carried out using PFGE and multilocus sequence typing. Carbapenemase-encoding genes and plasmid replicase genes were identified by PCR. The genetic location of blaOXA-58 was analyzed using S1-nuclease method. Plasmid conjugation and electrotransformation were performed to evaluate the transferability of blaOXA-58-harboring plasmids. The genetic structure surrounding blaOXA-58 was determined by cloning experiments. The twelve isolates included two Acinetobacter pittii isolates (belong to one pulsotype, three Acinetobacter nosocomialis isolates (belong to two pulsotypes and seven Acinetobacter baumannii isolates (belong to two pulsotypes/sequence types. A. baumannii ST91 was found to be a potential multidrug resistant risk clone carrying both blaOXA-58 and blaOXA-23. blaOXA-58 located on plasmids varied from ca. 52 kb to ca. 143 kb. All plasmids can be electrotransformed to A. baumannii recipient, but were untypeable by the current replicon typing scheme. A novel plasmid replicase named repAci10 was identified in blaOXA-58-harboring plasmids of two A. pittii isolates, three A. nosocomialis isolates and two A. baumannii isolates. Four kinds of genetic contexts of blaOXA-58 were identified. The transformants of plasmids with structure of IS6 family insertion sequence (ISOur1, IS1008 or IS15-ΔISAba3-like element-blaOXA-58 displayed carbapenem nonsusceptible, while others with structure of intact ISAba3-like element-bla

  6. Bisphosphonate-related osteonecrosis of the jaw: data from the French national pharmacovigilance database.

    Science.gov (United States)

    de Boissieu, Paul; Gaboriau, Louise; Morel, Aurore; Trenque, Thierry

    2016-10-01

    The aim of this study was to describe bisphosphonate-related osteonecrosis of the jaw (BRONJ) in the French national pharmacovigilance database. BRONJ was identified with the standardized MedDRA query (SMQ) 'osteonecrosis' among all data from 1985 to 31 December 2014. Because this SMQ was not specific to the jaw localization, selection of cases based on anatomy was performed after data extraction. For each case, demographic and medical information was analysed, as well as data about notification (year of notification, year of occurrence, outcome, seriousness). Known associated factors for BRONJ were also documented: dentoalveolar surgery, glucocorticoids, chemotherapy, anti-angiogenics, denosumab. Among 1404 SMQ notifications, 663 were located in the jaws and 629 were associated with bisphosphonate use. BRONJ reported in the database mainly affected women (n = 443, 71%) with an oncological indication (n = 440, 70%). BRONJ was considered as serious in 91%. Outcome was unfavourable for 92% of cases. Associated factors were identified for 70% of the patients. A peak of notification was noted in 2014 (13% of all cases), but on analysis by year of occurrence instead of by year of notification, this peak disappeared. SMQ 'osteonecrosis' appears to be an adequate tool to analyse BRONJ in a pharmacovigilance database. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  7. Systematic review of paediatric studies of adverse drug reactions from pharmacovigilance databases.

    Science.gov (United States)

    Cliff-Eribo, Kennedy Obebi; Sammons, Helen; Choonara, Imti

    2016-10-01

    To perform a systematic review of studies describing paediatric adverse drug reactions (ADRs) conducted from national pharmacovigilance databases. A systematic literature search of studies describing results for paediatric ADRs from national pharmacovigilance databases was performed. PubMed database, Embase and MEDLINE were searched up to March 2015. The descriptive studies included were analysed for country of origin, reporters, and ADR reporting rate, drugs, ADRs and number of fatalities. 20 studies were identified. Doctors were the largest group of reporters in all the studies, and with more consumer reports seen in USA. The studies ranged from 3 - 37 years. The highest ADR reporting rate was 1458 reports per year per million children in Cuba. Antibiotics and vaccines were the most frequently reported drugs, in almost all the studies. The most frequent ADRs were skin and nervous system disorders. The highest proportion of fatalities and serious reports was from North America. Drugs used for treating attention deficit hyperactivity disorders (ADHD) and isotretinoin were the most frequently reported drugs for ADRs in North America. There were geographical differences in drugs responsible for ADRs and their seriousness, especially in North America. Very few studies were conducted in Asia and Latin America, none were found from Africa.

  8. Drugs and dilated cardiomyopathies: a case/noncase study in the French PharmacoVigilance Database

    Science.gov (United States)

    Montastruc, Guillaume; Favreliere, Sylvie; Sommet, Agnès; Pathak, Atul; Lapeyre-Mestre, Maryse; Perault-Pochat, Marie-Christine; Montastruc, Jean-Louis

    2010-01-01

    AIMS To evaluate putative associations between drugs and dilated cardiomyopathy. METHODS We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were all the observations with dilated cardiomyopathy registered into the FPVD between 1 January 1990 and 30 June 2007. Noncases were all other reports other than those studied. Anthracyclines were used as positive controls. Data were expressed as reporting odds ratio (ROR) with their 95% confidence intervals. RESULTS Out of the 258 729 adverse drug reaction (ADR) reports recorded in the FPVD between 1 January 1990 and 30 June 2007, 47 (22 men, mean age 49 years) were defined as dilated cardiomyopathy. In these 47 patients, 67 drugs were ‘suspect’. A significant ROR was found with cytotoxic (epirubicin, mitoxantrone, cyclophosphamide, gemcitabine, fluorouracil) and antiretroviral (lamividune, zidovudine, abacavir) but also with isotretinoin, prednisone, appetite suppressant (clobenzorex) and psychotropic [antipsychotic (clozapine, olanzapine), lithium, antidepressant (clomipramine, amitriptyline, fluvoxamine)] drugs. CONCLUSIONS The present study describes an association between some drugs and reports of dilated cardiomyopathies. This relationship involves not only some already suspected drugs (anthracyclines, antiretrovirals), but also other drugs (antipsychotics, lithium, antidepressants, retinoids) less known to induce such an ADR. Despite the mandatory limits of this kind of study (underreporting, confounding factors …), these data represent a pharmacovigilance signal and could contribute to establish further prospective studies in order to confirm such signals. PMID:20233200

  9. Causality assessment in pharmacovigilance: The French method and its successive updates.

    Science.gov (United States)

    Miremont-Salamé, Ghada; Théophile, Hélène; Haramburu, Françoise; Bégaud, Bernard

    2016-04-01

    The methods for causality assessment of adverse drug reactions were developed in the 1970s and 1980s, alongside the development of pharmacovigilance. The French method is one of the earlier of these, following on from the pioneering works by Irey and Karch and Lasagna. Initially published in 1978, it was updated in 1985, and again in 2011. The main alterations to the original method are presented in tables annexed to this paper. The successive versions improved the presentation, provided more formalised definitions of the criteria for assessing causality, while at the same time ensuring the method remained easy to use. Causality assessment enables the causal link between a drug and the occurrence of an adverse reaction to be formalised and explained. It contributes to diagnosis, and to determining the action to be taken in case of an adverse drug reaction. It can contribute to the quality and the relevance of the data stored in pharmacovigilance databases. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  10. Therapeutic drug monitoring as a measure of proactive pharmacovigilance in child and adolescent psychiatry.

    Science.gov (United States)

    Gerlach, Manfred; Egberts, Karin; Dang, Su-Yin; Plener, Paul; Taurines, Regina; Mehler-Wex, Claudia; Romanos, Marcel

    2016-11-01

    Off-label or unlicensed use of psychotropic drugs is common rather than the exception in child and adolescent psychiatry. This use exposes patients to an unknown additional risk of ineffective or even harmful treatment. In addition, treatment with psychotropic drugs during a period of life when the patient undergoes marked developmental hormonal and neurobiological changes often requires different dosing regimes in later life and may result in adverse drug reactions, which are either not seen in adults at all or not in the same frequency. Areas covered: Given these critical safety issues, efficient pharmacovigilance methods as part of routine practice are essential for the improvement of patient care. The purpose of this article is to introduce methods to increase the safety of psychotropic drug use in youngsters. In particular, therapeutic drug monitoring (TDM) as a routine measure of proactive pharmacovigilance is discussed. Expert opinion: Given the special features of psychopharmacological therapy in children and adolescents in day-to-day clinical practise, proactive surveillance by using a close standardized 'patient monitoring' and long-term follow-up with TDM is very important. This approach could minimize the risk of exposing paediatric patients to ineffective treatments of uncertain or unknown risks.

  11. Unexpected drug-induced Raynaud phenomenon: Analysis from the French national pharmacovigilance database.

    Science.gov (United States)

    Bouquet, Émilie; Urbanski, Geoffrey; Lavigne, Christian; Lainé-Cessac, Pascale

    2017-10-01

    To estimate the association between exposure to medicinal products and Raynaud phenomenon. The study used the data of all adverse drug reactions notified to the French national pharmacovigilance database. All cases reported between 1st January 1995 and 10th December 2012 were selected. A case/non-case method was used to measure disproportionality of the association between drug exposure and Raynaud phenomenon. The cases concerned all observations involving Raynaud phenomenon. Non-cases comprised all other reports of adverse drug reactions over the same period. Among the 307,128 adverse drug reaction reports selected from the French national pharmacovigilance database, 175 involved Raynaud phenomenon, most of them affecting women (61.1%). The mean age was 50.1 years, and 8% had a past medical history of Raynaud phenomenon. According to the summaries of product characteristics, 42.3% of these cases were exposed to drugs known to induce Raynaud phenomenon. Unexpected Raynaud phenomenons (unlisted in the summaries of product characteristics) were associated with exposure to drugs for which Raynaud phenomenons are published (interferons, ribavirin, gemcitabine) or for which Raynaud phenomenons are not published (hepatitis B vaccine, isotretinoin, leflunomide, hydroxycarbamide, rofecoxib, telmisartan, zolmitriptan). The case/non-case method is usually used to generate signals. Further epidemiological studies are now necessary to confirm these findings. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  12. Statistical and graphical approaches for disproportionality analysis of spontaneously-reported adverse events in pharmacovigilance.

    Science.gov (United States)

    Zink, Richard C; Huang, Qin; Zhang, Lu-Yong; Bao, Wen-Jun

    2013-05-01

    Combine disproportionality analysis with dynamically interactive graphics to understand spontaneously-reported adverse events in pharmacovigilance. Four statistical methods, including Reporting Odds Ratio, Proportional Reporting Ratio, Multi-Item Gamma Poisson Shrinker and Bayesian Confidence Propagation Neural Network that are used for computing disproportionality are described. Tree maps and other graphical techniques are used to display the disproportionality results. Spontaneously-reported adverse events in pharmacovigilance are collected from physicians, patients, or the medical literature by regulatory agencies, pharmaceutical companies and device manufacturers to monitor the safety of a product once it reaches the market. In order to identify potential safety-signals, disproportionality analysis methods compare the rate at which a particular event of interest co-occurs with a given drug with the rate this event occurs without the drug in the event database. Tree maps are employed to interactively display the adverse events for particular drugs and compare the adverse events among the drugs. Interactive graphical displays of disproportionality allow the analyst to quickly identify safety signals and perform additional follow-up analyses. Combining statistical methods with dynamically interactive graphics affords insights into the data inaccessible by traditional analysis methods. Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  13. Harnessing scientific literature reports for pharmacovigilance. Prototype software analytical tool development and usability testing.

    Science.gov (United States)

    Sorbello, Alfred; Ripple, Anna; Tonning, Joseph; Munoz, Monica; Hasan, Rashedul; Ly, Thomas; Francis, Henry; Bodenreider, Olivier

    2017-03-22

    We seek to develop a prototype software analytical tool to augment FDA regulatory reviewers' capacity to harness scientific literature reports in PubMed/MEDLINE for pharmacovigilance and adverse drug event (ADE) safety signal detection. We also aim to gather feedback through usability testing to assess design, performance, and user satisfaction with the tool. A prototype, open source, web-based, software analytical tool generated statistical disproportionality data mining signal scores and dynamic visual analytics for ADE safety signal detection and management. We leveraged Medical Subject Heading (MeSH) indexing terms assigned to published citations in PubMed/MEDLINE to generate candidate drug-adverse event pairs for quantitative data mining. Six FDA regulatory reviewers participated in usability testing by employing the tool as part of their ongoing real-life pharmacovigilance activities to provide subjective feedback on its practical impact, added value, and fitness for use. All usability test participants cited the tool's ease of learning, ease of use, and generation of quantitative ADE safety signals, some of which corresponded to known established adverse drug reactions. Potential concerns included the comparability of the tool's automated literature search relative to a manual 'all fields' PubMed search, missing drugs and adverse event terms, interpretation of signal scores, and integration with existing computer-based analytical tools. Usability testing demonstrated that this novel tool can automate the detection of ADE safety signals from published literature reports. Various mitigation strategies are described to foster improvements in design, productivity, and end user satisfaction.

  14. Drugs and dilated cardiomyopathies: A case/noncase study in the French PharmacoVigilance Database.

    Science.gov (United States)

    Montastruc, Guillaume; Favreliere, Sylvie; Sommet, Agnès; Pathak, Atul; Lapeyre-Mestre, Maryse; Perault-Pochat, Marie-Christine; Montastruc, Jean-Louis

    2010-03-01

    To evaluate putative associations between drugs and dilated cardiomyopathy. We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were all the observations with dilated cardiomyopathy registered into the FPVD between 1 January 1990 and 30 June 2007. Noncases were all other reports other than those studied. Anthracyclines were used as positive controls. Data were expressed as reporting odds ratio (ROR) with their 95% confidence intervals. Out of the 258 729 adverse drug reaction (ADR) reports recorded in the FPVD between 1 January 1990 and 30 June 2007, 47 (22 men, mean age 49 years) were defined as dilated cardiomyopathy. In these 47 patients, 67 drugs were 'suspect'. A significant ROR was found with cytotoxic (epirubicin, mitoxantrone, cyclophosphamide, gemcitabine, fluorouracil) and antiretroviral (lamividune, zidovudine, abacavir) but also with isotretinoin, prednisone, appetite suppressant (clobenzorex) and psychotropic [antipsychotic (clozapine, olanzapine), lithium, antidepressant (clomipramine, amitriptyline, fluvoxamine)] drugs. The present study describes an association between some drugs and reports of dilated cardiomyopathies. This relationship involves not only some already suspected drugs (anthracyclines, antiretrovirals), but also other drugs (antipsychotics, lithium, antidepressants, retinoids) less known to induce such an ADR. Despite the mandatory limits of this kind of study (underreporting, confounding factors . . .), these data represent a pharmacovigilance signal and could contribute to establish further prospective studies in order to confirm such signals.

  15. Pharmacovigilance in oncology: pattern of spontaneous notifications, incidence of adverse drug reactions and under-reporting

    Directory of Open Access Journals (Sweden)

    Marília Berlofa Visacri

    2014-04-01

    Full Text Available The high toxicity and narrow therapeutic window of antineoplastic agents makes pharmacovigilance studies essential in oncology. The objectives of the current study were to analyze the pattern of spontaneous notifications of adverse drug reactions (ADRs in oncology patients and to analyze the incidence of ADRs reported by outpatients on antineoplastic treatment in a tertiary care teaching hospital. To compose the pattern of ADR, the notification forms of reactions in oncology patients in 2010 were reviewed, and the reactions were classified based on the drug involved, mechanism, causality, and severity. To evaluate the incidence of reactions, a questionnaire at the time of chemotherapy was included, and the severity was classified based on the Common Terminology Criteria. The profiles of the 10 responses reported to the Pharmacovigilance Sector were type B, severe, possible, and they were primarily related to platinum compounds and taxanes. When the incidence of reactions was analyzed, it was observed that nausea, alopecia, fatigue, diarrhea, and taste disturbance were the most frequently reported reactions by oncology patients, and the grade 3 and 4 reactions were not reported. Based on this analysis, it is proposed that health professionals should be trained regarding notifications and clinical pharmacists should increasingly be brought on board to reduce under-reporting of ADRs.

  16. New initiatives for pharmacovigilance in South Korea: introducing the Korea Institute of Drug Safety and Risk Management (KIDS).

    Science.gov (United States)

    Shin, Ju-Young; Jung, Sun-Young; Ahn, So-Hyeon; Lee, Shin Haeng; Kim, Su-Jin; Seong, Jong-Mi; Chung, Soo-Youn; Park, Byung-Joo

    2014-11-01

    Pharmacovigilance plays a vital role in ensuring that patients receive appropriate medical products that are safe and effective. This paper aims to describe the history of pharmacovigilance in Korea and introduce the establishment and goal of the KIDS. In Korea, the adverse drug reactions (ADR) reporting system was launched in 1988 by the Korea Ministry of Food and Drug Safety (MFDS) and spontaneous ADR reports have been collected from health care professionals and the general public. Although the ADR reporting system has begun, the reporting rate was very low in the first 10 years, and safety actions were done passively in response to the US Food and Drug Administration (FDA) or European Medicines Agency (EMA)'s safety alert and communications. Therefore, the Korea Institute of Drug Safety and Risk Management (KIDS) was established in April 2012 as a new initiative for pharmacovigilance. The KIDS will continue to contribute to the improvement of Korean pharmacovigilance by collecting, managing, and analyzing consumer-centered drug safety information. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD database and the GALEN platform. The Galenda project.

    Science.gov (United States)

    Bousquet, P-J; Demoly, P; Romano, A; Aberer, W; Bircher, A; Blanca, M; Brockow, K; Pichler, W; Torres, M J; Terreehorst, I; Arnoux, B; Atanaskovic-Markovic, M; Barbaud, A; Bijl, A; Bonadonna, P; Burney, P G; Caimmi, S; Canonica, G W; Cernadas, J; Dahlen, B; Daures, J-P; Fernandez, J; Gomes, E; Gueant, J-L; Kowalski, M L; Kvedariene, V; Mertes, P-M; Martins, P; Nizankowska-Mogilnicka, E; Papadopoulos, N; Ponvert, C; Pirmohamed, M; Ring, J; Salapatas, M; Sanz, M L; Szczeklik, A; Van Ganse, E; De Weck, A L; Zuberbier, T; Merk, H F; Sachs, B; Sidoroff, A

    2009-02-01

    Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments.

  18. Epistaxis and other haemorrhagic events associated with the smoking cessation medicine varenicline : a case series from two national pharmacovigilance centres

    NARCIS (Netherlands)

    Harrison-Woolrych, Mira; Harmark, Linda; Tan, Ming; Maggo, Simran; van Grootheest, Kees

    Purpose To present a case series of haemorrhagic events associated with varenicline identified from the New Zealand (NZ) and Netherlands national pharmacovigilance centres and propose a possible mechanism for these adverse events. Methods Reports of epistaxis and other haemorrhagic events (in all

  19. Iodometric and Molecular Detection of ESBL Production Among Clinical Isolates of E. coli Fingerprinted by ERIC-PCR: The First Egyptian Report Declares the Emergence of E. coli O25b-ST131clone Harboring blaGES.

    Science.gov (United States)

    El-Badawy, Mohamed F; Tawakol, Wael M; Maghrabi, Ibrahim A; Mansy, Moselhy S; Shohayeb, Mohamed M; Ashour, Mohammed S

    2017-09-01

    The extensive use of β-lactam antibiotics has led to emergence and spread of extended-spectrum β-lactamases (ESBLs). This study was conducted to investigate the prevalence of 7 different ESBL genes (bla TEM , bla SHV , bla CTX-M , bla VEB , bla PER , bla GES , and bla OXA-10 ) and O25b-ST131 high-risk clone among 61 clinical isolates of Escherichia coli. Also, one broad-spectrum β-lactamase (bla OXA-1 ) was investigated. This study was also constructed to evaluate iodometric overlay method in detection of ESBL production. Phenotypic identification of E. coli isolates using API 20E revealed 18 distinct biotypes. DNA fingerprinting using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) differentiated all isolates into 2 main phylogenetic groups with 60 distinct genetic profiles. Elevated values of minimal inhibitory concentration (MIC) 50 and MIC 90 for third- and fourth-generation cephalosporins were observed. Phenotypic tests revealed that 85.24% of isolates were ESBL producers. The incidence rates of bla TEM , bla SHV , bla CTX-M , bla GES , bla OXA-1 , and bla OXA-10 among E. coli ESBL producer phenotype were 69.23%, 25%, 96.15%, 3.85%, 11.54%, and 48%, respectively. On the other hand, bla VEB and bla PER were not detected. Sequencing of bla TEM and bla SHV revealed that bla TEM-214 and bla SHV-11 were the most prevalent variants. Group characterization of bla CTX-M revealed that bla CTX-M-1 was the most prevalent group of bla CTX-M family. It was found that 30.77% of E. coli ESBL producers belonged to O25b-ST131 clone harboring bla CTX-M-15 . This study concluded that iodometric overlay method was 100% sensitive in detection of ESBL production. To our knowledge, this is the first Egyptian study that declares the emergence of E. coli O25b-ST131 harboring bla GES .

  20. Detection of extended-spectrum β-lactamases (blaCTX-M-1 and blaTEM in Escherichia coli, Salmonella spp., and Klebsiella pneumoniae isolated from poultry in North Eastern India

    Directory of Open Access Journals (Sweden)

    H. Lalzampuia

    2014-11-01

    Full Text Available Aim: The present study was conducted to record the association of extended spectrum β-lactamases (ESBLs producing enteric bacteria with diarrhea of poultry birds in Mizoram, India. Materials and Methods: Fecal samples were collected from poultry birds with the history of diarrhea from different parts of Mizoram. Samples were processed for isolation and identification of Escherichia coli, Salmonella, and Klebsiella pneumoniae. All the isolates were subjected to antibiotic sensitivity assays. Phenotypically, ESBLs production ability was determined by double discs synergy test (DDST method. ESBLs producing isolates were subjected to polymerase chain reaction (PCR for detection of ESBLs genes. Plasmids were cured by acridine orange. Transfer of resistance from donor to recipient strains was done by in vitro horizontal method. Results: A total of 134 enteric bacteria was isolated, of which 102 (76.12%, 21 (15.67% and 11 (8.21% were E. coli, Salmonella spp. and K. pneumoniae, respectively. By DDST 7 (5.22% isolates (6 E. coli and 1 K. pneumoniae were ESBLs producer. PCR analysis confirmed 5 (3.73% (4 E. coli and 1 K. pneumoniae isolates harboured blaCTX-M-1 gene and/or blaTEM gene. All the isolates were carrying plasmids ranging between 0.9 kb and ~30 kb. Of the 4 isolates positive for blaCTX-M-1 and/or blaTEM, 2 (1.84% were confirmed for blaCTX-M-1 gene in their plasmid. No blaTEM gene was detected from plasmid. The resistance plasmid could not be transferred to the recipient by in vitro horizontal gene transfer method. Conclusion: ESBLs producing enteric bacteria are circulating in poultry in North Eastern Region of India. As poultry is one of the most common food animals in this region, these organisms may enter in human population through them.

  1. Antibiotic Resistance Patterns and a Survey of Metallo-β-Lactamase Genes Including bla-IMP and bla-VIM Types in Acinetobacter baumannii Isolated from Hospital Patients in Tehran.

    Science.gov (United States)

    Aghamiri, Samira; Amirmozafari, Nour; Fallah Mehrabadi, Jalil; Fouladtan, Babak; Hanafi Abdar, Mojtaba

    2016-01-01

    Metallo-β-lactamases (MBLs) producing strains of Acinetobacter baumannii are serious etiological agents of hospital infections worldwide. Among the β- lactams, carbapenems are the most effective antibiotics used against A. baumannii. However, resistance to these drugs among clinical strains of A. baumannii has been increasing in recent years. In this study, the antimicrobial sensitivity patterns of A. baumannii strains isolated from eleven different hospitals in Tehran, Iran, and the prevalence of MBL genes (bla-VIM and bla-IMP) were determined. During a period of 5 months, 176 isolates of A. baumannii were collected from different clinical specimens from hospitalized patients in Tehran. All isolates were confirmed by biochemical methods. The isolates were tested for antibiotic sensitivity by the Kirby-Bauer disk diffusion method. Following minimum inhibitory concentration determination, imipenem-resistant isolates were further tested for MBL production by the double disk synergy test (DDST) method. PCR assays were performed for the detection of the MBL genes bla-IMP and bla-VIM. The DDST phenotypic method indicated that among the 169 imipenem-resistant isolates, 165 strains were MBL positive. The PCR assays revealed that 63 of the overall isolates (36%) carried the bla-VIM gene and 70 strains (40%) harbored bla-IMP. It is obvious that nosocomial infections associated with multidrug-resistant Acinetobacter spp. are on the rise. Therefore, the determination of antibiotic sensitivity patterns and screening for MBL production among A. baumannii isolates is important for controlling clinical Acinetobacter infections. © 2016 S. Karger AG, Basel.

  2. Detection of blaOXA-23 in Acinetobacter spp. isolated from patients of a university hospital

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    Laís Lisboa Corrêa

    Full Text Available INTRODUCTION: Acinetobacter spp. have emerged as notorious pathogens involved in healthcareassociated infections. Carbapenems are important antimicrobial agents for treating infections due to multidrug resistant Acinetobacter spp. Different mechanisms may confer resistance to these drugs in the genus, particularly production of class D carbapenemases. OXA-23-like family has been pointed out as one of the predominant carbapenamases among Acinetobacter. The present work aimed to investigate the occurrence of OXA-23-like carbapenemases among Acinetobacter isolates recovered from patients of a university hospital in Niterói, RJ, Brazil. METHODS: Antimicrobial susceptibility profiles were determined by disk-diffusion. Imipenem resistant isolates were submitted to Modified Hodge Test in order to screen for carbapenemase production, and later to polymerase chain reaction (PCR to investigate the presence of blaOXA-23. RESULTS: Imipenem and meropenem resistance rates were 71.4% and 69.7%, respectively. The Modified Hodge Test revealed carbapenemase production among 76 (89.4% of the 85 imipenem resistant isolates analyzed; according to PCR results, 81 isolates (95.4% carried the blaOXA-23 gene. CONCLUSIONS: OXA-23-like enzymes may be an important mechanism of carbapenem resistance among isolates present in the hospital studied.

  3. Pathogenicity of pan-drug-resistant Serratia marcescens harbouring blaNDM-1.

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    Gruber, Teresa M; Göttig, Stephan; Mark, Laura; Christ, Sara; Kempf, Volkhard A J; Wichelhaus, Thomas A; Hamprecht, Axel

    2015-04-01

    To characterize a pan-drug-resistant Serratia marcescens clinical isolate carrying the New Delhi metallo-β-lactamase (NDM)-1. The presence of β-lactamase genes was examined by PCR and sequencing. Antibiotic susceptibility was determined by antibiotic gradient test. Transformation assays, transconjugation assays, PFGE and PCR-based replicon typing were used for plasmid analysis. Horizontal gene transfer was evaluated by liquid mating using Escherichia coli J53 as a recipient. Pathogenicity of NDM-1 expressing S. marcescens was analysed using the Galleria mellonella infection model. S. marcescens isolate SM1890 was non-susceptible to all tested antibiotics, with minocycline retaining intermediate activity. blaNDM-1 was located on a 140 kb IncA/C-type plasmid which was transferable to E. coli and Klebsiella pneumoniae by conjugation. The LD50 of the NDM-positive, SM1890 isolate was higher than that of other, NDM-1 negative, S. marcescens strains. The presence of a blaNDM-1-harbouring IncA/C plasmid resulted in marked resistance to β-lactam antibiotics, but had no significant effect on virulence of isogenic strains. Because of the intrinsic resistance of S. marcescens to colistin and reduced susceptibility to tigecycline, treatment options for infections by NDM-1-positive isolates are extremely limited in this species. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Virulence of Klebsiella pneumoniae isolates harboring bla KPC-2 carbapenemase gene in a Caenorhabditis elegans model.

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    Jean-Philippe Lavigne

    Full Text Available Klebsiella pneumoniae carbapenemase (KPC is a carbapenemase increasingly reported worldwide in Enterobacteriaceae. The aim of this study was to analyze the virulence of several KPC-2-producing K. pneumoniae isolates. The studied strains were (i five KPC-2 clinical strains from different geographical origins, belonging to different ST-types and possessing plasmids of different incompatibility groups; (ii seven transformants obtained after electroporation of either these natural KPC plasmids or a recombinant plasmid harboring only the bla KPC-2 gene into reference strains K. pneumoniae ATCC10031/CIP53153; and (iii five clinical strains cured of plasmids. The virulence of K. pneumoniae isolates was evaluated in the Caenorhabditis elegans model. The clinical KPC producers and transformants were significantly less virulent (LT50: 5.5 days than K. pneumoniae reference strain (LT50: 4.3 days (p<0.01. However, the worldwide spread KPC-2 positive K. pneumoniae ST258 strains and reference strains containing plasmids extracted from K. pneumoniae ST258 strains had a higher virulence than KPC-2 strains belonging to other ST types (LT50: 5 days vs. 6 days, p<0.01. The increased virulence observed in cured strains confirmed this trend. The bla KPC-2 gene itself was not associated to increased virulence.

  5. Gene blaCTX-M Mutation as Risk Factor of Antibiotic Resistance

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    Devinna Kang

    2017-06-01

    Full Text Available Currently there are more than half from all antibiotics used in the world which is belong to β lactam group, but clinical effectiveness of the antibiotics are limited by antibiotic resistance of microorganisms as causative agents from infectious diseases. Several resistance mechanisms for Enterobacteriaceae are mostly caused by enzymatic hydrolysis of antibiotics specific enzymes, called β lactamases. β lactamases represent a large group of enzyme which is genetically and functionally different as extended‑spectrum β-lactamase (ESBL and known as greatest threat of resistence. Plasmid localization from the encoded gene and enzyme distribution among the pathogen increases every year. Most widespread and clinically relevant ESBL are class A ESBL of Temoniera (TEM, Sulphydryl variable (SHV and Cefotaxime (CTX-M types. The purpose of this review was to analyze variant of blaCTX-M gene which cause the most increase incidence of antibiotic resistance. The methods of this review were data-based searching based on Pubmed, Scopus and Google Scholar, without limitation of index factor by using the keyword “blaCTX-M”, “Extended-spectrum β-lactamase”, and “antibiotic resistance”. The conclusion of the review is CTX-M type ESBL have replaced TEM and SHV type as dominant enzyme in last decade. ESBL produced by Klebsiella pneumoniae have emerged as one of major nosocomial pathogens. Nosocomial infection caused by CTX-M-15 in Klebsiella pneumoniae dramatically increased in recent years.

  6. Detection of blaOXA-23 in Acinetobacter spp. isolated from patients of a university hospital

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    Laís Lisboa Corrêa

    2012-12-01

    Full Text Available INTRODUCTION: Acinetobacter spp. have emerged as notorious pathogens involved in healthcareassociated infections. Carbapenems are important antimicrobial agents for treating infections due to multidrug resistant Acinetobacter spp. Different mechanisms may confer resistance to these drugs in the genus, particularly production of class D carbapenemases. OXA-23-like family has been pointed out as one of the predominant carbapenamases among Acinetobacter. The present work aimed to investigate the occurrence of OXA-23-like carbapenemases among Acinetobacter isolates recovered from patients of a university hospital in Niterói, RJ, Brazil. METHODS: Antimicrobial susceptibility profiles were determined by disk-diffusion. Imipenem resistant isolates were submitted to Modified Hodge Test in order to screen for carbapenemase production, and later to polymerase chain reaction (PCR to investigate the presence of blaOXA-23. RESULTS: Imipenem and meropenem resistance rates were 71.4% and 69.7%, respectively. The Modified Hodge Test revealed carbapenemase production among 76 (89.4% of the 85 imipenem resistant isolates analyzed; according to PCR results, 81 isolates (95.4% carried the blaOXA-23 gene. CONCLUSIONS: OXA-23-like enzymes may be an important mechanism of carbapenem resistance among isolates present in the hospital studied.

  7. A putative multi-replicon plasmid co-harboring beta-lactamase genes blaKPC-2, blaCTX-M-14 and blaTEM-1 and trimethoprim resistance gene dfrA25 from a Klebsiella pneumoniae sequence type (ST 11 strain in China.

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    Yu Tang

    Full Text Available The global emergence of Klebsiella pneumoniae carbapenemase (KPC-producing Klebsiella pneumoniae poses a major public health threat requiring immediate and aggressive action. Some older generation antibiotics, such as trimethoprim, serve as alternatives for treatment of infections. Here, we determined the complete nucleotide sequence of plasmid pHS091147, which co-harbored the carbapenemase (blaKPC-2 and trimethoprim resistance genes (dfrA25 from a Klebsiella pneumoniae sequence type (ST 11 clone recovered in Shanghai, China. pHS091147 had three replication genes, several plasmid-stability genes and an intact type IV secretion system gene cluster. Besides blaKPC-2 and dfrA25, pHS091147 carried several other resistance genes, including β-lactamase genes blaTEM-1 and blaCTX-M-14, sulphonamide resistance gene sul1, a quinolone resistance gene remnant (ΔqnrB2, and virulence associated gene iroN. Notably, the multidrug-resistance region was a chimeric structure composed of three subregions, which shared strong sequence homology with several plasmids previously assigned in Genbank. To our knowledge, this is the first report of the co-localization of blaKPC-2 and dfrA25 on a novel putative multi-replicon plasmid in a Klebsiella pneumoniae ST11 clone.

  8. Survey of Antibiotic Resistance and Frequency of blaOXA-23 and blaOXA-24 Oxacillinase in Acinetobacter baumannii Isolated from Tracheal Tube Specimens of Patients Hospitalized in Intensive Care Units in Isfahan city

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    M Ghalebi

    2017-04-01

    chi-square tests. Results: All isolates were found resistant to ceftazidime, ceftriaxone, meropenem and imipenem and the lowest resistance were seen against colistin (0% and tigecycline (10%, respectively. All isolates were resistant to imipenem using Etest method with MIC ≥ 32 μg / ml. blaOXA-23 and blaOXA-24 genes were detected in 87.5% and 25% of isolates, respectively. Conclusion: Due to the results, treatment of A. baumannii isolates by carbapenems is ineffective and tigecycline or colistin could be used for treatment. Other studies for detection of other mechanisms for carbapenem resistance are recommended.

  9. Barriers to the success of an electronic pharmacovigilance reporting system in Kenya: an evaluation three years post implementation.

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    Agoro, Oscar O; Kibira, Sarah W; Freeman, Jenny V; Fraser, Hamish S F

    2017-10-12

    Electronic pharmacovigilance reporting systems are being implemented in many developing countries in an effort to improve reporting rates. This study sought to establish the factors that acted as barriers to the success of an electronic pharmacovigilance reporting system in Kenya 3 years after its implementation. Factors that could act as barriers to using electronic reporting systems were identified in a review of literature and then used to develop a survey questionnaire that was administered to pharmacists working in government hospitals in 6 counties in Kenya. The survey was completed by 103 out of the 115 targeted pharmacists (89.5%) and included free-text comments. The key factors identified as barriers were: unavailable, unreliable, or expensive Internet access; challenges associated with a hybrid system of paper and electronic reporting tools; and system usability issues. Coordination challenges at the national pharmacovigilance center and changes in the structure of health management in the country also had an impact on the success of the electronic reporting system. Different personal, organizational, infrastructural, and reporting system factors affect the success of electronic reporting systems in different ways, depending on the context. Context-specific formative evaluations are useful in establishing the performance of electronic reporting systems to identify problems and ensure that they achieve the desired objectives. While several factors hindered the optimal use of the electronic pharmacovigilance reporting system in Kenya, all were considered modifiable. Effort should be directed toward tackling the identified issues in order to facilitate use and improve pharmacovigilance reporting rates. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  10. Dissemination and genetic context analysis of bla(VIM-6) among Pseudomonas aeruginosa isolates in Asian-Pacific Nations.

    Science.gov (United States)

    Castanheira, M; Bell, J M; Turnidge, J D; Mendes, R E; Jones, R N

    2010-02-01

    VIM-6, previously reported in two strains from Singapore recovered in 2000, was detected in 16 isolates collected in 2006 in India (12 isolates), Indonesia (two), Korea and the Philippines (one each). High genetic variability was observed among VIM-6-producing isolates (12 ribotypes and 11 pulsed-field gel electrophoresis types), but clones were observed in India and Indonesia; bla(VIM-6)-carrying integrons of 3.9 kb and 5 kb were detected, and two of five Indian hospitals yielded isolates with both integrons. These two integrons, bla(VIM-6) was located in the first position, followed by bla(OXA-10) and aacA4. The 5-kb integrons also harboured aadA1 and a 331-bp open reading frame encoding a putative efflux pump.

  11. Further Spread of blaNDM-5 in Enterobacteriaceae via IncX3 Plasmids in Shanghai, China

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    Fangfang eZhang

    2016-03-01

    Full Text Available One hundred and two carbapenem-resistant Enterobacteriaceae (CRE strains were isolated in a teaching hospital in Shanghai, China from 2012 to 2015. In a follow-up study, 4 New Delhi metallo-β-lactamase-5 (NDM-5-producing strains were identified after screening these CRE strains, including 1 Klebsiella pneumoniae strain (RJ01, 1 Proteus mirabilis strain (RJ02, and 2 Escherichia coli strains (RJ03 and RJ04. All K. pneumoniae and E. coli isolates were resistant to carbapenems, third-generation cephalosporins, and piperacillin-tazobactam, but were susceptible to amikacin. No epidemiological links for either E. coli isolate were found by multilocus sequence typing (MLST and pulsed-field gel electrophoresis (PFGE. However, MLST revealed a novel sequence type, ST2250, of the K. pneumoniae RJ01 strain. Inc types and sizes of blaNDM-5-carrying plasmids differed among the 4 isolates, although in P. mirabilis RJ02 and E. coli RJ03, blaNDM-5 was carried by conjugative IncX3 plasmids of nearly the same size (~40 kb. Investigation of the genetic background of sequences flanking the blaNDM-5 gene showed that all 4 isolates shared the same genetic content (IS3000-ΔISAba125-IS5-blaNDM-5-ble-trpF-dsbC-IS26-ΔumuD, which was identical to that of the pNDM_MGR194 plasmid circulating in India. This is the first identification of blaNDM-5 in P. mirabilis, which suggests its further spread to Enterobacteriaceae, and indicates that IncX3 plasmids may play an important role in potentiating the spread of blaNDM.

  12. The role of the genetic elements bla oxa and IS Aba 1 in the Acinetobacter calcoaceticus-Acinetobacter baumannii complex in carbapenem resistance in the hospital setting.

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    Kobs, Vanessa Cristine; Ferreira, Jéssica Augustini; Bobrowicz, Thaís Alexandra; Ferreira, Leslie Ecker; Deglmann, Roseneide Campos; Westphal, Glauco Adrieno; França, Paulo Henrique Condeixa de

    2016-01-01

    Members of the Acinetobacter genus are key pathogens that cause healthcare-associated infections, and they tend to spread and develop new antibiotic resistance mechanisms. Oxacillinases are primarily responsible for resistance to carbapenem antibiotics. Higher rates of carbapenem hydrolysis might be ascribed to insertion sequences, such as the ISAba1 sequence, near bla OXA genes. The present study examined the occurrence of the genetic elements bla OXA and ISAba1 and their relationship with susceptibility to carbapenems in clinical isolates of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex. Isolates identified over 6 consecutive years in a general hospital in Joinville, Southern Brazil, were evaluated. The investigation of 5 families of genes encoding oxacillinases and the ISAba1 sequence location relative to bla OXA genes was conducted using polymerase chain reaction. All isolates presented the bla OXA-51-like gene (n = 78), and 91% tested positive for the bla OXA-23-like gene (n = 71). The presence of ISAba1 was exclusively detected in isolates carrying the bla OXA-23-like gene. All isolates in which ISAba1 was found upstream of the bla OXA-23-like gene (n = 69) showed resistance to carbapenems, whereas the only isolate in which ISAba1 was not located near the bla OXA-23-like gene was susceptible to carbapenems. The ISAba1 sequence position of another bla OXA-23-like-positive isolate was inconclusive. The isolates exclusively carrying the bla OXA-51-like gene (n = 7) showed susceptibility to carbapenems. The presence of the ISAba1 sequence upstream of the bla OXA-23-like gene was strongly associated with carbapenem resistance in isolates of the A. calcoaceticus-A. baumannii complex in the hospital center studied.

  13. The role of the genetic elements bla oxa and IS Aba 1 in the Acinetobacter calcoaceticus-Acinetobacter baumannii complex in carbapenem resistance in the hospital setting

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    Vanessa Cristine Kobs

    Full Text Available Abstract: INTRODUCTION: Members of the Acinetobacter genus are key pathogens that cause healthcare-associated infections, and they tend to spread and develop new antibiotic resistance mechanisms. Oxacillinases are primarily responsible for resistance to carbapenem antibiotics. Higher rates of carbapenem hydrolysis might be ascribed to insertion sequences, such as the ISAba1 sequence, near bla OXA genes. The present study examined the occurrence of the genetic elements bla OXA and ISAba1 and their relationship with susceptibility to carbapenems in clinical isolates of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex. METHODS: Isolates identified over 6 consecutive years in a general hospital in Joinville, Southern Brazil, were evaluated. The investigation of 5 families of genes encoding oxacillinases and the ISAba1 sequence location relative to bla OXA genes was conducted using polymerase chain reaction. RESULTS: All isolates presented the bla OXA-51-like gene (n = 78, and 91% tested positive for the bla OXA-23-like gene (n = 71. The presence of ISAba1 was exclusively detected in isolates carrying the bla OXA-23-like gene. All isolates in which ISAba1 was found upstream of the bla OXA-23-like gene (n = 69 showed resistance to carbapenems, whereas the only isolate in which ISAba1 was not located near the bla OXA-23-like gene was susceptible to carbapenems. The ISAba1 sequence position of another bla OXA-23-like-positive isolate was inconclusive. The isolates exclusively carrying the bla OXA-51-like gene (n = 7 showed susceptibility to carbapenems. CONCLUSIONS: The presence of the ISAba1 sequence upstream of the bla OXA-23-like gene was strongly associated with carbapenem resistance in isolates of the A. calcoaceticus-A. baumannii complex in the hospital center studied.

  14. blaOXA-48 carrying clonal colistin resistant-carbapenem resistant Klebsiella pneumoniae in neonate intensive care unit, India.

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    Singh, Santosh Kumar; Gupta, Minakshi

    2016-11-01

    Bacteria resistant to colistin, a last resort antibiotic reflect the pre-antibiotic era. In this study, colistin resistance carbapenem-resistant K. pneumoniae (COL R - CRKP) strains from neonate's intensive care unit were evaluated. Molecular analysis showed that all the four colistin resistant K. pneumoniae isolates were clonally related with strong biofilm formation ability and harbored bla SHV-34 and bla OXA-48 genes. Our result suggested the need of proper surveillance and adequate infection control to limiting the spread of these organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Adverse reactions to radiopharmaceuticals in France: analysis of the national pharmacovigilance database.

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    Laroche, Marie-Laure; Quelven, Isabelle; Mazère, Joachim; Merle, Louis

    2015-01-01

    Radiopharmaceuticals are regarded as safe by the nuclear medicine community, but up to now, no survey has been conducted with from the perspective of pharmacovigilance. To describe the adverse reactions to radiopharmaceuticals (ARRPs) reported to the French Pharmacovigilance Database (FPVD). We selected and described all reports encompassing at least one radiopharmaceutical in the FPVD. The annual incidence of reported ARRPs used in diagnosis was also estimated. From 1989 to 2013, 304 reports of ARRPs were identified (43.0% serious, 12 deaths) in 54.6% women and 45.4% men; the median age was 58 years. Five therapeutic radiopharmaceuticals ((131)I-sodium iodide, (131)I-lipiodol, (89)Sr-chloride, (153)Sm-lexidronam, and (90)Y-ibritumomab-tiuxetan) were involved in 48 reports (97 adverse reactions: 86.6% serious, 9 deaths). Pulmonary disorders represented 44.3% of ARRPs used for therapy, mainly related to (131)I-lipiodol. There were 34 diagnostic radiopharmaceuticals involved in 256 reports (451 adverse reactions: 38.1% serious, 3 deaths); 8 diagnostic products ((99m)Tc-oxidronate, (18)F-fluorodeoxyglucose, (99m)Tc-tin pyrophosphate, (99m)Tc-tetrofosmin, (99m)Tc-dimercaptosuccinic acid, (201)Tl-chloride, (99m)Tc-sestamibi, and (111)In-pentetate) accounted for two-thirds of ARRPs. The most frequent adverse reactions were skin (34.4%), general (18.2%), nervous (9.0%), and gastrointestinal disorders (7.0%). There were 25 cases of altered images and 10 medication errors. The annual incidence of reported adverse reactions ranged from 1.2 × 10(-5) to 3.4 × 10(-5) diagnostic administrations. Reported ARRPs occurred rarely and were more serious in the therapeutic than in the diagnostic field. The notification of ARRPs was able to provide new guidance for safe use, as was the case for (131)I-lipiodol. Therefore, it is important to report ARRPs to a pharmacovigilance system. © The Author(s) 2014.

  16. Linking NHS data for pediatric pharmacovigilance: Results of a Delphi survey.

    Science.gov (United States)

    Hopf, Y M; Francis, J; Helms, P J; Haughney, J; Bond, C

    2016-01-01

    Adverse drug events are a major cause of patient safety incidents. Current systems of pharmacovigilance under-report adverse drug reactions (ADRs), especially in children, leading to delays in their identification. This is of particular concern, as children especially have an increased vulnerability to ADRs. The objective was to seek consensus among healthcare professionals (HCPs) about barriers and facilitators to the linkage of routinely collected health data for pediatric pharmacovigilance in Scotland. A Delphi survey was conducted with a random sample of HCPs including nurses, pharmacists and doctors, working in primary or secondary care, in Scotland. Participants were identified from sampling frames of the target professionals such as an NHS workforce list for general practitioners and recruited by postal invitation. A total of 819 HCPs were invited to take part. Those agreeing to participate were given the option of completing the questionnaires online or as hard copy. Reminders were sent twice at a fortnightly interval. Questions content included description of professional role as well as testing for the willingness to support the proposed project and was informed by the Theoretical Domains Framework of Behavior Change (TDF) and earlier qualitative work. Three Delphi rounds were administered, including a first round for item generation. 121 of those invited agreed to take part (15%). The first round of the Delphi study included 21 open questions and generated over a 1000 individual statements from 61 participants that returned the questionnaires (50.4%). These were rationalized to 149 items for the second round in which participants rated their views on the importance (or not) of each item on a 9-point Likert scale (strongly disagree - strongly agree). After the third round, there was consensus on items that focused on professional standards, and practical requirements, overall there was support for data linkage and a multi-professional approach. It would

  17. IMPACT OF EDUCATIONAL INTERVENTION ON KNOWLEDGE, ATTITUDE AND PRACTICE OF PHARMACOVIGILANCE AMONG MEDICAL GRADUATES OF RURAL TERTIARY CARE, TEACHING HOSPITAL OF CENTRAL INDIA

    OpenAIRE

    VARMA SUSHIL KUMAR; KALE RANJANA; NAGPURE SHAILESH; BAHEKAR SATISH

    2013-01-01

    To assess the awareness of Pharmacovigilance among the medical graduates and to evaluate the need of inclusion of KAP (Knowledge, Attitude and Practice) of Pharmacovigilance in Internship Training Programme as an educational intervention.Material and Methods: The present study was conducted in the Internship orientation program in a rural hospital of central India. It was a Hospital Based Cross Sectional Study in which 65 Interns (medical graduates) were participated. Semi-structured, Pre-Des...

  18. Increased prevalence of carbapenem resistant Enterobacteriaceae in hospital setting due to cross-species transmission of the bla NDM-1 element and clonal spread of progenitor resistant strains.

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    Wang, Xuan; Chen, Gongxiang; Wu, Xiaoyan; Wang, Liangping; Cai, Jiachang; Chan, Edward W; Chen, Sheng; Zhang, Rong

    2015-01-01

    This study investigated the transmission characteristics of carbapenem-resistant Enterobacteriaceae (CRE) strains collected from a hospital setting in China, in which consistent emergence of CRE strains were observable during the period of May 2013 to February 2014. Among the 45 CRE isolates tested, 21 (47%) strains were found to harbor the bla NDM-1 element, and the rest of 24 CRE strains were all positive for bla KPC-2. The 21 bla NDM-1-borne strains were found to comprise multiple Enterobacteriaceae species including nine Enterobacter cloacae, three Escherichia coli, three Citrobacter freundii, two Klebsiella pneumoniae, two Klebsiella oxytoca, and two Morganella morganii strains, indicating that cross-species transmission of bla NDM-1 is a common event. Genetic analyses by PFGE and MLST showed that, with the exception of E. coli and E. cloacae, strains belonging to the same species were often genetically unrelated. In addition to bla NDM-1, several CRE strains were also found to harbor the bla KPC-2, bla VIM-1, and bla IMP-4 elements. Conjugations experiments confirmed that the majority of carbapenem resistance determinants were transferable. Taken together, our findings suggest that transmission of mobile resistance elements among members of Enterobacteriaceae and clonal spread of CRE strains may contribute synergistically to a rapid increase in the population of CRE in clinical settings, prompting a need to implement more rigorous infection control measures to arrest such vicious transmission cycle in CRE-prevalent areas.

  19. Dissemination and characterization of plasmids carrying oqxAB-bla CTX-M genes in Escherichia coli isolates from food-producing animals.

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    Bao-Tao Liu

    Full Text Available BACKGROUND: The association of PMQR and ESBLs in negative-bacteria isolates has been of great concern. The present study was performed to investigate the prevalence of co-transferability of oqxAB and bla CTX-M genes among the 696 Escherichia coli (E. coli isolates from food-producing animals in South China, and to characterize these plasmids. METHODS: The ESBL-encoding genes (bla(CTX-M, bla(TEM and bla(SHV, and PMQR (qnrA, qnrB, qnrS, qnrC, qnrD, aac(6'-Ib-cr, qepA, and oqxAB of these 696 isolates were determined by PCR and sequenced directionally. Conjugation, S1 nuclease pulsed-field gel electrophoresis (PFGE and Southern blotting experiments were performed to investigate the co-transferability and location of oqxAB and bla(CTX-M. The EcoRI digestion profiles of the plasmids with oqxAB-bla(CTX-M were also analyzed. The clonal relatedness was investigated by PFGE. RESULTS: Of the 696 isolates, 429 harbored at least one PMQR gene, with oqxAB (328 being the most common type; 191 carried bla(CTX-M, with bla(CTX-M-14 the most common. We observed a significant higher prevalence of bla(CTX-M among the oqxAB-positive isolates (38.7% than that (17.4% in the oqxAB-negative isolates. Co-transferability of oqxAB and bla(CTX-M was found in 18 of the 127 isolates carrying oqxAB-bla(CTX-M. These two genes were located on the same plasmid in all the 18 isolates, with floR being on these plasmids in 13 isolates. The co-dissemination of these genes was mainly mediated by F33:A-: B- and HI2 plasmids with highly similar EcoRI digestion profiles. Diverse PFGE patterns indicated the high prevalence of oqxAB was not caused by clonal dissemination. CONCLUSION: bla(CTX-M was highly prevalent among the oqxAB-positive isolates. The co-dissemination of oqxAB-bla(CTX-M genes in E. coli isolates from food-producing animals is mediated mainly by similar F33:A-: B- and HI2 plasmids. This is the first report of the co-existence of oqxAB, bla(CTX-M, and floR on the same

  20. Identificación genotípica de β-lactamasas de espectro espectro extendido (BLEE (blaTEM y blaSHV en Escherichia coli uropatógena

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    Yeffersson Grandas Franco

    2016-06-01

    Full Text Available Introducción: Las infecciones de tracto urinario (ITU son consideradas un problema de salud pública a nivel mundial debido a su incidencia y morbilidad. Entre los agentes causales que se aíslan con mayor frecuencia, se encuentra E. coli, con una prevalencia que va desde 40% al 95%. Actualmente, la problemática de las ITU ha venido en aumento, debido a la aparición de resistencia bacteriana a agentes antimicrobianos, influenciado por la presión selectiva, la preexistencia de genes de resistencia y el uso indiscriminado de antibióticos. Objetivo: Identificar molecularmente β-lactamasas de espectro extendido (blaTEM y blaSHV, en E. coli uropatógena, aislada en pacientes ambulatorios que asisten a un laboratorio clínico de tercer nivel de complejidad. Materiales y métodos: Estudio descriptivo de corte transversal. En este trabajo se estudiaron 250 cepas de las cuales 120 eran presuntivas de producir β-lactamasas de acuerdo al método de Kirby-bauer que se realizó años anteriores por el semillero de Inmunidad e Infección. Los genes de interés se amplificaron mediante PCR. Se utilizó Klebsiella pneumoniae ATCC 700603 como control positivo. Una vez amplificado el gen se llevó a cabo el corrido electroforético en gel de agarosa donde el producto amplificado fue de 470 pb en el caso de blaSHV y de 1080 pb para blaTEM. Los fenotipos compatibles con producción de β-lactamasas se analizaron por medio de distribución de frecuencia usando el software WHONET 5,6. La distribución de frecuencia de los genes analizados se calculó usando el software MedCalc versión 15.2.2 (Bélgica – Software BBVA. Resultados: De las cepas analizadas, el 52,8% portadoras del gen blaTEM y el 2,8% del gen blaSHV-2. Se encontró co-existencia de los genes blaSHV-2 y blaTEM en el 1,68% del total de las cepas. De todas las cepas presuntivas de producir BLEE (n=120, 94 fueron productoras de BLEE, lo que nos indicaría que las 21 cepas restantes, implementan

  1. Molecular heterogeneity of bla(VIM-2)-containing integrons from Pseudomonas aeruginosa plasmids encoding the VIM-2 metallo-beta-lactamase.

    Science.gov (United States)

    Pallecchi, L; Riccio, M L; Docquier, J D; Fontana, R; Rossolini, G M

    2001-02-20

    A bla(VIM-2) metallo-beta-lactamase determinant, identical to that previously identified in Pseudomonas aeruginosa COL-1 isolate from a French hospital, was detected on a 28-kb plasmid carried by a nosocomial isolate of P. aeruginosa from Verona, Italy. In this plasmid the bla(VIM-2) determinant was inserted into a class 1 integron of original structure, named In72, that contains a partially deleted intI1 integrase gene and two gene cassettes. The first cassette carries an aacA4 aminoglycoside acetyl transferase determinant. The second cassette carries a bla(VIM-2) determinant followed by a partially deleted attC site. The structure of In72 was notably different from that of In56, the bla(VIM-2)-containing integron found in the COL-1 isolate, revealing the existence of molecular heterogeneity among bla(VIM-2)-containing integrons in clinical isolates of P. aeruginosa from Europe.

  2. [Evaluation of the website of the Nord-Pas-de-Calais regional pharmacovigilance center].

    Science.gov (United States)

    Rochoy, Michaël; Béné, Johana; Messaadi, Nassir; Auffret, Marine; Gautier, Sophie

    2016-06-01

    We posted the Nord-Pas-de-Calais regional pharmacovigilance center website and distributed a survey to its potential users between August 2014 and October 2014 (135 general practitioners, 45 pharmacists, 14 patients). Satisfaction was 7.3±1.6 out of 10 points for the visual aspect, 7.8±1.5 out of 10 points for navigation and 7.6±1.4 out of 10 points for content. The website was declared useful by 98% respondents, particularly for the reporting of adverse drugs reactions (89%). Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  3. Overview of pharmacovigilance practices at the largest academic healthcare system in the State of Qatar.

    Science.gov (United States)

    Al Hail, Moza; Elkassem, Wessam; Hamad, Anas; Abdulrouf, Pallivalappila; Thomas, Binny; Stewart, Derek

    2018-04-03

    Adverse Drug Reactions (ADRs) are major global concern, adversely impacting patient safety and health outcomes. ADRs cause significant morbidity and mortality among hospitalised patients, causing greater length of hospital stay, increased healthcare costs and patient dissatisfaction to the treatments. Pharmacovigilance (PV), a process of detecting, monitoring and preventing drug-related harm, plays a vital role to ensure patient safety. ADR reporting is the cornerstone of PV. PV practices in Qatar are relatively new and are evolving rapidly. The purpose of this article is to explore the medication safety practices (notably ADR reporting) at the largest academic healthcare center in Qatar. The article further provides evidence on how information related to ADRs are generated and interpreted. Furthermore, it describes how a designated center for monitoring medication safety activities was established at the largest healthcare provider in Qatar.

  4. Knowledge, attitudes and practice of pharmacovigilance among health care professionals in Indonesia

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    Grace Wangge

    2016-07-01

    Abstract Background: World Health Organization (WHO defines pharmacovigilance (PV as a science and activities related to detection, assessment, understanding and prevention of adverse effect or any other drug related problem. It aims to enhance patient care and patient safety in drug use. Although Indonesia has joined WHO international drug safety monitoring program since 1970s, the implementation is not applied effectively especially in developing country and there are poor contribution of health care professionals (HCPs as an agent of the program. In this study, we assessed current knowledge, activities and practice of PV among HCPs in Indonesia. Methods: This is a preliminary survey using a questionnaire distributed among HCPs through health seminar and internet. The questionnaire consists of statement/question about knowledge(6, activities(6 and whether HCPs who encounter ADRs handle and report it correctly.  If the respondents gave 80 % suitable answers in the knowledge or attitude sections, they were categorized as having “good” knowledge or attitude. We analyzed whether knowledge, attitude and other characteristic had any influence on the respodents PV practice. Results: We included 109 questionnaires from 118 distributed questionnaires. Most of the respondents were females (90 respondents, 82.6%, medical doctors (100 respondents, 91.7%, and were working in primary health care level. Good knowledge was found in 28 (25.7 % of respondents, while good attitude towards PV were found in less than 20 % (18 of the respondents. Only 4 (3.7 % of total respondents did a good pharmacovigilance practice.  We found no significant association between level of knowledge, attitude and other factors to the poor pratice of PV. Conclusion: The knowledge, activities and practices of pharmacovigilance among HCPs in Indonesia were poor and requires a continuous socialization among HCPs in different level of care. Key Words: pharmacovigilance, health care professionals, patient

  5. Should methods of correction for multiple comparisons be applied in pharmacovigilance?

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    Lorenza Scotti

    2015-12-01

    Full Text Available Purpose. In pharmacovigilance, spontaneous reporting databases are devoted to the early detection of adverse event ‘signals’ of marketed drugs. A common limitation of these systems is the wide number of concurrently investigated associations, implying a high probability of generating positive signals simply by chance. However it is not clear if the application of methods aimed to adjust for the multiple testing problems are needed when at least some of the drug-outcome relationship under study are known. To this aim we applied a robust estimation method for the FDR (rFDR particularly suitable in the pharmacovigilance context. Methods. We exploited the data available for the SAFEGUARD project to apply the rFDR estimation methods to detect potential false positive signals of adverse reactions attributable to the use of non-insulin blood glucose lowering drugs. Specifically, the number of signals generated from the conventional disproportionality measures and after the application of the rFDR adjustment method was compared. Results. Among the 311 evaluable pairs (i.e., drug-event pairs with at least one adverse event report, 106 (34% signals were considered as significant from the conventional analysis. Among them 1 resulted in false positive signals according to rFDR method. Conclusions. The results of this study seem to suggest that when a restricted number of drug-outcome pairs is considered and warnings about some of them are known, multiple comparisons methods for recognizing false positive signals are not so useful as suggested by theoretical considerations.

  6. The impact of database restriction on pharmacovigilance signal detection of selected cancer therapies.

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    Hauben, Manfred; Hung, Eric; Wood, Jennifer; Soitkar, Amit; Reshef, Daniel

    2017-05-01

    The aim of this study was to investigate whether database restriction can improve oncology drug pharmacovigilance signal detection performance. We used spontaneous adverse event (AE) reports in the United States (US) Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Positive control (PC) drug medical concept (DMC) pairs were selected from safety information not included in the product's first label but subsequently added as label changes. These medical concepts (MCs) were mapped to the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PTs) used in FAERS to code AEs. Negative controls (NC) were MCs with circumscribed PTs not included in the corresponding US package insert (USPI). We calculated shrinkage-adjusted observed-to-expected (O/E) reporting frequencies for the aforementioned drug-PT pairs. We also formulated an adjudication framework to calculate performance at the MC level. Performance metrics [sensitivity, specificity, positive and negative predictive value (PPV, NPV), signal/noise (S/N), F and Matthews correlation coefficient (MCC)] were calculated for each analysis and compared. The PC reference set consisted of 11 drugs, 487 PTs, 27 MCs, 37 drug-MC combinations and 638 drug-event combinations (DECs). The NC reference set consisted of 11 drugs, 9 PTs, 5 MCs, 40 drug-MC combinations and 67 DECs. Most drug-event pairs were not highlighted by either analysis. A small percentage of signals of disproportionate reporting were lost, more noise than signal, with no gains. Specificity and PPV improved whereas sensitivity, NPV, F and MCC decreased, but all changes were small relative to the decrease in sensitivity. The overall S/N improved. This oncology drug restricted analysis improved the S/N ratio, removing proportionately more noise than signal, but with significant credible signal loss. Without broader experience and a calculus of costs and utilities of correct versus incorrect classifications in

  7. Distribution ofblaTEM,blaSHV, andblaCTX-Mgenes among ESBL-producingP. aeruginosaisolated from Qazvin and Tehran hospitals, Iran.

    Science.gov (United States)

    Peymani, A; Naserpour-Farivar, T; Zare, E; Azarhoosh, K H

    2017-06-01

    Pseudomonas aeruginosa is as an important opportunistic human pathogen, which is associated with several clinical infections that are usually difficult to treat because of resistance to multiple antimicrobials. The production of extendedspectrum ß-lactamases (ESBLs) is an important mechanism of ß-lactam resistance. The aims of this study were to determine the prevalence of ESBLs, antimicrobial susceptibility, and to detect the bla TEM , bla SHV , and bla CTX-M genes. In this study, carried out from March 2013 to December 2014, 266 P. aeruginosa isolates were collected from patients admitted to teaching hospitals of Qazvin and Tehran, Iran. All isolates were initially screened for ESBL production by disk diffusion method and were further confirmed using a combined disk method. Antimicrobial susceptibility of ESBL-producing isolates was determined by standard disk diffusion method. Polymerase Chain Reaction (PCR) and sequencing techniques were employed for detection of bla TEM , bla SHV , and bla CTX-M genes. In total, 262 (98.5%) P. aeruginosa isolates were nonsusceptible to the used extended spectrum cephalosporins, and, among these, 75 (28.6%) isolates were ESBL producers. Fifty-nine (78.7%) of ESBL-producing isolates showed multidrug-resistance pattern. Of 75 ESBL-positive isolates, the bla TEM-1 (26.7%) was the most common gene, followed by bla CTX-M-15 (17.3%), bla SHV-1 (6.7%), and bla SHV-12 (4%), either alone or in combination. The results of this study showed the notable prevalence of ESBLs among the clinical isolates of P. aeruginosa in Iran, indicating the urgency for the implementation of appropriate follow-up measures for infection control and proper administration of antimicrobial agents in our medical settings.

  8. Shewanella species as the origin of blaOXA-48 genes: insights into gene diversity, associated phenotypes and possible transfer mechanisms.

    Science.gov (United States)

    Tacão, Marta; Araújo, Susana; Vendas, Maria; Alves, Artur; Henriques, Isabel

    2018-03-01

    Chromosome-encoded beta-lactamases of Shewanella spp. have been indicated as probable progenitors of bla OXA-48 -like genes. However, these have been detected in few Shewanella spp. and dissemination mechanisms are unclear. Thus, our main objective was to confirm the role of Shewanella species as progenitors of bla OXA-48 -like genes. In silico analysis of Shewanella genomes was performed to detect bla OXA-48 -like genes and context, and 43 environmental Shewanella spp. were characterised. Clonal relatedness was determined by BOX-PCR. Phylogenetic affiliation was assessed by 16S rDNA and gyrB sequencing. Antibiotic susceptibility phenotypes were determined. The bla OXA-48 -like genes and genetic context were inspected by PCR, hybridisation and sequence analysis. Gene variants were cloned in Escherichia coli and MICs were determined. Shewanella isolates were screened for integrons, plasmids and insertion sequences. Analysis of Shewanella spp. genomes showed that putative bla OXA-48 -like is present in the majority and in an identical context. Isolates presenting unique BOX profiles affiliated with 11 Shewanella spp. bla OXA-48 -like genes were detected in 22 isolates from 6 species. Genes encoded enzymes identical to OXA-48, OXA-204, OXA-181, and 7 new variants differing from OXA-48 from 2 to 82 amino acids. IS1999 was detected in 24 isolates, although not in the vicinity of bla OXA-48 genes. Recombinant E. coli strains presented altered MICs. The presence/absence of bla OXA-48 -like genes was species-related. Gene variants encoded enzymes with hydrolytic spectra similar to OXA-48-like from non-shewanellae. From the mobile elements previously described in association with bla OXA-48 -like genes, only the IS1999 was found in Shewanella, which indicates its relevance in bla OXA-48 -like genes transfer to other hosts. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  9. Genotypic and Antimicrobial Susceptibility of Carbapenem-Resistant Acinetobacter baumannii: Analysis of ISAba Elements and blaOXA-23-like Genes Including A New Variant

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    Abbas eBahador

    2015-11-01

    Full Text Available Carbapenem-resistant Acinetobacter baumannii (CR-AB causes serious nosocomial infections, especially in ICU wards of hospitals, worldwide. Expression of blaOXA genes is the chief mechanism of conferring carbapenem resistance among CR-AB. Although some blaOXA genes have been studied among CR-AB isolates from Iran, their blaOXA-23-like genes have not been investigated. We used a multiplex-PCR to detect Ambler class A, B, and D carbapenemases of 85 isolates, and determined that 34 harbored blaOXA-23-like genes. Amplified fragment length polymorphism (AFLP genotyping, followed by DNA sequencing of blaOXA-23-like amplicons of CR-AB from each AFLP group was used to characterize their blaOXA-23-like genes. We also assessed the antimicrobial susceptibility pattern of CR-AB isolates, and tested whether they harbored insertion sequences ISAba1 and ISAba4. Sequence comparison with reference strain A. baumannii (NCTC12156 revealed five types of mutations in blaOXA-23-like genes; including one novel variant and four mutants that were already reported from China and the USA. All of the blaOXA-23-like genes mutations were associated with increased minimum inhibitory concentrations (MICs against imipenem. ISAba1 and ISAba4 sequences were detected upstream of blaOXA-23 genes in 19% and 7% of isolates, respectively. The isolation of CR-AB with new blaOXA-23 mutations including some that have been reported from the USA and China highlights CR-AB pervasive distribution, which underscores the importance of concerted national and global efforts to control the spread of CR-AB isolates worldwide.

  10. Epidemiological characteristics of blaNDM-1 in Enterobacteriaceae and the Acinetobacter calcoaceticus-Acinetobacter baumannii complex in China from 2011 to 2012.

    Science.gov (United States)

    Ou, Weimei; Cui, Lanqing; Li, Yun; Zheng, Bo; Lv, Yuan

    2014-01-01

    The study aimed to investigate the prevalence and epidemiological characteristics of blaNDM-1 (encoding New Delhi metallo-β-lactamase 1) in Enterobacteriaceae and the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ABC) in China from July 2011 to June 2012. PCR was used to screen for the presence of blaNDM-1 in all organisms studied. For blaNDM-1-positive strains, 16S rRNA analysis and Analytical Profile Index (API) strips were used to identify the bacterial genus and species. The ABCs were reconfirmed by PCR detection of blaOXA-51-like. Antibiotic susceptibilities of the bacteria were assessed by determining minimum inhibitory concentration (MIC) of them using two-fold agar dilution test, as recommended by the Clinical and Laboratory Standards Institute (CLSI). Molecular typing was performed using pulsed-field gel electrophoresis (PFGE). S1 nuclease-pulsed-field gel electrophoresis (S1-PFGE) and Southern blot hybridization were conducted to ascertain the gene location of blaNDM-1. Conjugation experiments were conducted to determine the transmission of blaNDM-1-positive strains. Among 2,170 Enterobacteriaceae and 600 ABCs, seven Enterobacteriaceae strains and two A. calcoaceticus isolates from five different cities carried the blaNDM-1 gene. The seven Enterobacteriaceae strains comprised four Klebsiella pneumoniae, one Enterobacter cloacae, one Enterobacter aerogen and one Citrobacter freundii. All seven were non-susceptible to imipenem, meropenem or ertapenem. Two A. calcoaceticus species were resistant to imipenem and meropenem. Three K. pneumoniae showed the same PFGE profiles. The blaNDM-1 genes of eight strains were localized on plasmids, while one was chromosomal. Compared with previous reports, the numbers and species containing the blaNDM-1 in Enterobacteriaceae have significantly increased in China. Most of them are able to disseminate the gene, which is cause for concern. Consecutive surveillance should be implemented and should also focus

  11. ß-lactamases produced by amoxicillin-clavulanate-resistant enterobacteria isolated in Buenos Aires, Argentina: A new blaTEMgene

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    José A Di Conza

    Full Text Available Resistance to ß-lactam/ß-lactamase inhibitors in enterobacteria is a growing problem that has not been intensively studied in Argentina. In the present work, 54/843 enterobacteria collected in a teaching hospital of Buenos Aires city were ampicillin-sulbactam-resistant isolates remaining susceptible to second-and third-generation cephalosporins. The enzymatic mechanisms present in the isolates, which were also amoxicillin-clavulanic acid (AMC-resistant (18/54 were herein analyzed. Sequencing revealed two different variants of blaTEM-1, being blaTEM-1b the most frequently detected allelle (10 Escherichia coli, 3 Klebsiella pneumoniae, 2 Proteus mirabilis and 1 Raoultella terrigena followed by blaTEM-1a(1 K. pneumoniae. Amoxicillin-clavulanate resistance seems to be mainly associated with TEM-1 overproduction (mostly in E. coli or co-expressed with OXA-2-like and/or SHV ß-lactamases (K. pneumoniae and P. mirabilis. A new blaTEMvariant (TEM-163 was described in an E. coli strain having an AMC MIC value of 16/8 µg/ml. TEM-163 contains Arg275Gln and His289Leu amino acid substitutions. On the basis of the high specific activity and low IC50 for clavulanic acid observed, the resistance pattern seems to be due to overproduction of the new variant of broad spectrumß-lactamase rather than to an inhibitor-resistant TEM (IRT-like behavior.

  12. Whole genome sequencing of Escherichia coli encoding blaNDM isolated from humans and companion animals in Egypt

    Science.gov (United States)

    Companion animals are a source of zoonotic infections and especially important considering the potential of companion animals to harbor antibiotic resistant pathogens. In this study, blaNDM positive Escherichia coli from companion animals, humans, and the environment from Mansoura, Egypt were charac...

  13. Diseminación de blaIMP-8 en enterobacterias aisladas en un hospital de Buenos Aires

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    Ana M Togneri

    Full Text Available Entre agosto de 2008 y diciembre de 2011 se detectaron en el Hospital Interzonal General de Agudos «Evita» de Lanús 6 aislamientos de enterobacterias productoras de metalo-ß-lactamasas, distribuidos en tres especies: Enterobacter cloacae (4, Klebsiella oxytoca (1 y Citrobacter freundii (1. Los seis aislamientos presentaron un perfil de multirresistencia y se confirmó la presencia del gen blaIMP-8. Cinco aislamientos además expresaron la ß-lactamasa de espectro extendido PER-2. El gen blaIMP-8 fue hallado como primer casete de un integrón de clase 1. Sin embargo, la secuencia 3´ conservada no pudo detectarse en tres aislamientos. En todos los casos, el gen blaIMP-8 fue transferido por conjugación a Escherichia coli resistente a azida. Mediante PFGE se observó que los cuatro aislamientos de E. cloacae no estuvieron genéticamente relacionados. Estos son los primeros hallazgos de metalo-ß-lactamasas en la institución, que sugieren una posible diseminación horizontal del gen blaIMP-8 intra e interespecies.

  14. blaCTX-M-I group extended spectrum beta lactamase-producing Salmonella typhi from hospitalized patients in Lagos, Nigeria

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    Akinyemi KO

    2015-05-01

    Full Text Available Kabiru O Akinyemi,1 Bamidele A Iwalokun,2 Olajide O Alafe,1 Sulaiman A Mudashiru,1 Christopher Fakorede,11Department of Microbiology, Lagos State University, Ojo, Lagos, Nigeria; 2Biochemistry and Nutrition Division, Nigerian Institute of Medical Research, Yaba, Lagos, NigeriaPurpose: The global spread of blaCTX-M-I extended-spectrum beta-lactamase (ESBL-producing Salmonella spp. remains a major threat to treatment and control. Evidence of emergence and spread of this marker are lacking in Nigeria. This study investigated blaCTX-M-I ESBL production among Salmonella isolates from hospitalized patients.Methods: Patients (158 total made up of two groups were evaluated. Group A was composed of 135 patients with persistent pyrexia and group B was composed of 23 gastroenteritis patients and their stool samples. Samples were cultured, and isolates were identified and were subjected to antibiotic susceptibility testing by standard methods. Isolates were further screened for ESBL production, blaCTX-M-I genes and transferability by double disk synergy test, plasmid extraction, polymerase chain reaction, and conjugation experiment.Results: Thirty-five (25.9% Salmonella isolates were identified from group A, of which 74.3% were S. typhi, 22.9% were S. paratyphi and two (5.7% were invasive non-typhoidal S. enteritidis. Nine Plasmodium falciparum infections were recorded, four of which were identified as co-infections with typhoidal Salmonella. Only two (8.7% S. enteritidis samples were obtained from group B (P>0.05. A total of 24 isolates were ESBL-positive, eliciting resistance to five to seven antibiotics, and were multiple-drug resistant. ESBL production due to the blaCTX-M-I gene cluster was detected in eleven (45.8% Salmonella isolates. Nine (81.8% of the eleven blaCTX-M-I ESBL producers were S. typhi and two (18.2% isolates were S. enteritidis. Four of nine S. typhi blaCTX-M-I ESBL-producing strains harbored 23 kb self-transmissible plasmid that was co

  15. Molecular epidemiology of outbreak-related pseudomonas aeruginosa strains carrying the novel variant blaVIM-17 metallo-beta-lactamase gene.

    Science.gov (United States)

    Siarkou, Victoria I; Vitti, Danai; Protonotariou, Efthimia; Ikonomidis, Alexandros; Sofianou, Danai

    2009-04-01

    A study was designed to investigate the molecular epidemiological characteristics of multidrug-resistant outbreak-related Pseudomonas aeruginosa isolates collected in a university hospital in northern Greece. Of 29 nonreplicate P. aeruginosa isolates resistant to carbapenems and ceftazidime, 14 were positive for metallo-beta-lactamase production. PCR analyses with primers specific for bla(VIM) and bla(IMP) revealed that 13 isolates carried a novel bla(VIM-2) gene variant, designated bla(VIM-17), and only 1 isolate carried bla(VIM-2), a gene predominant among P. aeruginosa strains in Greek hospitals. Pulsed-field gel electrophoresis of XbaI-digested genomic DNAs showed a close genetic relationship for 12 of 13 bla(VIM-17)-carrying outbreak-related isolates, which were of the O11 serotype; the clonally unrelated isolate carrying bla(VIM-17) was of the O12 serotype. PCR mapping strategies for the detection of class 1 integrons and sequencing approaches revealed the presence of integrons containing one bla(VIM) cassette flanked by two aacA29 cassettes. These integrons were similar but not identical to In59 (GenBank accession number AF263519) initially described in France. All isolates carrying bla(VIM-17), regardless of their genetic profile, had an identical integron, named In59.3, indicating that although the hospital outbreak was mainly due to clonal dissemination, the horizontal transmission of the bla(VIM-17)-containing integron among P. aeruginosa isolates should also have occurred. An outbreak-related isolate and a control strain, both of which carried the bla(VIM-2) gene but which were clonally distinct, had an identical integron, named In59.2, which differed only at the level of the bla(VIM) gene from In59.3 integrons, suggesting a common ancestry. The spread of the bla(VIM-17)-containing integron in clonally unrelated P. aeruginosa isolates without any evidence of plasmid carriage is probably associated with a transposon.

  16. Knowledge, perception, practices and barriers of healthcare professionals in Bosnia and Herzegovina towards adverse drug reaction reporting and pharmacovigilance

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    Maša Amrain

    2014-09-01

    Full Text Available Introduction: Pharmacovigilance is an arm of patient care. No one wants to harm patients, but unfortunately any medicine will sometimes do just this. Underreporting of adverse drug reactions by healthcare professionals is a major problem in many countries. In order to determine whether our pharmacovigilance system could be improved, and identify reasons for under-reporting, a study to investigate the role of health care professionals in adverse drug reaction (ADR reporting was performed.Methods: A pretested questionnaire comprising of 20 questions was designed for assessment of knowledge, perceptions, practice and barriers toward ADR reporting on a random sample of 1000 healthcare professionals in Bosnia and Herzegovina.Results: Of the 1000 respondents, 870 (87% completed the questionnaire. The survey showed that 62.9% health care professionals would report ADR to the Agency for Medicinal Products and Medical Device of Bosnia and Herzegovina (ALMBIH. Most of surveyed respondents has a positive perception towards ADR reporting, and believes that this is part of their professional and legal obligation, and they also recognize the importance of reporting adverse drug reactions. Only small percent (15.4% of surveyed health care professionals reported adverse drug reaction.Conclusions: The knowledge of ADRs and how to report them is inadequate among health care professionals. Perception toward ADR reporting was positive, but it is not reflected in the actual practice of ADRs, probably because of little experience and knowledge regarding pharmacovigilance. Interventions such as education and training, focusing on the aims of pharmacovigilance, completing the ADR form and clarifying the reporting criteria are strongly recommended.

  17. The importance of monitoring adverse drug reactions in elderly patients: the results of a long-term pharmacovigilance programme.

    Science.gov (United States)

    Carnovale, Carla; Gentili, Marta; Fortino, Ida; Merlino, Luca; Clementi, Emilio; Radice, Sonia; ViGer Group

    2016-01-01

    To recognise and prevent ADRs (including DDIs) in the elderly through a 4-year post-marketing active pharmacovigilance programme. The programme was designed to enhance high quality spontaneous reporting of ADRs in elderly patients by sampling the Italian population and was termed 'Pharmacovigilance in Geriatry (ViGer)'. ADRs were collected for adults aged over 65 years of age treated in nursing homes, continuing care retirement communities and territorial health services in Lombardy. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analysed with respect to time, sex, category of ADR, seriousness, suspected medicines, notoriety. We analysed all the potential DDIs. We detected 1073 cases reports corresponding to 2110 ADRs. Vaccines, antibacterials for systemic use and antineoplastic agents were the pharmacotherapeutic subgroups most frequently involved. 18% of ADRs reports were classified as serious. In 752 reports patients were described as in polytherapy; in 55 patients (7.3%) the reported ADR were probably preventable because of DDIs involvement. The ViGer project demonstrated that active pos-marketing pharmacovigilance programmes are a valid strategy to increase awareness on geriatrics pharmacology, reduce underreporting and provide important information on previous unknown ADRs and DDIs, resulting in a therapy optimisation in clinical practice in the geriatric setting.

  18. Imipenem-resistant Pseudomonas aeruginosa strains carry metallo-beta-lactamase gene bla(VIM) in a level I Iranian burn hospital.

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    Bahar, Mohammad Ali; Jamali, Shohreh; Samadikuchaksaraei, Ali

    2010-09-01

    In this study, we aimed to determine the distribution of bla(VIM) and bla(IMP) transferable genes in Pseudomonas aeruginosa isolates from infected burn wounds in an Iranian level I burn care center. These genes confer imipenem resistance and increase the mortality rate of burn patients. P. aeruginosa isolates from burn patients were tested for antibiotic susceptibility with Kirby-Bauer disk diffusion method and for production of metallo-beta-lactamase (MBL) by EDTA disk method. DNA was purified from isolates with positive MBL results and underwent PCR for detection of bla(VIM) and bla(IMP) genes. MBL was produced by 23 imipenem-resistant isolates and bla(VIM) gene was detected in all of these isolates. None of the isolates carried bla(IMP) gene. Mortality rate of infection with MBL-producing Pseudomonas strains was 82.6% in this hospital while the mortality rate for non-MBL-producing Pseudomonas was 22.7%. We found that all MBL-producing isolates in this hospital carry bla(VIM) gene. This result is similar to the previous Iranian study and emphasizes the importance of VIM family of MBLs in Iran. Timely identification of these strains and strict isolation methods can prevent spread of this transferable gene to other Gram-negative bacteria and prevent the subsequent outbreak of high mortality. 2009 Elsevier Ltd and ISBI. All rights reserved.

  19. Detection of an Escherichia coli Sequence Type 167 Strain with Two Tandem Copies of blaNDM-1 in the Chromosome.

    Science.gov (United States)

    Shen, Ping; Yi, Maoli; Fu, Ying; Ruan, Zhi; Du, Xiaoxing; Yu, Yunsong; Xie, Xinyou

    2017-01-01

    New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae has disseminated rapidly throughout the world and poses an urgent threat to public health. Previous studies confirmed that the bla NDM-1 gene is typically carried in plasmids but rarely in chromosome. We discovered a multidrug-resistant Escherichia coli strain Y5, originating from a urine sample and containing the bla NDM-1 gene, which did not transfer by either conjugation or electrotransformation. We confirmed the possibility of its chromosome location by S1-pulsed-field gel electrophoresis (PFGE) and XbaI-PFGE, followed by Southern blotting. To determine the genomic background of bla NDM-1 , the genome of Y5 was completely sequenced and compared to other reference genomes. The results of our study revealed that this isolate consists of a 4.8-Mbp chromosome and three plasmids, it is an epidemic clone of sequence type (ST) 167, and it shows 99% identity with Escherichia coli 6409 (GenBank accession no. CP010371), which lacks the same bla NDM-1 gene-surrounding structure as Y5. The bla NDM-1 gene is embedded in the chromosome along with two tandem copies of an insertion sequence common region 1 (ISCR1) element (sul1-ARR-3-cat-bla NDM-1 -bleo-ISCR1), which appears intact in the plasmid from Proteus mirabilis (GenBank accession no. KP662515). The genomic context indicates that the ISCR1 element mediated the bla NDM-1 transposition from a single source plasmid to the chromosome. Our study is the first report of an Enterobacteriaceae strain harboring a chromosomally integrated bla NDM-1 , which directly reveals the vertical spreading pattern of the gene. Close surveillance is urgently needed to monitor the emergence and potential spread of ST167 strains that harbor bla NDM-1 . Copyright © 2016 American Society for Microbiology.

  20. IncA/C Plasmid Carrying bla(NDM-1), bla(CMY-16), and fosA3 in a Salmonella enterica Serovar Corvallis Strain Isolated from a Migratory Wild Bird in Germany.

    Science.gov (United States)

    Villa, L; Guerra, B; Schmoger, S; Fischer, J; Helmuth, R; Zong, Z; García-Fernández, A; Carattoli, A

    2015-10-01

    A Salmonella enterica serovar Corvallis strain was isolated from a wild bird in Germany. This strain carried the IncA/C2 pRH-1238 plasmid. Complete sequencing of the plasmid was performed, identifying the blaNDM-1, blaCMY-16, fosA3, sul1, sul2, strA, strB, aac(6')-Ib, aadA5, aphA6, tetA(A), mphA, floR, dfrA7, and merA genes, which confer clinically relevant resistance to most of the antimicrobial classes, including β-lactams with carbapenems, fosfomycin, aminoglycosides, co-trimoxazole, tetracyclines, and macrolides. The strain likely originated from the Asiatic region and was transferred to Germany through the Milvus migrans migratory route. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. High prevalence of blaOXA-23 in Acinetobacter spp. and detection of blaNDM-1 in A. soli in Cuba: report from National Surveillance Program (2010–2012

    Directory of Open Access Journals (Sweden)

    D. Quiñones

    2015-09-01

    Full Text Available As a first national surveillance of Acinetobacter in Cuba, a total of 500 Acinetobacter spp. isolates recovered from 30 hospitals between 2010 and 2012 were studied. Acinetobacter baumannii–calcoaceticus complex accounted for 96.4% of all the Acinetobacter isolates, while other species were detected at low frequency (A. junii 1.6%, A. lwoffii 1%, A. haemolyticus 0.8%, A. soli 0.2%. Resistance rates of isolates were 34–61% to third-generation cephalosporins, 49–50% to β-lactams/inhibitor combinations, 42–47% to aminoglycosides, 42–44% to carbapenems and 55% to ciprofloxacin. However, resistance rates to colistin, doxycycline, tetracycline and rifampin were less than 5%. Among carbapenem-resistant isolates, 75% harboured different blaOXA genes (OXA-23, 73%; OXA-24, 18%; OXA-58, 3%. The blaNDM-1 gene was identified in an A. soli strain, of which the species was confirmed by sequence analysis of 16S rRNA gene, rpoB, rpoB–rpoC and rpoL–rpoB intergenic spacer regions and gyrB. The sequences of blaNDM-1 and its surrounding genes were identical to those reported for plasmids of A. baumannii and A. lwoffi strains. This is the first report of blaNDM-1 in A. soli, together with a high prevalence of OXA-23 carbapenemase for carbapenem resistance in Acinetobacter spp. in Cuba.

  2. A pharmacovigilance study of adults on highly active antiretroviral therapy, South Africa: 2007 – 2011

    Science.gov (United States)

    Dube, Nomathemba Michell; Summers, Robert; Tint, Khin-San; Mayayise, Guistee

    2012-01-01

    Background Of the 1.6 million South African people infected with human immunodeficiency virus (HIV), approximately 970,000 (55%) have been initiated on HAART. Despite these numbers, very little has been published about the safety profile of antiretroviral (ARV) medicines in the country. This study was performed at the Medunsa National Pharmacovigilance Centre and aimed to describe the demographic characteristics of patients enrolled in the pharmacovigilance surveillance study; highly active antiretroviral therapy (HAART) initiation regimen patterns; reasons for regimen changes; and adverse effects of ARV medicines. Methods A cohort study of HIV-infected individuals aged 15 years or older who were on ARV medicines was conducted at four sentinel sites. Results After HAART initiation, with an average lapse of 17.8 months (range: 0 – 83.8 months), 2,815 patients were enrolled into the study. Results show that patients were observed for 1,606.2 person-years for pharmacy visits (collection of ARV medicines) and 817.1 person-years for clinical visits (consultation with the doctor). Females constituted 69.6% (1,958/2,815) of the study population. Almost all patients initiated HAART on first-line regimens (2,801/2,815). Some patients (6.7%, 190/2,815) dropped out of the study after HAART initiation. Reasons for regimen changes were not recorded for 2.5% (22/891) of the patients who changed regimens. The primary reason for regimen changes was drug-related toxicity (76.1%, 678/891), mostly evident in patients taking first-line regimens. Adverse effects experienced by patients were polyneuropathy (24.0%, 163/678); lipodystrophy (23.9%, 162/678); neuropathy (10.6%, 72/678); and suspected lactic acidosis (3.8%, 26/678). Conclusion The majority of prescribers complied with the HAART guidelines and initiated most patients on first-line regimens. However, adverse effects are evident in patients taking first-line regimens. We recommend that the Department of Health should

  3. A description of signals during the first 18 months of the EMA pharmacovigilance risk assessment committee.

    Science.gov (United States)

    Pacurariu, Alexandra C; Coloma, Preciosa M; van Haren, Anja; Genov, Georgy; Sturkenboom, Miriam C J M; Straus, Sabine M J M

    2014-12-01

    New pharmacovigilance legislation in the European Union has underlined the importance of signal management, giving the European Medicines Agency's newly established Pharmacovigilance Risk Assessment Committee (PRAC) the mandate to oversee all aspects of the use of medicinal products including detection, assessment, minimization, and communication relating to the risk of adverse reactions. In this study, we describe the signals as brought to the PRAC during the first 18 months of its operation and the ensuing regulatory actions. Data were collected from publicly available sources, for the period July 2012-December 2013, classified according to predefined rules, and described using the appropriate descriptive statistics. Suspected adverse drug reactions were categorized into the Medical Dictionary for Regulatory Affairs and drug names were mapped to the Anatomical Therapeutic Chemical codes. During the study period, 125 signals concerning 96 medicinal products were discussed by the PRAC. The majority of signals were triggered by spontaneous reports (62%) and the median drug age (since marketing authorization) for drugs that prompted a signal was 12 years, significantly less compared with drugs that had no signal within the same period (20 years). The mean time until a decision was reached by the PRAC was 75 days (median 30 days, range 0-273) with 43% of all decisions taken during the first meeting. The decisions to start a referral and to send a direct healthcare professional communication took the least amount of time [54 days (median 27 days, range 0-186) and 51 days (median 0 days, range 0-153)]. The importance of spontaneous reporting in signal detection and monitoring of safety issues throughout the entire life cycle of a medicinal product is confirmed in this study. The amount of time a drug has been on the market is correlated with the number of signals detected. The PRAC decision-making process seems efficient particularly with respect to serious concerns

  4. mcr-1 and blaKPC-3 in Escherichia coli Sequence Type 744 after Meropenem and Colistin Therapy, Portugal.

    Science.gov (United States)

    Tacão, Marta; Tavares, Rafael Dos Santos; Teixeira, Pedro; Roxo, Inês; Ramalheira, Elmano; Ferreira, Sónia; Henriques, Isabel

    2017-08-01

    Escherichia coli Ec36 was recovered from a patient in Portugal after treatment with meropenem and colistin. Besides an IncF plasmid with Tn1441d-bla KPC-3 , already reported in clinical strains in this country, E. coli Ec36 co-harbored an IncX4::mcr-1 gene. Results highlight emerging co-resistance to carbapenems and polymyxins after therapy with drugs from both classes.

  5. Hip region muscular dystrophy and emergence of motor deficits in dysferlin-deficient Bla/J mice.

    Science.gov (United States)

    Nagy, Nadia; Nonneman, Randal J; Llanga, Telmo; Dial, Catherine F; Riddick, Natallia V; Hampton, Tom; Moy, Sheryl S; Lehtimäki, Kimmo K; Ahtoniemi, Toni; Puoliväli, Jukka; Windish, Hillarie; Albrecht, Douglas; Richard, Isabelle; Hirsch, Matthew L

    2017-03-01

    The identification of a dysferlin-deficient animal model that accurately displays both the physiological and behavior aspects of human dysferlinopathy is critical for the evaluation of potential therapeutics. Disease progression in dysferlin-deficient mice is relatively mild, compared to the debilitating human disease which manifests in impairment of particular motor functions. Since there are no other known models of dysferlinopathy in other species, locomotor proficiency and muscular anatomy through MRI (both lower leg and hip region) were evaluated in dysferlin-deficient B6.A- Dysf prmd /GeneJ (Bla/J) mice to define disease parameters for therapeutic assessment. Despite the early and progressive gluteal muscle dystrophy and significant fatty acid accumulation, the emergence of significant motor function deficits was apparent at approximately 1 year of age for standard motor challenges including the rotarod, a marble bury test, grip strength, and swimming speed. Earlier observations of decreased performance for Bla/J mice were evident during extended monitoring of overall exploration and rearing activity. Comprehensive treadmill gait analyses of the Bla/J model indicated significant differences in paw placement angles and stance in relation to speed and platform slope. At 18 months of age, there was no significant difference in the life expectancy of Bla/J mice compared to wild type. Consistent with progressive volume loss and fatty acid accumulation in the hip region observed by MRI, mass measurement of individual muscles confirmed gluteal and psoas muscles were the only muscles demonstrating a significant decrease in muscle mass, which is analogous to hip-girdle weakness observed in human dysferlin-deficient patients. Collectively, this longitudinal analysis identifies consistent disease parameters that can be indicators of efficacy in studies developing treatments for human dysferlin deficiency. © 2017 The Authors. Physiological Reports published by Wiley

  6. The sudden dominance of blaCTX-M harbouring plasmids in Shigella spp. Circulating in Southern Vietnam.

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    Nhu Thi Khanh Nguyen

    2010-06-01

    Full Text Available Plasmid mediated antimicrobial resistance in the Enterobacteriaceae is a global problem. The rise of CTX-M class extended spectrum beta lactamases (ESBLs has been well documented in industrialized countries. Vietnam is representative of a typical transitional middle income country where the spectrum of infectious diseases combined with the spread of drug resistance is shifting and bringing new healthcare challenges.We collected hospital admission data from the pediatric population attending the hospital for tropical diseases in Ho Chi Minh City with Shigella infections. Organisms were cultured from all enrolled patients and subjected to antimicrobial susceptibility testing. Those that were ESBL positive were subjected to further investigation. These investigations included PCR amplification for common ESBL genes, plasmid investigation, conjugation, microarray hybridization and DNA sequencing of a bla(CTX-M encoding plasmid.We show that two different bla(CTX-M genes are circulating in this bacterial population in this location. Sequence of one of the ESBL plasmids shows that rather than the gene being integrated into a preexisting MDR plasmid, the bla(CTX-M gene is located on relatively simple conjugative plasmid. The sequenced plasmid (pEG356 carried the bla(CTX-M-24 gene on an ISEcp1 element and demonstrated considerable sequence homology with other IncFI plasmids.The rapid dissemination, spread of antimicrobial resistance and changing population of Shigella spp. concurrent with economic growth are pertinent to many other countries undergoing similar development. Third generation cephalosporins are commonly used empiric antibiotics in Ho Chi Minh City. We recommend that these agents should not be considered for therapy of dysentery in this setting.

  7. Bacillus licheniformis BlaR1 L3 Loop Is a Zinc Metalloprotease Activated by Self-Proteolysis

    Science.gov (United States)

    Sépulchre, Jérémy; Amoroso, Ana; Joris, Bernard

    2012-01-01

    In Bacillus licheniformis 749/I, BlaP β-lactamase is induced by the presence of a β-lactam antibiotic outside the cell. The first step in the induction mechanism is the detection of the antibiotic by the membrane-bound penicillin receptor BlaR1 that is composed of two functional domains: a carboxy-terminal domain exposed outside the cell, which acts as a penicillin sensor, and an amino-terminal domain anchored to the cytoplasmic membrane, which works as a transducer-transmitter. The acylation of BlaR1 sensor domain by the antibiotic generates an intramolecular signal that leads to the activation of the L3 cytoplasmic loop of the transmitter by a single-point cleavage. The exact mechanism of L3 activation and the nature of the secondary cytoplasmic signal launched by the activated transmitter remain unknown. However, these two events seem to be linked to the presence of a HEXXH zinc binding motif of neutral zinc metallopeptidases. By different experimental approaches, we demonstrated that the L3 loop binds zinc ion, belongs to Gluzincin metallopeptidase superfamily and is activated by self-proteolysis. PMID:22623956

  8. Eco-pharmacovigilance of non-steroidal anti-inflammatory drugs: Necessity and opportunities.

    Science.gov (United States)

    He, Bing-Shu; Wang, Jun; Liu, Juan; Hu, Xia-Min

    2017-08-01

    Eco-pharmacovigilance (EPV) is a practical and powerful approach to minimize the potential risks posed by pharmaceutical residues in environment. However, it is impracticable to practise rigorous and unitary EPV process for all the existing and new pharmaceuticals. Here, we focused on non-steroidal anti-inflammatory drugs (NSAIDs), and discussed the necessity and potential opportunities of practising EPV of NSAIDs. We found that the consumption of NSAIDs is huge and ubiquitous across the globe. NSAIDs were worldwidely reported as one of the most dominant and frequently detected groups in environmental matrices including wastewater, surface water, suspended solids, sediments, groundwater, even drinking water. Besides, there is definitive evidence for the adverse impacts of NSAID residues on scavenging birds and aquatic species. These data suggested the necessity of implementing EPV of NSAIDs. From the perspective of drug administration, we identified some things that can be done as management practice options for EPV implementation on NSAIDs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Safety of Factor XIII Concentrate: Analysis of More than 20 Years of Pharmacovigilance Data

    Science.gov (United States)

    Solomon, Cristina; Korte, Wolfgang; Fries, Dietmar; Pendrak, Inna; Joch, Christine; Gröner, Albrecht; Birschmann, Ingvild

    2016-01-01

    Background Plasma-derived factor XIII (FXIII) concentrate is an effective treatment for FXIII deficiency. We describe adverse drug reactions (ADRs) reported during pharmacovigilance monitoring of Fibrogammin®/Corifact® and review published safety data. Methods Postmarketing safety reports recorded by CSL Behring from June 1993 to September 2013 were analyzed. Clinical studies published during the same period were also reviewed. Results Commercial data indicated that 1,653,450,333 IU FXIII concentrate were distributed over the review period, equivalent to 1,181,036 doses for a 70 kg patient. 75 cases were reported (one/15,700 standard doses or 22,046,000 IU). Reports of special interest included 12 cases of possible hypersensitivity reactions (one/98,400 doses or 137,787,500 IU), 7 with possible thromboembolic events (one/168,700 doses or 236,207,200 IU), 5 of possible inhibitor development (one/236,200 doses or 330,690,100 IU), and 20 of possible pathogen transmission (one/59,100 doses or 82,672,500 IU). 19 pathogen transmission cases involved viral infection; 4 could not be analyzed due to insufficient data, but for all others a causal relationship to the product was assessed as unlikely. A review of published literature revealed a similar safety profile. Conclusion Assessment of ADRs demonstrated that FXIII concentrate carries a low risk of ADRs across various clinical situations, suggesting a favorable safety profile. PMID:27781024

  10. Facilitating adverse drug event detection in pharmacovigilance databases using molecular structure similarity: application to rhabdomyolysis

    Science.gov (United States)

    Vilar, Santiago; Harpaz, Rave; Chase, Herbert S; Costanzi, Stefano; Rabadan, Raul

    2011-01-01

    Background Adverse drug events (ADE) cause considerable harm to patients, and consequently their detection is critical for patient safety. The US Food and Drug Administration maintains an adverse event reporting system (AERS) to facilitate the detection of ADE in drugs. Various data mining approaches have been developed that use AERS to detect signals identifying associations between drugs and ADE. The signals must then be monitored further by domain experts, which is a time-consuming task. Objective To develop a new methodology that combines existing data mining algorithms with chemical information by analysis of molecular fingerprints to enhance initial ADE signals generated from AERS, and to provide a decision support mechanism to facilitate the identification of novel adverse events. Results The method achieved a significant improvement in precision in identifying known ADE, and a more than twofold signal enhancement when applied to the ADE rhabdomyolysis. The simplicity of the method assists in highlighting the etiology of the ADE by identifying structurally similar drugs. A set of drugs with strong evidence from both AERS and molecular fingerprint-based modeling is constructed for further analysis. Conclusion The results demonstrate that the proposed methodology could be used as a pharmacovigilance decision support tool to facilitate ADE detection. PMID:21946238

  11. Therapeutic monoclonal antibodies and the need for targeted pharmacovigilance in India.

    Science.gov (United States)

    Kalaivani, M; Singh, Abhishank; Kalaiselvan, V

    2015-01-01

    A growing number of innovative mAb therapeutics are on the global market, and biosimilar versions have now also been approved, including in India. Although efficacy and safety is demonstrated prior to approval, targeted pharmacovigilance is essential for the identification and assessment of risk for any mAb products. We analyzed the ADR data related to mAbs reported to the NCC-PvPI through the spontaneous reporting system Vigiflow during April 2011 to February 2014 to identify mAbs with the highest number of ADR including fatal/serious ADR. Only 0.72% reports were related to mAbs. Although 15 mAbs are approved in the country, only 6 mAbs were reported through Vigiflow. Rituximab was highly reported, and no fatal/serious ADR related to any mAbs were reported during the study period. Our study shows that PvPI is effective and robust system in the detection and assessment of risks associated with the use of mAbs.

  12. Dissemination of a bla(VIM-2)-carrying integron among Enterobacteriaceae species in Mexico: report from the SENTRY Antimicrobial Surveillance Program.

    Science.gov (United States)

    Morfin-Otero, Rayo; Rodriguez-Noriega, Eduardo; Deshpande, Lalitagauri M; Sader, Helio S; Castanheira, Mariana

    2009-03-01

    Three VIM-2-producing Enterobacteriaceae (two Enterobacter cloacae and one Klebsiella oxytoca) isolates recovered from patients in a Mexican hospital were characterized during the SENTRY Antimicrobial Surveillance Program (2005-2007). These strains carried identical bla(VIM-2) integrons in a 450-kb plasmid. The interspecies dissemination of this bla(VIM-2)-harboring element emphasizes the potential for spread of genetic structures carrying metallo-beta-lactamases that could limit therapeutic options in this geographic region.

  13. blaVIM-7, an Evolutionarily Distinct Metallo-β-Lactamase Gene in a Pseudomonas aeruginosa Isolate from the United States

    OpenAIRE

    Toleman, Mark A.; Rolston, Kenneth; Jones, Ronald N.; Walsh, Timothy R.

    2004-01-01

    As part of the CANCER Antimicrobial Surveillance Program in North America, a Pseudomonas aeruginosa isolate, strain 07-406, was shown to possess a metallo-β-lactamase, designated VIM-7. blaVIM-7 is located on a 24-kb plasmid which can be readily transferred into Enterobacteriaceae and other pseudomonads. This is the first report of a mobile metallo-β-lactamase gene, blaVIM-7, being detected within the United States.

  14. Development of a novel regulatory pharmacovigilance prioritisation system: an evaluation of its performance at the UK Medicines and Healthcare products Regulatory Agency.

    Science.gov (United States)

    Seabroke, Suzie; Wise, Lesley; Waller, Patrick

    2013-10-01

    The prioritisation of drug safety issues for further evaluation or regulatory action is critical to ensure that acceptable timelines and appropriate resource allocation are defined to meet public health and regulatory obligations. Our objective was to develop, pilot and implement a novel tool for prioritising pharmacovigilance issues within the Medicines and Healthcare products Regulatory Agency (MHRA). An initial system was developed empirically and then piloted over a 10-month period in the pharmacovigilance signal management meeting at the MHRA that discusses potential pharmacovigilance issues, and determines, through consensus, their priority and a timescale for action. The priority assigned by the tool was compared with the priority decided by collective judgement at the meeting. Once an acceptable level of concordance between the tool and the meeting had been achieved, the finalised tool was implemented into routine use at the MHRA, with an evaluation of its performance conducted after the first year. The Regulatory Pharmacovigilance Prioritisation System (RPPS) tool prioritises pharmacovigilance issues according to the following four broad categories, each with four inputs: strength of evidence, public health implications, agency regulatory obligations and public perceptions. A weighted scoring system links the inputs to a pre-defined number of points where if a threshold is reached then the points are awarded. The overall priority is determined by the sum of all points obtained from each of the inputs. The pilot study included a total of 73 pharmacovigilance issues during the 10-month study period, with an overall exact agreement between the RPPS priority and the collective judgement of the meeting of 60.3 %. Where exact agreement was not obtained, the RPPS generally prioritised the issues slightly higher than the meeting. Over the first year following implementation, the RPPS achieved an overall exact agreement of 82.2 %. Following the pilot study and

  15. ESBL, plasmidic AmpC, and associated quinolone resistance determinants in coliforms isolated from hospital effluent: first report of qnrB2, qnrB9, qnrB19, and blaCMY-4 in Algeria.

    Science.gov (United States)

    Anssour, Lynda; Messai, Yamina; Derkaoui, Meriem; Alouache, Souhila; Estepa, Vanesa; Somalo, Sergio; Torres, Carmen; Bakour, Rabah

    2014-04-01

    The characterization of extended-spectrum beta-lactamases , plasmidic AmpC (pAmpC), and associated plasmid-mediated quinolone resistance (PMQR) determinants in cefotaxime-resistant coliforms isolated from hospital effluent in Algiers showed blaCTX-M genes in 89%, blaTEM-1 in 79·8%, and pAmpC genes (blaCIT) in 2·7% isolates. Association of ISEcp1B with blaCTX-M was found in all CTX-M+ isolates, and 97·2% harboured class 1 integrons. Sequencing showed blaCTX-M-15, blaCTX-M-3, and blaCMY-4 genes. blaCTX-M-3 and blaCTX-M-15 were located in Inc L/M conjugative plasmids. The PMQR determinants identified were qnrB1, qnrB2, qnrB9, qnrB19, qnrS2, and aac(6')-Ib-cr. qnrB2, qnrB9, qnrB19, and blaCMY-4 are described for the first time in Algeria and qnrB19 for the first time in non-clinical environments. This study highlights the major potential role of hospital effluents as providers of resistance genes to natural environments.

  16. Evaluation of 'SAEFVIC', A Pharmacovigilance Surveillance Scheme for the Spontaneous Reporting of Adverse Events Following Immunisation in Victoria, Australia.

    Science.gov (United States)

    Clothier, Hazel J; Crawford, Nigel W; Russell, Melissa; Kelly, Heath; Buttery, Jim P

    2017-06-01

    Australia is traditionally an early adopter of vaccines, therefore comprehensive and effective post-licensure vaccine pharmacovigilance is critical to maintain confidence in immunisation, both nationally and internationally. With adverse event following immunisation (AEFI) surveillance the responsibility of Australian jurisdictions, Victoria operates an enhanced passive AEFI surveillance system integrated with clinical services, called 'SAEFVIC' (Surveillance of Adverse Events Following Vaccination In the Community). The aim of this study was to evaluate Victoria's current AEFI surveillance system 'SAEFVIC' and inform ongoing quality improvement of vaccine pharmacovigilance in Victoria and Australia. We conducted a retrospective structured desktop evaluation of AEFI reporting received by SAEFVIC from 2007 to 2014, to evaluate the system according to its stated objectives, i.e. to improve AEFI reporting; provide AEFI signal detection; and to maintain consumer confidence in vaccination. AEFI reporting has tripled since SAEFVIC commenced (incidence risk ratio [IRR] 3.04, 95% confidence interval [CI] 2.35-3.93), raising Victoria to be the lead jurisdiction by AEFI reporting volume and to rank third by population reporting rate nationally. The largest increase was observed in children. Data were utilised to investigate potential signal events and inform vaccine policy. Signal detection required clinical suspicion by surveillance nurses, or prior vaccine-specific concerns. Subsequent vaccination post-AEFI was documented for 56.2% (95% CI 54.1-58.4) of reports, and the proportion of children due or overdue for vaccination was 2.3% higher for those reporting AEFI compared with the general population. SAEFVIC has improved AEFI surveillance, facilitates signal investigation and validation, and supports consumer confidence in immunisation. Expansion of the system nationally has the potential to improve capacity and capability of vaccine pharmacovigilance, particularly

  17. Validation and Reproducibility of the Updated French Causality Assessment Method: an Evaluation by Pharmacovigilance Centres & Pharmaceutical Companies.

    Science.gov (United States)

    Théophile, Hélène; Dutertre, Jean-Paul; Gérardin, Marie; Valnet-Rabier, Marie-Blanche; Bidault, Irène; Guy, Claire; Haramburu, Françoise; Hillaire-Buys, Dominique; Méglio, Carmine; Arimone, Yannick

    2015-01-01

    Assess the validity and reproducibility of the updated version of the French causality assessment method in conditions approaching real-life use. A random sample of 31 drug-event pairs from the French pharmacovigilance database was assessed by the consensual judgement of three experts (gold standard). Separately, a team from a pharmacovigilance centre (PhVC) and another from a pharmaceutical company assessed these pairs using the current method, then with the updated method. To test the inter- and intra-rater reproducibility, two seniors and two juniors from a PhVC and a pharmaceutical company assessed the pairs twice with the updated method. A weighted kappa coefficient was used to measure the agreement of the two causality assessment methods with the consensual expert judgement (validity) as well as the agreement of the updated causality assessment over time (intra-rater reproducibility) and between evaluators (inter-rater reproducibility). Agreement between the current method and consensual expert judgement was fair for the PhVC team (weighted kappa [Kw] 0.33) and moderate for the pharmaceutical company team (Kw 0.41). For the updated method, agreement was better for both the PhVC (Kw 0.58) and the pharmaceutical company (Kw 0.52) teams. The inter- and intra-rater reproducibility of the updated method based on the intrinsic imputability was satisfactory overall (Kw 0.30-0.91). Discrepancies between evaluations from PhVC and pharmaceutical companies were observed with the updated method. The updated method performed better than the current one for drug causality assessment, suggesting that it should be used in routine pharmacovigilance. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  18. Interstitial lung disease induced by fluoxetine: Systematic review of literature and analysis of Vigiaccess, Eudravigilance and a national pharmacovigilance database.

    Science.gov (United States)

    Deidda, Arianna; Pisanu, Claudia; Micheletto, Laura; Bocchetta, Alberto; Del Zompo, Maria; Stochino, Maria Erminia

    2017-06-01

    We investigated a pulmonary adverse drug reaction possibly induced by fluoxetine, the Interstitial Lung Disease, by performing a systematic review of published case reports on this subject, a review of the World Health Organization VigiAccess database, of the European EudraVigilance database and of a national Pharmacovigilance database (Italian Pharmacovigilance Network). The research found a total of seven cases linking fluoxetine to Interstitial Lung Disease in the literature. 36 cases of interstitial lung disease related to fluoxetine were retrieved from the VigiAccess database (updated to July 2016), and 36 reports were found in EudraVigilance database (updated to June 2016). In the Italian Pharmacovigilance database (updated to August 2016), we found only one case of Interstitial Lung Disease, codified as "pulmonary disease". Our investigation shows that fluoxetine might be considered as a possible cause of Interstitial Lung Disease. In particular, although here we do not discuss the assessment of benefits and harms of fluoxetine, since this antidepressant is widely used, our review suggests that fluoxetine-induced Interstitial Lung Disease should be considered in patients with dyspnea, associated or not with dry cough, who are treated with this drug. An early withdrawn of fluoxetine could be useful to obtain a complete remission of this adverse drug reaction and special attention should be particularly devoted to long-term therapy, and to female and elderly patients. Although the spontaneous reporting system is affected by important limitations, drug post- marketing surveillance represents an important tool to evaluate the real world effectiveness and safety of drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Effectiveness of pharmacovigilance: multifaceted educational intervention related to the knowledge, skills and attitudes of multidisciplinary hospital staff

    Directory of Open Access Journals (Sweden)

    Fabiana Rossi Varallo

    Full Text Available OBJECTIVES: Most educational interventions in pharmacovigilance are designed to encourage physicians to report adverse drug reactions. However, multidisciplinary teams may play an important role in reporting drug-related problems. This study assessed the impact of a multifaceted educational intervention in pharmacovigilance on the knowledge, skills and attitudes of hospital professionals. METHOD: This prospective, open-label, non-randomized study was performed in a medium-complexity hospital in São Paulo, Brazil. The intervention involved four activities: 1 an interactive lecture, 2 a practical class, 3 a pre-post questionnaire administered to professionals on a multidisciplinary team, and 4 educational material. The intervention’s impact on the professionals’ knowledge and skills was assessed using the World Health Organization’s definitions. The intervention’s effect on the professionals’ attitudes was analysed by the prevalence of adverse drug event reports (adverse drug reactions, medication errors, therapeutic failure and drug quality deviations and the relevance (seriousness and expectancy of the events. RESULTS: One hundred seventy-three professionals were enrolled. A 70-fold increase in the number of adverse drug event reports was observed during the 12 months post-intervention. The intervention improved the professionals’ form-completion skills (p<0.0001 and their knowledge of pharmacovigilance (p<0.0001. The intervention also contributed to detecting serious drug-induced events. The nursing staff reported medication errors, and pharmacists and physiotherapists recognized serious adverse drug reactions. Physicians communicated suspicions of therapeutic failure. CONCLUSIONS: A multidisciplinary approach to drug-safety assessments contributes to identifying new, relevant drug-related problems and improving the rate of adverse drug event reporting. This strategy may therefore be applied to improve risk communication in

  20. Epidemiological characteristics of blaNDM-1 in Enterobacteriaceae and the Acinetobacter calcoaceticus-Acinetobacter baumannii complex in China from 2011 to 2012.

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    Weimei Ou

    Full Text Available The study aimed to investigate the prevalence and epidemiological characteristics of blaNDM-1 (encoding New Delhi metallo-β-lactamase 1 in Enterobacteriaceae and the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ABC in China from July 2011 to June 2012.PCR was used to screen for the presence of blaNDM-1 in all organisms studied. For blaNDM-1-positive strains, 16S rRNA analysis and Analytical Profile Index (API strips were used to identify the bacterial genus and species. The ABCs were reconfirmed by PCR detection of blaOXA-51-like. Antibiotic susceptibilities of the bacteria were assessed by determining minimum inhibitory concentration (MIC of them using two-fold agar dilution test, as recommended by the Clinical and Laboratory Standards Institute (CLSI. Molecular typing was performed using pulsed-field gel electrophoresis (PFGE. S1 nuclease-pulsed-field gel electrophoresis (S1-PFGE and Southern blot hybridization were conducted to ascertain the gene location of blaNDM-1. Conjugation experiments were conducted to determine the transmission of blaNDM-1-positive strains.Among 2,170 Enterobacteriaceae and 600 ABCs, seven Enterobacteriaceae strains and two A. calcoaceticus isolates from five different cities carried the blaNDM-1 gene. The seven Enterobacteriaceae strains comprised four Klebsiella pneumoniae, one Enterobacter cloacae, one Enterobacter aerogen and one Citrobacter freundii. All seven were non-susceptible to imipenem, meropenem or ertapenem. Two A. calcoaceticus species were resistant to imipenem and meropenem. Three K. pneumoniae showed the same PFGE profiles. The blaNDM-1 genes of eight strains were localized on plasmids, while one was chromosomal.Compared with previous reports, the numbers and species containing the blaNDM-1 in Enterobacteriaceae have significantly increased in China. Most of them are able to disseminate the gene, which is cause for concern. Consecutive surveillance should be implemented and should

  1. Classification of Recombinant Biologics in the EU: Divergence Between National Pharmacovigilance Centers.

    Science.gov (United States)

    Klein, Kevin; De Bruin, Marie L; Broekmans, Andre W; Stolk, Pieter

    2015-12-01

    Biological medicinal products (biologics) are subject to specific pharmacovigilance requirements to ensure that biologics are identifiable by brand name and batch number in adverse drug reaction (ADR) reports. Since Member States collect ADR data at the national level before the data is aggregated at the European Union (EU) level, it is important that an unambiguous understanding of which medicinal products belong to the biological product category exists. This study aimed to identify the level of consistency between Member States regarding the classification of biologics by national authorities responsible for ADR reporting. A sample list of recombinant biologics from the European Medicines Agency database of European Public Assessment Reports was created to analyze five Member States (Belgium, the Netherlands, Spain, Sweden, and the UK) according to which products were classified as biologics by each Member State. We calculated the Fleiss kappa value to analyze interrater reliability. A considerable divergence was identified regarding the classification of the 146 recombinant biologics from the sample list: one Member State classified 100 % of the recombinant biologics from the sample list as biologics, whereas the classification rates in the remaining four Member States ranged between 70 and 88 % for products available on the national market. The interrater reliability for 87 products available on the market in all five Member States was considered poor. Discrepancies exist between Member States in the classification of biologics; less divergence exists for common well-known biologics. These findings highlight the need to think about the best approaches to translate EU legislation into national practices. Additionally, we recommend a publicly available and frequently updated list of centrally authorized biologics.

  2. Neonatal adverse drug reactions: an analysis of reports to the French pharmacovigilance database.

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    Kaguelidou, Florentia; Beau-Salinas, Frédérique; Jonville-Bera, Annie Pierre; Jacqz-Aigrain, Evelyne

    2016-10-01

    Term and preterm neonates are at high risk for serious adverse drug reactions (ADRs). A descriptive study of reports registered in the French pharmacovigilance database from 1986 to 2012 were obtained. All reports concerning neonates (≤1 month of life) with direct drug exposure were retrieved. Characteristics of the reports, including reported ADR(s), drug(s) and the causality assessment using the French causality assessment method, were described. A total of 1688 reports were analyzed and more than half of them were classified as serious (n = 995). Median age at ADR occurrence was 9 days. Overall, 3127 ADRs were described in these reports in relation to 2238 suspect/interacting drugs. The most commonly reported system organ classes (SOCs) were injury, poisoning and procedural complications (16%), general disorders and administration site conditions (12.5%) and blood and lymphatic system disorders (12%). In the majority of ADRs reported (73%), infants fully recovered and less than 4% of neonates deceased as a consequence of the reported ADR. One out of five ADRs was associated with drug administration errors. Therapeutic classes commonly incriminated were anti-infectives, nervous system and alimentary tract drugs. Substances most frequently related to serious ADRs were zidovudine, ibuprofen and nevirapine. Among the 10 most frequently encountered drug-ADR pairs, two substances were mainly implicated, zidovudine in haematological adverse reactions and phytomenadione in maladministrations. Anti-infective drugs, mainly antiretroviral therapy, account for the majority of ADRs reported in neonates. The specific issue of drug maladministration and medication errors remains to be addressed in neonates. © 2016 The British Pharmacological Society.

  3. Eosinophilic drug reactions detected by a prospective pharmacovigilance programme in a tertiary hospital.

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    Ramírez, Elena; Medrano-Casique, Nicolás; Tong, Hoi Y; Bellón, Teresa; Cabañas, Rosario; Fiandor, Ana; González-Ramos, Jessica; Herranz, Pedro; Trigo, Elena; Muñoz, Mario; Borobia, Alberto M; Carcas, Antonio J; Frías, Jesús

    2017-02-01

    We conducted a prospective evaluation of all eosinophilic drug reactions (EDRs) through the Prospective Pharmacovigilance Program from Laboratory Signals at Hospital to find out the incidence and distribution of these entities in our hospital, their causative drugs, and predictors. All peripheral eosinophilia >700 × 10 6  cells l -1 detected at admission or during hospitalisation, were prospectively monitored over 42 months. The spectrum of the localised or systemic manifestation of EDR, the incidence, the distribution of causative drugs, and the predictors were analysed. The incidence of EDR was 16.67 (95% Poisson confidence interval [CI]: 9.90-25.98) per 10 000 admissions. Of 274 cases of EDR, 154 (56.2%) cases in 148 patients were asymptomatic hypereosinophilia. In the remaining 120 (43.8%) cases, there was other involvement. Skin and soft tissue reactions were detected in 36 (13.1%) cases; visceral EDRs in 19(7.0%) cases; and drug-induced eosinophilic cutaneous and visceral manifestations were detected in the remaining 65 (23.7%) cases, 64 of which were potential drug reaction with eosinophilia and systemic symptoms (DRESS). After adjusting for age, sex, and hospitalisation wards, predictors of symptomatic eosinophilia were earlier onset of eosinophilia (hazard ratio [HR], 10.49; 95%CI: 3.13-35.16) higher eosinophil count (HR, 8.51; 95%CI: 3.28-22.08), and a delayed onset of corticosteroids (HR, 1.34; 95%CI: 1.01-1.73). A higher eosinophil count in patients with DRESS was significantly associated with greater impairment of liver function, prolonged hospitalisation, higher cumulative doses of corticosteroids, and if hypogammaglobinaemia was detected, a reactivation of human-herpesvirus 6 was subsequently detected. Half (53.3%, 64/120 cases) of symptomatic EDRs were potential DRESS. The main predictor of severity of EDR was an early severe eosinophilia. © 2016 The British Pharmacological Society.

  4. [Fibrates and risk of venous thromboembolism: Case/no-case study in French pharmacovigilance database].

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    Humbert, Xavier; Dolladille, Charles; Sassier, Marion; Valnet-Rabier, Marie-Blanche; Vial, Thierry; Guitton, Emmanuelle; Page, Annabelle; Sole, Elodie; Auriche, Pascal; Coquerel, Antoine; Alexandre, Joachim; Fedrizzi, Sophie

    2017-12-01

    Several studies have investigated the occurrence of venous thromboembolic events (phlebitis and pulmonary embolism) [VTE] and fibrates. Fibrates could be associated with VTE although published data are contradictory. The objective of this study is to confirm the link between VTE and fibrates. Retrospective disproportionality analysis (case/non-case method) from observations recorded consecutively in the French pharmacovigilance database between 1985 and 2016. Cases were defined as embolic and thrombotic events, thrombophlebitis; Non-cases were other adverse events reported over the same period. We measured the disproportionality of exposure to each fibrate among cases and no-cases. The analysis was validated with a positive control (drospirenone) and a negative control (paracetamol). We compared 19,436 cases (including 161 mentioning fibrates) to 563,310 non-cases (including 3228 fibrates). Reports of VTE were significantly associated with fenofibrate (ROR=1.83; 95% CI=[1.53; 2.2]) but not with other fibrates: bézafibrate (ROR=0.44; 95% CI=[0.2; 0.99]), ciprofibrate (ROR=1.15; 95% CI=[0.76; 1.73]) and gemfibrozil (ROR=0.91; 95% CI=[0.45; 1.84]). With this study, we confirm the link between VTE and fenofibrate. It is therefore advisable to remain cautious when prescribing fenofibrate, in particular in case of past history of VTE and to declare systematically any venous thromboembolic adverse events observed with these drugs. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  5. Drug-induced progressive multifocal leukoencephalopathy: a case/noncase study in the French pharmacovigilance database.

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    Colin, Olivier; Favrelière, Sylvie; Quillet, Alexandre; Neau, Jean-Philippe; Houeto, Jean-Luc; Lafay-Chebassier, Claire; Pérault-Pochat, Marie-Christine

    2017-04-01

    Progressive multifocal leukoencephalopathy (PML) is an often fatal demyelinating disease of the central nervous system. As effective treatment is unavailable, identification of all drugs that could be associated with PML is essential. The objective of this study was to investigate the putative association of reports of PML and drugs. We used the case/noncase method in the French PharmacoVigilance database (FPVD). Cases were reports of PML in the FPVD between January 2008 and December 2015. Noncases were all other reports during the same period. To assess the association between PML and drug intake, we calculated an adverse drug report odds ratio (ROR) with its 95% confidence interval. We have studied the delay of onset of PML for each drug concerned. Among the 101 cases of PML, 39 drugs were mentioned as suspect. The main therapeutic classes suspected with significant ROR were antineoplastic agents (n = 85), immunosuppressants (n = 67), and corticosteroids. A latent interval from the time of drug initiation to the development of PML is established: the median time to onset was 365 days (123-1095 days). The onset of PML is highly variable and differs among drug classes [from 1 to 96 months (IQR: 39.0-126)]. An association between PML and some immunosuppressant drugs was found as expected, but also with antineoplastic agents and glucocorticoids. An important delay of PML onset after stopping treatment is suspected and should alert prescribers. Prescribers but also patients should be informed about the potential associations with all these drugs. Monitoring could be necessary for many drugs to early detect PML. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  6. A framework for assessing the economic value of pharmacovigilance in low- and middle-income countries.

    Science.gov (United States)

    Babigumira, Joseph B; Stergachis, Andy; Choi, Hye Lyn; Dodoo, Alexander; Nwokike, Jude; Garrison, Louis P

    2014-03-01

    Pharmacovigilance (PV) programs are an essential component of national healthcare systems. Well-functioning PV programs can improve population health by identifying and reducing medicines-related problems (MRPs). Many low- and middle-income countries lack functional PV systems, but this deficiency has not been described in terms of the potential economic value of strengthening PV systems. The assessment of economic value for PV can support rational decision making at the country level. We propose a framework for assessing the economic value of PV. We divide national PV systems into four levels: (1) no PV, (2) basic PV, (3) semi-functional PV, and (4) functional PV. These categories represent increasing levels of investment in PV capacity at the national or health facility level for all available medicines, including vaccines. The proposed framework can be used to estimate the costs of PV (including the value of investments to increase PV capacity and the costs of managing MRPs) and outcomes associated with PV (including improvements in morbidity, mortality, and quality of life as a result of the reduction in MRPs). The quantitative approach proposed for assessing costs and benefits uses a decision-analytic modeling framework that would estimate the value of the consequences of MRPs adjusted for their probability of occurrence. This allows the quantification of value using monetary outcomes (cost-benefit analysis), natural units (cost-effectiveness analysis), or mortality adjusted for quality of life or disability (cost-utility analysis). Evidence generated using this framework could assist policy makers, program managers, and donors in evaluating investments that aim to increase the capacity and efficiency of national and facility-level PV programs in low- and middle-income countries.

  7. Deep learning for pharmacovigilance: recurrent neural network architectures for labeling adverse drug reactions in Twitter posts.

    Science.gov (United States)

    Cocos, Anne; Fiks, Alexander G; Masino, Aaron J

    2017-07-01

    Social media is an important pharmacovigilance data source for adverse drug reaction (ADR) identification. Human review of social media data is infeasible due to data quantity, thus natural language processing techniques are necessary. Social media includes informal vocabulary and irregular grammar, which challenge natural language processing methods. Our objective is to develop a scalable, deep-learning approach that exceeds state-of-the-art ADR detection performance in social media. We developed a recurrent neural network (RNN) model that labels words in an input sequence with ADR membership tags. The only input features are word-embedding vectors, which can be formed through task-independent pretraining or during ADR detection training. Our best-performing RNN model used pretrained word embeddings created from a large, non-domain-specific Twitter dataset. It achieved an approximate match F-measure of 0.755 for ADR identification on the dataset, compared to 0.631 for a baseline lexicon system and 0.65 for the state-of-the-art conditional random field model. Feature analysis indicated that semantic information in pretrained word embeddings boosted sensitivity and, combined with contextual awareness captured in the RNN, precision. Our model required no task-specific feature engineering, suggesting generalizability to additional sequence-labeling tasks. Learning curve analysis showed that our model reached optimal performance with fewer training examples than the other models. ADR detection performance in social media is significantly improved by using a contextually aware model and word embeddings formed from large, unlabeled datasets. The approach reduces manual data-labeling requirements and is scalable to large social media datasets. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  8. Effects of Optogenetic inhibition of BLA on Sleep Brief Optogenetic Inhibition of the Basolateral Amygdala in Mice Alters Effects of Stressful Experiences on Rapid Eye Movement Sleep.

    Science.gov (United States)

    Machida, Mayumi; Wellman, Laurie L; Fitzpatrick Bs, Mairen E; Hallum Bs, Olga; Sutton Bs, Amy M; Lonart, György; Sanford, Larry D

    2017-04-01

    Stressful events can directly produce significant alterations in subsequent sleep, in particular rapid eye movement sleep (REM); however, the neural mechanisms underlying the process are not fully known. Here, we investigated the role of the basolateral nuclei of the amygdala (BLA) in regulating the effects of stressful experience on sleep. We used optogenetics to briefly inhibit glutamatergic cells in BLA during the presentation of inescapable footshock (IS) and assessed effects on sleep, the acute stress response, and fear memory. c-Fos expression was also assessed in the amygdala and the medial prefrontal cortex (mPFC), both regions involved in coping with stress, and in brain stem regions implicated in the regulation of REM. Compared to control mice, peri-shock inhibition of BLA attenuated an immediate reduction in REM after IS and produced a significant overall increase in REM. Moreover, upon exposure to the shock context alone, mice receiving peri-shock inhibition of BLA during training showed increased REM without altered freezing (an index of fear memory) or stress-induced hyperthermia (an index of acute stress response). Inhibition of BLA during REM under freely sleeping conditions enhanced REM only when body temperature was high, suggesting the effect was influenced by stress. Peri-shock inhibition of BLA also led to elevated c-Fos expression in the central nucleus of the amygdala and mPFC and differentially altered c-Fos activity in the selected brain stem regions. Glutamatergic cells in BLA can modulate the effects of stress on REM and can mediate effects of fear memory on sleep that can be independent of behavioral fear. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  9. Genomic characterization of a large plasmid containing a blaNDM-1gene carried on Salmonella enterica serovar Indiana C629 isolate from China.

    Science.gov (United States)

    Wang, Wei; Baloch, Zulqarnain; Peng, Zixin; Hu, Yujie; Xu, Jin; Fanning, Séamus; Li, Fengqin

    2017-07-07

    The bla NDM-1 gene in Salmonella species is mostly reported in clinical cases, but is rarely isolated from red and white meat in China. A Salmonella Indiana (S. Indiana) isolate was cultured from a chicken carcass procured from a slaughterhouse in China. Antimicrobial susceptibility was tested against a panel of agents. Whole-genome sequencing of the isolate was carried out and data was analyzed. A large plasmid, denoted as plasmid pC629 (210,106 bp), containing a composite cassette, consisting of IS26-bla NDM-1 -ble MBL -△trpF-tat-cutA-ISCR1-sul1-qacE△1-aadA2-dfrA12-intI1-IS26 was identified. The latter locus was physically linked with bla OXA-1 , bla CTX-M-65 , bla TEM-1 -encoding genes. A mercury resistance operon merACDEPTR was also identified; it was flanked on the proximal side, among IS26 element and the distally located on the bla NDM-1 gene. Plasmid pC629 also contained 21 other antimicrobial resistance-encoding genes, such as aac(6')-Ib-cr, aac(3)-VI, aadA5, aph(4)-Ia, arr-3, blmS, brp, catB3, dfrA17, floR, fosA, mph(A), mphR, mrx, nimC/nimA, oqxA, oqxB, oqxR, rmtB, sul1, sul2. Two virulence genes were also identified on plasmid pC629. To the best of our knowledge, this is the first report of bla NDM-1 gene being identified from a plasmid in a S. Indiana isolate cultured from chicken carcass in China.

  10. Structural Variabilities in β-Lactamase (blaA of Different Biovars of Yersinia enterocolitica: Implications for β-Lactam Antibiotic and β-Lactamase Inhibitor Susceptibilities.

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    Neelja Singhal

    Full Text Available Yersiniosis caused by Yersinia enterocolitica has been reported from all continents. The bacterial species is divided into more than fifty serovars and six biovars viz. 1A, 1B, 2, 3, 4 and 5 which differ in geographical distribution, ecological niches and pathogenicity. Most Y.enterocolitica strains harbor chromosomal genes for two β-lactamases, blaA an Ambler class A penicillinase and blaB an Ambler class C inducible cephalosporinase. In the present study, susceptibility to b-lactam antibiotics and β-lactamase inhibitor was studied for Y. enterocolitica strains of biovars 1A, 1B, 2 and 4. We observed that β-lactamases were expressed differentially among strains of different biovars. To understand the molecular mechanisms underlying such differential expression, the sequences of genes and promoters of blaA were compared. Also, the variants of blaA present in different biovars were modeled and docked with amoxicillin and clavulanic acid. The mRNA secondary structures of blaA variants were also predicted in-silico. Our findings indicated that neither variations in the promoter regions, nor the secondary structures of mRNA contributed to higher/lower expression of blaA in different biovars. Analysis of H-bonding residues of blaA variants with amoxicillin and clavulanic acid revealed that if amino acid residues of a β-lactamase interacting with amoxicillin and the clavulanic acid were similar, clavulanic acid was effective in engaging the enzyme, accounting for a significant reduction in MIC of amoxicillin-clavulanate. This finding might aid in designing better β-lactamase inhibitors with improved efficiencies in future.

  11. Evaluation of Metallo-β-Lactamase-Production and Carriage of bla-VIM Genes in Pseudomonas aeruginosa Isolated from Burn Wound Infections in Isfahan

    Science.gov (United States)

    Saffari, Mahmood; Firoozeh, Farzaneh; Pourbabaee, Mohammad; Zibaei, Mohammad

    2016-01-01

    Background Metallo-β-lactamase-production among Gram-negative bacteria, including Pseudomonas aeruginosa, has become a challenge for treatment of infections due to these resistant bacteria. Objectives The aim of the current study was to evaluate the metallo-β-lactamase-production and carriage of bla-VIM genes among carbapenem-resistant P. aeruginosa isolated from burn wound infections. Patients and Methods A cross-sectional study was conducted from September 2014 to July 2015. One hundred and fifty P. aeruginosa isolates were recovered from 600 patients with burn wound infections treated at Imam-Musa-Kazem Hospital in Isfahan city, Iran. Carbapenem-resistant P. aeruginosa isolates were screened by disk diffusion using CLSI guidelines. Metallo-β-lactamase-producing P. aeruginosa isolates were identified using an imipenem-EDTA double disk synergy test (EDTA-IMP DDST). For detection of MBL genes including bla-VIM-1 and bla-VIM-2, polymerase chain reaction (PCR) methods and sequencing were used. Results Among the 150 P. aeruginosa isolates, 144 (96%) were resistant to imipenem by the disk diffusion method, all of which were identified as metallo-β-lactamase-producing P. aeruginosa isolates by EDTA-IMP DDST. Twenty-seven (18%) and 8 (5.5%) MBL-producing P. aeruginosa isolates harbored bla-VIM-1 and bla-VIM-2 genes, respectively. Conclusions Our findings showed a high occurrence of metallo-β-lactamase production among P. aeruginosa isolates in burn patient infections in our region. Also, there are P. aeruginosa isolates carrying the bla-VIM-1 and bla-VIM-2 genes in Isfahan province. PMID:28144604

  12. Characterization of blaCTX gene and Cross-resistance in Klebsiella pneumoniae Isolated from Hospitalized Patients

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    Gholamreza Pourali Sheshblouki

    2016-04-01

    Full Text Available Background and Aim: Klebsiella pneumoniae is a member of the Enterobacteriaceae family. There is a global emergence of multidrug-resistant (MDR strains of K. pneumoniae, a Gram-negative enteric bacterium that causes nosocomial and urinary tract infections. The aims of the present study were to identify the Klebsiella pneumoniae infections in hospitalized patients, characterization of blaCTX gene, detection cross-resistance and cefepime susceptible-dose dependent (SDD in isolates. Materials and Methods: In present study, 111 strains of Klebsiella pneumoniae were isolated from patients hospitalized in Ghotbadden, Faghihi and Nemazee hospitals (Shiraz, Iran. The isolates were identified as K.pneumoniae, based on biochemical tests embedded in the API-20E system. Susceptibility testing (disc diffusion was performed according clinical and laboratory standards institute (CLSI guidelines. Detection cefepime susceptible-dose dependent (SDD was performed. The detection of AmpC β-lactamases producing strains was done based on cefoxitin and cefepime disk tests. The blaCTX gene was detected in the isolates by PCR molecular method. Results: Total 111 Klebsiella pneumoniae isolates were studied. The less effective drug was ceftazidime (37.8% isolates were sensitive. All SDD strains were susceptible to colistin and imipenem. Colistin (96.4% and imipenem (88.3% were the most effective antibiotics against isolates. Respectively, 41.4% and 35.1% isolates displayed resistance to gentamicin and amikacin. All colistin resistant isolates were imipenem sensitive. The results of PCR on blaCTX gene showed that 70.3% of the isolates possess the gene. Conclusion: Carbapenem drugs are effective against Klebsieella pneumoniae infections. These results indicate that multidrug-resistant (MDR and extensively drug resistant (XDR strains of K.pneumoniae are rising, and fewer antibiotics may be useful for treating infections caused by these strains. Routine investigation and

  13. [Neurons in NAc core and BLA are activated during cocaine context-associated reward memory retrieval in mice].

    Science.gov (United States)

    Wang, Jun-Jun; Yao, Wen-Qing; Chen, Yue-Jun; Ma, Lan; Tao, Ye-Zheng

    2014-10-25

    The intense associative memories that develop between cocaine-paired contexts and rewarding stimuli make addiction hard to cure by contributing to cocaine seeking and relapse. So it's of great importance to examine the neurobiological basis of addiction memory. Cocaine conditioned place preference (CPP) used in this study is a form of Pavlovian conditioning which can establish associations between drug and contextual factors. c-Fos and Zif268 are commonly used immediate early gene (IEG) makers to identify neurons that are activated after a stimulus or behavioral conditioning. This study was designed to reveal neuronal c-Fos, Zif268 expression pattern in 10 brain regions following cocaine context-associated reward memory retrieval in mice, combining animal behavioral study and immunofluorescence method. C57BL/6 mice were randomly divided into 3 groups: Saline retrieval, Cocaine retrieval, and No retrieval of cocaine groups. Cocaine retrieval and No retrieval of cocaine underwent CPP training (one side paired with cocaine, and the other side with saline) except that No retrieval of cocaine group didn't undergo CPP test. Saline retrieval group received saline injections (i.p) on both sides. The results showed that: Neuronal c-Fos, Zif268 protein expression levels in nucleus accumbens (NAc) core both were elevated in Cocaine retrieval group compared with those in Saline retrieval (Control) group during cocaine context-associated reward memory retrieval. Zif268 protein expression level in basolateral amygdala (BLA) was also elevated in Cocaine retrieval group compared with that in control mice. Elevation was not seen in other regions such as hippocampus, prefrontal cortex (PFC). Thus, NAc core and BLA were activated during cocaine context-associated reward memory retrieval. The results suggest that neurons that are activated in NAc core and BLA are crucial basis of cocaine context-associated reward memory.

  14. The effect of BLA GABAB receptors in anxiolytic-like effect and aversive memory deficit induced by ACPA

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    Katayoon Kangarlu Haghighi

    2016-07-01

    Full Text Available Background: As a psychoactive plant, Cannabis sativa (Marijuana is widely used throughout the world. Several investigations have indicated that administration of Marijuana affects various cognitive and non-cognitive behaviors. These include anxiety-like behaviors and learning and memory deficit. It has been shown that three main cannabinoid receptors [i.e. CB1, CB2 and CB3 are involved in cannabinoids’ functions. CB1 receptors are abundantly expressed in the central nervous system regions such as hippocampus, amygdala, cerebellum and the cortex. Therefore, the neuropsychological functions of endocannabinoids are thought to be more linked to CB1 receptors. Among other brain regions, CB1 is highly expressed in the amygdala which is an integral component of the limbic circuitry. The amygdala plays a major role in the control of emotional behavior, including conditioned fear and anxiety. In present study we examined the possible roles of basolateral amygdala (BLA GABAB receptors in arachydonilcyclopropylamide (ACPA-induced anxiolytic-like effect and aversive memory deficit in adult male mice. Methods: This experimental study was conducted from September 2013 to December 2014 in Institute for Studies in Theoretical Physics and Mathematics, School of Cognitive Sciences, Tehran and Male albino NMRI mice (Pasture Institute, Iran, weighting 27-30 g, were used. Bilateral guide-cannulae were implanted to allow intra BLA microinjection of the drugs. We used Elevated Plus Maze (EPM to examine memory and anxiety behavior (test-retest protocol. ACPA administrate intra-peritoneal and GABAB agonist and antagonist administrated intra-amygdala. Results: Data showed that pre-test treatment with ACPA induced anxiolytic-like and aversive memory deficit The results revealed that pre-test intra-BLA infusion of baclofen (GABAB receptor agonist impaired the aversive memory while phaclofen (GABAB receptor antagonist improved it. Interestingly, pretreatment with a sub

  15. [Serious adverse drug reactions with tramadol reported to the French pharmacovigilance database between 2011 and 2015].

    Science.gov (United States)

    Moulis, Florence; Rousseau, Vanessa; Abadie, Delphine; Masmoudi, Kamel; Micallef, Joëlle; Vigier, Caroline; Pierre, Sabrina; Dautriche, Anne; Montastruc, François; Montastruc, Jean-Louis

    2017-12-01

    Tramadol is an opioid and a serotonin reuptake inhibitor drug. It is approved for moderate to severe pain in adults. The aim of this study was to assess tramadol safety through a national pharmacovigilance study in France since dextropropoxyphen withdrawal in 2011. We described all serious adverse drug reactions (SADRs) reported with tramadol in adults in the French National PharmacoVigilance Database from August 1st, 2011 to December 31st, 2015. We identified 1512 SADRs during the study period. The most frequently reported SADRs were neurological (29.4%, including troubles of consciousness [13.2%] and seizures [6.7%]), psychiatric (22.8%, including confusions [14.6%] and hallucinations [7.3%]) and gastrointestinal (17.0%, mostly nausea and vomiting [9.6%]). Unexpected SADRs were also reported: hyponatremia, cholestatic hepatitis, serotonin syndrome. This study demonstrates new unexpected hepatic and metabolic SADRs. Tramadol alone can induce serotonin syndrome in overdose situations. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  16. Pharmacovigilance and adverse drug reaction reporting: a perspective of community pharmacists and pharmacy technicians in Sana’a, Yemen

    Science.gov (United States)

    Al-Worafi, Yaser Mohammed; Kassab, Yaman Walid; Alseragi, Wafa Mohammed; Almutairi, Masaad Saeed; Ahmed, Ali; Ming, Long Chiau; Alkhoshaiban, Ali Saleh; Hadi, Muhammad Abdul

    2017-01-01

    Objective The aim of this study was to compare the knowledge, attitude and barriers of pharmacy technicians and pharmacists toward pharmacovigilance, adverse drug reactions (ADRs) and ADR reporting in community pharmacies in Yemen. Methods This cross-sectional survey was conducted among community pharmacists and pharmacy technicians in the capital of Yemen, Sana’a. A total of 289 community pharmacies were randomly selected. The validated and pilot-tested questionnaire consisted of six sections: demographic data, knowledge about pharmacovigilance, experience with ADR reporting, attitudes toward ADR reporting, and the facilitators to improve ADR reporting. Results A total of 428 pharmacy technicians and pharmacists were contacted and 179 went on to complete a questionnaire (response rate: 41.8%). Of the 179 respondents, 21 (11.7%) were pharmacists and 158 (88.3%) were pharmacy technicians, of which, 176 (98.3%) were male and 3 (1.7%) were female. The mean age of the respondents was 25.87±2.63 years. There was a significant difference between the pharmacists and pharmacy technicians in terms of knowledge scores (PYemen to increase their awareness and participation in ADR reporting. PMID:28924350

  17. From Big Data to Smart Data for Pharmacovigilance: The Role of Healthcare Databases and Other Emerging Sources.

    Science.gov (United States)

    Trifirò, Gianluca; Sultana, Janet; Bate, Andrew

    2018-02-01

    In the last decade 'big data' has become a buzzword used in several industrial sectors, including but not limited to telephony, finance and healthcare. Despite its popularity, it is not always clear what big data refers to exactly. Big data has become a very popular topic in healthcare, where the term primarily refers to the vast and growing volumes of computerized medical information available in the form of electronic health records, administrative or health claims data, disease and drug monitoring registries and so on. This kind of data is generally collected routinely during administrative processes and clinical practice by different healthcare professionals: from doctors recording their patients' medical history, drug prescriptions or medical claims to pharmacists registering dispensed prescriptions. For a long time, this data accumulated without its value being fully recognized and leveraged. Today big data has an important place in healthcare, including in pharmacovigilance. The expanding role of big data in pharmacovigilance includes signal detection, substantiation and validation of drug or vaccine safety signals, and increasingly new sources of information such as social media are also being considered. The aim of the present paper is to discuss the uses of big data for drug safety post-marketing assessment.

  18. Hiccups in Parkinson's disease: an analysis of cases reported in the European pharmacovigilance database and a review of the literature.

    Science.gov (United States)

    Lertxundi, U; Marquínez, A C; Domingo-Echaburu, S; Solinís, M Á; Calvo, B; Del Pozo-Rodríguez, A; García, M; Aguirre, C; Isla, A

    2017-09-01

    Some reports have suggested an association between dopamine agonists and hiccups, involuntary contractions that merit full clinical attention because they can be very debilitating. Many drugs frequently used to treat hiccups are formally contraindicated in Parkinson's disease due to their liability to worsen motor symptoms, making the treatment of hiccups problematic in this disease. The objective of the present study was to analyze all spontaneous reports of hiccups from the European Pharmacovigilance Database in patients with Parkinson's disease and/or on dopaminergic drugs. Finally, we sought to identify evidence-based recommendations on the management of hiccups in Parkinson's disease. We searched for all reports of hiccups in the European Pharmacovigilance Database (EudraVigilance) and calculated proportional reporting ratios for dopamine agonists and hiccups. We reviewed the literature on Parkinson's disease, dopamine agonists, and hiccups, searching for specific treatment recommendations for hiccups in this disease. Both rotigotine and pramipexole fulfilled the criteria to generate a safety signal. We found 32 and 13 cases of hiccups associated with dopamine agonists in EudraVigilance and the literature, respectively. There were no specific recommendations for the management of hiccups in Parkinson's disease in the clinical guidelines consulted. We have found evidence that rotigotine and pramipexole are associated with the appearance of hiccups and that this adverse reaction occurs predominantly in males. Given the scarce information available, specific recommendations are needed in clinical guidelines for the adequate management of hiccups in Parkinson's disease.

  19. Hearing impairment associated with oral terbinafine use : a case series and case/non-case analysis in the Netherlands Pharmacovigilance Centre Lareb database and VigiBase™

    NARCIS (Netherlands)

    Scholl, Joep H G; van Puijenbroek, Eugene P

    2012-01-01

    BACKGROUND: The Netherlands Pharmacovigilance Centre Lareb received reports of six cases of hearing impairment in association with oral terbinafine use. This study describes these cases and provides support for this association from the Lareb database for spontaneous adverse drug reaction (ADR)

  20. An International Study of the Ability and Cost-Effectiveness of Advertising Methods to Facilitate Study Participant Self-Enrolment Into a Pilot Pharmacovigilance Study During Early Pregnancy

    NARCIS (Netherlands)

    Richardson, Jonathan Luke; Stephens, Sally; Thomas, Simon Hugh Lynton; Jamry-Dziurla, Anna; Jong-van den Berg, de Lolkje; Zetstra-van der Woude, Priscilla; Laursen, Maja; Hliva, Valerie; Mt-Isa, Shahrul; Bourke, Alison; Dreyer, Nancy A; Blackburn, Stella Cf

    2016-01-01

    BACKGROUND: Knowledge of the fetal effects of maternal medication use in pregnancy is often inadequate and current pregnancy pharmacovigilance (PV) surveillance methods have important limitations. Patient self-reporting may be able to mitigate some of these limitations, providing an adequately sized

  1. Emergence of dhfrXVb and blaCARB-4 gene cassettes in class 1 integrons from clinical Pseudomonas aeruginosa isolated in Amazon region

    Directory of Open Access Journals (Sweden)

    Érica L Fonseca

    2006-02-01

    Full Text Available Integrons play a role in horizontal acquisition and expression of genes, as well as gene reservoir, contributing for the resistance phenotype, particularly relevant to bacteria of clinical importance. We aimed to determine the composition and the organization of the class 1 integron variable region present in Pseudomonas aeruginosa clinical isolates from Brazil. Strains carrying class 1 integrons were resistant to the majority of antibiotics tested, except to imipenem and ceftazidime. Sequence analysis of the integron variable region revealed the presence of the blaCARB-4 gene into two distinct cassette arrays: aacA4-dhfrXVb-blaCARB-4 and aadB-aacA4-blaCARB-4 . dhfrXVb gene cassette, which is rare in Brazil and in P. aeruginosa species, was found in one isolate. PFGE analysis showed the spread of blaCARB-4 among P. aeruginosa clones. The occurrence of blaCARB-4 and dhfrXVb in Brazil may contribute for developing resistance to clinically important antibiotics, and shows a diversified scenarium of these elements occurring in Amazon clinical settings, where no study about integron dinamycs was performed to date.

  2. Detection of the IncX3 plasmid carrying blaKPC-3 in a Serratia marcescens strain isolated from a kidney-liver transplanted patient.

    Science.gov (United States)

    Gona, Floriana; Caio, Carla; Iannolo, Gioacchin; Monaco, Francesco; Di Mento, Giuseppina; Cuscino, Nicola; Fontana, Ignazio; Panarello, Giovanna; Maugeri, Gaetano; Mezzatesta, Maria Lina; Stefani, Stefania; Conaldi, Pier Giulio

    2017-10-01

    Dissemination of resistance to carbapenems among Enterobacteriaceae through plasmids is an increasingly important concern in health care worldwide. Here we report the first description of an IncX3 plasmid carrying the blaKPC-3 gene in a strain of Serratia marcescens isolated from a kidney-liver transplanted patient at the transplantation centre ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy). To localize the transposable element containing the resistance-associated gene Next-Generation Sequencing of the bacterial DNA was performed. S. marcescens was positive for blaKPC-3 and blaSHV-11 genes. The molecular analysis demonstrated that the blaKPC-3 gene of this bacterial strain was located in one copy of the Tn-3-like element Tn4401-a carried in a plasmid that is 53 392 bp in size and showed the typical IncX3 scaffold. Our data demonstrated the presence of a new blaKPC-3 harbouring the IncX3 plasmid in S. marcescens. The possible dissemination among Enterobacteriaceae of this type of plasmid should be monitored and evaluated in terms of clinical risk.

  3. Structures of Two Major Allergens, Bla g 4 and Per a 4, From Cockroaches and Their IgE Binding Epitopes

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Y.; Chan, S; Ong, T; Yit, L; Tiong, Y; Chew, F; Sivaraman, J; Mok, Y

    2009-01-01

    Inhalant allergens from cockroaches are an important cause of asthma to millions of individuals worldwide. Here we report for the first time the structures of two major cockroach allergens, Bla g 4 and Per a 4, that adopt a typical lipocalin fold but with distinct structural features as compared with other known lipocalin allergens. Both Bla g 4 and Per a 4 contain two long-range disulfide bonds linking the N and C termini to a beta-barrel. The C-terminal helix of Bla g 4 is bent and greatly extended toward the N terminus. Bla g 4 is found to be a monomer, whereas Per a 4 exists as a dimer in solution with a novel dimeric interface involving residues from loops at the top and bottom of the beta-barrel. Putative ligand binding sites of both allergens are determined by docking of the juvenile hormone III inside the beta-barrel and found to interact with the ligand using non-conserved residues. Bla g 4 and Per a 4 are found to be cross-reactive in sera IgE binding, at least in the Singaporean Chinese population tested. A major IgE binding epitope unique to Per a 4 is found on the loops at the bottom of the beta-barrel that may aid the development of hypoallergens for immunotherapy.

  4. Persistence of Multidrug-Resistant Acinetobacter baumannii Isolates Harboring blaOXA-23 and bap for 5 Years.

    Science.gov (United States)

    Sung, Ji Youn; Koo, Sun Hoe; Kim, Semi; Kwon, Gye Cheol

    2016-08-28

    The emergence and dissemination of carbapenemase-producing Acinetobacter baumannii isolates have been reported worldwide, and A. baumannii isolates harboring blaOXA-23 are often resistant to various antimicrobial agents. Antimicrobial resistance can be particularly strong for biofilm-forming A. baumannii isolates. We investigated the genetic basis for carbapenem resistance and biofilm-forming ability of multidrug-resistant (MDR) clinical isolates. Ninety-two MDR A. baumannii isolates were collected from one university hospital located in the Chungcheong area of Korea over a 5-year period. Multiplex PCR and DNA sequencing were performed to characterize carbapenemase and bap genes. Clonal characteristics were analyzed using REP-PCR. In addition, imaging and quantification of biofilms were performed using a crystal violet assay. All 92 MDR A. baumannii isolates involved in our study contained the blaOXA-23 and bap genes. The average absorbance of biomass in Bap-producing strains was much greater than that in non-Bap-producing strains. In our study, only three REP-PCR types were found, and the isolates showing type A or type B were found more than 60 times among unique patients during the 5 years of surveillance. These results suggest that the isolates have persisted and colonized for 5 years, and biofilm formation ability has been responsible for their persistence and colonization.

  5. Characterization of ST258 Colistin-Resistant, blaKPC-Producing Klebsiella pneumoniae in a Greek Hospital.

    Science.gov (United States)

    Mavroidi, Angeliki; Katsiari, Maria; Likousi, Sofia; Palla, Eleftheria; Roussou, Zoi; Nikolaou, Charikleia; Maguina, Asimina; Platsouka, Evangelia D

    2016-07-01

    The emergence of colistin resistance may further contribute to treatment failure of infection caused by multidrug-resistant (MDR) Klebsiella pneumoniae. The colistin resistance rates were determined and colistin-resistant carbapenemase-producing K. pneumoniae (COL-R CP-Kp) were characterized over an 18-month period in a Greek hospital. Out of 135 carbapenemase producers, 19 isolates (14%) were categorized as resistant to colistin. Phenotypic and molecular characterization of the COL-R CP-Kp isolates revealed that all were MDR blaKPC producers and, excluding one isolate of MLST ST383, belonged to the international clonal lineage ST258. Furthermore, PCR amplification and sequencing of the mgrB locus revealed nucleotide sequences of different sizes and insertions of IS1- and IS5-like mobile elements. The majority (63%) of the COL-R blaKPC producers was recovered from patients in the intensive care unit (ICU) and clinical data indicated that all patients should have acquired these isolates in the ICU. The findings of the present study underscore a concerning evolution of colistin resistance in a setting of high K. pneumoniae carbapenemase (KPC)-Kp endemicity, such as Greece. Thus, continuous surveillance, molecular characterization, prudent use of antibiotics, and implementation of infection control measures for K. pneumoniae are urgent.

  6. Pharmacovigilance in India, Uganda and South Africa with Reference to WHO’s Minimum Requirements

    Directory of Open Access Journals (Sweden)

    Karen Maigetter

    2015-05-01

    Full Text Available Background Pharmacovigilance (PV data are crucial for ensuring safety and effectiveness of medicines after drugs have been granted marketing approval. This paper describes the PV systems of India, Uganda and South Africa based on literature and Key Informant (KI interviews and compares them with the World Health Organization’s (WHO’s minimum PV requirements for a Functional National PV System. Methods A documentary analysis of academic literature and policy reports was undertaken to assess the medicines regulatory systems and policies in the three countries. A gap analysis from the document review indicated a need for further research in PV. KI interviews covered topics on PV: structure and practices of the system; current regulatory policy; capacity limitations, staffing, funding and training; availability and reporting of data; and awareness and usage of the systems. Twenty interviews were conducted in India, 8 in Uganda and 11 in South Africa with government officials from the ministries of health, national regulatory authorities, pharmaceutical producers, Non-Governmental Organizations (NGOs, members of professional associations and academia. The findings from the literature and KI interviews were compared with WHO’s minimum requirements. Results All three countries were confronted with similar barriers: lack of sufficient funding, limited number of trained staff, inadequate training programs, unclear roles and poor coordination of activities. Although KI interviews represented viewpoints of the respondents, the findings confirmed the documentary analysis of the literature. Although South Africa has a legal requirement for PV, we found that the three countries uniformly lacked adequate capacity to monitor medicines and evaluate risks according to the minimum standards of the WHO. Conclusion A strong PV system is an important part of the overall medicine regulatory system and reflects on the stringency and competence of the regulatory

  7. Pharmacovigilance in India, Uganda and South Africa with reference to WHO’s minimum requirements

    Science.gov (United States)

    Maigetter, Karen; Pollock, Allyson M.; Kadam, Abhay; Ward, Kim; Weiss, Mitchell G.

    2015-01-01

    Background: Pharmacovigilance (PV) data are crucial for ensuring safety and effectiveness of medicines after drugs have been granted marketing approval. This paper describes the PV systems of India, Uganda and South Africa based on literature and Key Informant (KI) interviews and compares them with the World Health Organization’s (WHO’s) minimum PV requirements for a Functional National PV System. Methods: A documentary analysis of academic literature and policy reports was undertaken to assess the medicines regulatory systems and policies in the three countries. A gap analysis from the document review indicated a need for further research in PV. KI interviews covered topics on PV: structure and practices of the system; current regulatory policy; capacity limitations, staffing, funding and training; availability and reporting of data; and awareness and usage of the systems. Twenty interviews were conducted in India, 8 in Uganda and 11 in South Africa with government officials from the ministries of health, national regulatory authorities, pharmaceutical producers, Non-Governmental Organizations (NGOs), members of professional associations and academia. The findings from the literature and KI interviews were compared with WHO’s minimum requirements. Results: All three countries were confronted with similar barriers: lack of sufficient funding, limited number of trained staff, inadequate training programs, unclear roles and poor coordination of activities. Although KI interviews represented viewpoints of the respondents, the findings confirmed the documentary analysis of the literature. Although South Africa has a legal requirement for PV, we found that the three countries uniformly lacked adequate capacity to monitor medicines and evaluate risks according to the minimum standards of the WHO. Conclusion: A strong PV system is an important part of the overall medicine regulatory system and reflects on the stringency and competence of the regulatory bodies in

  8. Pharmacovigilance in India, Uganda and South Africa with reference to WHO's minimum requirements.

    Science.gov (United States)

    Maigetter, Karen; Pollock, Allyson M; Kadam, Abhay; Ward, Kim; Weiss, Mitchell G

    2015-03-09

    Pharmacovigilance (PV) data are crucial for ensuring safety and effectiveness of medicines after drugs have been granted marketing approval. This paper describes the PV systems of India, Uganda and South Africa based on literature and Key Informant (KI) interviews and compares them with the World Health Organization's (WHO's) minimum PV requirements for a Functional National PV System. A documentary analysis of academic literature and policy reports was undertaken to assess the medicines regulatory systems and policies in the three countries. A gap analysis from the document review indicated a need for further research in PV. KI interviews covered topics on PV: structure and practices of the system; current regulatory policy; capacity limitations, staffing, funding and training; availability and reporting of data; and awareness and usage of the systems. Twenty interviews were conducted in India, 8 in Uganda and 11 in South Africa with government officials from the ministries of health, national regulatory authorities, pharmaceutical producers, Non-Governmental Organizations (NGOs), members of professional associations and academia. The findings from the literature and KI interviews were compared with WHO's minimum requirements. All three countries were confronted with similar barriers: lack of sufficient funding, limited number of trained staff, inadequate training programs, unclear roles and poor coordination of activities. Although KI interviews represented viewpoints of the respondents, the findings confirmed the documentary analysis of the literature. Although South Africa has a legal requirement for PV, we found that the three countries uniformly lacked adequate capacity to monitor medicines and evaluate risks according to the minimum standards of the WHO. A strong PV system is an important part of the overall medicine regulatory system and reflects on the stringency and competence of the regulatory bodies in regulating the market ensuring the safety and

  9. The molecular phenomena of the blaZ genes forming betalactamase enzymes structure in Staphylococcus aureus resistant to beta-lactam antibiotics (ampicillin

    Directory of Open Access Journals (Sweden)

    Mieke Satari

    2010-09-01

    Full Text Available Background: Nowadays, infectious disease still an important problem. One of the bacteria causing infectious diseases is Staphylococcus aureus (S. aureus. In the effort to deal with infections caused by S. aureus, beta-lactam antibiotics, such as ampicillin, are used. In fact, it is unfortunately known that many of S. aureus bacteria are resistant to this group of antibiotics. Because of nucleotide base changes in the structure of the genes blaZ which encode beta-lactamase enzymes in S. aureus. Purpose: The objective of this study was to analyze the nucleotide base changes in the structure of the genes blaZ forming beta-lactamase enzymes in S. aureus resistant to ampicillin based on molecular point of view. Methods: Molecular examinations was conducted by isolating the genes, forming beta-lactamase enzyme, which length was 845bp, from 7 isolates of S. aureus resistant to ampicillin by using PCR technique. The results of blaZ amplification were then subjected to homology by using Tn 552 of S. aureus obtained from bank of genes. Results: Based on the result of the homology, it was found that there was a change in purine base TG, which was a pyrimidine base at the -37 position of the initial codon of blaZ. This change, however, did not affect the strength of the promoter since the number of A and T is still more than the number of G and C. In the structure of the blaZ gene there was even no mutation or deletion or nucleotide base substitution found, so it would not affect the effectiveness of beta-lactamase enzyme. Conclusion: It can be concluded that the resistance of S. aureus towards ampicillin was not caused by nucleotide base deletion/substation. It is suspected that there were other causes leading to the resistance, including the overproduction of beta-lactamase enzyme of the blaZ gene, causing the degradation of beta-lactam antibiotics.Latar belakang: Penyakit infeksi sampai saat ini masih merupakan masalah. Salah satu bakteri penyebab

  10. Outbreaks in distinct regions due to a single Klebsiella pneumoniae clone carrying a bla VIM-1 metallo-{beta}-lactamase gene.

    Science.gov (United States)

    Ikonomidis, Alexandros; Tokatlidou, Despina; Kristo, Ioulia; Sofianou, Danai; Tsakris, Athanassios; Mantzana, Paraskevi; Pournaras, Spyros; Maniatis, Antonios N

    2005-10-01

    From December 2004 to March 2005, 27 Klebsiella pneumoniae clinical isolates that were positive by the imipenem-EDTA double-disk synergy test and that exhibited a single macro-restriction pattern were recovered in two distinct Greek hospitals. The isolates carried a transferable bla(VIM-1) metallo-beta-lactamase gene in a class 1 integron. Reverse transcriptase PCR showed that the gene was similarly expressed in low- and high-level carbapenem-resistant isolates, indicating the existence of additional resistance mechanisms. The clonal spread of VIM-1-producing K. pneumoniae strains in distinct regions where up to now bla(VIM-2) and bla(VIM-4) alleles were common is worrisome.

  11. Double Copies of bla(KPC-3)::Tn4401a on an IncX3 Plasmid in Klebsiella pneumoniae Successful Clone ST512 from Italy.

    Science.gov (United States)

    Fortini, Daniela; Villa, Laura; Feudi, Claudia; Pires, João; Bonura, Celestino; Mammina, Caterina; Endimiani, Andrea; Carattoli, Alessandra

    2016-01-01

    A carbapenem-resistant sequence type 512 (ST512) Klebsiella pneumoniae carbapenemase 3 (KPC-3)-producing K. pneumoniae strain showing a novel variant plasmid content was isolated in Palermo, Italy, in 2014. ST512 is a worldwide successful clone associated with the spread of bla(KPC) genes located on the IncFIIk pKpQIL plasmid. In our ST512 strain, the bla(KPC-3) gene was unusually located on an IncX3 plasmid, whose complete sequence was determined. Two copies of bla(KPC-3)::Tn4401a caused by intramolecular transposition events were detected in the plasmid. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Characterization of a new integron containing bla(VIM-1) and aac(6')-IIc in an Enterobacter cloacae clinical isolate from Greece.

    Science.gov (United States)

    Galani, Irene; Souli, Maria; Chryssouli, Zoi; Orlandou, Konstantina; Giamarellou, Helen

    2005-05-01

    A clinical isolate of Enterobacter cloacae exhibiting reduced susceptibility to imipenem and a positive EDTA-disc synergy test was studied for carbapenemase production. MICs were determined with standard procedures as well as using a higher inoculum. Isoelectric focusing of cell extracts was used for detection of beta-lactamases. PCR assays with primers specific for the bla(VIM) gene and the conserved segments of class 1 integrons and sequence analyses were carried out to identify the gene and to map the metallo-beta-lactamase encoding integron. Transferability of the gene was assessed with conjugation experiments using the filter mating technique. To identify the location of the bla(VIM-1) gene, Southern hybridization was carried out in genomic DNA using an internal fragment of the bla(VIM-1) gene as a probe, amplified by PCR. The isolate was resistant to extended-spectrum beta-lactams. The MICs of carbapenems were below the resistance breakpoints but rose above resistance breakpoints when an inoculum of 10(8) cfu/mL was used. Isoelectric focusing detected a beta-lactamase with a pI of 6.1, which exhibited imipenem-hydrolysing activity in a microbiological assay. Ceftazidime and imipenem resistance were not transferable by conjugation. PCR assays identified the bla(VIM-1) gene in the variable region of a class 1 integron which also carried the aac(6')-IIc gene. The bla(VIM-1) probe hybridized with an approximately 130 kb fragment of genomic DNA, suggesting a chromosomal location of the gene. We describe a novel class 1 integron containing bla(VIM-1) and aac(6')-IIc genes in an E. cloacae clinical isolate.

  13. Complete sequencing of the bla(NDM-1)-positive IncA/C plasmid from Escherichia coli ST38 isolate suggests a possible origin from plant pathogens.

    Science.gov (United States)

    Sekizuka, Tsuyoshi; Matsui, Mari; Yamane, Kunikazu; Takeuchi, Fumihiko; Ohnishi, Makoto; Hishinuma, Akira; Arakawa, Yoshichika; Kuroda, Makoto

    2011-01-01

    The complete sequence of the plasmid pNDM-1_Dok01 carrying New Delhi metallo-β-lactamase (NDM-1) was determined by whole genome shotgun sequencing using Escherichia coli strain NDM-1_Dok01 (multilocus sequence typing type: ST38) and the transconjugant E. coli DH10B. The plasmid is an IncA/C incompatibility type composed of 225 predicted coding sequences in 195.5 kb and partially shares a sequence with bla(CMY-2)-positive IncA/C plasmids such as E. coli AR060302 pAR060302 (166.5 kb) and Salmonella enterica serovar Newport pSN254 (176.4 kb). The bla(NDM-1) gene in pNDM-1_Dok01 is terminally flanked by two IS903 elements that are distinct from those of the other characterized NDM-1 plasmids, suggesting that the bla(NDM-1) gene has been broadly transposed, together with various mobile elements, as a cassette gene. The chaperonin groES and groEL genes were identified in the bla(NDM-1)-related composite transposon, and phylogenetic analysis and guanine-cytosine content (GC) percentage showed similarities to the homologs of plant pathogens such as Pseudoxanthomonas and Xanthomonas spp., implying that plant pathogens are the potential source of the bla(NDM-1) gene. The complete sequence of pNDM-1_Dok01 suggests that the bla(NDM-1) gene was acquired by a novel composite transposon on an extensively disseminated IncA/C plasmid and transferred to the E. coli ST38 isolate.

  14. Isolation, Antimicrobial Susceptibility Profile and Detection ofSul1,blaTEM, andblaSHV in Amoxicillin-Clavulanate-Resistant Bacteria Isolated From Retail Sausages in Kampar, Malaysia.

    Science.gov (United States)

    Tew, Lih-Shin; She, Li-Yen; Chew, Choy-Hoong

    2016-10-01

    Due to the overuse of antibiotics in livestock as a growth-promoting agent, the emergence of multi-antibiotic resistant bacteria is becoming a concern. In this study, we aimed to detect the presence and discover the molecular determinants of foodborne bacteria in retail sausages resistant towards the antibacterial agent amoxicillin-clavulanate. Two grams of sausages were chopped into small pieces and transferred into sterile Luria-Bertani (LB) enrichment broths overnight before they were plated on MacConkey agar petri dishes. The bacteria isolated were then screened for amoxicillin-clavulanate resistance, and an antimicrobial susceptibility test of each isolate was performed by using the disc diffusion method. Double synergy and phenotypic tests were carried out to detect the presence of extended spectrum β-lactamase (ESBL). API 20E kit was used to identify the Enterobacteriaceae . All isolates were further examined by polymerase chain reaction (PCR) for resistant genes bla OXA-1, bla OXA-10, plasmid-mediated AmpC ( bla CMY and bla DHA), and the chromosome-mediated AmpC, Sul 1, bla TEM, and bla SHV genes. A total of 18 amoxicillin-clavulanate resistant isolates were obtained from seven different types of retail sausages. Only half of them were identified as Enterobacteriaceae , but none were ESBL-producers. All the 18 isolated strains demonstrated resistance towards amoxicillin-clavulanate, penicillin and oxacillin (100%), cefotaxime (71.4%), cefpodoxime (66.7%), and ampicillin (83.3%). bla TEM was the most frequently detected β-lactamase gene. Both plasmid- and chromosomal-bound bla TEM genes were detected in all of the isolated Enterobacteriaceae . bla SHV and Sul 1 accounted for 22.2% and 11.1% of the amoxicillin-clavulanate resistant isolates, respectively, whereas bla AMPC, bla CMY, bla DHA, bla OXA-1, and bla OXA-10 were not found in any of the isolates. The only one ESBL-producing bacteria detected in this study was Chryseobacterium meningosepticum , which

  15. Joint medicine-information and pharmacovigilance services could improve detection and communication about drug-safety problems

    Directory of Open Access Journals (Sweden)

    Schjøtt J

    2014-07-01

    Full Text Available Jan Schjøtt,1–3 Jenny Bergman3 1Section of Clinical Pharmacology, Laboratory of Clinical Biochemistry, Haukeland University Hospital, 2Institute of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, 3Regional Medicines Information and Pharmacovigilance Centre (RELIS Vest, Haukeland University Hospital, Bergen, Norway Background: RELIS is a Norwegian network of four regional medicine-information and pharmacovigilance centers where pharmacists and clinical pharmacologists provide feedback to health care professionals in spontaneous drug-related questions and adverse drug-reaction (ADR reports published in a question–answer pair (QAP database (the RELIS database and the Norwegian ADR database, respectively. Objective: To describe the potential of RELIS's dual service to improve detection and communication of drug-safety problems. Materials and methods: We searched the RELIS database for QAPs about ADRs with use of the Norwegian ADR database as a reference. We also searched the Norwegian ADR database for reports that used the RELIS database as a reference. Both searches were limited to the years 2003–2012. We then selected the example of pregabalin and drug abuse after the marketing of Lyrica in Norway in September 2004 to illustrate RELIS's potential to detect new drug-safety information through a limited number of QAPs and ADR reports. Results: A total of 5,427 (26% of 21,071 QAPs in the RELIS database concerned ADRs. QAPs from this database were used as references in 791 (4% of a total of 22,090 reports in the Norwegian ADR database. The Norwegian ADR database was used as a reference in 363 (7% of 5,427 QAPs that concerned ADRs. Between September 2004 and September 2008, RELIS received eleven questions and 13 ADR reports about suspicion of Lyrica (pregabalin and different aspects of abuse. Conclusion: RELIS processes data through two databases that facilitate communication about ADRs. Our service also has the

  16. Association of the Extended-Spectrum β-Lactamase Gene blaTLA-1 with a Novel ISCR Element, ISCR20▿

    Science.gov (United States)

    Berçot, Beatrice; Poirel, Laurent; Silva-Sanchez, Jesus; Nordmann, Patrice

    2010-01-01

    The blaTLA-1 gene encoding an extended-spectrum β-lactamase was identified in 11 enterobacterial isolates from Mexico City, Mexico. This gene was located on different plasmids and plasmid types with different sizes and incompatibility groups. It was associated with a novel insertion sequence, ISCR20, encoding a putative transposase that shared only 20% amino acid identity with the most closely related transposase of ISCR1. The ISCR20 element provided specific promoter sequences for expression of the blaTLA-1 gene. PMID:20585120

  17. Prevalence and characterization of plasmid-mediated blaESBL with their genetic environment in Escherichia coli and Klebsiella pneumoniae in patients with pneumonia.

    Science.gov (United States)

    Wang, Xiao-rong; Chen, Ji-chao; Kang, Yu; Jiang, Ning; An, Shu-chang; Gao, Zhan-cheng

    2012-03-01

    The extended spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the major pathogens causing pneumonia and have a significant impact on the clinical course. Limited data exist on molecular characterization of ESBL-producing E. coli and K. pneumoniae that cause pneumonia. The aim of this study was to investigate the comprehensive multilevel characteristics of E. coli and K. pneumoniae causing pneumonia in China for the first time. E. coli (17) and K. pneumoniae (21) isolates responsible for pneumonia were isolated from 1270 specimens collected in a prospective multi-center study in eight teaching hospitals in China from June to December in 2007. The susceptibilities, ESBL confirmation, sequence typing, blaCTX-M and blaSHV genes, their genetic environment and plasmid Inc/rep types were determined. Sixteen E. coli (94.1%) and eleven K. pneumoniae (52.4%) isolates were ESBL producers. About 77.8% and 66.7% of them were resistance to ciprofloxacin and levofloxacin, and 100% were susceptible to imipenem. The most prevalent ESBL gene was CTX-M-14, followed by SHV-2, CTX-M-15, CTX-M-3, CTX-M-65, SHV-12, SHV-26 and SHV-28. SHV-1 and SHV-11 were also detected and coexisted with blaCTX-Ms in five strains, and three strains contained only SHV-1. All CTX-M-14 were detected ISEcp1 upstream and nine were found IS903 downstream and the majority of them (64.3%) were carried by IncF plasmids. All blaSHV were flanked by recF and deoR, located on IncF, IncN, IncX and IncH plasmids. Two SHV-2, one SHV-1 and the only SHV-28 were further preceded by IS26. Genes lacY and lacZ were detected at further upstream of two blaSHV-1. The K. pneumoniae carrying SHV-28 was susceptible to β-lactams, and no mutations or deletions in gene or promoter sequences were identified to account for susceptibility. Multilocus sequence typing experiments showed the ESBL-producing strains were genetically diverse. The rate of occurrence of blaESBL in E

  18. Probable Interspecies Transfer of the bla(VIM-4) Gene between Enterobacter cloacae and Klebsiella pneumoniae in a Single Infant Patient.

    Science.gov (United States)

    Piekarska, Katarzyna; Zacharczuk, Katarzyna; Rzeczkowska, Magdalena; Wołkowicz, Tomasz; Januszkiewicz, Aleksandra; Podsiadły, Edyta; Demkow, Urszula; Gierczyński, Rafał

    2015-01-01

    We report the interspecies transfer of the bla(VLM-4) gene in MBL-producing Enterobacter cloacae and Klebsiella pneumoniae isolates from a newborn patient who had received meropenem therapy. We show evidence that gene bla(VIM-4) was transmitted as a part of the class-1 integron on a ca. -90 kb conjugative plasmid. High homology of nucleotide sequence was observed between the integron found in VIM-4 producing E. cloacae and K. pneumoniae strains tested and class-1 integrons previously reporteded in Pseudomonas aeruginosa from Hungary and Poland. This finding may suggest P. aeruginosa as a potential source of acquired VIM-4 in Enterobacteriaceae.

  19. Complete sequence of the IncA/C1 plasmid pCf587 carrying blaPER-2 from Citrobacter freundii.

    Science.gov (United States)

    Ruggiero, Melina; Girlich, Delphine; Dabos, Laura; Power, Pablo; Naas, Thierry; Gutkind, Gabriel

    2018-02-20

    The bla PER-2 harboring plasmid pCf587 (191,541 bp) belongs to lineage IncA/C 1 and is closely related to pRA1. It contains a large resistance island including the bla PER-2 gene between two copies of IS Kox2 -like elements, the toxin-antitoxin module pemK-pemI, several other resistance genes inserted within a Tn 2 transposon, a Tn 21 -like structure, and a class 1 integron. pCf587 belongs into ST 13, a new pMLST. Copyright © 2018 American Society for Microbiology.

  20. Spread of bla(VIM-1)-producing E. coli in a university hospital in Greece. Genetic analysis of the integron carrying the bla(VIM-1) metallo-beta-lactamase gene.

    Science.gov (United States)

    Scoulica, Efstathia V; Neonakis, Ioannis K; Gikas, Achilleas I; Tselentis, Yannis J

    2004-03-01

    Bla(VIM-1) gene was detected in four Escherichia coli clinical isolates with both reduced susceptibility to carbapenems and an ESBL phenotype. The VIM-1 determinant was located within the variable region of a Class I integron along with a 6'-N-aminoglycoside acetyltransferase gene (aac(6')-Ib) and it could be transferred by conjugation. In all four clinical isolates the VIM-1 gene cassette presented a characteristic duplication of the 3' end coding 153 nucleotides followed by the first 14 nucleotides of the 59 base element (59be) that however did not seem to affect either the integrity of the coding sequence or the 59be of the gene cassette. These clinical isolates not only harbored the same Class I integron, but they also shared the same discrete ribotype-pattern, indicative for their clonal origin. Spread of carbapenem resistance genes among Enterobacteriaceae in hospital is a matter of great concern.

  1. Frequency of virulence factors in high biofilm formation blaKPC-2 producing Klebsiella pneumoniae strains from hospitals.

    Science.gov (United States)

    Fu, Li; Huang, Mei; Zhang, XinZhou; Yang, XiaoYing; Liu, Yao; Zhang, LuHua; Zhang, ZhiKun; Wang, GuangXi; Zhou, YingShun

    2018-03-01

    The aim of this study is to determine the frequency of virulence genes in high biofilm formation bla KPC-2 producing Klebsiella pneumoniae strains collected over a period of two years. A total of 43 non-repetitive high biofilm bla KPC-2 producing isolates were screened from 429 strains. The MIC of carbapenems (imipenem and meropenem) ranged from 4 to 32 μg/ml. The OD595 value of the biofilm ranged from 0.56 to 2.56. The K1, K2, K5, K20, K54, K57 genotypes, MLST and virulence factors, including entB, ybtS, mrkD, fimH, rmpA, allS, iutA, kfu, wcaG, aerobaction, fecIRA, shiF, magA and pagO gene, were determined by PCR. The results showed that, among the 43 isolates, 5 of 43 were K1 type, 25 of 43 were K2 type, 4 strains and 2 strains were K5 and K57 respectively. The MLST results showed that 23/43 strains were ST11, followed by ST433(4/43), ST107(4/43), ST690(4/43), ST304(2/43), ST2058(1/43), ST1(1/43), ST146(1/43), ST914(1/43), ST2636(1/43), ST2637(1/43). As to the virulence factors, all 43 strains carried entB, ybtS and mrkD gene, followed by fimH(38/43), rmpA(14/43), allS(34/43), iutA(27/43), kfu(25/43), wcaG(21/43), aerobaction(16/43), fecIRA(15/43), shiF(10/43), magA(5/43) and pagO(5/43). This study demonstrated that high frequency of virulence factors emerging in high biofim bla KPC-2 producing strains. It also suggested that we should continue to focus on the toxicity variation and it's high time to enhance clinical awareness to the infections causing by Klebsiella pneumoniae. Copyright © 2018. Published by Elsevier Ltd.

  2. A Pharmacovigilance Study in First Episode of Psychosis: Psychopharmacological Interventions and Safety Profiles in the PEPs Project.

    Science.gov (United States)

    Bioque, Miquel; Llerena, Adrián; Cabrera, Bibiana; Mezquida, Gisela; Lobo, Antonio; González-Pinto, Ana; Díaz-Caneja, Covadonga M; Corripio, Iluminada; Aguilar, Eduardo J; Bulbena, Antoni; Castro-Fornieles, Josefina; Vieta, Eduard; Lafuente, Amàlia; Mas, Sergi; Parellada, Mara; Saiz-Ruiz, Jerónimo; Cuesta, Manuel J; Bernardo, Miguel

    2016-04-01

    The characterization of the first episode of psychosis and how it should be treated are principal issues in actual research. Realistic, naturalistic studies are necessary to represent the entire population of first episode of psychosis attended in daily practice. Sixteen participating centers from the PEPs project recruited 335 first episode of psychosis patients, aged 7 to 35 years. This article describes and discusses the psychopharmacological interventions and safety profiles at baseline and during a 60-day pharmacovigilance period. The majority of first episode of psychosis patients received a second-generation antipsychotic (96.3%), orally (95%), and in adjusted doses according to the product specifications (87.2%). A total of 24% were receiving an antipsychotic polytherapy pattern at baseline, frequently associated with lower or higher doses of antipsychotics than the recommended ones. Eight patients were taking clozapine, all in monotherapy. Males received higher doses of antipsychotic (P=.043). A total of 5.2% of the patients were being treated with long-acting injectable antipsychotics; 12.2% of the patients received anticholinergic drugs, 12.2% antidepressants, and 13.7% mood stabilizers, while almost 40% received benzodiazepines; and 35.52% reported at least one adverse drug reaction during the pharmacovigilance period, more frequently associated with higher antipsychotic doses and antipsychotic polytherapy (85.2% vs 45.5%, Psecurity issues, support future research of determinate pharmacological strategies for the treatment of early phases of psychosis, such as the role of clozapine, long-acting injectable antipsychotics, antipsychotic combination, and the use of benzodiazepines. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  3. Effectiveness of pharmacovigilance: multifaceted educational intervention related to the knowledge, skills and attitudes of multidisciplinary hospital staff.

    Science.gov (United States)

    Varallo, Fabiana Rossi; Planeta, Cleopatra S; Mastroianni, Patricia de Carvalho

    2017-01-01

    Most educational interventions in pharmacovigilance are designed to encourage physicians to report adverse drug reactions. However, multidisciplinary teams may play an important role in reporting drug-related problems. This study assessed the impact of a multifaceted educational intervention in pharmacovigilance on the knowledge, skills and attitudes of hospital professionals. This prospective, open-label, non-randomized study was performed in a medium-complexity hospital in São Paulo, Brazil. The intervention involved four activities: 1) an interactive lecture, 2) a practical class, 3) a pre-post questionnaire administered to professionals on a multidisciplinary team, and 4) educational material. The intervention's impact on the professionals' knowledge and skills was assessed using the World Health Organization's definitions. The intervention's effect on the professionals' attitudes was analysed by the prevalence of adverse drug event reports (adverse drug reactions, medication errors, therapeutic failure and drug quality deviations) and the relevance (seriousness and expectancy) of the events. One hundred seventy-three professionals were enrolled. A 70-fold increase in the number of adverse drug event reports was observed during the 12 months post-intervention. The intervention improved the professionals' form-completion skills (ppharmacovigilance (p<0.0001). The intervention also contributed to detecting serious drug-induced events. The nursing staff reported medication errors, and pharmacists and physiotherapists recognized serious adverse drug reactions. Physicians communicated suspicions of therapeutic failure. A multidisciplinary approach to drug-safety assessments contributes to identifying new, relevant drug-related problems and improving the rate of adverse drug event reporting. This strategy may therefore be applied to improve risk communication in hospitals.

  4. The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.

    Science.gov (United States)

    Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa

    2016-01-01

    With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Possibility of Database Research as a Means of Pharmacovigilance in Japan Based on a Comparison with Sertraline Postmarketing Surveillance.

    Science.gov (United States)

    Hirano, Yoko; Asami, Yuko; Kuribayashi, Kazuhiko; Kitazaki, Shigeru; Yamamoto, Yuji; Fujimoto, Yoko

    2017-06-20

    Many pharmacoepidemiologic studies using large-scale databases have recently been utilized to evaluate the safety and effectiveness of drugs in Western countries. In Japan, however, conventional methodology has been applied to postmarketing surveillance (PMS) to collect safety and effectiveness information on new drugs to meet regulatory requirements. Conventional PMS entails enormous costs and resources despite being an uncontrolled observational study method. This study is aimed at examining the possibility of database research as a more efficient pharmacovigilance approach by comparing a health care claims database and PMS with regard to the characteristics and safety profiles of sertraline-prescribed patients. The characteristics of sertraline-prescribed patients recorded in a large-scale Japanese health insurance claims database developed by MinaCare Co. Ltd. were scanned and compared with the PMS results. We also explored the possibility of detecting signals indicative of adverse reactions based on the claims database by using sequence symmetry analysis. Diabetes mellitus, hyperlipidemia, and hyperthyroidism served as exploratory events, and their detection criteria for the claims database were reported by the Pharmaceuticals and Medical Devices Agency in Japan. Most of the characteristics of sertraline-prescribed patients in the claims database did not differ markedly from those in the PMS. There was no tendency for higher risks of the exploratory events after exposure to sertraline, and this was consistent with sertraline's known safety profile. Our results support the concept of using database research as a cost-effective pharmacovigilance tool that is free of selection bias . Further investigation using database research is required to confirm our preliminary observations. Copyright © 2017. Published by Elsevier Inc.

  6. Farmacovigilância da heparina no Brasil Heparin pharmacovigilance in Brazil

    Directory of Open Access Journals (Sweden)

    Daniela Rezende Garcia Junqueira

    2011-06-01

    in Brazil was conducted. RESULTS: Five companies were granted a permission to market unfractioned heparin in Brazil. Three of them are porcine in origin and two of them are bovine in origin, with only one explicitly showing this information in the package insert. The effectiveness and safety of heparin studied in non-Brazilian populations may not represent the Brazilian reality, since most countries no longer produce bovine heparin. The currently marketed heparin has approximately 10% less anticoagulant activity than that previously produced and this change may have clinical implications. CONCLUSIONS: Evidence about the lack of dose interchangeability between bovine and porcine heparins and the unique safety profile of these drugs indicates the need to follow the treatment and the patients' response. Events threatening the patient's safety must be reported to the pharmacovigilance system in each particular country.

  7. First Report of bla CTX-M-15-Type ESBL-Producing Klebsiella pneumoniae in Wild Migratory Birds in Pakistan.

    Science.gov (United States)

    Raza, Shahbaz; Mohsin, Mashkoor; Madni, Waqas Ahmed; Sarwar, Fatima; Saqib, Muhammad; Aslam, Bilal

    2017-03-01

    We investigated wild migratory birds faecal swabs for extended-spectrum β-lactamases-producing Klebsiella pneumoniae (ESBL-K. pneumoniae) from wetland habitats in Pakistan. ESBL-K. pneumoniae were analysed for MDR phenotype, ESBL genotype and genetic diversity. A total of 13 (8.6%) ESBL-K. pneumoniae were recovered. Of these, 8 (61%) isolates were MDR. DNA sequencing confirmed bla CTX-M-15 as the dominant ESBL genotype. BOX-PCR fingerprints showed most of the isolates are unrelated. This study is the first to report the wildlife contamination of CTX-M-15-producing K. pneumoniae in Pakistan. Due to long-range migration, these birds could be responsible for trans-boundary spread of multidrug-resistant bacteria.

  8. Investigation of Extensively Drug-Resistant blaOXA-23-Producing Acinetobacter baumannii Spread in a Greek Hospital.

    Science.gov (United States)

    Mavroidi, Angeliki; Katsiari, Maria; Palla, Eleftheria; Likousi, Sofia; Roussou, Zoi; Nikolaou, Charikleia; Platsouka, Evangelia D

    2017-06-01

    A rapid increase was observed in the incidence of extensively drug-resistant Acinetobacter baumannii (XDR Aba) isolates in a Greek hospital during 2014. To investigate the causes of this rise, the antimicrobial resistance profiles of all carbapenem-resistant (CARB-R) Aba isolates recovered during 2014-2015 were determined. Selected XDR Aba isolates (n = 13) were characterized by molecular methods. XDR Aba (48 isolates) represented 21.4% of the 224 CARB-R Aba recovered during the study period. The 13 selected XDR Aba isolates were positive for the blaOXA-23, the intrinsic blaOXA-51, and the adeB gene of the AdeABC efflux pump, and all belonged to the 3LST ST101, corresponding to the international clone II. Three bloodstream isolates possessed two amino acid substitutions (A138T+A226V) in the deduced amino acid sequences of the pmrB gene, which may be implicated in colistin resistance. This study demonstrates that this clone still evolves by obtaining an ever-increasing arsenal of antibiotic resistance mechanisms. The clinical characteristics of the intensive care unit (ICU) patients with XDR Aba were reviewed retrospectively. Infected ICU patients with XDR Aba displayed higher death rates compared with infected ICU patients susceptible to colistin and tigecycline CARB-R Aba, although there were no statistically significant differences. Conclusively, continuous surveillance and molecular characterization of XDR Aba, combined with strict infection control measures are mandatory for combating nosocomial infections caused by this organism.

  9. The IncI1 plasmid carrying the bla CTX-M-1 gene persists in in vitro culture of a Escherichia coli strain from broilers

    NARCIS (Netherlands)

    Fischer, E.A.J.; Dierikx, C.M.; Essen-Zandbergen, van A.; Roermund, van H.J.W.; Mevius, D.J.; Stegeman, A.; Klinkenberg, D.

    2014-01-01

    Commensal bacteria are a reservoir for antimicrobial-resistance genes. In the Netherlands, bacteria producing Extended Spectrum Beta-Lactamases (ESBL) are found on chicken-meat and in the gut of broilers at a high prevalence and the predominant ESBL-gene is the blaCTX-M-1 located on IncI1 plasmids.

  10. Complete Sequence of Four Multidrug-Resistant MOBQ1 Plasmids Harboring blaGES-5 Isolated from Escherichia coli and Serratia marcescens Persisting in a Hospital in Canada.

    Science.gov (United States)

    Boyd, David; Taylor, Geoffrey; Fuller, Jeff; Bryce, Elizabeth; Embree, Joanne; Gravel, Denise; Katz, Kevin; Kibsey, Pamela; Kuhn, Magdalena; Langley, Joanne; Mataseje, Laura; Mitchell, Robyn; Roscoe, Diane; Simor, Andrew; Thomas, Eva; Turgeon, Nathalie; Mulvey, Michael

    2015-06-01

    The usefulness of carbapenems for gram-negative infections is becoming compromised by organisms harboring carbapenemases, enzymes which can hydrolyze the drug. Currently KPC (class A), NDM (class B), and OXA-48 types (class D) are the most globally widespread carbapenemases. However, among the GES-type class A extended-spectrum β-lactamases (ESBLs) there are variants that hydrolyze carbapenems, with blaGES-5 being the most common. Two Escherichia coli and two Serratia marcescens harboring blaGES-5 on plasmids were isolated by the Canadian Nosocomial Infection Surveillance Program (CNISP) from four different patients in a single hospital over a 2-year period. Complete sequencing of the blaGES-5 plasmids indicated that all four had nearly identical backbones consisting of genes for replication, partitioning, and stability, but contained variant accessory regions consisting of mobile elements and antimicrobial resistance genes. The plasmids were of a novel replicon type, but belonged to the MOBQ1 group based on relaxase sequences, and appeared to be mobilizable, but not self-transmissible. Considering the time periods of bacterial isolation, it would appear the blaGES-5 plasmid has persisted in an environmental niche for at least 2 years in the hospital. This has implications for infection control and clinical care when it is transferred to clinically relevant gram-negative organisms.

  11. A Carbapenem-Resistant Pseudomonas aeruginosa Isolate Harboring Two Copies of blaIMP-34 Encoding a Metallo-β-Lactamase.

    Directory of Open Access Journals (Sweden)

    Tatsuya Tada

    Full Text Available A carbapenem-resistant strain of Pseudomonas aeruginosa, NCGM1984, was isolated in 2012 from a hospitalized patient in Japan. Immunochromatographic assay showed that the isolate was positive for IMP-type metallo-β-lactamase. Complete genome sequencing revealed that NCGM1984 harbored two copies of blaIMP-34, located at different sites on the chromosome. Each blaIMP-34 was present in the same structures of the class 1 integrons, tnpA(ISPa7-intI1-qacG-blaIMP-34-aac(6'-Ib-qacEdelta1-sul1-orf5-tniBdelta-tniA. The isolate belonged to multilocus sequence typing ST235, one of the international high-risk clones. IMP-34, with an amino acid substitution (Glu126Gly compared with IMP-1, hydrolyzed all β-lactamases tested except aztreonam, and its catalytic activities were similar to IMP-1. This is the first report of a clinical isolate of an IMP-34-producing P. aeruginosa harboring two copies of blaIMP-34 on its chromosome.

  12. Complete nucleotide sequence of pGA45, a 140,698-bp incFIIY plasmid encoding blaIMI-3-mediated carbapenem resistance, from river sediment

    Directory of Open Access Journals (Sweden)

    Bingjun eDang

    2016-02-01

    Full Text Available Plasmid pGA45 was isolated from the sediment of Haihe River using E. coli CV601 (gfp-tagged as recipients and indigenous bacteria from sediment as donors. This plasmid confers reduced susceptibility to imipenem which belongs to carbapenem group. Plasmid pGA45 was fully sequenced on an Illumina HiSeq 2000 sequencing system. The complete sequence of plasmid pGA45 was 140,698 bp in length with an average G+C content of 52.03%. Sequence analysis shows that pGA45 belongs to incFIIY group and harbors a backbone region shares high homology and gene synteny to several other incF plasmids including pNDM1_EC14653, pYDC644, pNDM-Ec1GN574, pRJF866, pKOX_NDM1 and pP10164-NDM. In addition to the backbone region, plasmid pGA45 harbors two notable features including one blaIMI-3-containing region and one type VI secretion system region. The blaIMI-3-containing region is responsible for bacteria carbapenem resistance and the type VI secretion system region is probably involved in bacteria virulence, respectively. Plasmid pGA45 represents the first complete nucleotide sequence of the blaIMI-harboring plasmid from environment sample and the sequencing of this plasmid provided insight into the architecture used for the dissemination of blaIMI carbapenemase genes.

  13. Tandem multiplication of the IS26-flanked amplicon with the bla(SHV-5) gene within plasmid p1658/97.

    Science.gov (United States)

    Zienkiewicz, Maksymilian; Kern-Zdanowicz, Izabela; Carattoli, Alessandra; Gniadkowski, Marek; Cegłowski, Piotr

    2013-04-01

    The IncF plasmid p1658/97 (c. 125 kb) from Escherichia coli isolates recovered during a clonal outbreak in a hospital in Warsaw, Poland, in 1997 contains the extended-spectrum β-lactamase (ESBL) gene bla(SHV-5), originated from the Klebsiella pneumoniae chromosome. A region containing the bla(SHV-5) gene is flanked by two IS26 copies and its copy number multiplies spontaneously within p1658/97 and RecA-deficient E. coli strains. Here, we demonstrate that the amplified IS26-bla(SHV-5) units were arranged in tandems, containing up to more than 10 units, which could raise ceftazidime MICs for host strains from 4 μg mL(-1) to more than 128 μg mL(-1). Successive deletions within p1658/97, located outside the amplifiable module and encompassing even as little as c. 15% of the plasmid, blocked the amplification. Moreover, the complementing re-introduction of the deleted fragments in trans did not restore the process. Similarly, insertions of a 1-kb DNA fragment into the amplicon inhibited its self-multiplication ability. The module was able to transmit into another IS26-containing plasmid by recombination. The results prompted us to speculate that local DNA structure, especially favorable in p1658/97, might have been responsible for the IS26-bla(SHV-5) multiplication ability. © 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  14. Diversity of plasmid replicons encoding the bla(CMY-2) gene in broad-spectrum cephalosporin-resistant Escherichia coli from livestock animals in Japan.

    Science.gov (United States)

    Hiki, Mototaka; Usui, Masaru; Kojima, Akemi; Ozawa, Manao; Ishii, Yoshikazu; Asai, Tetsuo

    2013-03-01

    Broad-spectrum cephalosporin (BSC) resistance has increased in Escherichia coli isolates from broiler chickens in Japan since 2004. The purpose of this study was to understand the epidemiology of BSC-resistant E. coli in livestock animals. Among 3274 E. coli isolates from 1767 feces of apparently healthy animals on 1767 farms between 2004 and 2009, 118 ceftiofur (CTF)-resistant isolates (CTF MIC ≥4 μg/mL) were identified on 74 farms. After elimination of apparently clonal isolates from a single animal, 75 selected CTF-resistant isolates (62 isolates from 61 broiler chickens, 10 isolates from 10 layer chickens, two isolates from two cows, and one isolate from a pig) were characterized. The bla(CMY-2) gene was most frequently detected in 50 isolates, followed by bla(CTX-M) (CTX-M-2: six isolates; CTX-M-14: four isolates; CTX-M-25: two isolates; CTX-M-1: one isolate) and bla(SHV) (SHV-12: seven isolates; SHV-2, SHV-2a, SHV-5: one isolate each). In particular, 42 of 62 broiler chicken isolates harbored bla(CMY-2). Pulsed-field gel electrophoresis analyses using XbaI revealed divergent profiles among the BSC-resistant isolates. The incompatibility groups of bla(CMY-2) plasmids from 34 of the 42 broiler chicken isolates belonged to IncIγ (10 isolates), IncA/C (nine isolates), IncB/O (seven isolates) and IncI1 (six isolates), or were nontypeable (two isolates). Co-transmission of resistance to non-β-lactam antibiotics was observed in transconjugants with IncA/C plasmids, but not with IncI1, IncIγ, and IncB/O plasmids except for one isolate with IncB/O. Our findings suggest that the bla(CMY-2) gene is a key player in BSC-resistant E. coli isolates and that coselection is unlikely to be associated with the abundance of bla(CMY-2) plasmids, except for IncA/C plasmids.

  15. Characterization of plasmids carrying oqxAB in bla(CTX-M)-negative Escherichia coli isolates from food-producing animals.

    Science.gov (United States)

    Liu, Bao-Tao; Li, Liang; Fang, Liang-Xing; Sun, Jian; Liao, Xiao-Ping; Yang, Qiu-E; Huang, Ting; Liu, Ya-Hong

    2014-12-01

    To study the characteristics of plasmids harboring oqxAB among bla(CTX-M)-negative Escherichia coli isolates and search for oqxAB-harboring plasmids similar to plasmids carrying oqxAB-bla(CTX-M) reported previously, conjugation experiment was performed for 115 randomly selected oqxAB-positive but bla(CTX-M)-negative E. coli isolates from diseased animals in Guangdong, China. S1 nuclease pulsed-field gel electrophoresis (PFGE) and southern blotting experiments were performed to investigate the location of oqxAB and other resistance genes. The EcoRI digestion profiles of the plasmids with oqxAB were also analyzed. The clonal relatedness of donor isolates was investigated by PFGE. In this study, 32 oqxAB transconjugants were successfully obtained and most transconjugants showed multidrug resistances. Eleven replicon combination types were found in these transconjugants. floR and oqxAB were found on the same plasmids in all nine transconjugants resistant to florfenicol. The sequences between floR and oqxAB were identical in most transconjugants and the two genes were both linked with tnp in insertion sequences. Nine F18:A-:B1 plasmids with only oqxAB shared identical EcoRI digestion profiles and the profiles were also identical with that of a plasmid carrying oqxAB-bla(CTX-M) found previously. Co-transfer of plasmids carrying oqxAB and fosA3, respectively, was also observed in one isolate. This study demonstrates the dissemination of oqxAB among bla(CTX-M)-negative E. coli isolates was mainly mediated by identical F18:A-:B1 plasmids. A novel arrangement of regions between floR and oqxAB might play an important role in the dissemination of floR-oqxAB. This is the first description of the genetic environment of the relationship between oqxAB and floR in E. coli.

  16. Norwegian patients and retail chicken meat share cephalosporin-resistant Escherichia coli and IncK/blaCMY-2 resistance plasmids.

    Science.gov (United States)

    Berg, E S; Wester, A L; Ahrenfeldt, J; Mo, S S; Slettemeås, J S; Steinbakk, M; Samuelsen, Ø; Grude, N; Simonsen, G S; Løhr, I H; Jørgensen, S B; Tofteland, S; Lund, O; Dahle, U R; Sunde, M

    2017-06-01

    In 2012 and 2014 the Norwegian monitoring programme for antimicrobial resistance in the veterinary and food production sectors (NORM-VET) showed that 124 of a total of 406 samples (31%) of Norwegian retail chicken meat were contaminated with extended-spectrum cephalosporin-resistant Escherichia coli. The aim of this study was to compare selected cephalosporin-resistant E. coli from humans and poultry to determine their genetic relatedness based on whole genome sequencing (WGS). Escherichia coli representing three prevalent cephalosporin-resistant multi-locus sequence types (STs) isolated from poultry (n=17) were selected from the NORM-VET strain collections. All strains carried an IncK plasmid with a bla CMY-2 gene. Clinical E. coli isolates (n=284) with AmpC-mediated resistance were collected at Norwegian microbiology laboratories from 2010 to 2014. PCR screening showed that 29 of the clinical isolates harboured both IncK and bla CMY-2 . All IncK/bla CMY-2 -positive isolates were analysed with WGS-based bioinformatics tools. Analysis of single nucleotide polymorphisms (SNP) in 2.5 Mbp of shared genome sequences showed close relationship, with fewer than 15 SNP differences between five clinical isolates from urinary tract infections (UTIs) and the ST38 isolates from poultry. Furthermore, all of the 29 clinical isolates harboured IncK/bla CMY-2 plasmid variants highly similar to the IncK/bla CMY-2 plasmid present in the poultry isolates. Our results provide support for the hypothesis that clonal transfer of cephalosporin-resistant E. coli from chicken meat to humans may occur, and may cause difficult-to-treat infections. Furthermore, these E. coli can be a source of AmpC-resistance plasmids for opportunistic pathogens in the human microbiota. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. Characterisation of β-lactam resistance mediated by blaZ in staphylococci recovered from captive and free-ranging wallabies.

    Science.gov (United States)

    Chen, Michelle M S; Boardman, Wayne S J; Smith, Ian; Goodman, Amanda E; Brown, Melissa H

    2015-09-01

    Staphylococci are commensal organisms of animals, but some species are opportunistic pathogens that are resistant to almost all antimicrobial agents in clinical use. Bacterial resistance to β-lactam antimicrobial agents is widespread and has been investigated in species isolated from humans in addition to food production and companion animals. However, minimal progress has been made towards identifying reservoirs of β-lactam-resistant staphylococci in wildlife. This study was aimed at investigating and characterising β-lactamase resistance from staphylococci of wallaby origin. Staphylococci from free-ranging and captive wallabies were assessed for their phenotypic susceptibility to β-lactam antimicrobial agents prior to sequence analysis of their blaZ and blaR1 genes. Deduced amino acid sequences were classified according to the Ambler molecular characterisation method, assigned a protein signature type and compared with sequences generated from previous studies involving isolates from humans, cattle and companion animals. All BlaZ sequences identified in this study were assignable to a pre-existing β-lactamase class and protein signature type, including the more recently discovered protein signature type 12. Three major phylogenetic groups were resolved upon phylogenetic analysis against published BlaZ sequences. This study has found antibiotic-resistant staphylococci both in free-ranging and captive wallaby populations and these bacteria harbour blaZ variants that are different to those recovered from humans, cattle and companion animals. Further studies of staphylococci from non-traditional sources are required in order to enhance our knowledge of the epidemiology of antibiotic resistance genes. Copyright © 2015 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  18. Safety of a pasteurized plasma-derived Factor VIII and von Willebrand factor concentrate: analysis of 33 years of pharmacovigilance data.

    Science.gov (United States)

    Kouides, Peter; Wawra-Hehenberger, Kathrin; Sajan, Anna; Mead, Henry; Simon, Toby

    2017-10-01

    Haemate-P/Humate-P (Humate-P) is a pasteurized human plasma-derived concentrate containing both Factor VIII and von Willebrand factor for treatment of hemophilia A and von Willebrand disease (VWD). We analyzed the safety of Humate-P based on more than 33 years of postmarketing pharmacovigilance data, representing an estimated exposure of approximately 25,000 patient-years. The analysis comprises reports of potential adverse drug reactions (ADRs) from all sources, reported as part of routine pharmacovigilance at CSL Behring. ADRs considered clinically relevant or potential risks of Humate-P were identified based on defined and standardized Medical Dictionary for Regulatory Activities queries. Recognizing the limitations of spontaneous reporting, we also reviewed the literature, including clinical trials with mandatory reporting. From 1982 to 2015, a total of 670 postmarketing cases had been reported via pharmacovigilance, for an overall reporting rate of approximately one ADR per 3900 administered standard doses. Of these cases, 343 involved ADRs considered clinically relevant risks (33 thromboembolic complications, 97 inhibitor formation, 110 hypersensitivity or allergic reactions) or potential risks (103 suspected virus transmissions) for Humate-P. Most thromboembolic complications occurred in patients undergoing surgery or with other known risk factors. Inhibitor formation occurred mostly in patients with hemophilia A (24 cases were high titer). Most patients with hypersensitivity or allergic reactions had VWD. None of the reported suspected virus transmission cases were confirmed to be associated with Humate-P. Reported results of company-sponsored studies showed a low incidence of adverse events possibly or probably related to Humate-P. More than 33 years of pharmacovigilance data continue to support the safety of Humate-P. © 2017 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

  19. Signal detection activity on EudraVigilance data: analysis of the procedure and findings from an Italian Regional Centre for Pharmacovigilance.

    Science.gov (United States)

    Monaco, Luca; Melis, Mauro; Biagi, Chiara; Donati, Monia; Sapigni, Ester; Vaccheri, Alberto; Motola, Domenico

    2017-03-01

    In July 2012 a new European legislation (Directive 2010/84/EU and Regulation No. 1235/2010) regarding pharmacovigilance has become effective. It has boosted the activity of Signal Detection through a monthly analysis of potential safety signals on EudraVigilance (EV). Our aim is to describe the procedure of signal detection on EV data and to present results obtained by the our pharmacovigilance centre. Data are extracted from EV database, which collects suspected Adverse Drug Reactions (ADRs) of medicinal products in Europe. We are appointed to supervise digoxin, nicardipine, delapril, manidipine and hydrochlorothiazide/ramipril. ADRs are coded through MedDRA Preferred Terms and collected in the electronic Reaction Monitoring Report (eRMR). Statistical analysis is based on the Proportional Reporting Ratio (PRR) as a measure of disproportionality. Up to April 2016 we have analyzed 45 eRMR for each drug. Two signals for nicardipine were submitted to the Pharmacovigilance Risk Assessment Committee of European Medicines Agency (EMA): acute pulmonary oedema (off-label use as tocolytic) and thrombocytopenia. Our experience shows the scientific and regulatory value of signal detection activity on EV data in order to continuously evaluate the benefit/risk profile of recent and older drugs.

  20. [The congress of the French Society of Pharmacology and Therapeutics celebrate in Nancy, 20 April 2016, 40 years of French Regional Pharmacovigilance Centres!].

    Science.gov (United States)

    Jonville-Béra, Annie-Pierre; Mallaret, Michel; Sgro, Catherine

    2016-09-01

    In 1976, the Regional Pharmacovigilance Centres were created in France to collect and analyze adverse drug reactions. Even if they have, to date, managed and transmitted more than 583,000 adverse drug reactions to the French and international health authorities, the missions of these university hospital structures supervised by clinical pharmacologists are not limited to this activity. They also provide a consulting and diagnostic aid for drug diseases. Their other main mission is information about drugs and their proper use for health professionals and patients on any matter relating to medicines. These queries are used to adjust and focus the training of health professionals in prevention of drug risks and improvement of drug use. Beside signal detection and identification of alerts, the 31 Regional Pharmacovigilance Centres collaborate with the French Drug Agency (Agence nationale de sécurité du medicament et des produits de santé [ANSM]) by achieving expertise on drugs and participation in various working groups and committees. Finally, Regional Pharmacovigilance Centres participate in scientific advancement through research and publication activities. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  1. Pharmacovigilance as a tool for safety and monitoring: a review of general issues and the specific challenges with end-stage renal failure patients

    Directory of Open Access Journals (Sweden)

    Jacob D

    2013-04-01

    Full Text Available Dalia Jacob,1 Belén Marrón,2 Jay Ehrlich,1 Peter A Rutherford3 1Baxter Healthcare Corporation, Deerfield, IL, USA; 2Baxter Healthcare Corporation, Madrid, Spain; 3Baxter Healthcare SA, Zurich, Switzerland Abstract: Pharmacovigilance is instrumental in helping to ensure patient safety for both newly released drugs and those that are well established in the market. However, while pharmacovigilance procedures are strictly regulated in the clinical trial setting, post-marketing adverse event reporting is not well implemented or enforced. As such, the underreporting of adverse events, in relation to drugs that are on the market, is estimated to be in the region of 90%. The identification of drug safety issues in patients with complex diseases and extensive comorbidities is therefore particularly challenging. Dialysis patients – those with end-stage renal disease and often other comorbidities such as diabetes, hypertension, and cardiovascular disease – are a population with significant treatment challenges. Patients receive dialysis using complex medical devices (eg, a peritoneal dialysis home cycler and also receive a range of pharmaceutical agents as part of dialysis itself (eg, peritoneal dialysis solutions. Many of the pharmaceutical agents used to treat these patients have been developed in populations without these complications and, therefore, an extensive knowledge of potential problems and contraindications in the dialysis population is lacking. It is important that the nephrology community understands the concept of pharmacovigilance – the pharmacologic science relating to the detection, assessment, understanding, and prevention of adverse effects, particularly long-term and short-term side effects, of medicines. Health care professionals (HCPs and providers, pharmaceutical companies, global regulatory agencies, and the patients themselves all play unique and critical roles in this process. This review defines the science of

  2. The Adverse Drug Reactions from Patient Reports in Social Media Project: Five Major Challenges to Overcome to Operationalize Analysis and Efficiently Support Pharmacovigilance Process

    Science.gov (United States)

    Dahamna, Badisse; Guillemin-Lanne, Sylvie; Darmoni, Stefan J; Faviez, Carole; Huot, Charles; Katsahian, Sandrine; Leroux, Vincent; Pereira, Suzanne; Richard, Christophe; Schück, Stéphane; Souvignet, Julien; Lillo-Le Louët, Agnès; Texier, Nathalie

    2017-01-01

    Background Adverse drug reactions (ADRs) are an important cause of morbidity and mortality. Classical Pharmacovigilance process is limited by underreporting which justifies the current interest in new knowledge sources such as social media. The Adverse Drug Reactions from Patient Reports in Social Media (ADR-PRISM) project aims to extract ADRs reported by patients in these media. We identified 5 major challenges to overcome to operationalize the analysis of patient posts: (1) variable quality of information on social media, (2) guarantee of data privacy, (3) response to pharmacovigilance expert expectations, (4) identification of relevant information within Web pages, and (5) robust and evolutive architecture. Objective This article aims to describe the current state of advancement of the ADR-PRISM project by focusing on the solutions we have chosen to address these 5 major challenges. Methods In this article, we propose methods and describe the advancement of this project on several aspects: (1) a quality driven approach for selecting relevant social media for the extraction of knowledge on potential ADRs, (2) an assessment of ethical issues and French regulation for the analysis of data on social media, (3) an analysis of pharmacovigilance expert requirements when reviewing patient posts on the Internet, (4) an extraction method based on natural language processing, pattern based matching, and selection of relevant medical concepts in reference terminologies, and (5) specifications of a component-based architecture for the monitoring system. Results Considering the 5 major challenges, we (1) selected a set of 21 validated criteria for selecting social media to support the extraction of potential ADRs, (2) proposed solutions to guarantee data privacy of patients posting on Internet, (3) took into account pharmacovigilance expert requirements with use case diagrams and scenarios, (4) built domain-specific knowledge resources embeding a lexicon, morphological rules

  3. Ulceration of the oral mucosa following direct contact with ferrous sulfate in elderly patients: a case report and a review of the French National Pharmacovigilance Database

    Directory of Open Access Journals (Sweden)

    Liabeuf S

    2014-04-01

    Full Text Available Sophie Liabeuf,1–3 Valérie Gras,1 Julien Moragny,1 Marie-Laure Laroche,4 Michel Andrejak1,3On behalf of the French National Network of Pharmacovigilance Centers1Regional Pharmacovigilance Center, Division of Clinical Pharmacology, Amiens University Medical Center and Jules Verne University of Picardy, Amiens, France; 2Clinical Research Centre, Clinical Pharmacology Division, Amiens University Medical Center and the Jules Verne University of Picardy, Amiens, France; 3INSERM U1088, Amiens, France; 4Regional Pharmacovigilance Center, Department of Pharmacology, Toxicology and Pharmacovigilance, Limoges University Medical Center, Limoges, FranceObjective: To report a series of cases of ulceration of the oral mucosa linked to direct contact with ferrous sulfate in elderly patients.Case summary: The first case report concerns the occurrence of widespread oral ulceration in an 87-year-old woman with Alzheimer’s disease. The ulceration extended from the side of the tongue to the floor of the mouth. No clear explanation was found and various local treatments were ineffective. Once it was realized that the ferrous sulfate tablets (given as an iron supplement were crushed prior to administration (due to the patient’s deglutition disorder, withdrawal of this treatment led to rapid resolution of the ulceration. Nine other cases of oral ulcerations associated with ferrous sulfate were identified in the French National Pharmacovigilance Database. All but one of the patients were over 80 years of age and the youngest patient (a 54-year-old had dysphagia associated with facial paralysis.Discussion: Only two other reports of oral ulceration due to ferrous sulfate have been published to date. Mucosal toxicity of ferrous sulfate (which is probably related to oxidative stress has previously been reported for the hypopharynx, the esophageal lumen, and (after inhalation of a tablet the tracheobronchial tree.Conclusion: The mucosal toxicity of ferrous

  4. Characterization of the pJB12 Plasmid from Pseudomonas aeruginosa Reveals Tn6352, a Novel Putative Transposon Associated with Mobilization of the blaVIM-2-Harboring In58 Integron

    OpenAIRE

    Botelho, João; Grosso, Filipa; Peixe, Luísa

    2017-01-01

    The blaVIM-2-carrying In58 integron has been linked to a chromosomal location in different bacterial species, including Pseudomonas aeruginosa. This work reports the first fully sequenced In58-harboring plasmid, which is significantly different from the two previously identified blaVIM-2-carrying plasmids in P. aeruginosa. blaVIM-2 might have been acquired by transposition of Tn6352, a novel transposon composed of the In58 and ISPa17 elements. The recognition of similar inverted repeat (IR) s...

  5. Identification of VIM-2-producing Pseudomonas aeruginosa from Tanzania is associated with sequence types 244 and 640 and the location of blaVIM-2 in a TniC integron.

    Science.gov (United States)

    Moyo, Sabrina; Haldorsen, Bjørg; Aboud, Said; Blomberg, Bjørn; Maselle, Samuel Y; Sundsfjord, Arnfinn; Langeland, Nina; Samuelsen, Ørjan

    2015-01-01

    Epidemiological data on carbapenemase-producing Gram-negative bacteria on the African continent are limited. Here, we report the identification of VIM-2-producing Pseudomonas aeruginosa isolates in Tanzania. Eight out of 90 clinical isolates of P. aeruginosa from a tertiary care hospital in Dar es Salaam were shown to harbor bla(VIM-2). The bla(VIM-2)-positive isolates belonged to two different sequence types (ST), ST244 and ST640, with bla(VIM-2) located in an unusual integron structure lacking the 3' conserved region of qacΔE1-sul1. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. The drugs that mostly frequently induce acute kidney injury: a case - noncase study of a pharmacovigilance database.

    Science.gov (United States)

    Pierson-Marchandise, Marion; Gras, Valérie; Moragny, Julien; Micallef, Joelle; Gaboriau, Louise; Picard, Sylvie; Choukroun, Gabriel; Masmoudi, Kamel; Liabeuf, Sophie

    2017-06-01

    Acute kidney injury (AKI) is associated with a high hospitalization rate, accelerated long-term decline in kidney function and a high mortality rate. Adverse drug reactions (ADRs) constitute one of the most important modifiable factors in the context of AKI. Most studies of drug-induced AKI have focused on a sole drug class. The objective of the present study was to establish a comprehensive overview of drug-induced AKI on the basis of spontaneously reported ADRs in the French national pharmacovigilance database (FPVD). We performed a case-noncase study of drug-induced AKI. Cases corresponded to the reports of AKI recorded in the FPVD between 1 January 2015 and 31 December 2015. The noncases corresponded to all other spontaneously reported ADRs (excluding AKI) recorded in the FPVD during the same period. Data were expressed as the reporting odds ratio (ROR) and the 95% confidence interval. Of the 38 782 ADRs recorded in the FPVD during the study period, 3.2% were classified as cases of AKI. A total of 1254 patients experienced AKI (males: 55%; mean age ± standard deviation: 68.7 ± 15.0 years). Overall, 15.2% of the patients required renal replacement therapy. Two or more concomitantly administered drugs were involved in 66% of the cases of AKI. The most frequently implicated drug classes were antibacterial agents for systemic use (29.5%), diuretics (18.5%), agents acting on the renin-angiotensin system (16.3%), antineoplastic agents (10.2%) and anti-inflammatory agents (5.4%). Gentamicin, eplerenone, spironolactone, candesartan, cisplatin and acyclovir had the highest RORs (>10). A comprehensive study of a national pharmacovigilance database enabled us to identify the drug classes that most frequently induced AKI. Even though most of the identified drugs were already known to induce AKI, the present work should raise physicians' awareness of the compounds responsible for triggering this potentially life-threatening condition. © 2016 The British

  7. Investigating patient narratives posted on Internet and their informativeness level for pharmacovigilance purpose: The example of comments about statins.

    Science.gov (United States)

    Kheloufi, Farid; Default, Anne; Blin, Olivier; Micallef, Joelle

    2017-09-01

    Health-related networks like patient health forums may be considered as potential sources of information to early detect pharmacovigilance issues or complete data on drug safety. However, the clinical and pharmacological relevancy of such a source has not been clearly explored. We aimed to describe the characteristics and the informativeness level of Internet narratives posted by patients and mentioning adverse drug reactions (ADRs) related to statins. A retrospective cross-sectional study was conducted on an Internet website dedicated to share experience on medicines. One day of December 2012, postings about simvastatin, rosuvastatin and atorvastatin publicly available on the website were collected. Their informativeness according to 16 key elements of information (including drug start and stop date, duration of treatment, time to onset and duration of the ADR, outcome, medical history, concomitant medication) was assessed. General information about reported ADRs was also investigated. Among the 96 postings related to statins, 72 (40 women, 32 men; mean age: 59 [40-78]) mentioned at least one ADR accounting for a total of 176 ADRs. Musculoskeletal and connective tissue disorders (42.6%) and nervous system disorders (15.3%) were the main represented ADRs. Only 2 patients mentioned ADRs that could be considered as serious but 24 patients mentioned they stopped or switched their treatment toward another lipid modifying agent because of the ADR. Mean number of available key elements of information per narrative was 6/16. Time to onset and duration of the ADR were respectively available in only 31% and 3% of the narratives. Medical history and concomitant medication were respectively lacking in 87% and 86% of the narratives. Outcome was found only in 39% of the narratives. Patient narratives posted on Internet include mainly non-serious expected ADR. However, their informativeness level is very incomplete and makes difficult their assessment and use for

  8. Are consumers ready to take part in the Pharmacovigilance System?--a Portuguese preliminary study concerning ADR reporting.

    Science.gov (United States)

    Matos, Cristiano; van Hunsel, Florence; Joaquim, João

    2015-07-01

    New pharmacovigilance legislation allows consumers to report adverse drug reactions (ADRs) directly to competent authorities in all European Union countries. Consumer reporting is available in Portugal since July 2012. In 2013, the National Pharmacovigilance System (SNF) had received 3461 spontaneous ADR reports, of which only 1.4% (n = 50) were from consumers. Consumer reporting could be one opportunity to reduce underreporting. The aim of this study was to describe the attitudes and knowledge of the general public regarding spontaneous reporting and the reasons and opinions that can influence consumers' ADR underreporting. A descriptive-correlational study was performed looking for consumers' attitudes and knowledge regarding spontaneous reporting. A 6-month survey was conducted from June to November 2013 in general adult consumers from a community pharmacy in Coimbra, Portugal, who used prescribed medicines or over-the-counter (OTC) drugs. Attitudes and opinions were surveyed by personal interview in a closed-answer questionnaire using a Likert scale. Questionnaires from healthcare professionals or incomplete ones were not considered. Data were analyzed using descriptive statistics, chi-square (χ(2)) tests, and Spearman's correlation coefficients. One thousand eighty-four questionnaires were collected (response rate of 81.1%) and 948 completed were selected for analysis. Of the respondents, 44.1% never heard about SNF. Younger people and those with a higher education were significantly more likely to be aware of SNF. Only one consumer had previously reported directly an ADR. Reporting ADRs indirectly through a healthcare professional (HCP) was preferred by 62.4%. The main reasons for consumers reporting spontaneous ADR would be the severity of reactions (81.1% agreed or strongly agreed) and worries about their situation (73.4% agreed or strongly agreed). Only weak and moderate correlations were found between studied statements.. Consumers are more likely to do

  9. Catastrophic floods and tropical storms over the last 120 years on the Dak Bla River, Central Vietnam

    Science.gov (United States)

    Tran, Trang; Stevens, Lora; Vu, Tich; Le, Thuyen

    2017-04-01

    Catastrophic floods are a common natural disaster in the Central Highlands of Vietnam. Given the region's rapid economic development, including an expanding agricultural base and hydroelectric dams, it is important to understand past flood frequency and magnitude. Although mountainous, the highly weathered landscape is not conducive to significant preservation of slack water deposits. Thus, grain size, magnetic susceptibility and carbon/nitrogen ratios of sediment cores from two abandoned channels of the Dak Bla River were used to identify major flood events during the last 120 years. There is a notable increase in magnitude during the late 20th century, with the most pronounced flood occurring in 1972 during the Second Indochina (American-Vietnam) War. The dramatic increase in sediment deposition during the late 20th century is believed to result from anthropogenic alteration of the catchment, including deforestation by bombing during the Second Indochina War and conversion of forest to cropland. Meteorological and river gauge data are rare in Vietnam and span only the last 40 years on the Dak Bla River. For the duration of these records, all major modern floods are triggered by tropical storms bringing excessive rain late in the wet season. Although non-conformable and young radiocarbon dates limit our ability to correlate earlier floods with known tropical storms, the number of direct typhoon strikes and floods during the last 120 years are similar suggesting a possible link beyond the instrumental record. From these data we propose that neither wet years (e.g strong monsoon years) or typhoons are individually responsible for major floods. Catastrophic flooding is a result of a direct tropical storm strike after a normal to wet monsoon season saturates the landscape. If this model is correct, it may be possible to create short-term predictions of flooding help mitigate large-scale disasters. The caveat is that the occurrence and tracks of tropical storms are

  10. Coexistence of blaOXA-23 with armA in quinolone-resistant Acinetobacter baumannii from a Chinese university hospital.

    Science.gov (United States)

    Shen, Min; Luan, Guangxin; Wang, Yanhong; Chang, Yaowen; Zhang, Chi; Yang, Jingni; Deng, Shanshan; Ling, Baodong; Jia, Xu

    2016-03-01

    A total of 101 Acinetobacter baumannii isolates were collected to determine the mechanisms of quinolone resistance and investigate the occurrence of carbapenem and high-level aminoglycoside resistance genes among quinolone-resistant strains. Among 77 quinolone-resistant A. baumannii harbored mutations of gyrA and parC, 41 isolates, which belonged to European clone II, had resistance to aminoglycosides and carbapenems due to the expression of armA and acquisition of blaOXA-23. Most of sequence type belonged to clonal complex 92. These results suggested hospital dissemination of multidrug-resistant A. baumannii carrying blaOXA-23, armA, and mutations of quinolone resistance-determining regions in western China. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. [Combination of bla(VIM-1) and qnrS2 on the same plasmid in Klebsiella oxytoca and Klebsiella pneumoniae isolates in Seville].

    Science.gov (United States)

    Rodríguez-Martínez, José M; Conejo, M Carmen; Díaz de Alba, Paula; López-Cerero, Lorena; Fernandez-Echauri, Pedro; Pascual, Alvaro

    2012-05-01

    Combined resistance to quinolones and β-lactams is common in Enterobacteriaceae. The appearance in enterobacteria coding for metallo-β-lactamases and determinants of plasmid-mediated quinolone resistance are an emerging problem in our country. The susceptibility was determined by E-test. The resistance genes were detected by PCR and the corresponding plasmids were characterised. This study describes 2 strains (1 Klebsiella oxytoca, 1 Klebsiella pneumoniae) carrying the genes qnrS2 and blaVIM-1 in a transferable plasmid of 70-Kb isolated in surveillance cultures at the University Hospital Virgen Macarena in Seville. This is the first combination of qnrS2 and bla(VIM-1) on the same non-typeable plasmid isolated in our centre. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  12. Norwegian patients and retail chicken meat share cephalosporin-resistant Escherichia coli and IncK/blaCMY-2 resistance plasmids

    DEFF Research Database (Denmark)

    Berg, E. S.; Wester, A. L.; Ahrenfeldt, Johanne

    2017-01-01

    In 2012 and 2014 the Norwegian monitoring programme for antimicrobial resistance in the veterinary and food production sectors (NORM-VET) showed that 124 of a total of 406 samples (31%) of Norwegian retail chicken meat was contaminated with extended-spectrum cephalosporin-resistant Escherichia coli....... The aim of this study was to compare selected cephalosporin-resistant E. coli from humans and poultry to determine their genetic relatedness based on whole genome sequencing (WGS). E. coli representing three prevalent cephalosporin-resistant multi-locus sequence types (STs) isolated from poultry (n=17...... urinary tract infections, and the ST38 isolates from poultry. Furthermore, all of the 29 clinical isolates harboured IncK/blaCMY-2 plasmid variants highly similar to the IncK/blaCMY-2 plasmid present in the poultry isolates. Our results provide support for the hypothesis that clonal transfer...

  13. Detection of Ampicillin Resistance Genes (bla in Clinical Isolates of Escherichia coli with Polymerase Chain Reaction Method

    Directory of Open Access Journals (Sweden)

    Tiana Milanda

    2014-09-01

    Full Text Available Escherichia coli is a rod negative Gram which could be pathogenic, if its value increases or located in outer gastrointestinal tract. Pathogenic E. coli will produce enterotoxin which will cause diarrhoea or infection in urine tract. Ampicilin was one of particular antibiotics to overcome infection. Ampicilin nowadays is no longer used as primary medicine, because of its resistance case. The aim of this research is to detect the presence of gene which is responsible to ampicilin resistant E. coli. We used isolated midstream urine from cystitis object in Hasan Sadikin Hospital (RSHS as samples. Polymerase Chain Reaction (PCR method (colony-PCR and DNA-PCR were done to invenstigate the antibiotic resistency. Based on the result of antibiotic susceptibility testing to ampicillin, E. coli samples were resistant to ampicilin. Elektroforegram products of colony-PCR and DNA-PCR showed that the resistance case of ampicilin caused by bla gene (199 bp. Selective and rational antibiotic treatment is required to prevent ampicillin resistance in patients with symptoms

  14. Italian monitoring registries: a tool for a safer use of innovative drugs? Data from the national pharmacovigilance system.

    Science.gov (United States)

    Magro, Lara; Arzenton, Elena; Moretti, Ugo; Sottosanti, Laura; Potenza, Simona; Leone, Roberto

    2016-12-01

    Our aim was to investigate the ADR reports of drugs with a monitoring registry (MR drugs), in particular those related to abuse/misuse, medication error, overdose, which might indicate an unsafe use. We compared these reports with those of similar drugs without a registry (non-MR drugs), thus verifying whether the registries could be useful tools for a safer use of innovative drugs. All ADR reports included in the Italian Pharmacovigilance Network database from January 1 st 2013 to December 31 st 2015 (vaccines and literature cases excluded) were analysed. We compared the ADR reports of MR and non-MR drugs with the same ATC class at III level. The percentage of ADR reports with a completed 'Section 7' was significantly lower for MR compared to non-MR drugs (2.0 versus 6.2, p < 0.001). The difference concerned in particular the ADR reports related to abuse/misuse, medication errors and overdose. These reports, more strictly related to inappropriate use, were less frequent for MR drugs in all the considered ATC classes. Our study suggests that monitoring registries could be a useful tool for the reduction of frequency of ADRs related to inappropriate use, besides the control of pharmaceutical budget.

  15. Hepatotoxicity associated with agomelatine and other antidepressants: Disproportionality analysis using pooled pharmacovigilance data from the Uppsala Monitoring Centre.

    Science.gov (United States)

    Gahr, Maximilian; Zeiss, René; Lang, Dirk; Connemann, Bernhard J; Schönfeldt-Lecuona, Carlos

    2015-07-01

    Since its marketing approval, the attention to the hepatic side-effect profile of the antidepressant agomelatine (AGM) has gradually increased. Several cases of severe hepatotoxic adverse drug reactions (ADR) have been reported and the European Medicines Agency has released a safety warning regarding AGM-associated hepatotoxicity. However, there are insufficient data for an adequate safety assessment of AGM-related hepatotoxicity. Therefore, we performed a quantitative signal detection analysis using pharmacovigilance data from the Uppsala Monitoring Centre from the WHO that records ADR data from worldwide sources; we calculated reporting odds ratios (ROR) as measures for disproportionality within a case/non-case approach for AGM and several other antidepressants. AGM was statistically associated with an increased risk of hepatotoxicity (ROR 6.4 [95%CI 5.7-7.2]) as well as both positive controls: amineptine (ROR 38.4 [95%CI 33.8-43.6]) and nefazodone (ROR 3.2 [95%CI 3.0-3.5]). Following amineptine, AGM was associated with the second highest ROR, followed by tianeptine (ROR 4.4 [95%CI 3.6-5.3]), mianserin (ROR 3.6 [95%CI 3.3-3.9]), and nefazodone. These results support the hypothesis that AGM is associated with relevant hepatotoxicity. However, the used data and applied method do not allow a quantitative evaluation of hepatotoxicity or assessment of substance-specific differences regarding the extent of hepatotoxicity. © 2015, The American College of Clinical Pharmacology.

  16. Adverse Effects of Cholinesterase Inhibitors in Dementia, According to the Pharmacovigilance Databases of the United-States and Canada.

    Directory of Open Access Journals (Sweden)

    Thibault B Ali

    Full Text Available This survey analyzes two national pharmacovigilance databases in order to determine the major adverse reactions observed with the use of cholinesterase inhibitors in dementia. We conducted a statistical analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS and the Canada Vigilance Adverse Reaction Database (CVARD concerning the side effects of cholinesterase inhibitors. The statistics calculated for each adverse event were the frequency and the reporting odds ratios (ROR. A total of 9877 and 2247 reports were extracted from the FAERS and CVARD databases, respectively. A disproportionately higher frequency of reports of death as an adverse event for rivastigmine, compared to the other acetylcholinesterase inhibiting drugs, was observed in both the FAERS (ROR = 3.42; CI95% = 2.94-3.98; P<0.0001 and CVARD (ROR = 3.67; CI95% = 1.92-7.00; P = 0.001 databases. While cholinesterase inhibitors remain to be an important therapeutic tool against Alzheimer's disease, the disproportionate prevalence of fatal outcomes with rivastigmine compared with alternatives should be taken into consideration.

  17. Angioedema Triggered by Medication Blocking the Renin/Angiotensin System: Retrospective Study Using the French National Pharmacovigilance Database.

    Science.gov (United States)

    Faisant, Charles; Armengol, Guillaume; Bouillet, Laurence; Boccon-Gibod, Isabelle; Villier, Céline; Lévesque, Hervé; Cottin, Judith; Massy, Nathalie; Benhamou, Ygal

    2016-01-01

    Bradykinin-mediated angioedema (AE) is a rare side effect of some medications, including angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). In France, side-effects to treatments are reported to the national pharmacovigilance database. The national MedDRA database was searched using the term "angioedema". Patients were included if they met the clinical criteria corresponding to bradykinin-mediated AE, if their C1-inhibitor levels were normal, and if they were treated with an ACEi or an ARB. 7998 cases of AE were reported between 1994 and 2013. Among these, 112 met the criteria for bradykinin-mediated AE with normal C1-inhibitor levels. On the 112 drug-AE, patients were treated with an ARB in 21% of cases (24 patients), or an ACEi in 77% of cases (88 patients), in combination with another treatment in 17 cases (mTORi for 3 patients, iDPP-4 for 1 patient, hormonal treatment for 7 patients). ENT involvement was reported in 90% of cases (tongue: 48.2%, larynx: 23.2%). The median duration of treatment before the first attack was 720 days, and the mean duration of attacks was 36.6 h. Forty-one percent (19/46) of patients relapsed after discontinuing treatment. Angioedema triggered by medication blocking the renin/angiotensin system is rare but potentially severe, with a high risk of recurrence despite cessation of the causative drug.

  18. Knowledge, attitudes, and practices of pharmacovigilance and ADRs spontaneous reporting among pediatricians and pediatric residents in Jordan.

    Science.gov (United States)

    Mukattash, Tareq Lewis; Alwadi, Maysa Wadah; Abu-Farha, Rana K; Jarab, Anan; Alzubiedi, Sameh A; Alwedyan, Tareq

    2018-03-08

    Parmacovigilance (PV) is the science that responsible for ADRs reporting and accordingly medication safety. Pediatrics age group is a special concern as they have a higher risk for developing ADRs; this put more burdens on pediatricians for early detection and reporting of ADRs. The present study aims to explore pediatricians' knowledge, attitude, and practices of pharmacovigilance. A structured validated questionnaire was designed to achieve the study goals. A convenient sample of 142 pediatricians took part in the study Results: The majority of pediatricians had a poor knowledge score about pharmacovigilince and ADRs reporting. On the other hand, 71% of respondents had a good attitude score towards reporting ADRs. When exploring their own practice, pediatricians has a low reporting rate. The results of the present study reveals that pediatricians lack knowledge of PV and ADRs reporting. However, they have a good attitude towards ADRs reporting and enhancing their PV practice. This is still not reflected in their own practice. Further training and education about ADRs reporting is very important to move toward safer medications in children. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. A research framework for pharmacovigilance in health social media: Identification and evaluation of patient adverse drug event reports.

    Science.gov (United States)

    Liu, Xiao; Chen, Hsinchun

    2015-12-01

    Social media offer insights of patients' medical problems such as drug side effects and treatment failures. Patient reports of adverse drug events from social media have great potential to improve current practice of pharmacovigilance. However, extracting patient adverse drug event reports from social media continues to be an important challenge for health informatics research. In this study, we develop a research framework with advanced natural language processing techniques for integrated and high-performance patient reported adverse drug event extraction. The framework consists of medical entity extraction for recognizing patient discussions of drug and events, adverse drug event extraction with shortest dependency path kernel based statistical learning method and semantic filtering with information from medical knowledge bases, and report source classification to tease out noise. To evaluate the proposed framework, a series of experiments were conducted on a test bed encompassing about postings from major diabetes and heart disease forums in the United States. The results reveal that each component of the framework significantly contributes to its overall effectiveness. Our framework significantly outperforms prior work. Published by Elsevier Inc.

  20. Linked health data for pharmacovigilance in children: perceived legal and ethical issues for stakeholders and data guardians.

    Science.gov (United States)

    Hopf, Yvonne Marina; Bond, Christine B; Francis, Jill J; Haughney, John; Helms, Peter J

    2014-02-12

    The inclusion of the Community Health Index in the recording of National Health Service (NHS) contacts in Scotland facilitates national linkage of data such as prescribing and healthcare utilisation. This linkage could be the basis for identification of adverse drug reactions. The aim of this article is to report the views of healthcare professionals on data sharing, ownership and the legal and other applicable frameworks relevant to linkage of routinely collected paediatric healthcare data. Qualitative study using semistructured face-to-face interviews addressing the study aims. Purposive sample of professional stakeholders (n=25) including experts on ethics, data protection, pharmacovigilance, data linkage, legal issues and prescribing. Interviews were audio-recorded, transcribed and thematically analysed using a framework approach. Participants identified existing data sharing systems in the UK. Access to healthcare data should be approved by the data owners. The definition of data ownership and associated legal responsibilities for linked healthcare data were seen as important factors to ensure accountability for the use of linked data. Yet data owners were seen as facilitators of the proposed data linkage. Twelve frameworks (legal, regulatory and governance) applicable to the linkage of healthcare data were identified. A large number of potentially relevant legal and regulatory frameworks were identified. Ownership of the linked data was seen as an extension of responsibility for, or guardianship of, the source datasets. The consensus emerging from the present study was that clarity is required on the definition of data sharing, data ownership and responsibilities of data owners.

  1. β-lactamases produced by amoxicillin-clavulanate-resistant enterobacteria isolated in Buenos Aires, Argentina: a new blaTEM gene.

    Science.gov (United States)

    Di Conza, José A; Badaracco, Alejandra; Ayala, Juan; Rodríguez, Cynthia; Famiglietti, Angela; Gutkind, Gabriel O

    2014-01-01

    Resistance to β-lactam/β-lactamase inhibitors in enterobacteria is a growing problem that has not been intensively studied in Argentina. In the present work, 54/843 enterobacteria collected in a teaching hospital of Buenos Aires city were ampicillin-sulbactam-resistant isolates remaining susceptible to second- and third-generation cephalosporins. The enzymatic mechanisms present in the isolates, which were also amoxicillin-clavulanic acid (AMC)-resistant (18/54) were herein analyzed. Sequencing revealed two different variants of blaTEM-1, being blaTEM-1b the most frequently detected allelle (10 Escherichia coli, 3 Klebsiella pneumoniae, 2 Proteus mirabilis and 1 Raoultella terrigena) followed by blaTEM-1a (1 K. pneumoniae). Amoxicillin-clavulanate resistance seems to be mainly associated with TEM-1 overproduction (mostly in E. coli) or co-expressed with OXA-2-like and/or SHV β-lactamases (K. pneumoniae and P. mirabilis). A new blaTEM variant (TEM-163) was described in an E. coli strain having an AMC MIC value of 16/8μg/ml. TEM-163 contains Arg275Gln and His289Leu amino acid substitutions. On the basis of the high specific activity and low IC50 for clavulanic acid observed, the resistance pattern seems to be due to overproduction of the new variant of broad spectrum β-lactamase rather than to an inhibitor-resistant TEM (IRT)-like behavior. Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España. All rights reserved.

  2. Outbreak of a novel Enterobacter sp. carrying blaCTX-M-15 in a neonatal unit of a tertiary care hospital in Tanzania.

    Science.gov (United States)

    Mshana, Stephen E; Gerwing, Lisa; Minde, Mercy; Hain, Torsten; Domann, Eugen; Lyamuya, Eligius; Chakraborty, Trinad; Imirzalioglu, Can

    2011-09-01

    Enterobacter hormaechei and Cronobacter sakazakii are amongst the most important causes of outbreaks of neonatal sepsis associated with powdered milk. In this study, we report for the first time an outbreak of a novel Enterobacter sp. harbouring bla(CTX-M-15) in a neonatal unit in Tanzania. Seventeen Gram-negative enteric isolates from neonatal blood cultures were studied. Antibiotic susceptibility was assessed by disc diffusion testing, and the presence of the bla(CTX-M-15) gene was established by polymerase chain reaction (PCR) and sequencing. Isolates were typed by pulsed-field gel electrophoresis (PFGE). Identification by biochemical profiling was followed by nucleotide sequencing of 16S ribosomal DNA (rDNA), rpoB and hsp60 alleles. Environmental sampling was done and control measures were established. Isolates were initially misidentified based on their fermentation characteristics and agglutination as Salmonella enterica serotype Paratyphi. All isolates were resistant to multiple antibiotics, except for ciprofloxacin and carbapenems, and were found to harbour bla(CTX-M-15) on a 291-kb narrow-range plasmid. PFGE analysis indicated the clonal outbreak of a single strain, infecting 17 neonates with a case fatality rate of 35%. The same strain was isolated from a milk bucket. Phylogenetic analysis using 16S rDNA, rpoB and hsp60 sequences permitted no definitive identification, clustering the strains in the Enterobacter cloacae complex with similarities of 92-98.8%. The data describe an outbreak of a novel bla(CTX-M-15)-positive, multiresistant Enterobacter strain in an African neonatal unit that can easily be misidentified taxonomically. These data highlight the need for constant surveillance of bacteria harbouring extended-spectrum β-lactamases as well as improvements in hygiene measures in developing countries. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  3. Molecular epidemiology of bla OXA-23 -producing carbapenem-resistant Acinetobacter baumannii in a single institution over a 65-month period in north China.

    Science.gov (United States)

    Ning, Nian-Zhi; Liu, Xiong; Bao, Chun-Mei; Chen, Su-Ming; Cui, En-Bo; Zhang, Ju-Ling; Huang, Jie; Chen, Fang-Hong; Li, Tao; Qu, Fen; Wang, Hui

    2017-01-05

    Carbapenem-resistant Acinetobacter baumannii poses a significant threat to hospitalized patients, as few therapeutic options remain. Thus, we investigated the molecular epidemiology and mechanism of resistance of carbapenem-resistant A.baumannii isolates in Beijing, China. Carbapenem-resistant A.baumannii isolates (n = 101) obtained between June 2009 and November 2014 were used. Multilocus sequence typing (MLST) and PCR assays for class C and D β-lactamase were performed on all isolates. S1 nuclease pulsed-field gel electrophoresis (PFGE) and Southern blot hybridization were performed to identify the resistance gene location. All 101 A.baumannii isolates were highly resistant to frequently used antimicrobials, and were considered multidrug resistant. A total of 12 sequence types (STs) were identified, including 10 reported STs and 2 novel STs. Eighty-seven isolates were classified to clonal complex 92 (CC92), among which ST191 and ST195 were the most common STs. The bla OXA-23 gene was positive in most (n = 95) of the A.baumannii isolates. Using S1-nuclease digestion PFGE and Southern blot hybridization, 3 patterns of plasmids carrying bla OXA-23 were confirmed. ST191 and ST195 (both harboring bla OXA-23 ) caused outbreaks during the study period, and this is the first report of outbreaks caused by ST191 and ST195 in north China. bla OXA-23 -producing A.baumannii ST191 and ST 195 isolates can disseminate in a hospital and are potential nosocomial outbreak strains. Surveillance of imipenem-resistant A.baumannii and antimicrobial stewardship should be strengthened.

  4. Plasmid Profile Analysis and bla VIM Gene Detection of Metalo β-lactamase (MBL) Producing Pseudomonas aeruginosa Isolates from Clinical Samples.

    Science.gov (United States)

    S, Jayanthi; M, Jeya

    2014-06-01

    Pseudomonas aeruginosa is a frequent colonizer of hospitalized patients. They are responsible for serious infections such as meningitis, urological infections, septicemia and pneumonia. Carbapenem resistance of Pseudomonas aeruginosa is currently increasingly reported which is often mediated by production of metallo-β-lactamase (MBL). Multidrug resistant Pseudomonas aeruginosa isolates may involve reduced cell wall permeability, production of chromosomal and plasmid mediated β lactamases, aminoglycosides modifying enzymes and an active multidrug efflux mechanism. This study is aimed to detect the presence and the nature of plasmids among metallo-β-lactamase producing Pseudomonas aeruginosa isolates. Also to detect the presence of bla VIM gene from these isolates. Clinical isolates of Pseudomonas aeruginosa showing the metalo-β-lactamase enzyme (MBL) production were isolated. The MBL production was confirmed by three different methods. From the MBL producing isolates plasmid extraction was done by alkaline lysis method. Plasmid positive isolates were subjected for blaVIM gene detection by PCR method. Two thousand seventy six clinical samples yielded 316 (15.22%) Pseudomonas aeruginosa isolates, out of which 141 (44.62%) were multidrug resistant. Among them 25 (17.73%) were metallo-β-lactamase enzyme producers. Plasmids were extracted from 18 out of 25 isolates tested. Five out of 18 isolates were positive for the blaVIM gene detection by the PCR amplification. The MBL producers were susceptible to polymyxin /colistin with MIC ranging from 0.5 - 2μg/ml. Molecular detection of specific genes bla VIM were positive among the carbapenem resistant isolates.

  5. pIMP-PH114 carrying bla IMP-4 in a Klebsiella pneumoniae strain is closely related to other multidrug-resistant IncA/C2 plasmids.

    Science.gov (United States)

    Ho, Pak-Leung; Lo, Wai-U; Chan, Jane; Cheung, Yuk-Yam; Chow, Kin-Hung; Yam, Wing-Cheong; Lin, Chi-Ho; Que, Tak-Lun

    2014-02-01

    The IncA/C plasmids are broad host-range vehicles which have been associated with wide dissemination of CMY-2 among Enterobacteriaceae of human and animal origins. Acquired metallo-β-lactamases (MBLs) such as the IMP-type enzymes are increasingly reported in multidrug-resistant Gram-negative bacteria worldwide, particularly in Enterobacteriaceae. We described the complete sequence of the first IMP-4-encoding IncA/C2 plasmid, pIMP-PH114 (151,885 bp), from a sequence type 1 Klebsiella pneumoniae strain that was recovered from a patient who was hospitalized in the Philippines. pIMP-PH114 consists of a backbone from the IncA/C2 plasmids, with the insertion of a novel Tn21-like class 1 integron composite structure (containing the cassette array bla IMP-4-qacG-aacA4-catB3, followed by a class C β-lactamase bla DHA-1 and the mercury resistance operon, merRTPCADE) and a sul2-floR encoding region. Phylogenetic analysis of the IncA/C repA sequences showed that pIMP-PH114 formed a subgroup with other IncA/C plasmids involved in the international spread of CMY-2, TEM-24 and NDM-1. Identical bla IMP-4 arrays have been described among different Enterobacteriaceae and Acinetobacter spp. in China, Singapore and Australia but the genetic context is different. The broad host range of IncA/C plasmids may have facilitated dissemination of the bla IMP-4 arrays among different diverse groups of bacteria.

  6. Identification and characterization of a novel aac(6')-Iag associated with the blaIMP-1-integron in a multidrug-resistant Pseudomonas aeruginosa.

    Science.gov (United States)

    Kobayashi, Kanao; Hayashi, Ikue; Kouda, Syuntaro; Kato, Fuminori; Fujiwara, Tamaki; Kayama, Shizuo; Hirakawa, Hideki; Itaha, Hideyuki; Ohge, Hiroki; Gotoh, Naomasa; Usui, Tsuguru; Matsubara, Akio; Sugai, Motoyuki

    2013-01-01

    In a continuing study from Dec 2006 to Apr 2008, we characterized nine multi-drug resistant Pseudomonas aeruginosa strains isolated from four patients in a ward at the Hiroshima University Hospital, Japan. Pulsed-field gel electrophoresis of SpeI-digested genomic DNAs from the isolates suggested the clonal expansion of a single strain; however, only one strain, NK0009, was found to produce metallo-β-lactamase. PCR and subsequent sequencing analysis indicated NK0009 possessed a novel class 1 integron, designated as In124, that carries an array of four gene cassettes: a novel aminoglycoside (AG) resistance gene, aac(6')-Iag, blaIMP-1, a truncated form of blaIMP-1, and a truncated form of aac(6')-Iag. The aac(6')-Iag encoded a 167-amino-acid protein that shows 40% identity with AAC(6')-Iz. Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin. A conjugation experiment and subsequent Southern hybridization with the gene probes for blaIMP-1 and aac(6')-Ig strongly suggested In124 is on a conjugal plasmid. Transconjugants acquired resistance to gentamicin and were resistant to virtually all AGs, suggesting that the In124 conjugal plasmid also possesses a gene conferring resistance to gentamicin.

  7. Crystal Structure of Cockroach Allergen Bla g 2, an Unusual Zinc Binding Aspartic Protease with a Novel Mode of Self-inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Gustchina, Alla; Li, Mi; Wunschmann, Sabina; Chapman, Martin D.; Pomes, Anna; Wlodawer, Alexander (INDOOR Bio.); (NIH)

    2010-07-19

    The crystal structure of Bla g 2 was solved in order to investigate the structural basis for the allergenic properties of this unusual protein. This is the first structure of an aspartic protease in which conserved glycine residues, in two canonical DTG triads, are substituted by different amino acid residues. Another unprecedented feature revealed by the structure is the single phenylalanine residue insertion on the tip of the flap, with the side-chain occupying the S1 binding pocket. This and other important amino acid substitutions in the active site region of Bla g 2 modify the interactions in the vicinity of the catalytic aspartate residues, increasing the distance between them to {approx}4 {angstrom} and establishing unique direct contacts between the flap and the catalytic residues. We attribute the absence of substantial catalytic activity in Bla g 2 to these unusual features of the active site. Five disulfide bridges and a Zn-binding site confer stability to the protein, which may contribute to sensitization at lower levels of exposure than other allergens.

  8. Social Isolation During Adolescence Induces Anxiety Behaviors and Enhances Firing Activity in BLA Pyramidal Neurons via mGluR5 Upregulation.

    Science.gov (United States)

    Lin, Song; Li, Xin; Chen, Yi-Hua; Gao, Feng; Chen, Hao; Hu, Neng-Yuan; Huang, Lang; Luo, Zheng-Yi; Liu, Ji-Hong; You, Qiang-Long; Yin, Ya-Nan; Li, Ze-Lin; Li, Xiao-Wen; Du, Zhuo-Jun; Yang, Jian-Ming; Gao, Tian-Ming

    2017-09-15

    Social isolation during the vulnerable period of adolescence contributes to the occurrence of psychiatric disorders and profoundly affects brain development and adult behavior. Although the impact of social isolation during adolescence on anxiety behaviors has been well studied, much less is known about the onset and underlying mechanisms of these behaviors. We observed that following 2 weeks, but not 1 week, of social isolation, adolescent mice exhibited anxiety behaviors. Strikingly, the mGluR5 protein levels in the amygdala increased concomitantly with anxiety behaviors, and both intraperitoneal administration and intra-basolateral amygdala (BLA) infusion of MPEP, a metabotropic glutamate receptor 5 antagonist, normalized anxiety behaviors. Furthermore, electrophysiological studies showed that 2 weeks of social isolation during adolescence facilitated pyramidal neuronal excitability in the BLA, which could be normalized by MPEP. Together, these results reveal a critical period in adolescence during which social isolation can induce anxiety behaviors and facilitate BLA pyramidal neuronal excitability, both of which are mediated by mGluR5, thus providing mechanistic insights into the onset of anxiety behaviors after social isolation during adolescence.

  9. High-level fluoroquinolone resistant Salmonella enterica serovar Kentucky ST198 epidemic clone with IncA/C conjugative plasmid carrying bla(CTX-M-25) gene.

    Science.gov (United States)

    Wasyl, Dariusz; Kern-Zdanowicz, Izabela; Domańska-Blicharz, Katarzyna; Zając, Magdalena; Hoszowski, Andrzej

    2015-01-30

    Multidrug resistant Salmonella Kentucky strains have been isolated from turkeys in Poland since 2009. Multiple mutations within chromosomal genes gyrA and parC were responsible for high-level ciprofloxacin resistance. One of the isolates was extended spectrum β-lactamase- (ESBL) positive: the strain 1643/2010 carried a conjugative 167,779 bps plasmid of IncA/C family. The sequence analysis revealed that it carried a blaCTX-M-25 gene and an integron with another β-lactamase encoding gene-blaOXA-21. This is the first known report of a CTX-M-25 encoding gene both in Poland and in Salmonella Kentucky world-wide, as well as in the IncA/C plasmid. Analysis of the integron showed a novel arrangement of gene cassettes-aacA4, aacC-A1 and blaOXA-21 where the latter might result from an intergeneric gene transfer. The study confirmed Salmonella Kentucky population isolated in Poland belongs to global epidemics of high level fluoroquinolone resistant clone ST198 that can carry rare β-lactamase genes. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Characterization of IncN plasmids carrying blaCTX-M-1 and qnr genes in Escherichia coli and Salmonella from animals, the environment and humans

    DEFF Research Database (Denmark)

    Dolejska, Monika; Villa, Laura; Hasman, Henrik

    2013-01-01

    DNA purified from the respective E. coli transformants.Results Three types of IncN plasmids carrying blaCTX-M-1, qnrS1 and qnrB19 genes were identified in strains isolated from the Czech Republic, Poland, Slovakia, Denmark, Italy and the Netherlands, corresponding to pMLST sequence type (ST) 1, ST3...... and ST8, respectively. Related plasmids circulating in human and animal isolates were identified. Complete nucleotide sequences of the ST1 pHHA45 plasmid carrying blaCTX-M-1, isolated from E. coli from pigs in Denmark, and the ST3 pKT58A plasmid harbouring qnrS1, identified in E. coli from a water bird......Objectives The aim of the study was to characterize a collection of Escherichia coli and Salmonella harbouring qnr and blaCTX-M-1 genes on IncN plasmids isolated from humans, food-producing, companion and wild animals, and the environment from six European countries.Methods Nineteen IncN plasmids...

  11. Internet plan and planning

    Directory of Open Access Journals (Sweden)

    Kahriman Emina

    2008-01-01

    Full Text Available Paper discuss specific features of internet plan as well as planning as management process in general in the contemporary environment. No need to stress out that marketing plan and marketing planning is core activity in approaching to market. At the same time, there are a lot specific c request in preparing marketing plan comparing to business planning due to marketing plan is an essential part. The importance of internet plan and planning rely on specific features of the internet network but as a part of general corporate as well as marketing strategy.

  12. Loop-mediated isothermal amplification assay targeting the blaCTX-M9 gene for detection of extended spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

    Science.gov (United States)

    Thirapanmethee, Krit; Pothisamutyothin, Kanokporn; Nathisuwan, Surakit; Chomnawang, Mullika T; Wiwat, Chanpen

    2014-12-01

    Extended-spectrum β-lactamases (ESBLs) produced by Enterobacteriaceae are one of the resistance mechanisms to most β-lactam antibiotics. ESBLs are currently a major problem in both hospitals and community settings worldwide. Rapid and reliable means of detecting ESBL-producing bacteria is necessary for identification, prevention and treatment. Loop-mediated isothermal amplification (LAMP) is a technique that rapidly amplifies DNA with high specificity and sensitivity under isothermal conditions. This study was aimed to develop a convenient, accurate and inexpensive method for detecting ESBL-producing bacteria by a LAMP technique. ESBLs-producing Escherichia coli and Klebsiella pneumoniae were isolated from a tertiary hospital in Bangkok, Thailand and reconfirmed by double-disk synergy test. A set of four specific oligonucleotide primers of LAMP for detection of bla(CTX-M9) gene was designed based on bla(CTX-M9) from E. coli (GenBank Accession No. AJ416345). The LAMP reaction was amplified under isothermal temperature at 63°C for 60 min. Ladder-like patterns of band sizes from 226 bp of the bla(CTX-M9) DNA target was observed. The LAMP product was further analyzed by restriction digestion with MboI and TaqI endonucleases. The fragments generated were approximately 168, 177 and 250 bp in size for MboI digestion and 165, 193, 229, 281 and 314 bp for TaqI digestion, which is in agreement with the predicted sizes. The sensitivity of the LAMP technique to bla(CTX-M9) was greater than that of the PCR method by at least 10,000-fold. These results showed that the LAMP primers specifically amplified only the bla(CTX-M9) gene. Moreover, the presence of LAMP amplicon was simply determined by adding SYBR Green I in the reaction. In conclusion, this technique for detection of ESBLs is convenient, reliable and easy to perform routinely in hospitals or laboratory units in developing countries. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  13. Sistema de Farmacovigilância do Ceará: um ano de experiência Ceará State Pharmacovigilance System: a year of experience

    Directory of Open Access Journals (Sweden)

    Helena Lutéscia Coêlho

    1999-09-01

    Full Text Available No presente trabalho, o relato do primeiro ano de atividade do Sistema de Farmacovigilância do Ceará (SIFACE é apresentado como estratégia para a discussão de questões práticas e metodológicas envolvendo as dificuldades na implantação de atividade dessa natureza no Brasil. O SIFACE está sendo estruturado pelo GPUIM (Grupo de Prevenção ao Uso Indevido de Medicamentos, tendo como ponto de apoio as unidades de farmácias hospitalares. Foram processadas 63 notificações (119 suspeitas de reação adversa, em sua maioria correspondentes a mulheres (55,7% e a pacientes de 0-14 anos (34,4%, sendo os antibióticos e as reações dermatológicas os medicamentos e os tipos de reações mais freqüentes, respectivamente. Em 20% dos casos houve reexposição dos pacientes a fármacos aos quais aqueles eram intolerantes, o que ressalta a importância preventiva da farmacovigilância.This paper summarizes the first year of activity of the Ceará State Pharmacovigilance System (SIFACE as a strategy to discuss practical and methodological problems related to developing pharmacovigilance in Brazil. SIFACE is being structured by the Group for the Prevention of Improper Use of Pharmaceuticals (GPUIM, based on hospital pharmacies. A total of 63 reports (119 suspected adverse drug reactions, or ADRs were processed, the majority among women (55.7% and children (34.4%. Antibiotics were the drug group most frequently involved, and the most common reactions were dermatological. In 20% of the cases, patients had been re-exposed to drugs previously reported as producing adverse reactions, thus highlighting the importance of pharmacovigilance to prevent ADRs.

  14. Allodemic distribution of plasmids co-harbouring blaCTX-M-15/aac(6')-Ib-cr/qnrB in Klebsiella pneumoniae is the main source of extended-spectrum β-lactamases in Uruguay's paediatric hospital.

    Science.gov (United States)

    Garcia-Fulgueiras, V; Araujo, L; Bado, I; Cordeiro, N F; Mota, M I; Laguna, G; Algorta, G; Vignoli, R

    2017-06-01

    This study aimed to describe the characteristics of clinical isolates of extended-spectrum β-lactamase (ESBL)-producing enterobacteria (EPE) in Uruguay's paediatric hospital. ESBLs, qnr alleles and aac(6')-Ib-cr were sought and characterised in EPE isolated between March 2010 and March 2012. Transfer of resistance determinants was assessed by conjugation. Incompatibility (Inc) groups, plasmid toxin-antitoxin systems (TAS) and plasmid size were determined in transconjugants. Clonality was analysed by pulsed-field gel electrophoresis. Multilocus sequence typing was done for ESBL-producing Klebsiella pneumoniae. A total of 77 EPE isolates were characterised, comprising 43% K. pneumoniae, 19.5% Serratia marcescens, 19.5% Escherichia coli, 17% Enterobacter cloacae and 1% Klebsiella oxytoca. ESBLs belonged mainly to the bla CTX-M family (69.6%) [bla CTX-M-15 (45%) and bla CTX-M-2 (31%)]. The aac(6')-Ib-cr/qnrB duplex was the most frequently detected plasmid-mediated quinolone resistance mechanism; this association was detected in K. pneumoniae harbouring bla CTX-M-15 . Transconjugants were obtained for 71% of the EPE. Amongst transconjugants, certain combinations were found between ESBLs and Inc group, e.g. IncA/C-bla CTX-M-2 , IncHI1/HI2-bla CTX-M-9 and IncHI1/HI2-bla SHV-12 . In addition, the combination ccdAB-bla CTX-M-15 was also found. K. pneumoniae isolates harbouring bla CTX-M-15 /aac(6')-Ib-cr/qnrB showed allodemic behaviour, with a predominance of ST14, ST45 and ST48. In this study, epidemiological changes in ESBL distribution could be explained by the spread of K. pneumoniae harbouring bla CTX-M-15 /aac(6')-Ib-cr/qnrB, encoded mainly on conjugative plasmids featuring ccdAB TAS. Since reports of TAS in K. pneumoniae plasmids are scarce, new strategies are needed to combat intrinsic selection pressure exerted by the association, in conjugative plasmids, of resistance mechanisms with TAS. Copyright © 2017 International Society for Chemotherapy of Infection and

  15. Prevalence of extended-spectrum cephalosporin-resistant Escherichia coli in a farrowing farm: ST1121 clone harboring IncHI2 plasmid contributes to the dissemination of blaCMY-2

    Directory of Open Access Journals (Sweden)

    Hui eDeng

    2015-11-01

    Full Text Available Abstract During a regular monitoring of antimicrobial resistance in a farrowing farm in Southern China, 117 Escherichia coli isolates were obtained from sows and piglets. Compared with the isolates from piglets, the isolates from sows exhibited higher resistance rates to the tested cephalosporins. Correspondingly, the total detection rate of the blaCMY-2/blaCTX-M genes in the sow isolates (34.2% was also significantly higher than that of the piglet isolates (13.6% (p<0.05. The blaCMY-2 gene had a relatively high prevalence (11.1% in the E. coli isolates. MLST and PFGE analysis revealed the clonal spread of ST1121 E. coli in most (7/13 of the blaCMY-2-positive isolates. An indistinguishable IncHI2 plasmid harboring blaCMY-2 was also identified in each of the seven ST1121 E. coli isolates. Complete sequence analysis of this IncHI2 plasmid (pEC5207 revealed that pEC5207 may have originated through recombination of an IncHI2 plasmid with a blaCMY-2-carrying IncA/C plasmid like pCFSAN007427_01. In addtion to blaCMY-2, pEC5207 also carried other resistance determinants for aminoglycosides (aacA7, sulfonamides (sul1, as well as heavy metals ions, such as Cu and Ag. The susceptibility testing showed that the pEC5207 can mediate both antibiotic and heavy metal resistance. This highlights the role of pEC5207 in co-selection of blaCMY-2-positive isolates under the selective pressure of heavy metals, cephalosporins and other antimicrobials. In conclusion, clonal spread of an ST1121 type E. coli strain harboring an IncHI2 plasmid contributed to the dissemination of blaCMY-2 in a farrowing farm in Southern China. We also have determined the first complete sequence analysis of a blaCMY-2-carrying IncHI2 plasmid.

  16. Renin angiotensin system blockers-associated angioedema in the Thai population: analysis from Thai National Pharmacovigilance Database.

    Science.gov (United States)

    Win, Thet Su Zin; Chaiyakunapruk, Nathorn; Suwankesawong, Wimon; Dilokthornsakul, Piyameth; Nathisuwan, Surakit

    2015-09-01

    Renin-angiotensin-aldosterone system (RAS) blockers are commonly used for cardiovascular diseases. Currently, little information exists for the Asian population on angioedema, a rare yet serious adverse event. This study aimed to describe characteristics of RAS blockers-associated angioedema (RASBA) in Thai patients. A retrospective study using the national pharmacovigilance database of Thailand was undertaken. Cases indicating the presence of angioedema with RAS blockers uses from 1984-2011 were identified. Patient demographics, co-morbidities, concomitant drugs, information for the RAS blockers and angioedema were obtained as well as causality assessment and quality of reports. A total of 895 cases were identified. Mean age was 59.9+12.8 years and 66.5% being female. Most angioedema events (48.6%) occurred during the first week of treatment. Angiotensin converting enzyme inhibitors (87.7%) were the most commonly implicated agents followed by angiotensin receptor blockers (10.5%), aldosterone antagonist (2.1%) and direct renin inhibitor (0.2%). Out of the 895 cases incorporated in this study, 165 (18.4%) were classified as serious events and resulted in hospitalization. The overall case fatality rate was 0.4%. Respiratory disturbance occurred in 46 cases (5.1%). Patients with respiratory complications tended to be younger (53.4+13.9 vs 60.3+12.7 years old; p=0.002) and with higher frequency of allergy history (26.1% vs 14.7%; p=0.032) compared to those without respiratory complications. Based on multivariate logistic regression, the adjusted OR for history of allergy was 2.23 (95%CI: 1.04 - 4.78, p = 0.041). RASBA in Thai population occurred mostly in elderly female patients and often led to hospitalization. Since large number of patients is regularly exposed to RAS-blockers, a nationwide attempt to raise awareness of clinicians when prescribing RAS-blockers is prudent.

  17. vigiRank for statistical signal detection in pharmacovigilance: First results from prospective real-world use.

    Science.gov (United States)

    Caster, Ola; Sandberg, Lovisa; Bergvall, Tomas; Watson, Sarah; Norén, G Niklas

    2017-08-01

    vigiRank is a data-driven predictive model for emerging safety signals. In addition to disproportionate reporting patterns, it also accounts for the completeness, recency, and geographic spread of individual case reporting, as well as the availability of case narratives. Previous retrospective analysis suggested that vigiRank performed better than disproportionality analysis alone. The purpose of the present analysis was to evaluate its prospective performance. The evaluation of vigiRank was based on real-world signal detection in VigiBase. In May 2014, vigiRank scores were computed for pairs of new drugs and WHO Adverse Reaction Terminology critical terms with at most 30 reports from at least 2 countries. Initial manual assessments were performed in order of descending score, selecting a subset of drug-adverse drug reaction pairs for in-depth expert assessment. The primary performance metric was the proportion of initial assessments that were decided signals during in-depth assessment. As comparator, the historical performance for disproportionality- guided signal detection in VigiBase was computed from a corresponding cohort of drug-adverse drug reaction pairs assessed between 2009 and 2013. During this period, the requirement for initial manual assessment was a positive lower endpoint of the 95% credibility interval of the Information Component measure of disproportionality, observed for the first time. 194 initial assessments suggested by vigiRank's ordering eventually resulted in 6 (3.1%) signals. Disproportionality analysis yielded 19 signals from 1592 initial assessments (1.2%; P < .05). Combining multiple strength-of-evidence aspects as in vigiRank significantly outperformed disproportionality analysis alone in real-world pharmacovigilance signal detection, for VigiBase. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

  18. Pharmacovigilance analysis of adverse event reports for aliskiren hemifumarate, a first-in-class direct renin inhibitor

    Directory of Open Access Journals (Sweden)

    Ali AK

    2011-08-01

    Full Text Available Ayad K AliDepartment of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USABackground: The purpose of this study was to examine the postmarketing safety profile of aliskiren hemifumarate, a first-in-class direct renin inhibitor.Methods: The US Adverse Event Reporting System (AERS was utilized to conduct a retrospective pharmacovigilance analysis by applying the Multi-item Gamma Poisson Shrinker data mining algorithm to calculate empiric Bayes geometric mean (EBGM values of aliskiren-related adverse event reports. Reports received from January 2007 through December 2008 are included in this analysis.Results: In total, 1592 reports for aliskiren are identified in the AERS. Aliskiren was associated with reports of angioedema (EBGM 3.9, 95% confidence interval [CI] 3.2–4.7 and renal dysfunction (EBGM 3.4, 95% CI 2.6–4.5. Reports of hyperkalemia, dry cough, and diarrhea were also linked to aliskiren (EBGM 7.4, 95% CI 3.4–13.0, EBGM 11.0, 95% CI 7.8–14.2, EBGM 4.3, 95% CI 3.2–5.8, respectively.Conclusion: Angioedema and renal dysfunction are potential adverse events associated with exposure to aliskiren. Patients with signs and symptoms of angioedema should stop aliskiren and seek urgent medical help. Aliskiren should not be used by patients with a risk of renal impairment. Additional studies are warranted to quantify further the risk of these events in patients with hypertension.Keywords: aliskiren, postmarketing safety surveillance, adverse event reporting system

  19. Adverse reactions to contrast media: an analysis of spontaneous reports in the database of the pharmacovigilance programme of India.

    Science.gov (United States)

    Kalaiselvan, Vivekanandan; Sharma, Surbhi; Singh, Gyanendra Nath

    2014-09-01

    Contrast media are used widely to improve medical imaging. Like all other pharmaceuticals, these agents are not completely devoid of risk, and continuous monitoring of adverse reactions with these agents is important. Spontaneous reporting is the simplest method for understanding the safety profile of pharmaceutical products after their approval. Our objective was to identify the pattern and characteristics of adverse reactions attributed to contrast media in the Indian population reported to the National Coordination Centre for the Pharmacovigilance Programme of India (NCC-PvPI). Individual case safety reports (ICSRs) attributed to contrast media submitted spontaneously to the NCC-PvPI were extracted from the database for July 2010 to September 2013. We analysed these reports for information related to reporter's professional category, patient's age and sex, reporter's diagnosis of the reaction, seriousness of the reaction, type of contrast media exposure, system organ class (SOC) affected (as described in World Health Organization Adverse Reaction Terminology [WHO-ART]) and outcome. Of the total 59,915 ICSRs in the database, 415 (0.7%) were suspected adverse reactions to contrast media; 44 reports were serious, including three fatal cases. The most affected SOCs were skin and appendage disorders, body as a whole-general disorders, gastrointestinal system disorders and respiratory system disorders. Hypersensitivity reactions were reported in the majority of ICSRs. The contrast media with the highest number of reports were iohexol (40.7%), iomeprol (17.8%), iopamidol (12%) and diatrizoate (12%). Most of the reactions to contrast media were allergic-like, and no previously unrecognised adverse reactions were observed in the Indian population. Further data and increased awareness among healthcare professionals is required to signal and prevent the consequences of adverse reactions attributed to contrast media.

  20. Pharmacovigilance from social media: mining adverse drug reaction mentions using sequence labeling with word embedding cluster features.

    Science.gov (United States)

    Nikfarjam, Azadeh; Sarker, Abeed; O'Connor, Karen; Ginn, Rachel; Gonzalez, Graciela

    2015-05-01

    Social media is becoming increasingly popular as a platform for sharing personal health-related information. This information can be utilized for public health monitoring tasks, particularly for pharmacovigilance, via the use of natural language processing (NLP) techniques. However, the language in social media is highly informal, and user-expressed medical concepts are often nontechnical, descriptive, and challenging to extract. There has been limited progress in addressing these challenges, and thus far, advanced machine learning-based NLP techniques have been underutilized. Our objective is to design a machine learning-based approach to extract mentions of adverse drug reactions (ADRs) from highly informal text in social media. We introduce ADRMine, a machine learning-based concept extraction system that uses conditional random fields (CRFs). ADRMine utilizes a variety of features, including a novel feature for modeling words' semantic similarities. The similarities are modeled by clustering words based on unsupervised, pretrained word representation vectors (embeddings) generated from unlabeled user posts in social media using a deep learning technique. ADRMine outperforms several strong baseline systems in the ADR extraction task by achieving an F-measure of 0.82. Feature analysis demonstrates that the proposed word cluster features significantly improve extraction performance. It is possible to extract complex medical concepts, with relatively high performance, from informal, user-generated content. Our approach is particularly scalable, suitable for social media mining, as it relies on large volumes of unlabeled data, thus diminishing the need for large, annotated training data sets. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.

  1. Muscular Adverse Drug Reactions Associated with Proton Pump Inhibitors: A Disproportionality Analysis Using the Italian National Network of Pharmacovigilance Database.

    Science.gov (United States)

    Capogrosso Sansone, Alice; Convertino, Irma; Galiulo, Maria Teresa; Salvadori, Stefano; Pieroni, Stefania; Knezevic, Tamara; Mantarro, Stefania; Marino, Alessandra; Hauben, Manfred; Blandizzi, Corrado; Tuccori, Marco

    2017-10-01

    Proton pump inhibitors (PPIs) have been implicated in the occurrence of moderate to severe myopathies in several case reports. This study was performed to assess the reporting risk of muscular adverse drug reactions (ADRs) associated with PPIs in the Italian National Network of Pharmacovigilance database. A disproportionality analysis (case/non-case) was performed using spontaneous reports collected in the database between July 1983 and May 2016. Reporting odds ratio (ROR) and 95% confidence intervals (CIs) were calculated as a measure of disproportionality. In a secondary and tertiary analysis, we explored the association of PPIs with muscular ADRs after taking into account the masking effect of statins. Moreover, the possibility of an interaction between PPIs and statins, leading to the occurrence of muscular ADRs, was also tested. The study was carried out on 274,108 reports. The ROR of muscular ADRs for PPIs, adjusted for age and gender, was 1.484 (95% CI 1.204-1.829; p < 0.001), whereas the ROR for rhabdomyolysis was 0.621 (95% CI 0.258-1.499). Similar results were obtained in the secondary analysis. The tertiary analysis, where PPIs were considered regardless of whether their role was suspected or concomitant, showed a potential disproportionate reporting for the combination PPIs-rhabdomyolysis (ROR 1.667, 95% CI 1.173-2.369; p < 0.01). The PPIs-statins combination was not associated with an enhanced ROR of muscular ADRs/rhabdomyolysis compared with statins alone. This explorative study suggests that the class of PPIs could be involved in reports of muscular ADRs, rather than any other ADR, more frequently than any non-statin drug. Our results must be corroborated by further studies.

  2. [National Campaign of Vaccination against the flu A (H1N1)v: National Follow-up of Pharmacovigilance].

    Science.gov (United States)

    Durrieu, Geneviève; Caillet, Céline; Lacroix, Isabelle; Jacquet, Alexis; Faucher, Angeline; Ouaret, Shéhérazade; Sommet, Agnès; Perault-Pochat, Marie-Christine; Kreft-Jaïs, Carmen; Castot, Anne; Damase-Michel, Christine; Montastruc, Jean-Louis

    2011-01-01

    The present study was performed to evaluate safety data collected by the French Network of Pharmacovigilance centres network, from October 21, 2009 to June 15, 2010. French Health Authorities (Afssaps [Agence française de sécurité sanitaire des produits de santé]) heightened awareness to extensive notifications with online health practitioners' reports and patients' reports via the Regional Centre concerned. During the campaign, 4.1 millions doses of Pandemrix(®) and 1.6 million doses of Panenza(®) were administered. Following Pandemrix(®), 4 183 adverse effects (AEs) were reported including 193 "serious" AEs. Concerning Panenza(®), 591 AEs were reported including 70 "serious" AE. The most frequently reported "serious" AEs were neurological for both Pandemrix(®) (38.9%, mainly isolated ascending paresthesia without any other neurological symptom and complication) and Panenza(®) (28.9%). Febrile convulsions were the most common neurological AEs with Panenza(®) in children. All reported deaths (n = 22) described causes other than recent A(H1N1)v vaccination. No causal relationship was established between these AEs and vaccination. Among AEs of "special" interest, 13 reports of confirmed GBS and 15 reports of demyelinating disorders were notified. No report of narcolepsy was made during the study period. For both vaccines, neurological AEs (isolated ascending paresthesia with Pandemrix(®) and febrile convulsions with Panenza(®)) were among the most frequently reported "serious" AEs. Despite limits of this survey based on spontaneous reporting, the study did not detect any safety signals, at least with an 8-month follow-up. © 2011 Société Française de Pharmacologie et de Thérapeutique.

  3. Specialist Cohort Event Monitoring studies: a new study method for risk management in pharmacovigilance.

    Science.gov (United States)

    Layton, Deborah; Shakir, Saad A W

    2015-02-01

    The evolving regulatory landscape has heightened the need for innovative, proactive, efficient and more meaningful solutions for 'real-world' post-authorization safety studies (PASS) that not only align with risk management objectives to gather additional safety monitoring information or assess a pattern of drug utilization, but also satisfy key regulatory requirements for marketing authorization holder risk management planning and execution needs. There is a need for data capture across the primary care and secondary care interface, or for exploring use of new medicines in secondary care to support conducting PASS. To fulfil this need, event monitoring has evolved. The Specialist Cohort Event Monitoring (SCEM) study is a new application that enables a cohort of patients prescribed a medicine in the hospital and secondary care settings to be monitored. The method also permits the inclusion of a comparator cohort of patients receiving standard care, or another counterfactual comparator group, to be monitored concurrently, depending on the study question. The approach has been developed in parallel with the new legislative requirement for pharmaceutical companies to undertake a risk management plan as part of post-authorization safety monitoring. SCEM studies recognize that the study population comprises those patients who may have treatment initiated under the care of specialist health care professionals and who are more complex in terms of underlying disease, co-morbidities and concomitant medications than the general disease population treated in primary care. The aims of this paper are to discuss the SCEM new-user study design, rationale and features that aim to address possible bias (such as selection bias) and current applications.

  4. Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events

    Directory of Open Access Journals (Sweden)

    Acquavella J

    2016-07-01

    Full Text Available John Acquavella,1 Vera Ehrenstein,1 Morten Schiødt,2 Uffe Heide-Jørgensen,1 Anders Kjellman,3,4 Svein Hansen,5 Cecilia Larsson Wexell,6,7 Bente Brokstad Herlofson,8 Sven Erik Noerholt,9 Haijun Ma,10 Katarina Öhrling,11 Rohini K Hernandez,12 Henrik Toft Sørensen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Oral and Maxillofacial Surgery, Rigshospitalet, Copenhagen, Denmark; 3Department of Urology, Karolinska University Hospital, 4Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden; 5Cancer Registry of Norway, Oslo University Hospital, Oslo, Norway; 6Department of Oral and Maxillofacial Surgery, Södra Älvsborg Hospital, Borås, Sweden; 7Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 8Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway; 9Department of Oral and Maxillofacial Surgery, Aarhus University Hospital, Aarhus, Denmark; 10Global Biostatistical Science, Amgen Inc., Thousand Oaks, CA, USA; 11Clinical Development, Amgen Inc., Thousand Oaks, CA, USA; 12Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA Objective: Osteonecrosis of the jaw (ONJ is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post-authorization safety study of cancer patients treated with antiresorptive therapies. Methods: As part of a comprehensive pharmacovigilance plan, developed with regulators’ input, the study will estimate incidence of ONJ and of serious infections among adult cancer patients with bone metastases treated with denosumab (120 mg subcutaneously or zoledronic acid (4 mg intravenously, adjusted for renal function

  5. Can drugs induce or aggravate sleep apneas? A case-noncase study in VigiBase®, the WHO pharmacovigilance database.

    Science.gov (United States)

    Linselle, Mélanie; Sommet, Agnès; Bondon-Guitton, Emmanuelle; Moulis, Florence; Durrieu, Geneviève; Benevent, Justine; Rousseau, Vanessa; Chebane, Leila; Bagheri, Haleh; Montastruc, François; Montastruc, Jean-Louis

    2017-06-01

    The potential favorizing role of drugs in sleep apnea syndrome (SAS) is unknown. This study investigates drugs associated with SAS in a pharmacovigilance database. SAS recorded as adverse drug reactions (ADRs) in VigiBase ® , the WHO pharmacovigilance database (more than 11 million reports), from 1978 to 2015 was selected. The risk of SAS reports was estimated using the case-noncase method, with cases being SAS and noncases all other recorded ADRs. During this 37-year period, 3325 ADRs including the word SAS were registered (0.05% of the database). Mean age was 51.2 ± 16.9 years with 52% men. ADRs were 'serious' in around 82% of cases. The case-noncase study found an association between SAS and exposition with sodium oxybate, rofecoxib, quetiapine, and clozapine for individual drugs and coxibs, antipsychotics, benzodiazepines, and opium alkaloids for drug classes. The potential role of other drugs is discussed. This study suggests that SAS can be associated with some drugs (mainly psychotropics) that are able to reveal or aggravate such a disease. Physicians should take into account the role of drugs in the etiological appraisal and management of SAS. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  6. Filling quality of the reports of adverse drug reactions received at the Pharmacovigilance Centre of São Paulo (Brazil): missing information hinders the analysis of suspected associations.

    Science.gov (United States)

    Ribeiro, Adalton; Lima, Silvana; Zampieri, Maria-Elisa; Peinado, Mirtes; Figueras, Albert

    2017-12-01

    The completeness and accuracy of the reports of suspected adverse drug reactions is important in pharmacovigilance. The aim of the present study was to analyze the quality of the information included in the reports sent to the Pharmacovigilance Centre of São Paulo (Brazil). A sample of 999 reports received from January 2013 to December 2014 was selected. The quality of the filled information was evaluated according to a 'sufficiency' criterion to apply the Karch-Lasagna causality algorithm. There were 820 reports from manufacturers and 179 from health centres. Only 4.4% (44) were fully filled, thus allowing the adequate analysis of the causal relationship between the suspected medication and the adverse event. In 30% of the reports from manufacturers, the information about the critical variables was lacking or incomplete, preventing the adequate evaluation of the report. It was also noted that the reports' poor filling quality was not related with less severity or with old and well-known medicines. The poor quality of the information included in the reports received by this centre, especially those sent by pharmaceutical manufacturers, hampers the identification of potential safety signals. Measures to improve the quality of the reports must be urgently adopted.

  7. Adverse drug reactions reporting in Calabria (Southern Italy) in the four-year period 2011-2014: impact of a regional pharmacovigilance project in light of the new European Legislation.

    Science.gov (United States)

    Leporini, Christian; Marrazzo, Giuseppina; Mumoli, Laura; Esposito, Stefania; Gallelli, Luca; Mangano, Giovanna; Brancati, Giacomino; De Francesco, Emanuela Adele; Russo, Emilio; De Sarro, Giovambattista

    2017-05-01

    The number of suspected adverse drug reactions (ADRs) yearly submitted to the Italian Network of Pharmacovigilance (RNF) has progressively increased after the new European Pharmacovigilance legislation (July 2012). These results have mostly reflected the agreements between Italian Medicines Agency (AIFA) and Italian Regions, enabling the implementation of active pharmacovigilance projects. A project was funded by the AIFA in Calabria region (Southern Italy) in 2010 to increase ADRs reporting and promote a safer medicines' use. Based on this background, we investigated the trend of ADRs in Calabria in 2011-2014, trying to analyze the possible entailments of the new law. Quantitative and descriptive analysis of ADRs submitted by Calabrian healthcare professionals and patients to the RNF database between 2011 and 2014. A sharp rise in regional reporting rate was observed over study period. Calabrian Pharmacovigilance system completely fulfilled the World Health Organization gold standard for ADR reporting rate, both in 2013 and 2014. However, heterogeneity was observed regarding reporting health facilities, healthcare professionals and patients among the study years. These findings reflect the success of the project performed in Calabria. However, this initiative should go on in the next future to obtain better and more homogeneous reporting behavior.

  8. Characterization of Acinetobacter baumannii clinical isolates carrying bla(OXA-23) carbapenemase and 16S rRNA methylase armA genes in Yemen.

    Science.gov (United States)

    Bakour, Sofiane; Alsharapy, Samer Ahmed; Touati, Abdelaziz; Rolain, Jean-Marc

    2014-12-01

    The aim of this study was to investigate the molecular support of resistance to carbapenems, aminoglycosides, and fluoroquinolones in Acinetobacter baumannii clinical isolates collected from Yemen hospital. Three A. baumannii were isolated in February 2013 from three patients hospitalized at Al-Thawra University Hospital in Sana'a, Yemen. Antibiotic susceptibility testing was performed using the disk diffusion and E-test methods. Carbapenemase production was carried out by the modified Hodge test (MHT) and imipenem-ethylenediaminetetraacetic acid (EDTA) methods. Carbapenem, aminoglycoside, and fluoroquinolone resistance determinants were studied by polymerase chain reaction and sequencing. The epidemiological relatedness of the three strains was studied using multilocus sequence typing (MLST). The isolates were resistant to almost all antibiotics tested with very high imipenem, amikacin, and ciprofloxacin minimum inhibitory concentrations (>32, >256, and >32 mg/L, respectively). The microbiological tests showed that the three A. baumannii were MHT positive, besides, the activity of β-lactamases was not inhibited by EDTA. All the three isolates contained the naturally occurring bla(OXA-51)-like gene and the bla(OXA-23)-like carbapenemase-encoding gene. The 16S rRNA methylase armA gene was detected in the three isolates. In addition, screening for genes encoding the aminoglycoside-modifying enzymes (AMEs) demonstrated that one isolate contained the acetyltransferase gene aac(6')-Ib. Fluoroquinolone resistance was associated with a single mutation Ser83Leu in the quinolone resistance determining region of the gyrA gene in all isolates. The MLST showed that the sequence type (ST) obtained corres