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Sample records for antibiotic therapy enhancement

  1. Systemic antibiotic therapy in periodontics

    Directory of Open Access Journals (Sweden)

    Anoop Kapoor

    2012-01-01

    Full Text Available Systemic antibiotics in conjunction with scaling and root planing (SRP, can offer an additional benefit over SRP alone in the treatment of periodontitis, in terms of clinical attachment loss (CAL and pocket depth change, and reduced risk of additional CAL loss. However, antibiotics are not innocuous drugs. Their use should be justified on the basis of a clearly established need and should not be substituted for adequate local treatment. The aim of this review is to discuss the rationale, proper selection, dosage and duration for antibiotic therapy so as to optimize the usefulness of drug therapy.

  2. [Proper antibiotic therapy. From penicillin to pharmacogenomic].

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    Caramia, G; Ruffini, E

    2012-04-01

    Antibiotics have always been considered one of the wonder discoveries of the 20th century. The use of penicillin by Flaming, opened up the golden era of antibiotics and now is hard to imagine the practice of medicine without antibiotics. Life-threatening infections, such as meningitis, endocarditis, bacteremic pneumonia sepsis, would again prove fatal. Also aggressive chemotherapy and transplant procedures would prove impossible. Another real wonder has been the rise of antibiotic resistance soon after the clinical use of penicillin in hospitals and communities. Several study demonstrated an excessive amount of antibiotic prescribing for communities patients and inpatients and in some hospital up to 50% of antibiotic usage is inappropriate: the benefits of antibiotic treatment come with the risk of antibiotic resistance development. In hospitals, infections caused by antibiotic-resistant bacteria are associated with higher mortality, morbidity and prolonged hospital stay compared with infections caused by antibiotic-susceptible bacteria. A variety of strategies has been proposed to reduce the cost and improve the quality of medication use. Education, guidelines and evidence based recommendations are considered to be essential elements of any program designed to influence prescribing behavior and can provide a foundation of knowledge that will enhance and increase the acceptance of stewardship strategies. Evidence-based recommendations, an approach to clinical practice helping to make decisions based on clinical expertise and on intimate knowledge of the individual patient's situations, beliefs, and priorities, enhance antimicrobial stewardship, that include appropriate selection, dosing, route, and duration of antimicrobial therapy can maximize clinical cure or prevention of infection while limiting the unintended consequences, such as the emergence of resistance, adverse drug events, and cost. These evidence-based guidelines are not a substitute for clinical

  3. [Health economics and antibiotic therapy].

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    Leclercq, P; Bigdéli, M

    1995-01-01

    In the field of antibiotic therapy, particularly the methods of economic evaluation hold one's attention within the wide range of health economics' applications. Several tools allow a comparison of the outcomes of alternative strategies and thereby guide choices to the most appropriate solutions. After a brief recall of the methods classically used to evaluate health care strategy, the authors stress the importance and difficulty of fixing and applying a correct and satisfactory procedure for evaluation. An evaluation example of antibiotic therapy allows to illustrate the application of the principles confronting a field in which competition is intense and economic stakes stay large--a fact which naturally yields to seek after objective decision making criteria. The health care policies drawn by public authorities as well as the marketing strategies of the health sector trade are partly based on such evaluations. If these techniques are not intended for the practitioner in the first place, they should not be indifferent to him since they influence health authorities and thereby indirectly affect the therapeutic freedom of the physician.

  4. [Antibiotic therapy in patients with renal insufficiency].

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    Luckhaupt, H; Rose, K G

    1985-06-01

    For the otolaryngologist (ENT specialist), too, antibiotics are among the most frequently prescribed drugs. This article gives the essential fundamentals for the antibiotic treatment of patients with restricted kidney functions, as well as advice for antibiotic therapy in clinics and in medical practice.

  5. Antibiotic Dosing in Continuous Renal Replacement Therapy.

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    Shaw, Alexander R; Mueller, Bruce A

    2017-07-01

    Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  6. Osmotic Compounds Enhance Antibiotic Efficacy against Acinetobacter baumannii Biofilm Communities.

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    Falghoush, Azeza; Beyenal, Haluk; Besser, Thomas E; Omsland, Anders; Call, Douglas R

    2017-10-01

    Biofilm-associated infections are a clinical challenge, in part because a hydrated matrix protects the bacterial community from antibiotics. Herein, we evaluated how different osmotic compounds (maltodextrin, sucrose, and polyethylene glycol [PEG]) enhance antibiotic efficacy against Acinetobacter baumannii biofilm communities. Established (24-h) test tube biofilms (strain ATCC 17978) were treated with osmotic compounds in the presence or absence of 10× the MIC of different antibiotics (50 μg/ml tobramycin, 20 μg/ml ciprofloxacin, 300 μg/ml chloramphenicol, 30 μg/ml nalidixic acid, or 100 μg/ml erythromycin). Combining antibiotics with hypertonic concentrations of the osmotic compounds for 24 h reduced the number of biofilm bacteria by 5 to 7 log ( P baumannii strains were similarly treated with 400-Da PEG and tobramycin, resulting in a mean 2.7-log reduction in recoverable bacteria compared with tobramycin treatment alone. Multivariate regression models with data from different osmotic compounds and nine antibiotics demonstrated that the benefit from combining hypertonic treatments with antibiotics is a function of antibiotic mass and lipophilicity ( r 2 > 0.82; P baumannii and Escherichia coli K-12. Augmenting topical antibiotic therapies with a low-mass hypertonic treatment may enhance the efficacy of antibiotics against wound biofilms, particularly when using low-mass hydrophilic antibiotics. IMPORTANCE Biofilms form a barrier that protects bacteria from environmental insults, including exposure to antibiotics. We demonstrated that multiple osmotic compounds can enhance antibiotic efficacy against Acinetobacter baumannii biofilm communities, but viscosity is a limiting factor, and the most effective compounds have lower molecular mass. The synergism between osmotic compounds and antibiotics is also dependent on the hydrophobicity and mass of the antibiotics. The statistical models presented herein provide a basis for predicting the optimal combination of

  7. Silver enhances antibiotic activity against gram-negative bacteria.

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    Morones-Ramirez, J Ruben; Winkler, Jonathan A; Spina, Catherine S; Collins, James J

    2013-06-19

    A declining pipeline of clinically useful antibiotics has made it imperative to develop more effective antimicrobial therapies, particularly against difficult-to-treat Gram-negative pathogens. Silver has been used as an antimicrobial since antiquity, yet its mechanism of action remains unclear. We show that silver disrupts multiple bacterial cellular processes, including disulfide bond formation, metabolism, and iron homeostasis. These changes lead to increased production of reactive oxygen species and increased membrane permeability of Gram-negative bacteria that can potentiate the activity of a broad range of antibiotics against Gram-negative bacteria in different metabolic states, as well as restore antibiotic susceptibility to a resistant bacterial strain. We show both in vitro and in a mouse model of urinary tract infection that the ability of silver to induce oxidative stress can be harnessed to potentiate antibiotic activity. Additionally, we demonstrate in vitro and in two different mouse models of peritonitis that silver sensitizes Gram-negative bacteria to the Gram-positive-specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug. Finally, we used silver and antibiotic combinations in vitro to eradicate bacterial persister cells, and show both in vitro and in a mouse biofilm infection model that silver can enhance antibacterial action against bacteria that produce biofilms. This work shows that silver can be used to enhance the action of existing antibiotics against Gram-negative bacteria, thus strengthening the antibiotic arsenal for fighting bacterial infections.

  8. Antibiotic Therapy for Very Low Birth Weigh Newborns in NICU

    OpenAIRE

    Seyyed-Abolfazl Afjeh; Mohammad-Kazem Sabzehei; Seyyed-Ali-Reza Fahimzad; Farideh Shiva; Ahmad-Reza Shamshiri; Fatemeh Esmaili

    2016-01-01

    Background Prolonged empiric antibiotics therapy in neonates results in several adverse consequences including widespread antibiotic resistance, late onset sepsis (LOS), necrotizing enterocolitis (NEC), prolonged hospital course (HC) and increase in mortality rates. Objectives To assess the risk factors and the outcome of prolonged empiric antibiotic therapy in very low birth weight (VLBW) newborns. ...

  9. Inhaled Antibiotic Therapy in Chronic Respiratory Diseases

    Directory of Open Access Journals (Sweden)

    Diego J. Maselli

    2017-05-01

    Full Text Available The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM. These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.

  10. Toyota production system quality improvement initiative improves perioperative antibiotic therapy.

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    Burkitt, Kelly H; Mor, Maria K; Jain, Rajiv; Kruszewski, Matthew S; McCray, Ellesha E; Moreland, Michael E; Muder, Robert R; Obrosky, David Scott; Sevick, Mary Ann; Wilson, Mark A; Fine, Michael J

    2009-09-01

    To assess the role of a Toyota production system (TPS) quality improvement (QI) intervention on appropriateness of perioperative antibiotic therapy and in length of hospital stay (LOS) among surgical patients. Pre-post quasi-experimental study using local and national retrospective cohorts. We used TPS methods to implement a multifaceted intervention to reduce nosocomial methicillin-resistant Staphylococcus aureus infections on a Veterans Affairs surgical unit, which led to a QI intervention targeting appropriate perioperative antibiotic prophylaxis. Appropriate perioperative antibiotic therapy was defined as selection of the recommended antibiotic agents for a duration not exceeding 24 hours from the time of the operation. The local computerized medical record system was used to identify patients undergoing the 25 most common surgical procedures and to examine changes in appropriate antibiotic therapy and LOS over time. Overall, 2550 surgical admissions were identified from the local computerized medical records. The proportion of surgical admissions receiving appropriate perioperative antibiotics was significantly higher (P <.01) in 2004 after initiation of the TPS intervention (44.0%) compared with the previous 4 years (range, 23.4%-29.8%) primarily because of improvements in compliance with antibiotic therapy duration rather than appropriate antibiotic selection. There was no statistically significant decrease in LOS over time. The use of TPS methods resulted in a QI intervention that was associated with an increase in appropriate perioperative antibiotic therapy among surgical patients, without affecting LOS.

  11. Antibiotic Therapy for Very Low Birth Weigh Newborns in NICU

    Science.gov (United States)

    Afjeh, Seyyed-Abolfazl; Sabzehei, Mohammad-Kazem; Fahimzad, Seyyed-Ali-Reza; Shiva, Farideh; Shamshiri, Ahmad-Reza; Esmaili, Fatemeh

    2016-01-01

    Background Prolonged empiric antibiotics therapy in neonates results in several adverse consequences including widespread antibiotic resistance, late onset sepsis (LOS), necrotizing enterocolitis (NEC), prolonged hospital course (HC) and increase in mortality rates. Objectives To assess the risk factors and the outcome of prolonged empiric antibiotic therapy in very low birth weight (VLBW) newborns. Materials and Methods Prospective study in VLBW neonates admitted to NICU and survived > 2 W, from July 2011 - June 2012. All relevant perinatal and postnatal data including duration of antibiotics therapy (Group I 2W) and outcome up to the time of discharge or death were documented and compared. Results Out of 145 newborns included in the study, 62 were in group I, and 83 in Group II. Average duration of antibiotic therapy was 14 days (range 3 - 62 days); duration in Group I and Group II was 10 ± 2.3 vs 25.5 ± 10.5 days. Hospital stay was 22.3 ± 11.5 vs 44.3 ± 14.7 days, respectively. Multiple regression analysis revealed following risk factors as significant for prolonged empiric antibiotic therapy: VLBW especially stage II, 12 (8.3%) newborns died. Infant mortality alone and with LOS/NEC was higher in group II as compared to group I (P < 0.002 and < 0.001 respectively). Conclusions Prolonged empiric antibiotic therapy caused increasing rates of LOS, NEC, HC and infant mortality. PMID:27307961

  12. Pros and cons of antibiotic therapy for pouchitis.

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    Navaneethan, Udayakumar; Shen, Bo

    2009-10-01

    Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for patients with medically refractory ulcerative colitis or ulcerative colitis with dysplasia and for the majority of patients with familial adenomatous polyposis. However, pouchitis and other pouch-associated complications frequently occur following surgery. Pouchitis is the most common long-term complication of ileal pouch-anal anastomosis in patients with ulcerative colitis, with a cumulative prevalence of up to 50%. The pathogenesis of pouchitis is probably associated with alterations in commensal bacterial flora, and most patients with pouchitis respond favorably to antibiotic therapy. Antibiotic therapy is the mainstay of treatment for active pouchitis, with ciprofloxacin or metronidazole traditionally being first-line agents. Some patients may develop dependency on antibiotics, thus requiring long-term maintenance therapy. In a subset of patients, the disease course may be refractory to antibiotic therapy, which is one of the common causes of pouch failure, requiring permanent ileostomy or pouch excision. On the other hand, long-term antibiotic use is expensive and can be associated with adverse effects and bacterial resistance. There may also be the risk of secondary infections, such as Clostridium difficile and fungal infections. The risks and benefits should be carefully balanced in patients who require long-term antibiotic therapy, and safe, efficacious, non-antibiotic-based agents are needed.

  13. Randomized clinical trial of antibiotic therapy for uncomplicated appendicitis.

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    Park, H C; Kim, M J; Lee, B H

    2017-12-01

    Uncomplicated appendicitis may resolve spontaneously or require treatment with antibiotics or appendicectomy. The aim of this randomized trial was to compare the outcome of a non-antibiotic management strategy with that of antibiotic therapy in uncomplicated appendicitis. Patients presenting to a university teaching hospital with CT-verified uncomplicated simple appendicitis (appendiceal diameter no larger than 11 mm and without any signs of perforation) were randomized to management with a no-antibiotic regimen with supportive care (intravenous fluids, analgesia and antipyretics as necessary) or a 4-day course of antibiotics with supportive care. The primary endpoint was rate of total treatment failure, defined as initial treatment failure within 1 month and recurrence of appendicitis during the follow-up period. Some 245 patients were randomized within the trial, and followed up for a median of 19 months. The duration of hospital stay was shorter (mean 3·1 versus 3·7 days; P antibiotics. There was no difference in total treatment failure rate between the groups: 29 of 124 (23·4 per cent) in the no-antibiotic group and 25 of 121 (20·7 per cent) in the antibiotic group (P = 0·609). Eighteen patients (9 in each group) had initial treatment failure, 15 of whom underwent appendicectomy and three received additional antibiotics. Thirty-six patients (20 in the no-antibiotic group, 16 in the antibiotic group) experienced recurrence, of whom 30 underwent appendicectomy and six received further antibiotics. Treatment failure rates in patients presenting with CT-confirmed uncomplicated appendicitis appeared similar among those receiving supportive care with either a no-antibiotic regimen or a 4-day course of antibiotics. Registration number: KCT0000124 ( http://cris.nih.go.kr). © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  14. Immunostimulation asa method limiting unnecessary antibiotic therapy

    Directory of Open Access Journals (Sweden)

    Agnieszka Szczukocka-Zych

    2015-12-01

    Full Text Available Recurring respiratory tract infections are typical of childhood. This results from the fact that children are exposed to pathogens, usually in groups of people, and from the immaturity of the immune system. Most upper and lower respiratory tract infections are caused by viruses. Nevertheless, antibiotics, which target bacteria, are often prescribed. Antibiotic overuse leads to increased microbial resistance to these drugs, resulting in their inefficacy. Improper treatment of respiratory infections with antibiotics ultimately leads to treatment failure. An increase in antibiotic resistance of many bacterial strains is becoming a serious global problem and makes treatment much more difficult. It is a responsibility of each physician to use antibiotics properly and implement adequate prevention of recurring respiratory tract infections. For many years, it has been attempted to find effective agents that improve immunity in children. The pharmaceutical market offers various preparations advertised as immunostimulants, such as bacterial lysates, vitamins, dietary supplements, probiotics or herbal, animal and homeopathic products. The role of immunomodulatory substances is to promote the immune system to fight pathogens, reduce the frequency of infections and decrease the demand for antibiotics. Unfortunately, most immunomodulators do not have sufficiently reliable clinical trials that would confirm their efficacy.

  15. [Antibiotic therapy of hospital-acquired pneumonia and its pharmacoeconomics].

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    Kolář, Milan; Htoutou Sedláková, Miroslava; Urbánek, Karel; Uvízl, Radomír; Adamus, Milan; Imwensi, O P

    2016-03-01

    Important hospital-acquired infections include pneumonia, mainly because of the increasing resistance of bacterial pathogens to antimicrobials and the associated potential failure of antibiotic therapy. The present study aimed at determining the most frequent etiological agents of hospital-acquired pneumonia (HAP) and assessing the relationship between 30-day mortality and adequacy of antibiotic therapy. Based on the obtained information, optimal patterns of antibiotic therapy were to be defined, including a pharmacoeconomic perspective. In patients with clinically confirmed HAP, bacterial etiological agents were identified, their susceptibility to antimicrobials was determined and statistical methods were used to assess the relationship between adequacy of antibiotic therapy and 30-day mortality. The study comprised 68 patients with clinically confirmed HAP. The most common etiological agents were strains of Pseudomonas aeruginosa (30.8 %), Klebsiella pneumoniae (23.1 %) and Burkholderia cepacia complex (15.4 %). Gram-negative bacteria accounted for 86.5 % of all bacterial pathogens. The overall mortality reached 42.5 %. In the subgroup of patients with inadequate antibiotic therapy, 30-day mortality was significantly higher (83.3 %) than in the subgroup with adequate therapy (30.0 %; p = 0.002). The risk for 30-day mortality was 2.78 times higher in case of inadequate antibiotic therapy (95%CI: 1.52-5.07). The proportion of Pseudomonas aeruginosa strains was significantly higher in the subgroup of patients with inadequate antibiotic therapy than in those with adequate therapy (67 % vs. 27 %; p = 0.032). Results of the present study suggest a significant relationship between mortality of patients with HAP and ineffective antibiotic therapy due to resistance of the bacterial pathogen. Thus, it is clear that initial antibiotic therapy must be based on qualified assumption of sufficient activity against the most common bacterial pathogens and results of surveillance

  16. Utilisation of antibiotic therapy in community practice.

    LENUS (Irish Health Repository)

    McGowan, B

    2008-10-01

    The aim of the study was to identify outpatient antibiotic consumption between Jan 2000 and Dec 2005 through analysis of the HSE-Primary Care Reimbursement Services (PCRS) database as part of the Surveillance of Antimicrobial Resistance in Ireland (SARI) project. Total antibiotic consumption on the PCRS scheme between January 2000 and December 2005 expressed in Defined Daily Dose per 1000 PCRS inhabitants per day increased by 26%. The penicillin group represents the highest consumption accounting for approximately 50% of the total outpatient antibiotic use. Total DIDs for this group increased by 25% between 2000 and 2005. Co-amoxiclav and amoxicillin account for 80% of the total consumption of this group of anti-infectives. With the exception of aminoglycosides and sulfonamides which demonstrated a decrease in DID consumption of 47% and 8% respectively, all other groups of anti-infectives had an increase in DID consumption of greater than 25% during the study period. Antibiotic prescribing data is a valuable tool for assessing public health strategies aiming to optimise antibiotic prescribing.

  17. Comparative outcomes of β-lactam antibiotics in outpatient parenteral antibiotic therapy: treatment success, readmissions and antibiotic switches.

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    Lee, Boeun; Tam, Idy; Weigel, Bernard; Breeze, Janis L; Paulus, Jessica K; Nelson, Jason; Allison, Genève M

    2015-08-01

    β-Lactam antibiotics are commonly used in outpatient parenteral antimicrobial therapy (OPAT), but data regarding outcomes of long-term therapy are limited. The purpose of this study was to compare treatment success, readmission and antibiotic switch rates in patients treated with β-lactam antibiotics as OPAT. We carried out a retrospective review of all patients, discharged from Tufts Medical Center with cefazolin, ceftriaxone, ertapenem or oxacillin, between January 2009 and June 2013. A competing risks analysis was used to compare the cumulative incidence of first occurrence of treatment success, antibiotic switch and 30 day readmission for each drug. Four hundred patients were identified (cefazolin n = 38, ceftriaxone n = 104, ertapenem n = 128 and oxacillin n = 130). Baseline demographics were similar. Treatment success rates were higher for ceftriaxone and ertapenem (cefazolin 61%, ceftriaxone 81%, ertapenem 73% and oxacillin 58%; P antibiotic switches were accomplished without readmission. Adverse drug events (ADEs) were the most common reason for outpatient antibiotic switches (31/37, 84%). The ADE rate was higher for the oxacillin group (cefazolin 2.0 versus ceftriaxone 1.5 versus ertapenem 2.9 versus oxacillin 8.4 per 1000 OPAT days; P antibiotics is effective, but antibiotic switches for adverse events were more frequent with oxacillin use. Clinicians should be cognizant of the risk of readmissions and ADEs in OPAT patients, as the value of OPAT lies in reducing patient morbidity and readmissions by managing ADEs and preventing clinical failures. © The Author 2015. 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.

  18. Antibiotic Desensitization Therapy in Secondary Syphilis and Listeria Infection: Case Reports and Review of Desensitization Therapy

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    Magpantay, Gil; Madar, Cristian S; Hsue, Gunther; Belnap, Conrad

    2011-01-01

    Two adult cases, one of secondary syphilis and one of Listeria monocytogenes bacteremia, in which antibiotic desensitization therapy was utilized to assist treatment of active infection in the face of severe penicillin allergy. Clinical considerations are discussed that led to the decision to employ a formal desensitization procedure. Antibiotic desensitization protocols can facilitate optimal and safe antibiotic therapy in the appropriate clinical setting. PMID:22187514

  19. Home iv antibiotic therapy through a medical day care unit

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    Gourdeau, Marie; Deschênes, Louise; Caron, Martine; Desmarais, Marc

    1993-01-01

    An out-patient parenteral antibiotic therapy program provided through a medical day care unit was evaluated in a tertiary care hospital. From July 11, 1988 to December 31, 1990, 122 patients were treated either on site at the unit or at home with self-administered intravenous antibiotics. In all, 142 courses of parenteral antibiotics (mostly cephalosporins and clindamycin) were given for a total of 124 infections, mostly bone and soft tissue infections (67 of 124, 54%). The duration of out-pa...

  20. Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

    Science.gov (United States)

    Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart

    2013-01-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from 38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

  1. Antibiotic Therapy in Pyogenic Meningitis in Paediatric Patients

    International Nuclear Information System (INIS)

    Tajdin, F.; Rasheed, M.A.; Ashraf, M.; Khan, G.J.; Rasheed, H.; Ejaz, H.

    2013-01-01

    Objective: To isolate and identify the causative pathogen, antibiotic sensitivity testing and success rate of empirical antibiotic therapy in pyogenic meningitis. Study Design: Analytical study. Place and Duration of Study: The Children's Hospital and Institute of Child Health, Lahore, Pakistan, from March to July 2012. Methodology: The study was performed on 72 culture positive meningitis cases in children less than 15 years of age. This therapy was evaluated by monitoring the patient's clinical picture for 14 - 21 days. The collected data was analyzed by Chi-square test. Results: Seventeen different bacteria were isolated. The most commonly occurring bacteria were coagulase negative Staphylococci (25%), E. coli (12.5%), Klebsiella pneumoniae (8.3%), Streptococcus pneumoniae (8.3%) and Pseudomonas aeruginosa (8.3%). All the bacteria were sensitive to vancomycin (96.7%), meropenem (76.7%), amikacin (75%), ciprofloxacin (65.3%), chloramphenicol (46.5%), ceftazidime (44.2%), cefepime (41.9%), co-amoxiclav (38.0%), oxacillin (34.8%), cefotaxime (21.4%), penicillin (20.7%), ceftriaxone (18.6%), cefuroxime (14%) and ampicillin (6.9%). The combination of sulbactam and cefoperazone showed antimicrobial sensitivity of 81.4%. The success rate of empirical antibiotic therapy was 91.7%. Conclusion: It was found that Gram negative bacteria were the major cause of pyogenic meningitis. Mostly there were resistant strains against all commonly used antibiotics except vancomycin. All empirical antibiotic therapies were found to be most successful. (author)

  2. Enhancement of antibiotic effect via gold:silver-alloy nanoparticles

    International Nuclear Information System (INIS)

    Moreira dos Santos, Margarida; Queiroz, Margarida João; Baptista, Pedro V.

    2012-01-01

    A strategy for the development of novel antimicrobials is to combine the stability and pleiotropic effects of inorganic compounds with the specificity and efficiency of organic compounds, such as antibiotics. Here we report on the use of gold:silver-alloy (Au:Ag-alloy) nanoparticles, obtained via a single-step citrate co-reduction method, combined to conventional antibiotics to enhance their antimicrobial effect on bacteria. Addition of the alloy nanoparticles considerably decreased the dose of antibiotic necessary to show antimicrobial effect, both for bacterial cells growing in rich medium in suspension and for bacterial cells resting in a physiological buffer on a humid cellulose surface. The observed effect was more pronounced than the sum of the individual effects of the nanoparticles and antibiotic. We demonstrate the enhancement effect of Au:Ag-alloy nanoparticles with a size distribution of 32.5 ± 7.5 nm mean diameter on the antimicrobial effect of (i) kanamycin on Escherichia coli (Gram-negative bacterium), and (ii) a β-lactam antibiotic on both a sensitive and resistant strain of Staphylococcus aureus (Gram-positive bacterium). Together, these results may pave the way for the combined use of nanoparticle–antibiotic conjugates towards decreasing antibiotic resistance currently observed for certain bacteria and conventional antibiotics.

  3. Enhancement of antibiotic effect via gold:silver-alloy nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Moreira dos Santos, Margarida, E-mail: margarida.santos@fct.unl.pt; Queiroz, Margarida Joao; Baptista, Pedro V. [Universidade Nova de Lisboa, CIGMH, Departamento Ciencias da Vida, Faculdade de Ciencias e Tecnologia (Portugal)

    2012-05-15

    A strategy for the development of novel antimicrobials is to combine the stability and pleiotropic effects of inorganic compounds with the specificity and efficiency of organic compounds, such as antibiotics. Here we report on the use of gold:silver-alloy (Au:Ag-alloy) nanoparticles, obtained via a single-step citrate co-reduction method, combined to conventional antibiotics to enhance their antimicrobial effect on bacteria. Addition of the alloy nanoparticles considerably decreased the dose of antibiotic necessary to show antimicrobial effect, both for bacterial cells growing in rich medium in suspension and for bacterial cells resting in a physiological buffer on a humid cellulose surface. The observed effect was more pronounced than the sum of the individual effects of the nanoparticles and antibiotic. We demonstrate the enhancement effect of Au:Ag-alloy nanoparticles with a size distribution of 32.5 {+-} 7.5 nm mean diameter on the antimicrobial effect of (i) kanamycin on Escherichia coli (Gram-negative bacterium), and (ii) a {beta}-lactam antibiotic on both a sensitive and resistant strain of Staphylococcus aureus (Gram-positive bacterium). Together, these results may pave the way for the combined use of nanoparticle-antibiotic conjugates towards decreasing antibiotic resistance currently observed for certain bacteria and conventional antibiotics.

  4. Successful treatment of recurrent cholangitis with antibiotic maintenance therapy

    NARCIS (Netherlands)

    van den Hazel, S. J.; Speelman, P.; Tytgat, G. N.; van Leeuwen, D. J.

    1994-01-01

    The impact of antibiotic maintenance therapy on the incidence of biliary tract infection was evaluated in patients with recurrent cholangitis after resection of a malignancy at the hepatic confluence. Thirty-eight of 54 patients (70%) experienced episodes of cholangitis. In 14 of the 38 patients

  5. Antibiotic therapy for preventing infections in people with acute stroke

    NARCIS (Netherlands)

    Vermeij, Jan-Dirk; Westendorp, Willeke F.; Dippel, Diederik Wj; van de Beek, Diederik; Nederkoorn, Paul J.

    2018-01-01

    Stroke is the main cause of disability in high-income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve

  6. Antibiotic therapy for preventing infections in patients with acute stroke

    NARCIS (Netherlands)

    Westendorp, Willeke F.; Vermeij, Jan-Dirk; Vermeij, Frederique; den Hertog, Heleen M.; Dippel, Diederik W. J.; van de Beek, Diederik; Nederkoorn, Paul J.

    2012-01-01

    Background Stroke is the main cause of disability in high income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce infections and improve outcome.

  7. Streamlining antibiotic therapy with procalcitonin protocols: consensus and controversies.

    Science.gov (United States)

    Haubitz, Sebastian; Mueller, Beat; Schuetz, Philipp

    2013-04-01

    Accumulating evidence supports procalcitonin (PCT) as an accurate surrogate biomarker for likelihood and severity of bacterial infections. In community-acquired pneumonia and other respiratory infections, PCT-guided antibiotic therapy algorithms resulted in reduced antibiotic exposure while maintaining a similar or even better level of safety compared with standard care. Reductions in antibiotic use translate into lower treatment costs, decreased risk of side effects and decreased bacterial multiresistance. This is especially important, as acute respiratory infections represent the most frequent reason for antibiotic prescriptions worldwide. Still, there is some controversy about the benefits of PCT measurement in sepsis patients in the intensive care unit and for nonrespiratory infections. Highly sensitive PCT assays are readily available in many hospitals today, and point-of-care assays with high enough sensitivity for antibiotic guidance are expected to be available soon. Herein, the authors provide an overview of recent studies evaluating PCT in different clinical situations and an outlook of currently enrolling or upcoming interventional trials.

  8. Antibiotic polymeric nanoparticles for biofilm-associated infection therapy.

    Science.gov (United States)

    Cheow, Wean Sin; Hadinoto, Kunn

    2014-01-01

    Polymeric nanoparticles are highly attractive as drug delivery vehicles due to their high structural integrity, stability during storage, ease of preparation and functionalization, and controlled release capability. Similarly, lipid-polymer hybrid nanoparticles, which retain the benefits of polymeric nanoparticles plus the enhanced biocompatibility and prolonged circulation time owed to the lipids, have recently emerged as a superior alternative to polymeric nanoparticles. Drug nanoparticle complex prepared by electrostatic interaction of oppositely charged drug and polyelectrolytes represents another type of polymeric nanoparticle. This chapter details the preparation, characterization, and antibiofilm efficacy testing of antibiotic-loaded polymeric and hybrid nanoparticles and antibiotic nanoparticle complex.

  9. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD).

    Science.gov (United States)

    Herath, Samantha C; Poole, Phillippa

    2013-11-28

    an exacerbation was reduced (odds ratio (OR) 0.55; 95% confidence interval (CI) 0.39 to 0.77, 3 studies, 1262 participants, high quality). This represented a reduction from 69% of participants in the control group compared to 54% in the treatment group (95% CI 46% to 63%) and the number needed to treat to prevent one exacerbation (NNTb) was therefore 8 (95% CI 5 to 18). The frequency of exacerbations was also reduced with continuous prophylactic antibiotic treatment (rate ratio 0.73; 95% CI 0.58 to 0.91).Use of pulsed antibiotic treatment showed a non-significant reduction in the number of people with exacerbations (OR 0.87; 95% CI 0.69 to 1.09, 1 study, 1149 participants, moderate quality) and the test for interaction showed that this result was significantly different from the effect on exacerbations with continuous antibiotics.There was a statistically significant improvement in quality of life with both continuous and pulsed antibiotic treatment but this was smaller than the four unit improvement that is regarded as being clinically significant (MD -1.78; 95% CI -2.95 to -0.61, 2 studies, 1962 participants, moderate quality).Neither pulsed nor continuous antibiotics showed a significant effect on the secondary outcomes of frequency of hospital admissions, change in lung function, serious adverse events or all-cause mortality (moderate quality evidence).The adverse events that were recorded varied among the trials depending on the different antibiotics used. Azithromycin was associated with a significant hearing loss in the treatment group. The moxifloxacin pulsed study reported a significantly higher number of adverse events in the treatment arm due to the marked increase in gastrointestinal adverse events (P antibiotic resistance in the community is of major concern. One study found newly colonised patients to have higher rates of antibiotic resistance. Patients colonised with moxifloxacin-sensitive pseudomonas at initiation of therapy rapidly became resistant

  10. Home iv Antibiotic Therapy through a Medical Day Care Unit

    Directory of Open Access Journals (Sweden)

    Marie Gourdeau

    1993-01-01

    Full Text Available An out-patient parenteral antibiotic therapy program provided through a medical day care unit was evaluated in a tertiary care hospital. From July 11, 1988 to December 31, 1990, 122 patients were treated either on site at the unit or at home with self-administered intravenous antibiotics. In all, 142 courses of parenteral antibiotics (mostly cephalosporins and clindamycin were given for a total of 124 infections, mostly bone and soft tissue infections (67 of 124, 54%. The duration of out-patient therapy ranged from two to 62 days with a mean duration of 9.4 days if treated at the unit, or 13.2 days in the home care model (1476 patient-days. Vein access was peripheral and catheters remained functional for an average of 4.9 days (range 0.5 to 22 days. Only two patients experienced adverse drug reactions that necessitated modification of treatment. One other case was readmitted to the hospital for surgical debridement. The average cost per patient-day was $66 compared with $375 for in-hospital therapy. This program proved to be safe, efficient, and cost-effective.

  11. Antibiotic therapy for preventing infections in people with acute stroke.

    Science.gov (United States)

    Vermeij, Jan-Dirk; Westendorp, Willeke F; Dippel, Diederik Wj; van de Beek, Diederik; Nederkoorn, Paul J

    2018-01-22

    Stroke is the main cause of disability in high-income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve outcome. In the previous version of this Cochrane Review, published in 2012, we found that antibiotics did reduce the risk of infection but did not reduce the number of dependent or deceased patients. However, included studies were small and heterogeneous. In 2015, two large clinical trials were published, warranting an update of this Review. To assess the effectiveness and safety of preventive antibiotic therapy in people with ischaemic or haemorrhagic stroke. We wished to determine whether preventive antibiotic therapy in people with acute stroke:• reduces the risk of a poor functional outcome (dependency and/or death) at follow-up;• reduces the occurrence of infections in the acute phase of stroke;• reduces the occurrence of elevated body temperature (temperature ≥ 38° C) in the acute phase of stroke;• reduces length of hospital stay; or• leads to an increased rate of serious adverse events, such as anaphylactic shock, skin rash, or colonisation with antibiotic-resistant micro-organisms. We searched the Cochrane Stroke Group Trials Register (25 June 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5; 25 June 2017) in the Cochrane Library; MEDLINE Ovid (1950 to 11 May 2017), and Embase Ovid (1980 to 11 May 2017). In an effort to identify further published, unpublished, and ongoing trials, we searched trials and research registers, scanned reference lists, and contacted trial authors, colleagues, and researchers in the field. Randomised controlled trials (RCTs) of preventive antibiotic therapy versus control (placebo or open control) in people with acute ischaemic or haemorrhagic stroke. Two review authors independently selected

  12. The Efficacy of Perioperative Antibiotic Therapy in Tonsillectomy Patients.

    Science.gov (United States)

    Orłowski, Krzysztof; Lisowska, Grażyna; Misiołek, Hanna; Paluch, Zbigniew; Misiołek, Maciej

    2016-01-01

    While the results of early research suggested that perioperative antibiotic prophylaxis in tonsillectomy patients is associated with many benefits, these data were not confirmed by further studies and meta-analyses. The aim of this study was to investigate the usefulness and efficacy of antibiotic monotherapy in the healing of surgical wounds of patients undergoing bilateral resection of the palatine tonsils, based on an analysis of selected objective and subjective characteristics of wound healing during the postoperative period. The study included 50 men and women who underwent routine resection of the palatine tonsils. The patients were randomized into two groups: Group I, undergoing tonsillectomy with cefuroxime prophylaxis (n = 25), and Group II, who were not given perioperative antibiotic therapy (n = 25). The severity of signs and complaints recorded on postoperative days 1-10 was scored on 3- and 10-item scales. The only significant intergroup differences pertained to problems with swallowing food and fluids on postoperative days 4-6, 8 and 9 (less prevalent in Group II), postoperative use of analgesics on postoperative day 9 (less frequent in Group II), the degree of mucosal swelling in the operated area on postoperative days 3 and 7 (less severe in Group II), and the amount of fibrin covering the tonsillar niches on the third postoperative day (significantly higher in Group I). The administration of antibiotics for prevention or control of infection should be preceded by a comprehensive analysis of the potential benefits and risks. Perioperative use of antibiotics is justified only in selected cases, i.e. in individuals with comorbidities.

  13. Opportunistic microorganisms in patients undergoing antibiotic therapy for pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Silvia Maria Rodrigues Querido

    2011-12-01

    Full Text Available Antimicrobial therapy may cause changes in the resident oral microbiota, with the increase of opportunistic pathogens. The aim of this study was to compare the prevalence of Candida, Staphylococcus, Pseudomonas and Enterobacteriaceae in the oral cavity of fifty patients undergoing antibiotic therapy for pulmonary tuberculosis and systemically healthy controls. Oral rinsing and subgingival samples were obtained, plated in Sabouraud dextrose agar with chloramphenicol, mannitol agar and MacConkey agar, and incubated for 48 h at 37ºC. Candida spp. and coagulase-positive staphylococci were identified by phenotypic tests, C. dubliniensis, by multiplex PCR, and coagulase-negative staphylococci, Enterobacteriaceae and Pseudomonas spp., by the API systems. The number of Candida spp. was significantly higher in tuberculosis patients, and C. albicans was the most prevalent specie. No significant differences in the prevalence of other microorganisms were observed. In conclusion, the antimicrobial therapy for pulmonary tuberculosis induced significant increase only in the amounts of Candida spp.

  14. Antibiotics

    Science.gov (United States)

    Antibiotics are powerful medicines that fight bacterial infections. Used properly, antibiotics can save lives. They either kill bacteria or ... natural defenses can usually take it from there. Antibiotics do not fight infections caused by viruses, such ...

  15. ANTIBIOTIC RESISTANCE OF HELICOBACTER PYLORI AMONG CHILDREN AND THERAPY SELECTION

    Directory of Open Access Journals (Sweden)

    Ye.A. Kornienko

    2006-01-01

    Full Text Available The reason for the low therapy efficiency of many gastrobduodenal diseases is the increasing resistance to the antibiotics helicobacter pylori (Н. pylori, which is conditioned by the mutations of its various genes. The most practical importance is attributed to the 23s RRNA mutations, underlying resistance to claritromicin. According to the international consensus maastrichtb3, the scheme of treatment with the inhibitor of the proton pump, claritromicin and metronidasol is recommended as the 1st line therapy. The present work assesses the resistance of Н. pylori to claritromicin aided by pcrbdiagnostics of the 23s RRNA mutation of rna in the biopsy material of the mucous coat of stomach and standard treatment scheme efficiency if compared with the onebantibiotic scheme – amoxicillin, bismuth and inhibitor of the proton pump. 68 children with Н. pylori bassociated diseases have been examined. The frequency of resistance of Н. pylori to claritromicin made up 28%. The standard 10bday long scheme of treatment was efficient among 14% of the patients, the 7bday long schemes with amoxicillin, bismuth and omeprazole were efficient among 40% of the patients, the 10bday long schemes with amoxicillin, bismuth and omeprazole were efficient among 75% of the patients; with omeprazole replaced by esomeprazole the efficiency was observed among 83% of the patients along with the good treatment tolerance.Key words: helicobacter pylori, antibiotic resistance, eradication.

  16. Enhancement of antibiotic productions by engineered nitrate utilization in actinomycetes.

    Science.gov (United States)

    Meng, Sitong; Wu, Hang; Wang, Lei; Zhang, Buchang; Bai, Linquan

    2017-07-01

    Nitrate is necessary for primary and secondary metabolism of actinomycetes and stimulates the production of a few antibiotics, such as lincomycin and rifamycin. However, the mechanism of this nitrate-stimulating effect was not fully understood. Two putative ABC-type nitrate transporters were identified in Streptomyces lincolnensis NRRL2936 and verified to be involved in lincomycin biosynthesis. With nitrate supplementation, the transcription of nitrogen assimilation genes, nitrate-specific ABC1 transporter genes, and lincomycin exporter gene lmrA was found to be enhanced and positively regulated by the global regulator GlnR, whose expression was also improved. Moreover, heterologous expression of ABC2 transporter genes in Streptomyces coelicolor M145 resulted in an increased actinorhodin production. Further incorporation of a nitrite-specific transporter gene nirC, as in nirC-ABC2 cassette, led to an even higher actinorhodin production. Similarly, the titers of salinomycin, ansamitocin, lincomycin, and geldanamycin were increased with the integration of this cassette to Streptomyces albus BK3-25, Actinosynnema pretiosum ATCC31280, S. lincolnensis LC-G, and Streptomyces hygroscopicus XM201, respectively. Our work expanded the nitrate-stimulating effect to many antibiotic producers by utilizing the nirC-ABC2 cassette for enhanced nitrate utilization, which could become a general tool for titer increase of antibiotics in actinomycetes.

  17. [Rational antibiotic therapy in the dental office: Practical guidelines for decision-making].

    Science.gov (United States)

    Zadik, Y

    2016-04-01

    Although most dental and periodontal diseases are caused by bacteria, the usual therapy is mechanical/surgical rather than antimicrobial medications. However, sometimes antibiotic administration may be necessary in addition to or as an alternative to the surgical/mechanical treatment. Many studies have shown that the misuse of antibiotics by dentists may be mostly attributed to unnecessity or inefficient regimen, and could contribute to bacterial resistance to antibiotics. The article presents practical guidelines to the administration of antibiotics in the dental office.

  18. Some problems of antibiotic therapy in radiation sickness

    International Nuclear Information System (INIS)

    Shalnova, G.A.

    1975-01-01

    Data on the application of antibiotics and the mechanism of their action in radiation sickness are reviewed. Questions are discussed, such as the effect of antibiotics on the course and outcome of radiation sickness, the development of dysbacteriosis following irradiation, the effect of antibiotics on endogenic infection, the development of resistance of autoflora microbes to antibiotics in an irradiated organism and various aspects of the mechanism of action of antibiotics in radiation sickness. (author)

  19. A Multicenter Evaluation of Prolonged Empiric Antibiotic Therapy in Adult ICUs in the United States.

    Science.gov (United States)

    Thomas, Zachariah; Bandali, Farooq; Sankaranarayanan, Jayashri; Reardon, Tom; Olsen, Keith M

    2015-12-01

    The purpose of this study is to determine the rate of prolonged empiric antibiotic therapy in adult ICUs in the United States. Our secondary objective is to examine the relationship between the prolonged empiric antibiotic therapy rate and certain ICU characteristics. Multicenter, prospective, observational, 72-hour snapshot study. Sixty-seven ICUs from 32 hospitals in the United States. Nine hundred ninety-eight patients admitted to the ICU between midnight on June 20, 2011, and June 21, 2011, were included in the study. None. Antibiotic orders were categorized as prophylactic, definitive, empiric, or prolonged empiric antibiotic therapy. Prolonged empiric antibiotic therapy was defined as empiric antibiotics that continued for at least 72 hours in the absence of adjudicated infection. Standard definitions from the Centers for Disease Control and Prevention were used to determine infection. Prolonged empiric antibiotic therapy rate was determined as the ratio of the total number of empiric antibiotics continued for at least 72 hours divided by the total number of empiric antibiotics. Univariate analysis of factors associated with the ICU prolonged empiric antibiotic therapy rate was conducted using Student t test. A total of 660 unique antibiotics were prescribed as empiric therapy to 364 patients. Of the empiric antibiotics, 333 of 660 (50%) were continued for at least 72 hours in instances where Centers for Disease Control and Prevention infection criteria were not met. Suspected pneumonia accounted for approximately 60% of empiric antibiotic use. The most frequently prescribed empiric antibiotics were vancomycin and piperacillin/tazobactam. ICUs that utilized invasive techniques for the diagnosis of ventilator-associated pneumonia had lower rates of prolonged empiric antibiotic therapy than those that did not, 45.1% versus 59.5% (p = 0.03). No other institutional factor was significantly associated with prolonged empiric antibiotic therapy rate. Half of all

  20. Optimising the duration of antibiotic therapy for ventilator-associated pneumonia

    Directory of Open Access Journals (Sweden)

    J. Chastre

    2007-08-01

    Full Text Available Ventilator-associated pneumonia (VAP has traditionally been treated with a 14–21-day course of antibiotics. However, prolonged antibiotic therapy is associated with the emergence of multidrug-resistant strains, as well as higher toxicity and costs. In a large, randomised, controlled trial in patients with microbiologically confirmed VAP who received appropriate empirical antibiotic therapy, an 8-day antibiotic regimen was not associated with excess mortality or more episodes of recurrent pulmonary infection compared with a 15-day regimen. Amongst patients who developed recurrent infection, multidrug-resistant pathogens emerged less frequently in the group receiving 8 days of antibiotic therapy. The 8-day regimen was also not associated with excess mortality in the subgroup with VAP caused by nonfermentative Gram-negative bacilli, mostly Pseudomonas aeruginosa, although recurrent infections occurred more often. Pending confirmatory studies, an 8-day course of antibiotic therapy may be appropriate for many patients with ventilator-associated pneumonia, providing that initial antibiotic therapy is appropriate, the clinical course is favourable and extreme vigilance is maintained after stopping antibiotics. Patients whose initial treatment regimen was inappropriate, those infected with difficult-to-treat pathogens such as Pseudomonas aeruginosa, and immunocompromised patients and others at high risk for relapse are likely to require a longer duration of antibiotic therapy.

  1. Practical Considerations and the Intestinal Microbiome in Disease: Antibiotics for IBD Therapy.

    Science.gov (United States)

    Fedorak, Richard N; Ismond, Kathleen P

    2016-01-01

    The inflammatory bowel diseases, Crohn's and ulcerative colitis, have been treated with a range of antibiotics for inducing and maintaining remission, as well as the prevention of post-operative symptoms. To date, many studies have been performed assessing the efficacy of antibiotics when used alone, in combination with other antibiotics, or as an adjunctive therapy to other pharmaceutical treatments. Literature evidence supporting the use of antibiotics in IBD can be ambiguous, especially when considering the potential role of dysbiosis in the gastrointestinal tract. The review considers the systemic effect of antibiotics and the evidence base for their efficacy in the treatment of IBD. © 2016 S. Karger AG, Basel.

  2. [Peripherally inserted central catheter antibiotic therapy for cystic fibrosis patients].

    Science.gov (United States)

    Betegnie, A-L; Cracowski, C; Bedouch, P; Segond, C; Robein-Dobremez, M-J; Pin, I; Allenet, B

    2014-11-01

    Peripherally inserted central catheters (PICC) are more and more used for intravenous antibiotic infusions in cystic fibrosis (CF) patients in the Grenoble area (France). The aim of this study was to assess the use of this technique in this indication. 1. Retrospective evaluation of 102 consecutive PICC insertions over 3years and the incidence of adverse events during the therapy. 2. Prospective evaluation of 12 patient's satisfaction and their nurses over a 3-month period. 3. Comparative analysis of single domiciliary treatment costs using PICC versus peripheral catheter (PC). 102 PICC insertions were attempted in 31 patients. Seven failures and 7 complications occurred during the treatment requiring removal of the PICC, i.e. an overall success rate of 86.2% (88/102). Pain during PICC introduction was 4.2/10 (visual analogical scale). Mean satisfaction levels during therapy were 9.3/10 for patients and 8.7/10 for nurses. Compared with PC, all the patients said that PICC was "more comfortable". Differential costs of treatment with PC and with PICC at home were estimated at 57.15€ and 590.16€ respectively. PICC is an alternative to CP for intravenous antibiotherapy in CF patients, providing better safety and comfort. PICC use should be promoted in this indication. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  3. Cyclic antibiotic therapy for diverticular disease: a critical reappraisal.

    Science.gov (United States)

    Zullo, Angelo; Hassan, Cesare; Maconi, Giovanni; Manes, Gianpiero; Tammaro, Gianfranco; De Francesco, Vincenzo; Annibale, Bruno; Ficano, Leonardo; Buri, Luigi; Gatto, Giovanni; Lorenzetti, Roberto; Campo, Salvatore M; Ierardi, Enzo; Pace, Fabio; Morini, Sergio

    2010-09-01

    Different symptoms have been attributed to uncomplicated diverticular disease (DD). Poor absorbable antibiotics are largely used for uncomplicated DD, mainly for symptom treatment and prevention of diverticulitis onset. Controlled trials on cyclic administration of rifaximin in DD patients were evaluated. Four controlled, including 1 double-blind and 3 open-label, randomized studies were available. Following a long-term cyclic therapy, a significant difference emerged in the global symptoms score (range: 0-18) between rifaximin plus fibers (from 6-6.5 to 1-2) and fibers alone (from 6.7 to 2-3.8), although the actual clinically relevance of such a very small difference remains to be ascertained. Moreover, a similar global symptom score reduction (from 6 to 2.4) can be achieved by simply recommending an inexpensive high-fiber diet. Current data suggest that cyclic rifaximin plus fibers significantly reduce the incidence of the first episode of acute diverticulitis as compared to fibers alone (1.03% vs 2.75%), but a cost-efficacy analysis is needed before this treatment can be routinely recommended. The available studies have been hampered by some limitations, and definite conclusions could not be drawn. The cost of a long-life, cyclic rifaximin therapy administered to all symptomatic DD patients would appear prohibitive.

  4. Duration of antibiotic therapy for ventilator-associated pneumonia in burn patients.

    Science.gov (United States)

    Wahl, Wendy L; Taddonio, Michael A; Arbabi, Saman; Hemmila, Mark R

    2009-01-01

    Shorter compared with longer courses of antibiotic therapy for ventilator-associated pneumonia (VAP) in mixed medical-surgical intensive care units (ICUs) have been reported to produce equivalent outcomes. There have been few studies on the duration of antibiotic therapy for VAP in the burn population. We hypothesized that a shorter duration of antibiotic therapy for VAP would produce similar outcomes in our burn ICU. All burn patients from July 2001 to December 2006 admitted to the burn ICU requiring mechanical ventilation were studied. VAP was diagnosed prospectively by our Infection Control Liaison using bronchoalveolar lavage for cultures. Patients were cohorted into two groups: before July 1, 2004, antibiotic therapy duration was directed by the discretion of the attending physician (preprotocol), and after, the goal was 8 days of appropriate therapy or longer based on physician discretion (postprotocol). There were 98 patients treated for VAP with similar rates of inhalation injury, %TBSA burn size, age, and need for mechanical ventilation between the groups. The incidence of recurrent VAP was the same: 17% for the preprotocol and 15% for the postprotocol periods. The overall duration of antibiotic therapy did not change from 11 +/- 4 to 12 +/- 6 days. For patients treated longer than the target of 8 days, 66% had positive respiratory cultures at 4 days after initiation of antibiotic therapy. For the majority of patients with aspiration-type organisms or nonvirulent strains, there were fewer antibiotic days overall at 10 +/- 5 days (P VAP with the same bacteria. Despite a focused effort to decrease antibiotic usage for VAP in burn patients, the overall duration of therapy did not change. The majority of patients with virulent organisms such as methicillin-resistant Staphylococcus aureus or nonfermenting Gram-negative rods still had clinical signs of pneumonia and positive cultures, leading clinicians to continue antibiotics. In patients without virulent

  5. Osmotic therapies added to antibiotics for acute bacterial meningitis

    Science.gov (United States)

    Wall, Emma Cb; Ajdukiewicz, Katherine Mb; Bergman, Hanna; Heyderman, Robert S; Garner, Paul

    2018-01-01

    Background Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes. This is an update of a Cochrane Review first published in 2013. Objectives To evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability. Search methods We searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015). Selection criteria Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis. Data collection and analysis Two review authors independently screened the search results and selected trials for inclusion. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence. Main results We included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates. Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272

  6. [Nosocomial Clostridium difficile diarrhea--adverse effect of antibiotic therapy].

    Science.gov (United States)

    Lemeni, Daniela

    2010-01-01

    C. difficile is recognised as the main cause for colitis in hospitalised patients which are treated with antibiotics, chemotherapics or other drugs that disturb intestinal microbiota. Thus, a rapid and correct diagnostic of Clostridium difficile infections is essential for preventing nosocomial infection spread. Empiric therapy, regardless of the laboratory investigation results, is inadequate, especially in epidemic situations, as not all the cases of diarrhoea are due to C. difficile infection. Other risk factors for CDAD (Clostridiumn difficile Associated Diseases might be: prolonged hospitalization or residency in an asylum, age, existence of a severe chronic disease in the background nasogastric intubation, anti-ulcer drugs, at less extent gastrointestinal surgery, other immunosuppresive compounds etc. In our country, C. difficile infection is rather frequent in adults, though it is not always reported by clinicians. The circulation of endemic rybotype 027 in Romania is not well documented, the rybotype being extremely virulent and spread in other European countries. Hence the importance of extending the diagnostic capacity of C. difficile infection in order to allow detection of this rybotype among the strains isolated in our country.

  7. Silver-loaded nanotubular structures enhanced bactericidal efficiency of antibiotics with synergistic effect in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Xu N

    2017-01-01

    Full Text Available Na Xu,1,2,* Hao Cheng,3,4,* Jiangwen Xu,1 Feng Li,3 Biao Gao,1 Zi Li,3 Chenghao Gao,3 Kaifu Huo,5 Jijiang Fu,1,2 Wei Xiong3 1The State Key Laboratory of Refractories and Metallurgy, School of Materials and Metallurgy, Wuhan University of Science and Technology, 2Institute of Biology and Medicine, Wuhan University of Science and Technology, 3Orthopaedic Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 5Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Antibiotic-resistant bacteria have become a major issue due to the long-term use and abuse of antibiotics in treatments in clinics. The combination therapy of antibiotics and silver (Ag nanoparticles is an effective way of both enhancing the antibacterial effect and decreasing the usage of antibiotics. Although the method has been proved to be effective in vitro, no in vivo tests have been carried out at present. Herein, we described a combination therapy of local delivery of Ag and systemic antibiotics treatment in vitro in an infection model of rat. Ag nanoparticle-loaded TiO2 nanotube (NT arrays (Ag-NTs were fabricated on titanium implants for a customized release of Ag ion. The antibacterial properties of silver combined with antibiotics vancomycin, rifampin, gentamicin, and levofloxacin, respectively, were tested in vitro by minimum inhibitory concentration (MIC assay, disk diffusion assay, and antibiofilm formation test. Enhanced antibacterial activity of combination therapy was observed for all the chosen bacterial strains, including gram-negative Escherichia coli (ATCC 25922, gram

  8. Frequency of microbiologically correct antibiotic therapy increased by infectious disease consultations and microbiological results

    NARCIS (Netherlands)

    J.J. Kerremans (Jos); H.A. Verbrugh (Henri); M.C. Vos (Margreet)

    2012-01-01

    textabstractIn a prospective observational study of bacteremic patients we ascertained the influence of different parts of culture results on the correctness of empirical antibiotic therapy. Ninety-three bacteremic patients requiring antibiotic treatment were included. Patients who had consultations

  9. ESTHETIC OUTCOME OF SURGICAL EXCISION VERSUS ANTIBIOTIC THERAPY FOR NONTUBERCULOUS MYCOBACTERIAL CERVICOFACIAL LYMPHADENITIS IN CHILDREN

    NARCIS (Netherlands)

    Lindeboom, Jerome A.; Lindeboom, Robert; Bruijnesteijn van Coppenraet, Elisabeth S.; Kuijper, Ed J.; Tuk, Jacco; Prins, Jan M.

    2009-01-01

    One hundred children with microbiologically proven nontuberculous mycobacterial cervicofacial lymphadenitis were randomly assigned to excision of the involved lymph nodes, or antibiotic therapy consisting of clarithromycin and rifabutin. The esthetic outcome was rated using a revised and weighted

  10. Esthetic outcome of surgical excision versus antibiotic therapy for nontuberculous mycobacterial cervicofacial lymphadenitis in children

    NARCIS (Netherlands)

    Lindeboom, J.A.; Lindeboom, R.; Bruijnesteijn van Coppenraet, E.S.; Kuijper, E.J.; Tuk, J.; Prins, J.M.

    2009-01-01

    One hundred children with microbiologically proven nontuberculous mycobacterial cervicofacial lymphadenitis were randomly assigned to excision of the involved lymph nodes, or antibiotic therapy consisting of clarithromycin and rifabutin. The esthetic outcome was rated using a revised and weighted

  11. Conservative Wait-and-See Therapy Versus Antibiotic Treatment for Nontuberculous Mycobacterial Cervicofacial Lymphadenitis in Children

    NARCIS (Netherlands)

    Lindeboom, Jerome A.

    2011-01-01

    Background. In this explorative study, 50 children with microbiologically confirmed nontuberculous mycobacterial cervicofacial lymphadenitis were randomized to either receive antibiotic therapy or follow a conservative wait-and-see approach. Our primary objective was to assess the time for all

  12. Does appropriate empiric antibiotic therapy modify intensive care unit-acquired Enterobacteriaceae bacteraemia mortality and discharge?

    NARCIS (Netherlands)

    Pouwels, K B; Van Kleef, E; Vansteelandt, S; Batra, R; Edgeworth, J D; Smieszek, T; Robotham, J V

    2017-01-01

    BACKGROUND: Conflicting results have been found regarding outcomes of intensive care unit (ICU)-acquired Enterobacteriaceae bacteraemia and the potentially modifying effect of appropriate empiric antibiotic therapy. AIM: To evaluate these associations while adjusting for potential time-varying

  13. Effect of antibiotic therapy on the sensitivity of indium-111-labeled leukocyte scans

    International Nuclear Information System (INIS)

    Datz, F.L.; Thorne, D.A.

    1986-01-01

    Although 111 In-labeled leukocytes have been shown to be a useful technique for detecting infection, it has been postulated that antibiotic therapy may reduce the sensitivity of the leukocyte scan. Many patients with suspected bacterial infections are placed on antibiotics before a definite site of infection has been identified. Three hundred twelve leukocyte scans on 271 patients were retrospectively reviewed and classified as positive or negative, and as to whether or not they were being treated with antibiotics at the time the leukocyte scan was performed. The overall sensitivity, considering all 312 studies, was 90%. One hundred sixty-nine patient studies were on patients receiving antibiotics; 143 studies were on patients not on antibiotics. The sensitivity of the leukocyte scan was 88.7% in patients on antibiotic therapy; it was 92.1% in those who were not receiving antibiotics. The differences in sensitivity between the two groups were not significantly different (p less than 0.05). We conclude that antibiotic therapy does not affect the sensitivity of the 111 In-labeled leukocyte scan

  14. [Simple parameters of antibiotic utilization and diagnostic background of antimicrobial therapy in Hungarian hospitals in 1995].

    Science.gov (United States)

    Almási, I; Ternák, G

    1997-02-23

    This paper is published as second part of a survey on antibiotic utilisation of 8 Hungarian hospitals in January, 1995. The length of hospital stay of the patients receiving systemic antibiotic treatment was significantly higher (P profilaxis 32.7%, pneumonia 13.3% of the 753 diagnoses) and drugs (metronidazol 26.3%, aminoglycosides 20% of the 1455 antibiotics) most frequently found in cases of combined antibiotic therapy it was concluded that parallel treatment with two or more antibiotic was often unjustified. Only 11% of antibiotics was used as directed against known bacteria. It was found that the rate of the achieved microbiological examinations and targeted therapy was low even if microbiological samples were easy to obtain. It was not the main purpose of the survey to get data of the clinical diagnostic background of antibiotic therapy, but indirect signs showed that these drugs were often used without sufficient clinical evidences (anamnesis, physical status, labor, X-ray and other tests) of infection. Authors recommend further survey in order to find out the causes of insufficiency of diagnoses. They also propose elaboration of diagnostic protocols.

  15. Antibiotic therapy versus appendicectomy in uncomplicated acute appendicitis in terms of efficacy

    International Nuclear Information System (INIS)

    Zaidi, M.A.; Nazeer, T.B.; Aziz, O.B.A.; Asad, T.; Dar, Z.S.

    2017-01-01

    Objective: To compare antibiotic therapy and appendectomy in uncomplicated acute appendicitis in terms of efficacy. Study Design: Randomized controlled trial. Place and Duration of Study: Surgical Ward Forward Treatment Centre (FTC), 5 Mountain Medical Battalion Forward Kahuta Azad Jammu Kashmir (AJK), from Oct 2011 to Mar 2013. Material and Methods: A total of 103 patients with clinical diagnosis of acute appendicitis (AA) were admitted during the duration of study and divided into two groups by consecutive sampling. The antibiotic group consisted of 51 patients who received intravenous antibiotics for 48 hours and oral antibiotics for another 8 days. The appendectomy group comprised of 52 patients who all underwent standard appendectomy. All the patients were followed up at 1 month and 1 year for assessing efficacy and post treatment complications. Results: The efficacy of antibiotic treatment is 90.625 percent as compared to appendectomy which was 88.46 percent (p=0.759) at 1 month follow up after treatment. At one year post treatment, the comparison between the efficacy of antibiotic therapy (71.87 percent) and appendectomy (87.14 percent) remains statistically insignificant (p=0.055). Conclusion: Antibiotic therapy is comparable to appendectomy in AA in terms of efficacy at 1 month and 1 year post treatment. (author)

  16. Is there an improvement of antibiotic use in China? Evidence from the usage analysis of combination antibiotic therapy for type I incisions in 244 hospitals.

    Science.gov (United States)

    Zhou, Wen-Juan; Luo, Zhen-Ni; Tang, Chang-Min; Zou, Xiao-Xu; Zhao, Lu; Fang, Peng-Qian

    2016-10-01

    The improvement of antibiotic rational use in China was studied by usage analysis of combination antibiotic therapy for type I incisions in 244 hospitals. Five kinds of hospitals, including general hospital, maternity hospital, children's hospital, stomatological hospital and cancer hospital, from 30 provinces were surveyed. A systematic random sampling strategy was employed to select outpatient prescriptions and inpatient cases in 2011 and 2012. A total of 29 280 outpatient prescriptions and 73 200 inpatient cases from 244 hospitals in each year were analyzed. Data were collected with regards to the implementation of the national antibiotic stewardship program (NASP), the overall usage and the prophylactic use of antibiotic for type I incisions. Univariate analysis was used for microbiological diagnosis rate before antimicrobial therapy, prophylactic use of antibiotics for type I incision operation, and so on. For multivariate analysis, the use of antibiotics was dichotomized according to the guidelines, and entered as binary values into logistic regression analysis. The results were compared with the corresponding criteria given by the guidelines of this campaign. The antibiotic stewardship in China was effective in that more than 80% of each kind of hospitals achieved the criteria of recommended antibiotics varieties. Hospital type appeared to be a factor statistically associated with stewardship outcome. The prophylactic use of antibiotics on type I incision operations decreased by 16.22% (Pbench marking. More efforts addressing the root cause of antibiotics abuse would continue to improve the rational use of antibiotics in China.

  17. Early transition to oral antibiotic therapy for community-acquired pneumonia: duration of therapy, clinical outcomes, and cost analysis.

    Science.gov (United States)

    Omidvari, K; de Boisblanc, B P; Karam, G; Nelson, S; Haponik, E; Summer, W

    1998-08-01

    Our objective was to compare therapeutic outcome and analyse cost-benefit of a 'conventional' (7-day course of i.v. antibiotic therapy) vs. an abbreviated (2-day i.v. antibiotic course followed by 'switch' to oral antibiotics) therapy for in-patients with community-acquired pneumonia (CAP). We used a multicenter prospective, randomized, parallel group with a 28 day follow-up, at the University-based teaching hospitals: The Medical Center of Louisiana in New Orleans, LA and hospitals listed in the acknowledgement. Ninety-five patients were randomized to receive either a 'conventional' course of intravenous antibiotic therapy with cefamandole 1 g i.v. every 6 h for 7 days (n = 37), or an abbreviated course of intravenous therapy with cefamandole (1 g i.v. every 6 h for 2 days) followed by oral therapy with cefaclor (500 mg every 8 h for 5 days). No difference was found in the clinical courses, cure rates, survival or the resolution of the chest radiograph abnormalities among the two groups. The mean duration of therapy (6.88 days for the conventional group compared to 7-30 days for the early oral therapy group) and the frequencies of overall symptomatic improvement (97% vs. 95%, respectively) were similar in both groups. Patients who received early oral therapy had shorter hospital stays (7.3 vs. 9.71 days, P = 0.01), and a lower total cost of care ($2953 vs. $5002, P < 0.05). It was concluded that early transition to an oral antibiotic after an abbreviated course of intravenous therapy in CAP is substantially less expensive and has comparable efficacy to conventional intravenous therapy. Altering physicians' customary management of hospitalized patients with CAP can reduce costs with no appreciable additional risk of adverse patient outcome.

  18. Antibiotic therapy for stable non-CF bronchiectasis in adults

    DEFF Research Database (Denmark)

    Fjaellegaard, Katrine; Sin, Melda Dönmez; Browatzki, Andrea

    2017-01-01

    To provide an update on efficacy and safety of antibiotic treatments for stable non-cystic fibrosis (CF) bronchiectasis (BE). Systematic review based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was done. Twenty-six studies (1.898 patients) fulfilled......, exacerbations and QoL, whereas studies on aztreonam revealed no significant clinical improvements in the outcomes of interest, including exacerbation rate. Adverse events, including bronchospasm, have been reported in association with tobramycin and aztreonam. Several antibiotic treatment regimens have been...... shown to improve QoL and exacerbation rate, whereas findings regarding sputum production, lung function and admissions have been conflicting. Evidence-based treatment algorithms for antibiotic treatment of stable non-CF BE will have to await large-scale, long-term controlled studies....

  19. Synergistic antimicrobial therapy using nanoparticles and antibiotics for the treatment of multidrug-resistant bacterial infection

    Science.gov (United States)

    Gupta, Akash; Saleh, Neveen M.; Das, Riddha; Landis, Ryan F.; Bigdeli, Arafeh; Motamedchaboki, Khatereh; Rosa Campos, Alexandre; Pomeroy, Kenneth; Mahmoudi, Morteza; Rotello, Vincent M.

    2017-06-01

    Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. Antibiotic treatment of resistant infections further contributes to the rapidly increasing number of antibiotic-resistant species and strains. Synthetic macromolecules such as nanoparticles (NPs) exhibit broad-spectrum activity against MDR species, however lack of specificity towards bacteria relative to their mammalian hosts limits their widespread therapeutic application. Here, we demonstrate synergistic antimicrobial therapy using hydrophobically functionalized NPs and fluoroquinolone antibiotics for treatment of MDR bacterial strains. An 8-16-fold decrease in antibiotic dosage is achieved in presence of engineered NPs to combat MDR strains. This strategy demonstrates the potential of using NPs to ‘revive’ antibiotics that have been rendered ineffective due to the development of resistance by pathogenic bacteria.

  20. ANTIBIOTIC THERAPY OF ABSCESS OF THE LUNG AND BRONCHIECTASIS

    Science.gov (United States)

    Hewitt, William L.

    1952-01-01

    Since the fusospirochetal group of bacteria are the commonest etiologic agents in abscess of the lung, aqueous crystalline penicillin is the agent of first choice in the majority of cases. Streptomycin is indicated for a small group of cases in which Klebsiella is the etiologic agent. Aureomycin, chloramphenicol or terramycin may produce an excellent therapeutic response either initially or after therapeutic failure with penicillin. Administration of antibiotics by inhalation should be carried out in conjunction with systemic forms of treatment. In the treatment of bronchiectasis, the antibiotics are most useful in the control of acute exacerbations of pulmonary infection which punctuate the course of this disease. PMID:14935877

  1. Oral antibiotics enhance antibody responses to keyhole limpet hemocyanin in orally but not muscularly immunized chickens.

    Science.gov (United States)

    Murai, Atsushi; Kitahara, Kazuki; Okumura, Shouta; Kobayashi, Misato; Horio, Fumihiko

    2016-02-01

    Recent studies have emphasized the crucial role of gut microbiota in triggering and modulating immune response. We aimed to determine whether the modification of gut microbiota by oral co-administration of two antibiotics, ampicillin and neomycin, would lead to changes in the antibody response to antigens in chickens. Neonatal chickens were given or not given ampicillin and neomycin (0.25 and 0.5 g/L, respectively) in drinking water. At 2 weeks of age, the chicks were muscularly or orally immunized with antigenic keyhole limpet hemocyanin (KLH), and then serum anti-KLH antibody levels were examined by ELISA. In orally immunized chicks, oral antibiotics treatment enhanced antibody responses (IgM, IgA, IgY) by 2-3-fold compared with the antibiotics-free control, while the antibiotics did not enhance antibody responses in the muscularly immunized chicks. Concomitant with their enhancement of antibody responses, the oral antibiotics also lowered the Lactobacillus species in feces. Low doses of antibiotics (10-fold and 100-fold lower than the initial trial), which failed to change the fecal Lactobacillus population, did not modify any antibody responses when chicks were orally immunized with KLH. In conclusion, oral antibiotics treatment enhanced the antibody response to orally exposed antigens in chickens. This enhancement of antibody response was associated with a modification of the fecal Lactobacillus content, suggesting a possible link between gut microbiota and antibody response in chickens. © 2015 Japanese Society of Animal Science.

  2. Antibiotic therapy in preterm premature rupture of the membranes.

    Science.gov (United States)

    Yudin, Mark H; van Schalkwyk, Julie; Eyk, Nancy Van

    2009-09-01

    To review the evidence and provide recommendations on the use of antibiotics in preterm premature rupture of the membranes (PPROM). Outcomes evaluated include the effect of antibiotic treatment on maternal infection, chorioamnionitis, and neonatal morbidity and mortality. Published literature was retrieved through searches of Medline, EMBASE, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary and key words (PPROM, infection, and antibiotics). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and new material incorporated in the guideline to July 2008. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Guideline implementation should assist the practitioner in developing an approach to the use of antibiotics in women with PPROM. Patients will benefit from appropriate management of this condition. This guideline has been reviewed and approved by the Infectious Diseases Committee and the Maternal Fetal Medicine Committee of the SOGC, and approved by the Executive and Council of the SOGC. The Society of Obstetricians and Gynaecologists of Canada. 1. Following PPROM at 32 weeks' gestation, administration of antibiotics to prolong pregnancy is recommended if fetal lung maturity can not be proven and/or delivery is not planned. (I-A) 4

  3. Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes.

    Science.gov (United States)

    Abeles, Shira R; Ly, Melissa; Santiago-Rodriguez, Tasha M; Pride, David T

    2015-01-01

    Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances.

  4. Protocol for extended antibiotic therapy after laparoscopic cholecystectomy for acute calculous cholecystitis (Cholecystectomy Antibiotic Randomised Trial, CHART).

    Science.gov (United States)

    Pellegrini, Pablo; Campana, Juan Pablo; Dietrich, Agustín; Goransky, Jeremías; Glinka, Juan; Giunta, Diego; Barcan, Laura; Alvarez, Fernando; Mazza, Oscar; Sánchez Claria, Rodrigo; Palavecino, Martin; Arbues, Guillermo; Ardiles, Victoria; de Santibañes, Eduardo; Pekolj, Juan; de Santibañes, Martin

    2015-11-18

    Acute calculous cholecystitis represents one of the most common complications of cholelithiasis. While laparoscopic cholecystectomy is the standard treatment in mild and moderate forms, the need for antibiotic therapy after surgery remains undefined. The aim of the randomised controlled Cholecystectomy Antibiotic Randomised Trial (CHART) is therefore to assess if there are benefits in the use of postoperative antibiotics in patients with mild or moderate acute cholecystitis in whom a laparoscopic cholecystectomy is performed. A single-centre, double-blind, randomised trial. After screening for eligibility and informed consent, 300 patients admitted for acute calculus cholecystitis will be randomised into two groups of treatment, either receiving amoxicillin/clavulanic acid or placebo for 5 consecutive days. Postoperative evaluation will take place during the first 30 days. Postoperative infectious complications are the primary end point. Secondary end points are length of hospital stay, readmissions, need of reintervention (percutaneous or surgical reinterventions) and overall mortality. The results of this trial will provide strong evidence to either support or abandon the use of antibiotics after surgery, impacting directly in the incidence of adverse events associated with the use of antibiotics, the emergence of bacterial resistance and treatment costs. This study and informed consent sheets have been approved by the Research Projects Evaluating Committee (CEPI) of Hospital Italiano de Buenos Aires (protocol N° 2111). The results of the trial will be reported in a peer-reviewed publication. NCT02057679. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Carbohydrate-Based Host-Guest Complexation of Hydrophobic Antibiotics for the Enhancement of Antibacterial Activity.

    Science.gov (United States)

    Jeong, Daham; Joo, Sang-Woo; Shinde, Vijay Vilas; Cho, Eunae; Jung, Seunho

    2017-08-08

    Host-guest complexation with various hydrophobic drugs has been used to enhance the solubility, permeability, and stability of guest drugs. Physical changes in hydrophobic drugs by complexation have been related to corresponding increases in the bioavailability of these drugs. Carbohydrates, including various derivatives of cyclodextrins, cyclosophoraoses, and some linear oligosaccharides, are generally used as host complexation agents in drug delivery systems. Many antibiotics with low bioavailability have some limitations to their clinical use due to their intrinsically poor aqueous solubility. Bioavailability enhancement is therefore an important step to achieve the desired concentration of antibiotics in the treatment of bacterial infections. Antibiotics encapsulated in a complexation-based drug delivery system will display improved antibacterial activity making it possible to reduce dosages and overcome the serious global problem of antibiotic resistance. Here, we review the present research trends in carbohydrate-based host-guest complexation of various hydrophobic antibiotics as an efficient delivery system to improve solubility, permeability, stability, and controlled release.

  6. A clinical examination of antibiotics in continuous regional arterial infusion (CRAI) therapy for severe acute pancreatitis (SAP). A prospective randomized controlled trial of BIPM and IPM/CS

    International Nuclear Information System (INIS)

    Yamasaki, Shigemichi; Ishikura, Hiroyasu; Kamitani, Takanori

    2011-01-01

    Continuous regional arterial infusion (CRAI) therapy using both protease inhibitors and antibiotics are one of the specific therapeutic methods for severe acute pancreatitis (SAP). As for the administered antibiotics, imipenem/cilastatin sodium (IPM/CS) is generally chosen as a first step, but there are only a few reports comparing IPM/CS with other antibiotics. Therefore, we performed a prospective randomized controlled trial between biapenem (BIPM) and IPM/CS as CRAI antibiotics. Twelve patients with SAP were admitted to our institution during April, 2009 since August, 2006, and were randomized into two groups. They were treated with 120 mg/day of nafamostat mesilate and either 1.2 g/day of BIPM (n=6) or 2.0 g/day of IPM/CS (n=6) for CRAI therapy within 48 hours after the administration. The clinical data, inflammatory markers (WBC, CRP), serum pancreatic enzymes (lipase, tripsin, phospholipase A2, elastase 1 and pancreatic secretory trypsin inhibitor (PSTI) and contrast-enhanced abdominal Computed Tomography findings were compared between the two groups and the adverse effects were monitored. CRAI therapy was performed for seven days. The curative effect of this therapy was evaluated at the beginning of the treatment, the day 7 and the day 14. Our results suggested that BIPM was a non-recessive antibiotic which had an equal effect in CRAI therapy in comparison with IPM/CS. (author)

  7. Protocolized hyperventilation enhances electroconvulsive therapy.

    Science.gov (United States)

    de Arriba-Arnau, Aida; Dalmau, Antonia; Soria, Virginia; Salvat-Pujol, Neus; Ribes, Carmina; Sánchez-Allueva, Ana; Menchón, José Manuel; Urretavizcaya, Mikel

    2017-08-01

    Hyperventilation is recommended in electroconvulsive therapy (ECT) to enhance seizures and to increase patients' safety. However, more evidence is needed regarding its effects and the optimum method of application. This prospective study involving 21 subjects compared two procedures, protocolized hyperventilation (PHV) and hyperventilation as usual (HVau), applied to the same patient in two consecutive sessions. Transcutaneous partial pressure of carbon dioxide (TcPCO 2 ) was measured throughout all sessions. Ventilation parameters, hemodynamic measures, seizure characteristics, and side effects were also explored. PHV resulted in lower TcPCO 2 after hyperventilation (p=.008) and over the whole session (p=.035). The lowest TcPCO 2 was achieved after voluntary hyperventilation. Changes in TcPCO 2 from baseline showed differences between HVau and PHV at each session time-point (all p<.05). Between- and within-subjects factors were statistically significant in a general linear model. Seizure duration was greater in PHV sessions (p=.028), without differences in other seizure quality parameters or adverse effects. Correlations were found between hypocapnia induction and seizure quality indexes. Secondary outcomes could be underpowered. PHV produces hypocapnia before the stimulus, modifies patients' TcPCO 2 values throughout the ECT session and lengthens seizure duration. Voluntary hyperventilation is the most important part of the PHV procedure with respect to achieving hypocapnia. A specific ventilation approach, CO 2 quantification and monitoring may be advisable in ECT. PHV is easy to apply in daily clinical practice and does not imply added costs. Ventilation management has promising effects in terms of optimizing ECT technique. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. An assessment of antibiotic therapy of urinary tract infection in elderly, hospitalised patients.

    Science.gov (United States)

    McCaig, D J; Stewart, D; Harvey, Y; Downie, G; Scott, C J

    1995-11-01

    The aim of the study was to compare the antibiotic treatment actually received by elderly, hospitalised patients with urinary tract infection (UTI) with 'optimal' therapy (as gauged by compliance with antibiotic policy, infecting organism, sensitivity data, patient renal function and cost). UTI was more common in females and in catheterised patients and E.Coli was the commonest pathogen. Trimethoprim and co-amoxiclav were the drugs used most frequently for either empirical or sensitivity data-based treatment. In 96% of infections a drug with appropriate action was administered. Often, however, treatment could have been optimised by substituting a cheaper suitable antibiotic, by standardising duration of therapy and ensuring that doses were adjusted for renal impairment. Savings from the use of 'optimal' therapy were estimated at 17%. There is clearly considerable scope for positive input from the clinical pharmacist in this area.

  9. Developing New Antimicrobial Therapies: Are Synergistic Combinations of Plant Extracts/Compounds with Conventional Antibiotics the Solution?

    Science.gov (United States)

    Cheesman, Matthew J.; Ilanko, Aishwarya; Blonk, Baxter; Cock, Ian E.

    2017-01-01

    The discovery of penicillin nearly 90 years ago revolutionized the treatment of bacterial disease. Since that time, numerous other antibiotics have been discovered from bacteria and fungi, or developed by chemical synthesis and have become effective chemotherapeutic options. However, the misuse of antibiotics has lessened the efficacy of many commonly used antibiotics. The emergence of resistant strains of bacteria has seriously limited our ability to treat bacterial illness, and new antibiotics are desperately needed. Since the discovery of penicillin, most antibiotic development has focused on the discovery of new antibiotics derived from microbial sources, or on the synthesis of new compounds using existing antibiotic scaffolds to the detriment of other lines of discovery. Both of these methods have been fruitful. However, for a number of reasons discussed in this review, these strategies are unlikely to provide the same wealth of new antibiotics in the future. Indeed, the number of newly developed antibiotics has decreased dramatically in recent years. Instead, a reexamination of traditional medicines has become more common and has already provided several new antibiotics. Traditional medicine plants are likely to provide further new antibiotics in the future. However, the use of plant extracts or pure natural compounds in combination with conventional antibiotics may hold greater promise for rapidly providing affordable treatment options. Indeed, some combinational antibiotic therapies are already clinically available. This study reviews the recent literature on combinational antibiotic therapies to highlight their potential and to guide future research in this field. PMID:28989242

  10. How to measure the impacts of antibiotic resistance and antibiotic development on empiric therapy: new composite indices.

    Science.gov (United States)

    Hughes, Josie S; Hurford, Amy; Finley, Rita L; Patrick, David M; Wu, Jianhong; Morris, Andrew M

    2016-12-16

    We aimed to construct widely useable summary measures of the net impact of antibiotic resistance on empiric therapy. Summary measures are needed to communicate the importance of resistance, plan and evaluate interventions, and direct policy and investment. As an example, we retrospectively summarised the 2011 cumulative antibiogram from a Toronto academic intensive care unit. We developed two complementary indices to summarise the clinical impact of antibiotic resistance and drug availability on empiric therapy. The Empiric Coverage Index (ECI) measures susceptibility of common bacterial infections to available empiric antibiotics as a percentage. The Empiric Options Index (EOI) varies from 0 to 'the number of treatment options available', and measures the empiric value of the current stock of antibiotics as a depletable resource. The indices account for drug availability and the relative clinical importance of pathogens. We demonstrate meaning and use by examining the potential impact of new drugs and threatening bacterial strains. In our intensive care unit coverage of device-associated infections measured by the ECI remains high (98%), but 37-44% of treatment potential measured by the EOI has been lost. Without reserved drugs, the ECI is 86-88%. New cephalosporin/β-lactamase inhibitor combinations could increase the EOI, but no single drug can compensate for losses. Increasing methicillin-resistant Staphylococcus aureus (MRSA) prevalence would have little overall impact (ECI=98%, EOI=4.8-5.2) because many Gram-positives are already resistant to β-lactams. Aminoglycoside resistance, however, could have substantial clinical impact because they are among the few drugs that provide coverage of Gram-negative infections (ECI=97%, EOI=3.8-4.5). Our proposed indices summarise the local impact of antibiotic resistance on empiric coverage (ECI) and available empiric treatment options (EOI) using readily available data. Policymakers and drug developers can use the

  11. Clinical efficacy of cycling empirical antibiotic therapy for febrile neutropenia in pediatric cancer patients.

    Science.gov (United States)

    Teranishi, Hideto; Koga, Yuhki; Nishio, Hisanori; Kato, Wakako; Ono, Hiroaki; Kanno, Shunsuke; Nakashima, Kentaro; Takada, Hidetoshi

    2017-07-01

    Febrile neutropenia (FN) is the main treatment-related cause of mortality among children with cancer, as the prolonged use of broad-spectrum antibiotics can lead to antibiotic resistance in these patients. Antibiotic cycling has been reported to limit the emergence of antibiotic-resistant bacteria among adult patients. However, no studies have evaluated pediatric patients with FN. Between September 2011 and February 2014, 126 pediatric cancer patients were admitted to our center for chemotherapy and/or hematopoietic stem cell transplantation and were included in this study. Retrospective and prospective data collection were performed before and after antibiotic cycling, respectively. Between September 2011 and November 2012 (before antibiotic cycling was implemented), intravenous cefpirome was used as the empirical therapy for FN. Between December 2012 and February 2014 (after antibiotic cycling was implemented), the monthly antibiotic cycling involved intravenous piperacillin-tazobactam (PIPC/TAZ), intravenous meropenem or ciprofloxacin (CPFX), and intravenous cefepime in that order. For children aged ≥13 years, the monthly cycling involved intravenous PIPC/TAZ, and CPFX was administered. The detection rates for extended-spectrum β-lactamase producers in blood and stool culture samples decreased significantly after the implementation of antibiotic cycling (0.33/1000 patient-days vs 0/1000 patient-days, p = 0.03; 1.00/1000 patient-days vs 0/1000 patient-days, p Antibiotic cycling was associated with a decreased emergence of multidrug-resistant microbes. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. In vitro dilutions of thioridaxine with potential to enhance antibiotic ...

    African Journals Online (AJOL)

    Gram staining, catalase test and coagulase test were done on the resulting colonies to further confirm the strains as S. aureus. Antibiotic susceptibility test was done by agar disc diffusion method using sterile Mueller- Hinton agar plates before and after treatment with laboratory dilutions of thioridaxine. S. aureus strains 1, ...

  13. Increase in interleukin-8 production from circulating neutrophils upon antibiotic therapy in cystic fibrosis patients.

    Science.gov (United States)

    Montemurro, Pasqualina; Mariggiò, Maria A; Barbuti, Giovanna; Cassano, Amalia; Vincenti, Alessandra; Serio, Gabriella; Guerra, Lorenzo; Diana, Anna; Santostasi, Teresa; Polizzi, Angela; Fumarulo, Ruggiero; Casavola, Valeria; Manca, Antonio; Conese, Massimo

    2012-12-01

    It is not known whether antibiotic therapy for lung disease in cystic fibrosis (CF) has an influence on circulating polymorphonuclear neutrophil (PMN) function and apoptosis. Blood PMNs were obtained from 14 CF patients before and after antibiotic treatment for an acute exacerbation, and from 10 healthy controls. PMNs were evaluated for production of reactive oxygen species (ROS) by spectrophotometry, of cytokines in the conditioned medium by ELISA, and apoptotic response by cytofluorimetry. ROS and interleukin (IL)-8 were produced at higher levels by CF PMNs pre-therapy than control PMNs under basal conditions. IL-8 levels further increased after therapy. Early apoptotic response was higher in CF PMNs pre-therapy than in control PMNs, and this pattern did not change after antibiotic treatment. Circulating PMNs are primed in CF acute patients. Further studies are needed to consider PMN-produced IL-8 as a biomarker to evaluate response to antibiotic therapy in CF patients. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  14. Steering Evolution with Sequential Therapy to Prevent the Emergence of Bacterial Antibiotic Resistance.

    Directory of Open Access Journals (Sweden)

    Daniel Nichol

    2015-09-01

    Full Text Available The increasing rate of antibiotic resistance and slowing discovery of novel antibiotic treatments presents a growing threat to public health. Here, we consider a simple model of evolution in asexually reproducing populations which considers adaptation as a biased random walk on a fitness landscape. This model associates the global properties of the fitness landscape with the algebraic properties of a Markov chain transition matrix and allows us to derive general results on the non-commutativity and irreversibility of natural selection as well as antibiotic cycling strategies. Using this formalism, we analyze 15 empirical fitness landscapes of E. coli under selection by different β-lactam antibiotics and demonstrate that the emergence of resistance to a given antibiotic can be either hindered or promoted by different sequences of drug application. Specifically, we demonstrate that the majority, approximately 70%, of sequential drug treatments with 2-4 drugs promote resistance to the final antibiotic. Further, we derive optimal drug application sequences with which we can probabilistically 'steer' the population through genotype space to avoid the emergence of resistance. This suggests a new strategy in the war against antibiotic-resistant organisms: drug sequencing to shepherd evolution through genotype space to states from which resistance cannot emerge and by which to maximize the chance of successful therapy.

  15. Behavioral Therapy, Incentives Enhance Addiction Treatment

    Science.gov (United States)

    ... Research News From NIH Behavioral Therapy, Incentives Enhance Addiction Treatment Past Issues / Summer 2006 Table of Contents ... that people who are trying to end their addiction to marijuana can benefit from a treatment program ...

  16. Challenges and Future Prospects of Antibiotic Therapy: From Peptides to Phages Utilization

    Directory of Open Access Journals (Sweden)

    Santi M. Mandal

    2014-05-01

    Full Text Available Bacterial infections are raising serious concern across the globe. The effectiveness of conventional antibiotics is decreasing due to global emergence of multi-drug-resistant (MDR bacterial pathogens. This process seems to be primarily caused by an indiscriminate and inappropriate use of antibiotics in non-infected patients and in the food industry. New classes of antibiotics with different actions against MDR pathogens need to be developed urgently. In this context, this review focuses on several ways and future directions to search for the next generation of safe and effective antibiotics compounds including antimicrobial peptides, phage therapy, phytochemicals, metalloantibiotics, LPS and efflux pump inhibitors to control the infections caused by MDR pathogens.

  17. Dry cow therapy with a non-antibiotic intramammary teat seal - a review

    Directory of Open Access Journals (Sweden)

    Crispie Fiona

    2004-07-01

    Full Text Available Dry cow antibiotic therapy is used to eliminate existing intramammary infections and to prevent new infections in the dry period. It is implemented as part of a total management system known as the 'Five-Point Plan' for mastitis control. Recent public concerns over the widespread prophylactic use of antibiotics, coupled with an increasing interest in organic farming, have lead to a re-evaluation of the treatment of cows at drying-off. As a result, attention has focussed on the use of novel alternatives to antibiotic therapy at the end of lactation. One such therapy involves the application of a non-antibiotic bismuth-based intramammary teat seal designed for use in cows with low cell counts at the end of lactation. Like the keratin plug that forms naturally in teats of cows that have been dried-off, teat seal forms a physical barrier to invading pathogens. To date, a number of independent studies have shown that teat seal is as effective as traditional dry cow antibiotic products in preventing the occurrence of new infection during the dry period in cows with somatic cell counts of ≤200,000 cells ml-1 at drying-off. This paper reviews the efficacy of teat seal in preventing dry period mastitis in both conventional and organic dairying systems.

  18. Antibiotic Therapy for Acute Infiltrate-Complicated Calculous Cholecystitis

    Directory of Open Access Journals (Sweden)

    Yu. A. Nesterenko

    2007-01-01

    Full Text Available Objective: to summarize the results of treatment in 442 patients of various ages with acute calculous cholecystitis complicated by a compact perivesical infiltrate.Materials and methods. Bile from all the patients was bacteriologically studied. The implication of various antibiotics in limiting perivesical fat inflammation was determined.Results. The importance of decompressive treatments for complicated calculous cholecystitis has been ascertained. The advantages of microcholecystostomy have been revealed. There is evidence that it is expedient to use third-forth-generation cephalosporins, fluoroquinolones, and dioxidine in the combined treatment of destructive calculous cholecystitis complicated by an infiltrate. 

  19. Treatment failures after antibiotic therapy of uncomplicated urinary tract infections

    DEFF Research Database (Denmark)

    Bjerrum, Lars; Dessau, Ram B; Hallas, Jesper

    2002-01-01

    OBJECTIVES: The efficacy of sulfamethizole and pivmecillinam in the treatment of urinary tract infections (UTI) has been questioned because of an increase in the prevalence of resistant strains. The aim of this study was to describe the risk of treatment failures over the last 10 years. DESIGN......: Retrospective cohort study. MATERIAL: Data were retrieved from Odense Pharmaco Epidemiological Database and consisted of women receiving sulfamethizole (n = 44,716) or pivmecillinam (n = 3093) during the period 1990-99. MAIN OUTCOME MEASURES: Prescription of a new antibiotic drug appropriate for UTI within 4...

  20. Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections.

    Science.gov (United States)

    Kutob, Leila F; Justo, Julie Ann; Bookstaver, P Brandon; Kohn, Joseph; Albrecht, Helmut; Al-Hasan, Majdi N

    2016-11-01

    There is paucity of data evaluating intravenous-to-oral antibiotic switch options for Gram-negative bloodstream infections (BSIs). This retrospective cohort study examined the effectiveness of oral antibiotics for definitive treatment of Gram-negative BSI. Patients with Gram-negative BSI hospitalised for antibiotics were included in this study. The cohort was stratified into three groups based on bioavailability of oral antibiotics prescribed (high, ≥95%; moderate, 75-94%; and low, antibiotics were prescribed to 106, 179 and 77 patients, respectively, for definitive therapy of Gram-negative BSI. Mean patient age was 63 years, 217 (59.9%) were women and 254 (70.2%) had a urinary source of infection. Treatment failure rates were 2%, 12% and 14% in patients receiving oral antibiotics with high, moderate and low bioavailability, respectively (P = 0.02). Risk of treatment failure in the multivariate Cox model was higher in patients receiving antibiotics with moderate [adjusted hazard ratio (aHR) = 5.9, 95% CI 1.6-38.5; P = 0.005] and low bioavailability (aHR = 7.7, 95% CI 1.9-51.5; P = 0.003) compared with those receiving oral antimicrobial agents with high bioavailability. These data demonstrate the effectiveness of oral antibiotics with high bioavailability for definitive therapy of Gram-negative BSI. Risk of treatment failure increases as bioavailability of the oral regimen declines. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  1. Enhancement of antibiotic activity by Cordia verbenacea DC

    OpenAIRE

    Matias, Edinardo F.F.; Santos, Karla K. A.; Almeida, Thiago S.; Costa, José G.M. da; Coutinho, Henrique D.M.

    2010-01-01

    Escherichia coli is known to produce enterotoxins whose properties and its role in diarrheal disease has been extensively investigated. Some species of Staphylococcus are often recognized as etiological agents of many animal and human opportunistic infections. This study is the first test of change in resistance of antibiotic activity by Cordia verbenacea DC. against multiresistant strains of Escherichia coli and Staphylococcus aureus. In this study, the hexane and methanol extract of Cordia ...

  2. Triple combination antibiotic therapy for carbapenemase-producing Klebsiella pneumoniae: a systematic review.

    Science.gov (United States)

    Jacobs, David M; Safir, M Courtney; Huang, Dennis; Minhaj, Faisal; Parker, Adam; Rao, Gauri G

    2017-11-25

    The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections. The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2. Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients). Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

  3. Improvements in Behavioral Symptoms following Antibiotic Therapy in a 14-Year-Old Male with Autism

    Directory of Open Access Journals (Sweden)

    P. Lucas Ramirez

    2013-01-01

    Full Text Available This case report describes the benefits of antibiotic and antifungal therapy on behavior in a child with autism undergoing treatment for encopresis. Over the course of treatment, the child exhibited a reduction in aberrant behaviors, increased gastrointestinal function, and improved quality of life.

  4. Improvements in Behavioral Symptoms following Antibiotic Therapy in a 14-Year-Old Male with Autism

    OpenAIRE

    Ramirez, P. Lucas; Barnhill, Kelly; Gutierrez, Alan; Schutte, Claire; Hewitson, Laura

    2013-01-01

    This case report describes the benefits of antibiotic and antifungal therapy on behavior in a child with autism undergoing treatment for encopresis. Over the course of treatment, the child exhibited a reduction in aberrant behaviors, increased gastrointestinal function, and improved quality of life.

  5. Ultrasonic Enhancement of Antibiotic Action on Escherichia coli Biofilms: an In Vivo Model

    OpenAIRE

    Rediske, Andrea M.; Roeder, Beverly L.; Brown, Maren K.; Nelson, Jared L.; Robison, Rachel L.; Draper, David O.; Schaalje, G. Bruce; Robison, Richard A.; Pitt, William G.

    1999-01-01

    Biofilm infections are a common complication of prosthetic devices in humans. Previous in vitro research has determined that low-frequency ultrasound combined with aminoglycoside antibiotics is an effective method of killing biofilms. We report the development of an in vivo model to determine if ultrasound enhances antibiotic action. Two 24-h-old Escherichia coli (ATCC 10798) biofilms grown on polyethylene disks were implanted subcutaneously on the backs of New Zealand White female rabbits, o...

  6. Implementation of treatment guidelines to support judicious use of antibiotic therapy.

    Science.gov (United States)

    Deuster, S; Roten, I; Muehlebach, S

    2010-02-01

    Judicious use of antibiotics is essential considering the growth of antimicrobial resistance and escalating costs in health care. This intervention study used treatment guidelines to improve antibiotic therapy by changing prescribing practice. A before-after intervention study was performed in a 550-bed tertiary care teaching hospital in Switzerland, with an additional follow-up analysis 1 year later. The pre-intervention phase included chart analysis of current antibiotic use in 100 consecutive patients from the representative medical and surgical wards included in the study. Treatment guidelines were defined, taking into account published guidelines, the local antibacterial sensitivity of the pathogens, and the hospital antibiotic formulary defined by the drug and therapeutics committee. The guidelines were presented to the medical residents on a pocket card. They were informed and educated by the pharmacist (intervention). In the post-intervention phase immediately after the instruction, and in the follow-up phase 1 year later, a prospective analysis of antibiotic prescription was performed by chart review of 100 antibacterial treatments in consecutive patients to detect changes in antibiotic prescribing (treatment) and to determine whether these changes were sustained. The pre-intervention review of antibiotic use showed the need for therapy improvements in urinary tract infections (UTI) and hospital-acquired pneumonia (HAP). In the post-intervention phase 100% of UTI were treated as recommended, compared to 30% before the intervention (P UTI. Before implementation of the clinical guidelines, HAP was inappropriately treated like community-acquired pneumonia (CAP). Immediately after the intervention, 50% of HAP patients were treated as recommended, and 1 year later (follow-up phase) 56% of HAP patients received the recommended antibiotic medication. This change in prescription practice was significant (P < 0.05). Antibiotic treatment guidelines for the

  7. Long-term macrolide antibiotics in asthma therapy

    Directory of Open Access Journals (Sweden)

    Daisuke Takekoshi

    2011-10-01

    Full Text Available Macrolide antibiotics drew worldwide attention when their use was dramatically successful in the treatment of diffuse panbronchiolitis in 1980s. The success was attributed to their immunomodulatory effects, rather than their antimicrobial properties. Since then, studies have shown that macrolides exert their immunomodulatory effects through several mechanisms, including suppression of proinflammatory cytokines, promoting apoptosis of inflammatory cells, improving phagocytic function, ameliorating airway hypersecretion, and inhibiting production of reactive oxygen species. Macrolides have also been studied in the treatment of asthma. This review highlights the role of macrolides in the treatment of asthma, presenting an overview of the main clinical trials. Despite favourable preclinical data and reports of anecdotal successes, the results of clinical trials are conflicting. This may be due to the heterogeneous nature of asthma. Further studies are needed to identify particular subgroup of asthma that will respond to macrolides.

  8. Managing an outpatient parenteral antibiotic therapy team: challenges and solutions.

    Science.gov (United States)

    Halilovic, Jenana; Christensen, Cinda L; Nguyen, Hien H

    2014-01-01

    Outpatient parenteral antimicrobial therapy (OPAT) programs should strive to deliver safe, cost effective, and high quality care. One of the keys to developing and sustaining a high quality OPAT program is to understand the common challenges or barriers to OPAT delivery. We review the most common challenges to starting and managing an OPAT program and give practical advice on addressing these issues.

  9. Synergistic Interaction Between Phage Therapy and Antibiotics Clears Pseudomonas Aeruginosa Infection in Endocarditis and Reduces Virulence.

    Science.gov (United States)

    Oechslin, Frank; Piccardi, Philippe; Mancini, Stefano; Gabard, Jérôme; Moreillon, Philippe; Entenza, José M; Resch, Gregory; Que, Yok-Ai

    2017-03-01

    Increasing antibiotic resistance warrants therapeutic alternatives. Here we investigated the efficacy of bacteriophage-therapy (phage) alone or combined with antibiotics against experimental endocarditis (EE) due to Pseudomonas aeruginosa, an archetype of difficult-to-treat infection. In vitro fibrin clots and rats with aortic EE were treated with an antipseudomonas phage cocktail alone or combined with ciprofloxacin. Phage pharmacology, therapeutic efficacy, and resistance were determined. In vitro, single-dose phage therapy killed 7 log colony-forming units (CFUs)/g of fibrin clots in 6 hours. Phage-resistant mutants regrew after 24 hours but were prevented by combination with ciprofloxacin (2.5 × minimum inhibitory concentration). In vivo, single-dose phage therapy killed 2.5 log CFUs/g of vegetations in 6 hours (P 6 log CFUs/g of vegetations in 6 hours and successfully treating 64% (n = 7/11) of rats. Phage-resistant mutants emerged in vitro but not in vivo, most likely because resistant mutations affected bacterial surface determinants important for infectivity (eg, the pilT and galU genes involved in pilus motility and LPS formation). Single-dose phage therapy was active against P. aeruginosa EE and highly synergistic with ciprofloxacin. Phage-resistant mutants had impaired infectivity. Phage-therapy alone or combined with antibiotics merits further clinical consideration. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  10. Managing an outpatient parenteral antibiotic therapy team: challenges and solutions

    OpenAIRE

    Nguyen, Hien; Halilovic,Jenana; Christensen,Cinda

    2014-01-01

    Jenana Halilovic,1 Cinda L Christensen,2 Hien H Nguyen31University of the Pacific Thomas J Long School of Pharmacy, Stockton, CA, USA; 2Department of Pharmaceutical Services, University of California, Davis Health System, Sacramento, CA, USA; 3Division of Infectious Diseases, Section of Hospital Medicine, University of California, Davis Health System, Sacramento, CA, USAAbstract: Outpatient parenteral antimicrobial therapy (OPAT) programs should strive to deliver safe, cost effective, and hig...

  11. TACTICS OF BIOCENOSIS-SAVING THERAPY BY USE ANTIBIOTICS IN CHILDREN WITH ACUTE INTESTINAL INFECTIONS

    Directory of Open Access Journals (Sweden)

    L. N. Mazankova

    2017-01-01

    Full Text Available 50 children aged from 3 to 67 months with acute intestinal infections receiving antibiotic therapy, were clinically and microbiologically examined using gas-liquid chromatographic test with the measurement of short-chain fatty acids (SCFAs in coprofiltrates. The influence on the biocenosis is assessed upon treatment with an-tidiarrhoeal medication Gelatin tannat (Adiarin, which acts by forming a protective film on the surface of intestinal mucosa preventing loss of body fluids and microbial toxins. 20 children in the control group received antibiotics, sorbents, probiotics. The study has proved the clinical effect of Gelatin tannat, resulting in reduction of time to normalization of diarrhea and intoxication for 2 days, and data on the probiotic effect of the drug, similar to that of probiotics in the control group which expands the indications for the use of Gelatin tannat for prevention of antibiotic-associated diarrhea.  

  12. Rapid resolution of cellulitis in patients managed with combination antibiotic and anti-inflammatory therapy.

    Science.gov (United States)

    Dall, Lawrence; Peterson, Sandford; Simmons, Tom; Dall, Amy

    2005-03-01

    There is some evidence to suggest that host inflammatory response has some effect on the clinical manifestations of cellulitis. The objective of this pilot study was to investigate whether the addition of oral nonsteroidal anti-inflammatory (NSAI) therapy to antibiotic treatment hastens resolution of cellulitis-related inflammation. Patients presenting in the emergency department with signs and symptoms of class II cellulitis were assigned to receive treatment with either antibiotic therapy alone (intravenous, supplemented with oral cephalexin or an equivalent) for 10 days (n = 33) or antibiotic therapy for 10 days plus an oral anti-inflammatory (ibuprofen 400 mg every 6 hours) for 5 days (n = 31). Patients were discharged as soon as possible to complete their therapy on an outpatient basis. The addition of an oral anti-inflammatory agent significantly (P < .05) shortened the time to regression of inflammation and complete resolution of cellulitis. Twenty-four of 29 evaluable patients (82.8%) who received supplemental anti-inflammatory treatment showed regression of inflammation within 1 to 2 days compared with only 3 of 33 patients (9.1%) treated without an anti-inflammatory in the same time frame. All patients receiving adjunctive anti-inflammatory treatment experienced complete resolution of cellulitis in 4 to 5 days or less, while 24.2% (8/33) of patients treated with antibiotic alone required 6 to 7 days, and 6.1% (2/33) required 7 days or more (P < .05). This small preliminary study provides some promising data, suggesting that the supplemental use of anti-inflammatory therapy may hasten the time to regression of inflammation and complete resolution of cellulitis.

  13. Enhanced synergism of antibiotics with zinc oxide nanoparticles against extended spectrum β-lactamase producers implicated in urinary tract infections

    International Nuclear Information System (INIS)

    Bhande, Rashmi M.; Khobragade, C. N.; Mane, R. S.; Bhande, S.

    2013-01-01

    In this study, enhanced synergistic bioactivity of zinc oxide nanoparticles (ZnO NPs) with β-lactam antibiotics were evaluated against a panel of clinically isolated extended spectrum β-lactamase producers implicated in urinary tract infections. Chemically synthesized zinc oxide nanoparticles (15 nm) were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high resolution transmittance electron microscopy (HR-TEM), selective area electron diffraction (SAED), X-ray photoelectron spectroscopy (XPS), and UV–Visible spectrophotometry techniques. The antimicrobial potency (10 ± 0.66, 12, 11.33 ± 1.10, and 0.7 ± 0.66 mm inhibiting zone) and minimum inhibitory concentrations (80, 60, 30, 50 μg/ml) of ZnO NPs were tested separately whereas time–kill and membrane leakage assays were evaluated in combination with ZnO NPs+ cefotaxime, ampicillin, ceftriaxone, cefepime against the β-lactamase producer strains of E. coli, K. pneumoniae, S. paucimobilis, and P. aeruginosa, respectively. Time–kill curve dynamics of ZnO NPs with β-lactam antibiotics revealed enhanced bactericidal activity (50, 85, 58, 50 % fold inhibition) by delaying the exponential and stationary phases of all isolates when tested separately. Posttime–kill effect was studied on cell membrane by assaying leakage of reducing sugars (130.2, 124.7, 137, and 115.8 μg/bacterial dry weight of 1 mg (μg/mg) and proteins (15, 10, 16, 18 μg/mg). These assays revealed that membrane leakage was due to synergism of ZnO NPs+ β-lactam antibiotics which successfully damage cell membrane thereby leading to death of all ESBL producers. The results demonstrate the utilization of ZnO NPs as a potentiator of β-lactam antibiotics and suggest the possibility to use nanoparticles in a combination therapy to treat UTI.

  14. Enhanced synergism of antibiotics with zinc oxide nanoparticles against extended spectrum β-lactamase producers implicated in urinary tract infections

    Science.gov (United States)

    Bhande, Rashmi M.; Khobragade, C. N.; Mane, R. S.; Bhande, S.

    2013-01-01

    In this study, enhanced synergistic bioactivity of zinc oxide nanoparticles (ZnO NPs) with β-lactam antibiotics were evaluated against a panel of clinically isolated extended spectrum β-lactamase producers implicated in urinary tract infections. Chemically synthesized zinc oxide nanoparticles (15 nm) were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high resolution transmittance electron microscopy (HR-TEM), selective area electron diffraction (SAED), X-ray photoelectron spectroscopy (XPS), and UV-Visible spectrophotometry techniques. The antimicrobial potency (10 ± 0.66, 12, 11.33 ± 1.10, and 0.7 ± 0.66 mm inhibiting zone) and minimum inhibitory concentrations (80, 60, 30, 50 μg/ml) of ZnO NPs were tested separately whereas time-kill and membrane leakage assays were evaluated in combination with ZnO NPs+ cefotaxime, ampicillin, ceftriaxone, cefepime against the β-lactamase producer strains of E. coli, K. pneumoniae, S. paucimobilis, and P. aeruginosa, respectively. Time-kill curve dynamics of ZnO NPs with β-lactam antibiotics revealed enhanced bactericidal activity (50, 85, 58, 50 % fold inhibition) by delaying the exponential and stationary phases of all isolates when tested separately. Posttime-kill effect was studied on cell membrane by assaying leakage of reducing sugars (130.2, 124.7, 137, and 115.8 μg/bacterial dry weight of 1 mg (μg/mg) and proteins (15, 10, 16, 18 μg/mg). These assays revealed that membrane leakage was due to synergism of ZnO NPs+ β-lactam antibiotics which successfully damage cell membrane thereby leading to death of all ESBL producers. The results demonstrate the utilization of ZnO NPs as a potentiator of β-lactam antibiotics and suggest the possibility to use nanoparticles in a combination therapy to treat UTI.

  15. Changes in Bacterial Resistance Patterns of Pediatric Urinary Tract Infections and Rationale for Empirical Antibiotic Therapy

    Directory of Open Access Journals (Sweden)

    İbrahim Gökçe

    2017-10-01

    Full Text Available Background: The causative agent spectrum and resistance patterns of urinary tract infections in children are affected by many factors. Aims: To demonstrate antibiotic resistance in urinary tract infections and changing ratio in antibiotic resistance by years. Study Design: Retrospective cross-sectional study. Methods: We analysed antibiotic resistance patterns of isolated Gram (- bacteria during the years 2011-2014 (study period 2 in children with urinary tract infections. We compared these findings with data collected in the same centre in 2001-2003 (study period 1. Results: Four hundred and sixty-five uncomplicated community-acquired Gram (- urinary tract infections were analysed from 2001-2003 and 400 from 2011-2014. Sixty-one percent of patients were female (1.5 girls : 1 boy. The mean age of children included in the study was 3 years and 9 months. Escherichia coli was the predominant bacteria isolated during both periods of the study (60% in study period 1 and 73% in study period 2. Bacteria other than E. coli demonstrated a higher level of resistance to all of the antimicrobials except trimethoprim-sulfamethoxazole than E. coli bacteria during the years 2011-2014. In our study, we found increasing resistance trends of urinary pathogens for cefixime (from 1% to 15%, p0.05. Conclusion: In childhood urinary tract infections, antibiotic resistance should be evaluated periodically and empiric antimicrobial therapy should be decided according to antibiotic sensitivity results

  16. Appropriate antibiotic therapy improves Ureaplasma sepsis outcome in the neonatal mouse.

    Science.gov (United States)

    Weisman, Leonard E; Leeming, Angela H; Kong, Lingkun

    2012-11-01

    Ureaplasma causes sepsis in human neonates. Although erythromycin has been the standard treatment, it is not always effective. No published reports have evaluated Ureaplasma sepsis in a neonatal model. We hypothesized that appropriate antibiotic treatment improves Ureaplasma sepsis in a neonatal mouse model. Two ATCC strains and two clinical strains of Ureaplasma were evaluated in vitro for antibiotic minimum inhibitory concentration (MIC). In addition, FVB albino mice pups infected with Ureaplasma were randomly assigned to saline, erythromycin, or azithromycin therapy and survival, quantitative blood culture, and growth were evaluated. MICs ranged from 0.125 to 62.5 µg/ml and 0.25 to 1.0 µg/ml for erythromycin and azithromycin, respectively. The infecting strain and antibiotic selected for treatment appeared to affect survival and bacteremia, but only the infecting strain affected growth. Azithromycin improved survival and bacteremia against each strain, whereas erythromycin was effective against only one of four strains. We have established a neonatal model of Ureaplasma sepsis and observed that treatment outcome is related to infecting strain and antibiotic treatment. We speculate that appropriate antibiotic selection and dosing are required for effective treatment of Ureaplasma sepsis in neonates, and this model could be used to further evaluate these relationships.

  17. International experts' practice in the antibiotic therapy of infective endocarditis is not following the guidelines.

    Science.gov (United States)

    Tissot-Dupont, H; Casalta, J P; Gouriet, F; Hubert, S; Salaun, E; Habib, G; Fernandez-Gerlinger, M P; Mainardi, J L; Tattevin, P; Revest, M; Lucht, F; Botelho-Nevers, E; Gagneux-Brunon, A; Snygg-Martin, U; Chan, K L; Bishara, J; Vilacosta, I; Olmos, C; San Román, J A; López, J; Tornos, P; Fernández-Hidalgo, N; Durante-Mangoni, E; Utili, R; Paul, M; Baddour, L M; DeSimone, D C; Sohail, M R; Steckelberg, J M; Wilson, W R; Raoult, D

    2017-10-01

    The management of infective endocarditis (IE) may differ from international guidelines, even in reference centres. This is probably because most recommendations are not based on hard evidence, so the consensus obtained for the guidelines does not represent actual practices. For this reason, we aimed to evaluate this question in the particular field of antibiotic therapy. Thirteen international centres specialized in the management of IE were selected, according to their reputation, clinical results, original research publications and quotations. They were asked to detail their actual practice in terms of IE antibiotic treatment in various bacteriological and clinical situations. They were also asked to declare their IE-related in-hospital mortality for the year 2015. The global compliance with guidelines concerning antibiotic therapy was 58%, revealing the differences between theoretical 'consensus', local recommendations and actual practice. Some conflicts of interest were also probably expressed. The adherence to guidelines was 100% when the protocol was simple, and decreased with the seriousness of the situation (Staphylococus spp. 54%-62%) or in blood-culture-negative endocarditis (0%-15%) that requires adaptation to clinical and epidemiological data. Worldwide experts in IE management, although the majority of them were involved and co-signed the guidelines, do not follow international consensus guidelines on the particular point of the use of antibiotics. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  18. The enhanced effects of antibiotics irradiated of extremely high frequency electromagnetic field on Escherichia coli growth properties.

    Science.gov (United States)

    Torgomyan, Heghine; Trchounian, Armen

    2015-01-01

    The effects of extremely high frequency electromagnetic irradiation and antibiotics on Escherichia coli can create new opportunities for applications in different areas—medicine, agriculture, and food industry. Previously was shown that irradiated bacterial sensitivity against antibiotics was changed. In this work, it was presented the results that irradiation of antibiotics and then adding into growth medium was more effective compared with non-irradiated antibiotics bactericidal action. The selected antibiotics (tetracycline, kanamycin, chloramphenicol, and ceftriaxone) were from different groups. Antibiotics irradiation was performed with low intensity 53 GHz frequency during 1 h. The E. coli growth properties—lag-phase duration and specific growth rate—were markedly changed. Enhanced bacterial sensitivity to irradiated antibiotics is similar to the effects of antibiotics of higher concentrations.

  19. Managing an outpatient parenteral antibiotic therapy team: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Halilovic J

    2014-06-01

    Full Text Available Jenana Halilovic,1 Cinda L Christensen,2 Hien H Nguyen31University of the Pacific Thomas J Long School of Pharmacy, Stockton, CA, USA; 2Department of Pharmaceutical Services, University of California, Davis Health System, Sacramento, CA, USA; 3Division of Infectious Diseases, Section of Hospital Medicine, University of California, Davis Health System, Sacramento, CA, USAAbstract: Outpatient parenteral antimicrobial therapy (OPAT programs should strive to deliver safe, cost effective, and high quality care. One of the keys to developing and sustaining a high quality OPAT program is to understand the common challenges or barriers to OPAT delivery. We review the most common challenges to starting and managing an OPAT program and give practical advice on addressing these issues.Keywords: OPAT, quality, safety, program management

  20. Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial.

    Science.gov (United States)

    Salminen, Paulina; Paajanen, Hannu; Rautio, Tero; Nordström, Pia; Aarnio, Markku; Rantanen, Tuomo; Tuominen, Risto; Hurme, Saija; Virtanen, Johanna; Mecklin, Jukka-Pekka; Sand, Juhani; Jartti, Airi; Rinta-Kiikka, Irina; Grönroos, Juha M

    2015-06-16

    An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis. To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT). The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period. Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy. The primary end point for the surgical intervention was the successful completion of an appendectomy. The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period. There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of -27.0% (95% CI, -31.6% to ∞) (P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate noninferiority of

  1. Pseudomonas aeruginosa Bacteremia among Immunocompetent and Immunocompromised Patients: Relation to Initial Antibiotic Therapy and Survival.

    Science.gov (United States)

    Migiyama, Yohei; Yanagihara, Katsunori; Kaku, Norihito; Harada, Yosuke; Yamada, Koichi; Nagaoka, Kentaro; Morinaga, Yoshitomo; Akamatsu, Norihiko; Matsuda, Junichi; Izumikawa, Koichi; Kohrogi, Hirotsugu; Kohno, Shigeru

    2016-01-01

    Pseudomonas aeruginosa bacteremia occurs mainly in immunocompromised patients. However, P. aeruginosa bacteremia in immunocompetent patients has also been reported. The aim of this study was to evaluate the clinical characteristics of P. aeruginosa bacteremia in relation to the immune status of the patients. The medical records of 126 adult patients with P. aeruginosa bacteremia in Nagasaki University Hospital were retrospectively reviewed between January 2003 and December 2012. Of 126 patients with P. aeruginosa bacteremia, 60 patients (47.6%) were classified as immunocompetent. Mortality in immunocompetent patients tended to be lower than in immunocompromised patients (7-day mortality, 8% vs. 30%, P antibiotic therapy (HR: 0.21, P immunocompromised, but not immunocompetent patients, initial appropriate antibiotic therapy was associated with lower mortality (30-day mortality 20.5% vs. 66.7%, P < 0.01 by log-rank test).

  2. In-111 labeled leukocyte scintigraphy in patients with suspected inflammation after failed antibiotic therapy

    International Nuclear Information System (INIS)

    Nasu, Reiko; Akagi, Kiyoshi; Murata, Takashi; Uokawa, Kyousuke; Isoda, Hiroyoshi; Tanaka, Yoshimasa; Itagaki, Yasushi

    1998-01-01

    In-111 labeled leukocyte scintigrapy (In-111 WBC scan) was performed in 16 patients with inflammation suspected on the basis of laboratory findings, symptoms, and diagnostic imaging, but who had failed antibiotic therapy. In-111 WBC scans revealed an abnormal focus of radiotracer activity (positive scans) in five of 16 patients. No correlation was found between the peripheral WBC count and accumulation of In-111 WBC. Inflammatory disease suspected on the basis of the CRP level should be considered when In-111 WBC scanning results in negative findings. Our results indicated that In-111 WBC scanning has low sensitivity after antibiotic therapy. Selection of patients on the basis of persistent elevation of CRP may be valuable. (author)

  3. Low antibiotic resistance among anaerobic Gram-negative bacteria in periodontitis 5 years following metronidazole therapy.

    Science.gov (United States)

    Dahlen, G; Preus, H R

    2017-02-01

    The objective of this study was to assess antibiotic susceptibility among predominant Gram-negative anaerobic bacteria isolated from periodontitis patients who 5 years prior had been subject to mechanical therapy with or without adjunctive metronidazole. One pooled sample was taken from the 5 deepest sites of each of 161 patients that completed the 5 year follow-up after therapy. The samples were analyzed by culture. A total number of 85 anaerobic strains were isolated from the predominant subgingival flora of 65/161 patient samples, identified, and tested for antibiotic susceptibility by MIC determination. E-tests against metronidazole, penicillin, amoxicillin, amoxicillin + clavulanic acid and clindamycin were employed. The 73/85 strains were Gram-negative rods (21 Porphyromonas spp., 22 Prevotella/Bacteroides spp., 23 Fusobacterium/Filifactor spp., 3 Campylobacter spp. and 4 Tannerella forsythia). These were all isolated from the treated patients irrespective of therapy procedures (+/-metronidazole) 5 years prior. Three strains (Bifidobacterium spp., Propionibacterium propionicum, Parvimonas micra) showed MIC values for metronidazole over the European Committee on Antimicrobial Susceptibility Testing break point of >4 μg/mL. All Porphyromonas and Tannerella strains were highly susceptible. Metronidazole resistant Gram-negative strains were not found, while a few showed resistance against beta-lactam antibiotics. In this population of 161 patients who had been subject to mechanical periodontal therapy with or without adjunct metronidazole 5 years prior, no cultivable antibiotic resistant anaerobes were found in the predominant subgingival microbiota. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Does appropriate empiric antibiotic therapy modify intensive care unit-acquired Enterobacteriaceae bacteraemia mortality and discharge?

    Science.gov (United States)

    Pouwels, K B; Van Kleef, E; Vansteelandt, S; Batra, R; Edgeworth, J D; Smieszek, T; Robotham, J V

    2017-05-01

    Conflicting results have been found regarding outcomes of intensive care unit (ICU)-acquired Enterobacteriaceae bacteraemia and the potentially modifying effect of appropriate empiric antibiotic therapy. To evaluate these associations while adjusting for potential time-varying confounding using methods from the causal inference literature. Patients who stayed more than two days in two general ICUs in England between 2002 and 2006 were included in this cohort study. Marginal structural models with inverse probability weighting were used to estimate the mortality and discharge associated with Enterobacteriaceae bacteraemia and the impact of appropriate empiric antibiotic therapy on these outcomes. Among 3411 ICU admissions, 195 (5.7%) ICU-acquired Enterobacteriaceae bacteraemia cases occurred. Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU death [cause-specific hazard ratio (HR): 1.48; 95% confidence interval (CI): 1.10-1.99] and a reduced daily risk of ICU discharge (HR: 0.66; 95% CI: 0.54-0.80). Appropriate empiric antibiotic therapy did not significantly modify ICU mortality (HR: 1.08; 95% CI: 0.59-1.97) or discharge (HR: 0.91; 95% CI: 0.63-1.32). ICU-acquired Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU mortality. Furthermore, the daily discharge rate was also lower after acquiring infection, even when adjusting for time-varying confounding using appropriate methodology. No evidence was found for a beneficial modifying effect of appropriate empiric antibiotic therapy on ICU mortality and discharge. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  5. Efficacy and Safety of Procalcitonin-Guided Antibiotic Therapy in Lower Respiratory Tract Infections

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    Werner C. Albrich

    2013-01-01

    Full Text Available Background: In 14 randomized controlled studies to date, a procalcitonin (PCT-based algorithm has been proven to markedly reduce the use of antibiotics along with an unimpaired high safety and low complication rates in patients with lower respiratory tract infections (LRTIs. However, compliance with the algorithm and safety out of controlled study conditions has not yet been sufficiently investigated. Methods: We performed a prospective international multicenter observational post-study surveillance of consecutive adults with community-acquired LRTI in 14 centers (Switzerland (n = 10, France (n = 3 and the United States (n = 1. Results: Between September 2009 and November 2010, 1,759 patients were enrolled (median age 71; female sex 44.4%. 1,520 (86.4% patients had a final diagnosis of LRTI (community-acquired pneumonia (CAP, 53.7%; acute exacerbation of chronic obstructive pulmonary disease (AECOPD, 17.1%; and acute bronchitis, 14.4%. Compliance with the PCT-guided therapy (overall 68.2% was highest in patients with bronchitis (81.0% vs. AECOPD, 70.1%; CAP, 63.7%; p < 0.001, outpatients (86.1% vs. inpatients, 65.9%; p < 0.001 and algorithm-experienced centers (82.5% vs. algorithm-naive, 60.1%; p < 0.001 and showed significant geographical differences. The initial decision about the antibiotic therapy was based on PCT value in 72.4%. In another 8.6% of patients, antibiotics were administered despite low PCT values but according to predefined criteria. Thus, the algorithm was followed in 81.0% of patients. In a multivariable Cox hazard ratio model, longer antibiotic therapy duration was associated with algorithm-non-compliance, country, hospitalization, CAP vs. bronchitis, renal failure and algorithm-naïvety of the study center. In a multivariable logistic regression complications (death, empyema, ICU treatment, mechanical ventilation, relapse, and antibiotic-associated side effects were significantly associated with increasing CURB65-Score, CAP

  6. Antibiotic resistance in Pseudomonas aeruginosa biofilms: towards the development of novel anti-biofilm therapies.

    Science.gov (United States)

    Taylor, Patrick K; Yeung, Amy T Y; Hancock, Robert E W

    2014-12-10

    The growth of bacteria as structured aggregates termed biofilms leads to their protection from harsh environmental conditions such as physical and chemical stresses, shearing forces, and limited nutrient availability. Because of this highly adapted ability to survive adverse environmental conditions, bacterial biofilms are recalcitrant to antibiotic therapies and immune clearance. This is particularly problematic in hospital settings where biofilms are a frequent cause of chronic and device-related infections and constitute a significant burden on the health-care system. The major therapeutic strategy against infections is the use of antibiotics, which, due to adaptive resistance, are often insufficient to clear biofilm infections. Thus, novel biofilm-specific therapies are required. Specific features of biofilm development, such as surface adherence, extracellular matrix formation, quorum sensing, and highly regulated biofilm maturation and dispersal are currently being studied as targets to be exploited in the development of novel biofilm-specific treatments. Using Pseudomonas aeruginosa for illustrative purposes, this review highlights the antibiotic resistance mechanisms of biofilms, and discusses current research into novel biofilm-specific therapies. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Value of Prophylactic Postoperative Antibiotic Therapy after Bimaxillary Orthognathic Surgery: A Clinical Trial

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    Majid Eshghpour

    2014-10-01

    Full Text Available Introduction: Antibiotic therapy before or after orthognathic surgery is commonly recommended by surgeons to minimize the risk of wound infection. This article evaluates the value of Prophylactic antibiotic therapy in order to diminish the incidence of postoperative wound infection after orthognathic surgery.   Materials and Methods: Fifty candidates for bimaxillary orthognathic surgery were divided into cases and controls. Cefazolin (1g was administered intravenously to all participants 30 mins prior to surgery followed by a similar dose 4 hours later. Case-group patients ingested amoxicillin (500 mg orally for 7 days after surgery. Postoperative wound infection was assessed using clinical features, and the P-value significance was set at P  Results: Both groups were similar according to gender, age, and operating time. During the follow-up period no infection was observed in either the case or control group.   Conclusion:  The results of this study suggest that long-term postoperative antibiotic therapy is not essential for the prevention of postoperative infection, and that application of aseptic surgical technique and hygiene instruction after surgery are sufficient.

  8. [Domiciliary parenteral antibiotic therapy: a prospective analysis of the last 12 years].

    Science.gov (United States)

    Peláez Cantero, M J; Madrid Rodríguez, A; Urda Cardona, A L; Jurado Ortiz, A

    2014-08-01

    Parenteral antibiotic treatment has been classically developed in hospitals and is considered as a hospital procedure. The development of Hospital at Home Units (HHU) has led to an increase in outpatient parenteral antibiotic therapy (OPAT) in paediatrics patients. The objective of this study is to describe our experience, as an HHU integrated within a Paediatric Department, in home antimicrobial therapy over a period of 12 years. This prospective and descriptive study included every patient with a disease requiring parenteral antimicrobial therapy who was admitted to our HHU from January 2000 to December 2012. During the study there were 163 cases on OPAT. The mean age of the patients was 11.1 years, and the sample group was comprised of 33 males and 22 feamales. The main sources of the treated infections were respiratory tract (76%), catheter-related bloodstream (9.2%), and urinary tract infections (5.5%). Amikacin was the most widely used antibiotic. Almost all treatments (96.6%) were via an intravenous route. Catheter-associated complications were more common than drug-associated complications. Successful at-home treatment was observed in 90.2% of cases. OPAT is a good and safe alternative in many paediatric diseases. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  9. Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial.

    Science.gov (United States)

    Hou, Ming-Chih; Lin, Han-Chieh; Liu, Tsu-Te; Kuo, Benjamin Ing-Tieu; Lee, Fa-Yauh; Chang, Full-Young; Lee, Shou-Dong

    2004-03-01

    Bacterial infection may adversely affect the hemostasis of patients with gastroesophageal variceal bleeding (GEVB). Antibiotic prophylaxis can prevent bacterial infection in such patients, but its role in preventing rebleeding is unclear. Over a 25-month period, patients with acute GEVB but without evidence of bacterial infection were randomized to receive prophylactic antibiotics (ofloxacin 200 mg i.v. q12h for 2 days followed by oral ofloxacin 200 mg q12h for 5 days) or receive antibiotics only when infection became evident (on-demand group). Endoscopic therapy for the GEVB was performed immediately after infection work-up and randomization. Fifty-nine patients in the prophylactic group and 61 patients in the on-demand group were analyzed. Clinical and endoscopic characteristics of the gastroesophageal varices, time to endoscopic treatment, and period of follow-up were not different between the two groups. Antibiotic prophylaxis decreased infections (2/59 vs. 16/61; P actuarial probability of rebleeding was higher in patients without prophylactic antibiotics (P =.0029). The difference of rebleeding was mostly due to early rebleeding within 7 days (4/12 vs. 21/27, P =.0221). The relative hazard of rebleeding within 7 days was 5.078 (95% CI: 1.854-13.908, P <.0001). The multivariate Cox regression indicated bacterial infection (relative hazard: 3.85, 95% CI: 1.85-13.90) and association with hepatocellular carcinoma (relative hazard: 2.46, 95% CI: 1.30-4.63) as independent factors predictive of rebleeding. Blood transfusion for rebleeding was also reduced in the prophylactic group (1.40 +/- 0.89 vs. 2.81 +/- 2.29 units, P <.05). There was no difference in survival between the two groups. In conclusion, antibiotic prophylaxis can prevent infection and rebleeding as well as decrease the amount of blood transfused for patients with acute GEVB following endoscopic treatment.

  10. Dynamic contrast enhanced ultrasound for therapy monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Hudson, John M. [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Williams, Ross [Imaging Research, Sunnybrook Research Institute, Toronto, ON (Canada); Tremblay-Darveau, Charles; Sheeran, Paul S. [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Milot, Laurent [Department of Medical Imaging, University of Toronto, Toronto, ON (Canada); Bjarnason, Georg A. [Department of Medical Oncology, University of Toronto, and Sunnybrook Odette Cancer Centre, Toronto, ON (Canada); Burns, Peter N., E-mail: burns@sri.utoronto.ca [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Imaging Research, Sunnybrook Research Institute, Toronto, ON (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON (Canada)

    2015-09-15

    Quantitative imaging is a crucial component of the assessment of therapies that target the vasculature of angiogenic or inflamed tissue. Dynamic contrast-enhanced ultrasound (DCE-US) using microbubble contrast offers the advantages of being sensitive to perfusion, non-invasive, cost effective and well suited to repeated use at the bedside. Uniquely, it employs an agent that is truly intravascular. This papers reviews the principles and methodology of DCE-US, especially as applied to anti-angiogenic cancer therapies. Reproducibility is an important attribute of such a monitoring method: results are discussed. More recent technical advances in parametric and 3D DCE-US imaging are also summarised and illustrated.

  11. Glutathione-Disrupted Biofilms of Clinical Pseudomonas aeruginosa Strains Exhibit an Enhanced Antibiotic Effect and a Novel Biofilm Transcriptome

    Science.gov (United States)

    Das, Theerthankar; Ibugo, Amaye; Buckle, Edwina; Manefield, Mike; Manos, Jim

    2016-01-01

    Pseudomonas aeruginosa infections result in high morbidity and mortality rates for individuals with cystic fibrosis (CF), with premature death often occurring. These infections are complicated by the formation of biofilms in the sputum. Antibiotic therapy is stymied by antibiotic resistance of the biofilm matrix, making novel antibiofilm strategies highly desirable. Within P. aeruginosa biofilms, the redox factor pyocyanin enhances biofilm integrity by intercalating with extracellular DNA. The antioxidant glutathione (GSH) reacts with pyocyanin, disrupting intercalation. This study investigated GSH disruption by assaying the physiological effects of GSH and DNase I on biofilms of clinical CF isolates grown in CF artificial sputum medium (ASMDM+). Confocal scanning laser microscopy showed that 2 mM GSH, alone or combined with DNase I, significantly disrupted immature (24-h) biofilms of Australian epidemic strain (AES) isogens AES-1R and AES-1M. GSH alone greatly disrupted mature (72-h) AES-1R biofilms, resulting in significant differential expression of 587 genes, as indicated by RNA-sequencing (RNA-seq) analysis. Upregulated systems included cyclic diguanylate and pyoverdine biosynthesis, the type VI secretion system, nitrate metabolism, and translational machinery. Biofilm disruption with GSH revealed a cellular physiology distinct from those of mature and dispersed biofilms. RNA-seq results were validated by biochemical and quantitative PCR assays. Biofilms of a range of CF isolates disrupted with GSH and DNase I were significantly more susceptible to ciprofloxacin, and increased antibiotic effectiveness was achieved by increasing the GSH concentration. This study demonstrated that GSH, alone or with DNase I, represents an effective antibiofilm treatment when combined with appropriate antibiotics, pending in vivo studies. PMID:27161630

  12. A PCT algorithm for discontinuation of antibiotic therapy is a cost-effective way to reduce antibiotic exposure in adult intensive care patients with sepsis

    NARCIS (Netherlands)

    Kip, Michelle Maria Aleida; Kusters, Ron; IJzerman, Maarten Joost; Steuten, Lotte Maria Gertruda

    2015-01-01

    Objective: Procalcitonin (PCT) is a specific marker for differentiating bacterial from non-infective causes of inflammation. It can be used to guide initiation and duration of antibiotic therapy in intensive care unit (ICU) patients with suspected sepsis, and might reduce the duration of hospital

  13. Rapid bacterial antibiotic susceptibility test based on simple surface-enhanced Raman spectroscopic biomarkers

    Science.gov (United States)

    Liu, Chia-Ying; Han, Yin-Yi; Shih, Po-Han; Lian, Wei-Nan; Wang, Huai-Hsien; Lin, Chi-Hung; Hsueh, Po-Ren; Wang, Juen-Kai; Wang, Yuh-Lin

    2016-03-01

    Rapid bacterial antibiotic susceptibility test (AST) and minimum inhibitory concentration (MIC) measurement are important to help reduce the widespread misuse of antibiotics and alleviate the growing drug-resistance problem. We discovered that, when a susceptible strain of Staphylococcus aureus or Escherichia coli is exposed to an antibiotic, the intensity of specific biomarkers in its surface-enhanced Raman scattering (SERS) spectra drops evidently in two hours. The discovery has been exploited for rapid AST and MIC determination of methicillin-susceptible S. aureus and wild-type E. coli as well as clinical isolates. The results obtained by this SERS-AST method were consistent with that by the standard incubation-based method, indicating its high potential to supplement or replace existing time-consuming methods and help mitigate the challenge of drug resistance in clinical microbiology.

  14. Time to Guideline-Based Empiric Antibiotic Therapy in the Treatment of Pneumonia in a Community Hospital: A Retrospective Review.

    Science.gov (United States)

    Erwin, Beth L; Kyle, Jeffrey A; Allen, Leland N

    2016-08-01

    The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines for hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health care-associated pneumonia (HCAP) stress the importance of initiating prompt appropriate empiric antibiotic therapy. This study's purpose was to determine the percentage of patients with HAP, VAP, and HCAP who received guideline-based empiric antibiotic therapy and to determine the average time to receipt of an appropriate empiric regimen. A retrospective chart review of adults with HAP, VAP, or HCAP was conducted at a community hospital in suburban Birmingham, Alabama. The hospital's electronic medical record system utilized International Classification of Diseases, Ninth Revision (ICD-9) codes to identify patients diagnosed with pneumonia. The percentage of patients who received guideline-based empiric antibiotic therapy was calculated. The mean time from suspected diagnosis of pneumonia to initial administration of the final antibiotic within the empiric regimen was calculated for patients who received guideline-based therapy. Ninety-three patients met the inclusion criteria. The overall guideline adherence rate for empiric antibiotic therapy was 31.2%. The mean time to guideline-based therapy in hours:minutes was 7:47 for HAP and 28:16 for HCAP. For HAP and HCAP combined, the mean time to appropriate therapy was 21:55. Guideline adherence rates were lower and time to appropriate empiric therapy was greater for patients with HCAP compared to patients with HAP. © The Author(s) 2015.

  15. Manipulation of pH Shift to Enhance the Growth and Antibiotic Activity of Xenorhabdus nematophila

    Directory of Open Access Journals (Sweden)

    Yonghong Wang

    2011-01-01

    Full Text Available To evaluate the effects of pH control strategy on cell growth and the production of antibiotic (cyclo(2-Me-BABA-Gly by Xenorhabdus nematophila and enhance the antibiotic activity. The effects of uncontrolled- (different initial pH and controlled-pH (different constant pH and pH-shift operations on cell growth and antibiotic activity of X. nematophila YL00I were examined. Experiments showed that the optimal initial pH for cell growth and antibiotic production of X. nematophila YL001 occurred at 7.0. Under different constant pH, a pH level of 7.5 was found to be optimal for biomass and antibiotic activity at 23.71 g/L and 100.0 U/mL, respectively. Based on the kinetic information relating to the different constant pH effects on the fermentation of X. nematophila YL001, a two-stage pH control strategy in which pH 6.5 was maintained for the first 24 h, and then switched to 7.5 after 24 h, was established to improve biomass production and antibiotic activity. By applying this pH-shift strategy, the maximal antibiotic activity and productivity were significantly improved and reaching 185.0 U/mL and 4.41 U/mL/h, respectively, compared to values obtained from constant pH operation (100.0 U/mL and 1.39 U/mL/h.

  16. Prophylactic antibiotic therapy prior to dental treatment for patients with end-stage renal disease.

    Science.gov (United States)

    Werner, C W; Saad, T F

    1999-01-01

    In the United States, there is a large and growing population of patients undergoing dialysis because of end-stage renal disease (ESRD). These patients present special management considerations for dentists, including antibiotic prophylaxis for the prevention of bacterial endocarditis (BE). ESRD patients, particularly those with an arteriovenous shunt for hemodialysis access, are predisposed to valvular endocarditis. Thus, BE prevention is the primary goal of antibiotic prophylaxis prior to dental or other invasive procedures in these patients. Bacteremia may predispose to infection of synthetic vascular access grafts, although this form of endovascular infection in ESRD patients has not been as well-characterized as BE. Antibiotic prophylaxis may be of some benefit for prevention of synthetic graft infections as well as BE. Poor dentist and physician compliance with BE prophylaxis regimens, as well as errors in dosing, timing, or duration of prophylaxis, have been reported. These problems are of particular concern in the treatment of chronically ill patients. In this article, we review the rationale for prophylactic antibiotic therapy prior to dental procedures in ESRD patients with vascular access. We also elaborate on the current American Heart Association guidelines for BE prophylaxis, and address special considerations for ESRD patients.

  17. Antibiotic Therapy for Premature Rupture of Membranes and Preterm Labor and Effect on Fetal Outcome

    Science.gov (United States)

    Seelbach-Goebel, B.

    2013-01-01

    In Germany almost 10 % of children are born before the end of 37th week of gestation. In at least one quarter of these cases, ascending infection of the vagina plays a causative role, particularly during the early weeks of gestation. If, in addition to the decidua, the amniotic membrane, amniotic fluid and the umbilical cord are also affected, infection not only triggers uterine contractions and premature rupture of membranes but also initiates a systemic inflammatory reaction on the part of the fetus, which can increase neonatal morbidity. Numerous studies and meta-analyses have found that antibiotic therapy prolongs pregnancy and reduces neonatal morbidity. No general benefit of antibiotic treatment was found for premature uterine contractions. But it is conceivable that a subgroup of pregnant women would benefit from antibiotic treatment. It is important to identify this subgroup of women and offer them targeted treatment. This overview summarizes the current body of evidence on antibiotic treatment for impending preterm birth and the effect on neonatal outcomes. PMID:24771902

  18. Effect of sucralfate on antibiotic therapy for Helicobacter pylori infection in mice.

    Science.gov (United States)

    Watanabe, Koichiro; Murakami, Kazunari; Sato, Ryugo; Kashimura, Koji; Miura, Masahiro; Ootsu, Satoshi; Miyajima, Hajime; Nasu, Masaru; Okimoto, Tadayoshi; Kodama, Masaaki; Fujioka, Toshio

    2004-12-01

    It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.

  19. INTRAVENOUS REGIONAL ANTIBIOTIC PERFUSION THERAPY AS AN ADJUNCTIVE TREATMENT FOR DIGITAL LESIONS IN SEABIRDS.

    Science.gov (United States)

    Fiorello, Christine V

    2017-03-01

    Foot infections are a common problem among seabirds in wildlife rehabilitation. Pododermatitis and digital infections are often challenging to treat because of the presence of suboptimal substrates, abnormal weight-bearing due to injuries, and suboptimal nutritional or health status. Seabirds represent the majority of animals requiring rehabilitation after oil spills, and foot problems are a common reason for euthanasia among these birds. Antibiotic intravenous regional perfusion therapy is frequently used in humans and other species to treat infections of the distal extremities, but it has not been evaluated in seabirds. During the 2015 Refugio oil spill response, four birds with foot lesions (pododermatitis, osteomyelitis, or both) were treated with ampicillin/sulbactam administered intravenously to the affected limb(s) in addition to systemic antibiotics and anti-inflammatories. Three of the birds, all brown pelicans ( Pelecanus occidentalis ) recovered rapidly and were released. Two of these birds had acute pododermatitis and were treated once with intravenous regional perfusion. They were released approximately 3 wk after the perfusion therapy. The third pelican had osteomyelitis of a digit. It was treated twice with intravenous regional perfusion and was released about 1 mo after the initial perfusion therapy. The fourth bird, a Pacific loon ( Gavia pacifica ), was treated once with perfusion therapy but did not respond to treatment and was euthanatized. No serious adverse effects were observed. This technique should be explored further in avian species.

  20. Empiric antibiotic therapy in urinary tract infection in patients with risk factors for antibiotic resistance in a German emergency department.

    Science.gov (United States)

    Bischoff, Sebastian; Walter, Thomas; Gerigk, Marlis; Ebert, Matthias; Vogelmann, Roger

    2018-01-26

    The aim of this study was to identify clinical risk factors for antimicrobial resistances and multidrug resistance (MDR) in urinary tract infections (UTI) in an emergency department in order to improve empirical therapy. UTI cases from an emergency department (ED) during January 2013 and June 2015 were analyzed. Differences between patients with and without resistances towards Ciprofloxacin, Piperacillin with Tazobactam (Pip/taz), Gentamicin, Cefuroxime, Cefpodoxime and Ceftazidime were analyzed with Fisher's exact tests. Results were used to identify risk factors with logistic regression modelling. Susceptibility rates were analyzed in relation to risk factors. One hundred thirty-seven of four hundred sixty-nine patients who met the criteria of UTI had a positive urine culture. An MDR pathogen was found in 36.5% of these. Overall susceptibility was less than 85% for standard antimicrobial agents. Logistic regression identified residence in nursing homes, male gender, hospitalization within the last 30 days, renal transplantation, antibiotic treatment within the last 30 days, indwelling urinary catheter and recurrent UTI as risk factors for MDR or any of these resistances. For patients with no risk factors Ciprofloxacin had 90%, Pip/taz 88%, Gentamicin 95%, Cefuroxime 98%, Cefpodoxime 98% and Ceftazidime 100% susceptibility. For patients with 1 risk factor Ciprofloxacin had 80%, Pip/taz 80%, Gentamicin 88%, Cefuroxime 78%, Cefpodoxime 78% and Ceftazidime 83% susceptibility. For 2 or more risk factors Ciprofloxacin drops its susceptibility to 52%, Cefuroxime to 54% and Cefpodoxime to 61%. Pip/taz, Gentamicin and Ceftazidime remain at 75% and 77%, respectively. We identified several risk factors for resistances and MDR in UTI. Susceptibility towards antimicrobials depends on these risk factors. With no risk factor cephalosporins seem to be the best choice for empiric therapy, but in patients with risk factors the beta-lactam penicillin Piperacillin with Tazobactam

  1. Combination antibiotic therapy for the treatment of infective endocarditis due to enterococci.

    Science.gov (United States)

    Leone, Sebastiano; Noviello, Silvana; Esposito, Silvano

    2016-06-01

    Enterococci are common causes of infective endocarditis (IE) in both health care and community-based setting. Enterococcal IE requires bactericidal therapy for an optimal outcome. For decades, cell-wall-active antimicrobial agents (penicillins or vancomycin) in combination with aminoglycosides were the cornerstone of the treatment; however, the emergence of antibiotic resistance has significantly reduced the efficacy of these regimens. Data for this review were identified by searches of MEDLINE and references from relevant articles on antibiotic combination regimens for the treatment of enterococcal IE. Abstracts presented in scientific conferences were not searched for. New effective and safe combination treatments, including double-β-lactam and daptomycin/β-lactam combination, are proving useful for the management of IE due to enterococci.

  2. Changes in Bacterial Resistance Patterns of Pediatric Urinary Tract Infections and Rationale for Empirical Antibiotic Therapy.

    Science.gov (United States)

    Gökçe, İbrahim; Çiçek, Neslihan; Güven, Serçin; Altuntaş, Ülger; Bıyıklı, Neşe; Yıldız, Nurdan; Alpay, Harika

    2017-09-29

    The causative agent spectrum and resistance patterns of urinary tract infections in children are affected by many factors. To demonstrate antibiotic resistance in urinary tract infections and changing ratio in antibiotic resistance by years. Retrospective cross-sectional study. We analysed antibiotic resistance patterns of isolated Gram (-) bacteria during the years 2011-2014 (study period 2) in children with urinary tract infections. We compared these findings with data collected in the same centre in 2001-2003 (study period 1). Four hundred and sixty-five uncomplicated community-acquired Gram (-) urinary tract infections were analysed from 2001-2003 and 400 from 2011-2014. Sixty-one percent of patients were female (1.5 girls : 1 boy). The mean age of children included in the study was 3 years and 9 months. Escherichia coli was the predominant bacteria isolated during both periods of the study (60% in study period 1 and 73% in study period 2). Bacteria other than E. coli demonstrated a higher level of resistance to all of the antimicrobials except trimethoprim-sulfamethoxazole than E. coli bacteria during the years 2011-2014. In our study, we found increasing resistance trends of urinary pathogens for cefixime (from 1% to 15%, pUrinary pathogens showed a decreasing trend for nitrofurantoin (from 17% to 7%, p=0.0001). No significant trends were detected for ampicillin (from 69% to 71%), amoxicillin-clavulanate (from 44% to 43%), cefazolin (from 39% to 32%), trimethoprim-sulfamethoxazole (from 32% to 31%), cefuroxime (from 21% to 18%) and ceftriaxone (from 10% to 14%) between the two periods (p>0.05). In childhood urinary tract infections, antibiotic resistance should be evaluated periodically and empiric antimicrobial therapy should be decided according to antibiotic sensitivity results.

  3. [Clinical effect of different sequences of debridement-antibiotic therapy in treatment of severe chronic periodontitis].

    Science.gov (United States)

    Li, Yi; Xu, Li; Lu, Rui-fang; An, Yue-bang; Wang, Xian-e; Song, Wen-li; Meng, Huan-xi

    2015-02-18

    To evaluate the feasibility of full-mouth debridement (subgingival scaling and root planning, SRP) by 2 times within 1 week and compare the clinical effects of different sequences of debridement-antibiotic usage in patients with severe chronic periodontitis (CP). A double-blinded, placebo-controlled, randomized clinical trial was conducted in 30 severe CP patients (14 males and 16 females, 40.5 ± 8.4 years old on average from 35 to 60) receiving 3 different sequences of debridement-antibiotictherapy: Group A, antibiotic usage (metronidazole, MTZ, 0.2 g, tid, 7 d; amoxicillin, AMX 0.5 g, tid, 7 d) was started together with SRP (completed by 2 times in 7 d); Group B, antibiotic usage (MTZ 0.2 g, tid, 7 d; AMX 0.5 g, tid, 7 d) was started 1 d after SRP(completed by 2 times in 7 d); Group C, SRP alone[probing depth (PD), bleeding index (BI) and tooth mobility] was examined. The average full-mouth probing depth, the average full-mouth proximal probing depth (pPD), the percentage of sites with PD>5 mm (PD>5 mm%), the percentage of sites with proximal PD>5 mm (pPD>5 mm%), the average bleeding index (BI) and the percentage of sites with bleeding on probing (BOP%) were calculated. Clinical examinations were performed at baseline and 2 months post therapy. (1) Compared with baseline conditions, all the subjects showed clinical improvements in all the parameters evaluated 2 months post therapy, Pantibiotic usage at the same time comparing with patients using antibiotics after SRP or SRP alone.

  4. High-dose antibiotic therapy is superior to a 3-drug combination of prostanoids and lipid A derivative in protecting irradiated canines

    International Nuclear Information System (INIS)

    Kumar, K.S.; Srinivasan, V.; Toles, R.E.; Miner, V.L.; Jackson, W.E.; Seed, T.M.

    2002-01-01

    There is an urgent need to develop non-toxic radioprotectors. We tested the efficacy of a 3-drug combination (3-DC) of iloprost, misoprostol, and 3D-MPL (3-deacylated monophosphoryl lipid A) and the effects of postirradiation clinical support with high doses of antibiotics and blood transfusion. Canines were given 3-DC or the vehicle and exposed to 3.4 Gy or 4.1 Gy of 60 Co radiation. Canines irradiated at 4.1 Gy were also given clinical support, which consisted of blood transfusion and antibiotics (gentamicin, and cefoxitin or cephalexin). Peripheral blood cell profile and 60-day survival were used as indices of protection. At 3.4 Gy, 3-DC- or vehicle-treated canines without postirradiation clinical support survived only for 10 to 12 days. Fifty percent of the canines treated with 3-DC or vehicle and provided postirradiation clinical support survived 4.1-Gy irradiation. Survival of canines treated with vehicle before irradiation significantly correlated with postirradiation antibiotic treatments, but not with blood transfusion. The recovery profile of peripheral blood cells in 4.1 Gy-irradiated canines treated with vehicle and antibiotics was better than drug-treated canines. These results indicate that therapy with high doses of intramuscular aminoglycoside antibiotic (gentamicin) and an oral cephalosporin (cephalexin) enhanced survival of irradiated canines. Although blood transfusion correlated with survival of 3-DC treated canines, there were no additional survivors with 3-DC treated canines than the controls. (author)

  5. Strategies to enhance rational use of antibiotics in hospital : a guideline by the German Society for Infectious Diseases

    NARCIS (Netherlands)

    de With, K.; Allerberger, F.; Amann, S.; Apfalter, P.; Brodt, H. -R.; Eckmanns, T.; Fellhauer, M.; Geiss, H. K.; Janata, O.; Krause, R.; Lemmen, S.; Meyer, E.; Mittermayer, H.; Porsche, U.; Presterl, E.; Reuter, S.; Sinha, B.; Strauss, R.; Wechsler-Foerdoes, A.; Wenisch, C.; Kern, W. V.

    In the time of increasing resistance and paucity of new drug development there is a growing need for strategies to enhance rational use of antibiotics in German and Austrian hospitals. An evidence-based guideline on recommendations for implementation of antibiotic stewardship (ABS) programmes was

  6. Therapies aimed at the gut microbiota and inflammation: antibiotics, prebiotics, probiotics, synbiotics, anti-inflammatory therapies.

    LENUS (Irish Health Repository)

    Quigley, Eamonn M M

    2011-03-01

    Several recent observations have raised the possibility that disturbances in the gut microbiota and\\/or a low-grade inflammatory state may contribute to symptomatology and the etiology of irritable bowel syndrome (IBS). Consequent on these hypotheses, several therapeutic categories have found their way into the armamentarium of those who care for IBS sufferers. These agents include probiotics, prebiotics, antibiotics, and anti-inflammatory agents.

  7. Antibiotic resistance patterns of community-acquired urinary tract infections in children with vesicoureteral reflux receiving prophylactic antibiotic therapy.

    Science.gov (United States)

    Cheng, Chi-Hui; Tsai, Ming-Horng; Huang, Yhu-Chering; Su, Lin-Hui; Tsau, Yong-Kwei; Lin, Chi-Jen; Chiu, Cheng-Hsun; Lin, Tzou-Yien

    2008-12-01

    The goal was to examine bacterial antimicrobial resistance of recurrent urinary tract infections in children receiving antibiotic prophylaxis because of primary vesicoureteral reflux. We reviewed data retrospectively for children with documented vesicoureteral reflux in 2 hospitals during a 5-year follow-up period. The patients were receiving co-trimoxazole, cephalexin, or cefaclor prophylaxis or prophylaxis with a sequence of different antibiotics (alternative monotherapy). Demographic data, degree of vesicoureteral reflux, prophylactic antibiotics prescribed, and antibiotic sensitivity results of first urinary tract infections and breakthrough urinary tract infections were recorded. Three hundred twenty-four patients underwent antibiotic prophylaxis (109 with co-trimoxazole, 100 with cephalexin, 44 with cefaclor, and 71 with alternative monotherapy) in one hospital and 96 children underwent co-trimoxazole prophylaxis in the other hospital. Breakthrough urinary tract infections occurred in patients from both hospitals (20.4% and 25%, respectively). Escherichia coli infection was significantly less common in children receiving antibiotic prophylaxis, compared with their initial episodes of urinary tract infection, at both hospitals. Children receiving cephalosporin prophylaxis were more likely to have an extended-spectrum beta-lactamase-producing organism for breakthrough urinary tract infections, compared with children with co-trimoxazole prophylaxis. Antimicrobial susceptibilities to almost all antibiotics decreased with cephalosporin prophylaxis when recurrent urinary tract infections developed. The extent of decreased susceptibilities was also severe for prophylaxis with a sequence of different antibiotics. However, antimicrobial susceptibilities decreased minimally in co-trimoxazole prophylaxis groups. Children receiving cephalosporin prophylaxis are more likely to have extended-spectrum beta-lactamase-producing bacteria or multidrug-resistant uropathogens

  8. Multi-bacteria multi-antibiotic testing using surface enhanced Raman spectroscopy (SERS) for urinary tract infection (UTI) diagnosis

    Science.gov (United States)

    Hadjigeorgiou, Katerina; Kastanos, Evdokia; Pitris, Costas

    2013-06-01

    The inappropriate use of antibiotics leads to antibiotic resistance, which is a major health care problem. The current method for determination of bacterial susceptibility to antibiotics requires overnight cultures. However most of the infections cannot wait for the results to receive treatment, so physicians administer general spectrum antibiotics. This results in ineffective treatments and aggravates the rising problem of antibiotic resistance. In this work, a rapid method for diagnosis and antibiogram for a bacterial infection was developed using Surface Enhanced Raman Spectroscopy (SERS) with silver nanoparticles. The advantages of this novel method include its rapidness and efficiency which will potentially allow doctors to prescribe the most appropriate antibiotic for an infection. SERS spectra of three species of gram negative bacteria, Escherichia coli, Proteus spp., and Klebsiella spp. were obtained after 0 and 4 hour exposure to the seven different antibiotics. Bacterial strains were diluted in order to reach the concentration of (2x105 cfu/ml), cells/ml which is equivalent to the minimum concentration found in urine samples from UTIs. Even though the concentration of bacteria was low, species classification was achieved with 94% accuracy using spectra obtained at 0 hours. Sensitivity or resistance to antibiotics was predicted with 81%-100% accuracy from spectra obtained after 4 hours of exposure to the different antibiotics. This technique can be applied directly to urine samples, and with the enhancement provided by SERS, this method has the potential to be developed into a rapid method for same day UTI diagnosis and antibiogram.

  9. Comparative study of the efficacy of topical steroid and antibiotic combination therapy versus oral antibiotic alone when treating acute rhinosinusitis.

    Science.gov (United States)

    El-Hennawi, D M; Ahmed, M R; Farid, A M; Al Murtadah, A M

    2015-05-01

    Acute rhinosinusitis arises as a consequence of viral rhinitis, and bacterial infection can subsequently occur. Intranasal antibiotics as an adjunct to corticosteroids usually demonstrate the greatest symptom relief. We wanted to clinically evaluate the effects of a topical antibiotic and steroid combination administered intranasally, versus an oral antibiotic alone when treating acute rhinosinusitis. Forty patients with acute bacterial rhinosinusitis were divided into two groups. Group A received an antibiotic and steroid combination (ofloxacin 0.26 per cent and dexamethasone 0.053 per cent nasal drops) for 10 days, administered intranasally (5 drops in each nostril/8 hours). Group B, the control group, received an oral antibiotic alone (amoxicillin 90 mg/kg). Eight hours after commencing treatment, facial pain was more severe in group B and nasal obstruction was reduced in both groups. Ten days after commencing treatment, anterior nasal discharge was 0.15 per cent in group A and absent in group B. The application of a topical antibiotic and steroid combination into the nasal cavity is an effective way of treating uncomplicated, acute bacterial rhinosinusitis with the theoretical advantages of easy administration, high local drug concentration and minimal systemic adverse effects.

  10. Photodynamic and antibiotic therapy impair the pathogenesis of Enterococcus faecium in a whole animal insect model.

    Directory of Open Access Journals (Sweden)

    José Chibebe Junior

    Full Text Available Enterococcus faecium has emerged as one of the most important pathogens in healthcare-associated infections worldwide due to its intrinsic and acquired resistance to many antibiotics, including vancomycin. Antimicrobial photodynamic therapy (aPDT is an alternative therapeutic platform that is currently under investigation for the control and treatment of infections. PDT is based on the use of photoactive dye molecules, widely known as photosensitizer (PS. PS, upon irradiation with visible light, produces reactive oxygen species that can destroy lipids and proteins causing cell death. We employed Galleria mellonella (the greater wax moth caterpillar fatally infected with E. faecium to develop an invertebrate host model system that can be used to study the antimicrobial PDT (alone or combined with antibiotics. In the establishment of infection by E. faecium in G. mellonella, we found that the G. mellonella death rate was dependent on the number of bacterial cells injected into the insect hemocoel and all E. faecium strains tested were capable of infecting and killing G. mellonella. Antibiotic treatment with ampicillin, gentamicin or the combination of ampicillin and gentamicin prolonged caterpillar survival infected by E. faecium (P = 0.0003, P = 0.0001 and P = 0.0001, respectively. In the study of antimicrobial PDT, we verified that methylene blue (MB injected into the insect followed by whole body illumination prolonged the caterpillar survival (P = 0.0192. Interestingly, combination therapy of larvae infected with vancomycin-resistant E. faecium, with antimicrobial PDT followed by vancomycin, significantly prolonged the survival of the caterpillars when compared to either antimicrobial PDT (P = 0.0095 or vancomycin treatment alone (P = 0.0025, suggesting that the aPDT made the vancomycin resistant E. faecium strain more susceptible to vancomycin action. In summary, G. mellonella provides an invertebrate model host to

  11. Motuporamine Derivatives as Antimicrobial Agents and Antibiotic Enhancers against Resistant Gram-Negative Bacteria.

    Science.gov (United States)

    Borselli, Diane; Blanchet, Marine; Bolla, Jean-Michel; Muth, Aaron; Skruber, Kristen; Phanstiel, Otto; Brunel, Jean Michel

    2017-02-01

    Dihydromotuporamine C and its derivatives were evaluated for their in vitro antimicrobial activities and antibiotic enhancement properties against Gram-negative bacteria and clinical isolates. The mechanism of action of one of these derivatives, MOTU-N44, was investigated against Enterobacter aerogenes by using fluorescent dyes to evaluate outer-membrane depolarization and permeabilization. Its efficiency correlated with inhibition of dye transport, thus suggesting that these molecules inhibit drug transporters by de-energization of the efflux pump rather than by direct interaction of the molecule with the pump. This suggests that depowering the efflux pump provides another strategy to address antibiotic resistance. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  12. Influence of antibiotic therapy prior to admission on the efficacy of classical methods for the diagnosis of meningococcal disease.

    Science.gov (United States)

    Nemescu, Roxana Elena; Iancu, Luminiţa Smaranda; Dorneanu, Olivia Simona; Ursu, Ramona Gabriela; Dorobăţ, Carmen Mihaela

    2014-01-01

    To assess the influence of preadmission antibiotic therapy on the results of the classical methods for bacteriological confirmation of meningococcal disease (MD). Retrospective study of the MD cases diagnosed in the "St. Parascheva" Universitary Clinical Infectious Diseases Iaşi between 1994 and 2011. The etiological diagnosis was made by identifying the meningococcus in the CSF (cerebrospinal fluid) in 71.9% of the 323 patients and by blood culture in 8%. Preadmission antibiotic therapy received 39% of the patients, thus the sensitivity of test was significantly reduced: direct examination from 64.6% to 43.2% (p antibiotic therapy significantly increased the ratio of cases in which meningococcus was not detected in CSF by any of the classical methods (44% compared to 17.9% in the cases without prior treatment). The proportion of cases in which meningococcal isolation was done by two methods decreased from 38.5% to 19.2%, and of those by all three methods from 16.9% to 5.6% (p antibiotic therapy also decreased the rate of positive blood cultures from 14.7% to 3.5% (Fisher's exact test, p = 0.009). Antibiotic treatment prior to admission significantly decreases the percentage of patients with MD in which meningococcal isolation can be done; this requires the use of a more sensitive diagnosis method (ex. qPCR).

  13. Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms.

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    Nicolas Barraud

    Full Text Available The failure of antibiotic therapies to clear Pseudomonas aeruginosa lung infection, the key mortality factor for cystic fibrosis (CF patients, is partly attributed to the high tolerance of P. aeruginosa biofilms. Mannitol has previously been found to restore aminoglycoside sensitivity in Escherichia coli by generating a proton-motive force (PMF, suggesting a potential new strategy to improve antibiotic therapy and reduce disease progression in CF. Here, we used the commonly prescribed aminoglycoside tobramycin to select for P. aeruginosa persister cells during biofilm growth. Incubation with mannitol (10-40 mM increased tobramycin sensitivity of persister cells up to 1,000-fold. Addition of mannitol to pre-grown biofilms was able to revert the persister phenotype and improve the efficacy of tobramycin. This effect was blocked by the addition of a PMF inhibitor or in a P. aeruginosa mutant strain unable to metabolise mannitol. Addition of glucose and NaCl at high osmolarity also improved the efficacy of tobramycin although to a lesser extent compared to mannitol. Therefore, the primary effect of mannitol in reverting biofilm associated persister cells appears to be an active, physiological response, associated with a minor contribution of osmotic stress. Mannitol was tested against clinically relevant strains, showing that biofilms containing a subpopulation of persister cells are better killed in the presence of mannitol, but a clinical strain with a high resistance to tobramycin was not affected by mannitol. Overall, these results suggest that in addition to improvements in lung function by facilitating mucus clearance in CF, mannitol also affects antibiotic sensitivity in biofilms and does so through an active, physiological response.

  14. Interhemispheric subdural empyema diagnosed by CT and cured by antibiotic therapy

    International Nuclear Information System (INIS)

    Hayakawa, Isao; Fukui, Mitsufumi; Furuhashi, Norihisa; Kanda, Tadashi; Tazaki, Yoshiaki

    1981-01-01

    A case of interhemispheric subdural empyema cured by high doses of antibiotics was reported. A 23-year-old man was admitted with complaints of headache, fever and motor weakness of the left lower leg of 2 days' duration. The neurological examination revealed neck stiffness, motor weakness and sensory disturbance of left lower leg. The WBS count was 26,000/cumm, and ESR was 74 mm/hour. The CSF showed a pressure of 230 mm H 2 O and contained 1001/3 cells (63% polymorphonuclears, 37% lymphocytes) in association with slight elevation of protein but with normal sugar content. The CSF culture was negative. Administration of high doses of antibiotics was started on the first hospital day. On the fourth hospital day, Jacksonian seizures occurred in the left lower extremity, and were controlled by anticonvulsants. CT scans with contrast enhancement revealed an area of low density in the right interhemispheric space with irregular marginal enhancement. Right carotid arteriography demonstrated a small oval avascular space along the interhemispheric cistern. The abnormalities on CT scan disappeared after one month, when the patient was discharged without neurological deficit. Unlike the previously reported cases with interhemispheric subdural empyema commonly associated with a collection of pus over the cerebral convexities, a localized interhemispheric subdural empyema as was found in the present case appears to be a very rare condition. The interhemispheric subdural empyema has been thought to be exclusively surgical indication and, to the best of our knowlage, there is no report in the literature of a case with successful medical treatment. However, successful treatment by antibiotics alone may become more practical if the diagnoses could be made in the early stage with the aid of CT scan. (author)

  15. Interhemispheric subdural empyema diagnosed by CT and cured by antibiotic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, I.; Fukui, M.; Furuhashi, N.; Kanda, T.; Tazaki, Y. (Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Medicine)

    1981-09-01

    A case of interhemispheric subdural empyema cured by high doses of antibiotics was reported. A 23-year-old man was admitted with complaints of headache, fever and motor weakness of the left lower leg of 2 days' duration. The neurological examination revealed neck stiffness, motor weakness and sensory disturbance of left lower leg. The WBS count was 26,000/cumm, and ESR was 74 mm/hour. The CSF showed a pressure of 230 mm H/sub 2/O and contained 1001/3 cells (63% polymorphonuclears, 37% lymphocytes) in association with slight elevation of protein but with normal sugar content. The CSF culture was negative. Administration of high doses of antibiotics was started on the first hospital day. On the fourth hospital day, Jacksonian seizures occurred in the left lower extremity, and were controlled by anticonvulsants. CT scans with contrast enhancement revealed an area of low density in the right interhemispheric space with irregular marginal enhancement. Right carotid arteriography demonstrated a small oval avascular space along the interhemispheric cistern. The abnormalities on CT scan disappeared after one month, when the patient was discharged without neurological deficit. Unlike the previously reported cases with interhemispheric subdural empyema commonly associated with a collection of pus over the cerebral convexities, a localized interhemispheric subdural empyema as was found in the present case appears to be a very rare condition. The interhemispheric subdural empyema has been thought to be exclusively surgical indication and, to the best of our knowlage, there is no report in the literature of a case with successful medical treatment. However, successful treatment by antibiotics alone may become more practical if the diagnoses could be made in the early stage with the aid of CT scan.

  16. Ultrasonic enhancement of antibiotic action on Escherichia coli biofilms: an in vivo model.

    Science.gov (United States)

    Rediske, A M; Roeder, B L; Brown, M K; Nelson, J L; Robison, R L; Draper, D O; Schaalje, G B; Robison, R A; Pitt, W G

    1999-05-01

    Biofilm infections are a common complication of prosthetic devices in humans. Previous in vitro research has determined that low-frequency ultrasound combined with aminoglycoside antibiotics is an effective method of killing biofilms. We report the development of an in vivo model to determine if ultrasound enhances antibiotic action. Two 24-h-old Escherichia coli (ATCC 10798) biofilms grown on polyethylene disks were implanted subcutaneously on the backs of New Zealand White female rabbits, one on each side of the spine. Low-frequency (28.48-kHz) and low-power-density (100- and 300-mW/cm2) continuous ultrasound treatment was applied for 24 h with and without systemic administration of gentamicin. The disks were then removed, and the number of viable bacteria on each disk was determined. At the low ultrasonic power used in this study, exposure to ultrasound only (no gentamicin) caused no significant difference in bacterial viability. In the presence of antibiotic, there was a significant reduction due to 300-mW/cm2 ultrasound (P = 0.0485) but no significant reduction due to 100-mW/cm2 ultrasound. Tissue damage to the skin was noted at the 300-mW/cm2 treatment level. Further development of this technique has promise in treatment of clinical implant infections.

  17. Procalcitonin Testing to Guide Antibiotic Therapy in Acute Upper and Lower Respiratory Tract Infections.

    Science.gov (United States)

    Schuetz, Philipp; Wirz, Yannick; Mueller, Beat

    2018-03-06

    Is the use of procalcitonin for guiding antibiotic decisions in patients with acute upper and lower respiratory tract infections associated with improved clinical outcomes compared with usual care? Among patients with varying types and severity of acute respiratory infection, using procalcitonin to guide decisions about antibiotics is associated with lower rates of antibiotic exposure, antibiotic-related adverse effects, and mortality.

  18. Successful recovery of infective endocarditis-induced rapidly progressive glomerulonephritis by steroid therapy combined with antibiotics: a case report

    Directory of Open Access Journals (Sweden)

    Kikkawa Ryuichi

    2004-12-01

    Full Text Available Abstract Background The mortality rate among patients with infective endocarditis, especially associated with the presence of complications or coexisting conditions such as renal failure and the use of combined medical and surgical therapy remains still high. Prolonged parenteral administration of a bactericidal antimicrobial agent or combination of agents is usually recommended, however, the optimal therapy for infective endocarditis associated with renal injury is not adequately defined. Case presentation Patient was a 24-years old man who presented to our hospital with fever, fatigue, and rapidly progressive glomerulonephritis. He had a history of ventricular septum defect (VSD. A renal biopsy specimen revealed crescentic glomerulonephritis and echocardiogram revealed VSD with vegetation on the tricuspid valve. Specimens of blood demonstrated Propionibacterium Acnes. The intensive antibiotic therapy with penicillin G was started without clinical improvement of renal function or resolution of fever over the next 7 days. After the short-term treatment of low dose of corticosteroid combined with continuous antibiotics, high fever and renal insufficiency were dramatically improved. Conclusion Although renal function in our case worsened despite therapy with antibiotics, a short-term and low dose of corticosteroid therapy with antibiotics was able to recover renal function and the patient finally underwent tricuspid valve-plasty and VSD closure. We suggest that the patients with rapidly progressive glomerulonephritis associated with infective endocarditis might be treated with a short-term and low dose of corticosteroid successfully.

  19. Antibacterial Activity and Antibiotic-Enhancing Effects of Honeybee Venom against Methicillin-Resistant Staphylococcus aureus

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    Sang Mi Han

    2016-01-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA, along with other antibiotic resistant bacteria, has become a significant social and clinical problem. There is thus an urgent need to develop naturally bioactive compounds as alternatives to the few antibiotics that remain effective. Here we assessed the in vitro activities of bee venom (BV, alone or in combination with ampicillin, penicillin, gentamicin or vancomycin, on growth of MRSA strains. The antimicrobial activity of BV against MRSA strains was investigated using minimum inhibitory concentrations (MIC, minimum bactericidal concentrations (MBC and a time-kill assay. Expression of atl which encodes murein hydrolase, a peptidoglycan-degrading enzyme involved in cell separation, was measured by reverse transcription-polymerase chain reaction. The MICs of BV were 0.085 µg/mL and 0.11 µg/mL against MRSA CCARM 3366 and MRSA CCARM 3708, respectively. The MBC of BV against MRSA 3366 was 0.106 µg/mL and that against MRSA 3708 was 0.14 µg/mL. The bactericidal activity of BV corresponded to a decrease of at least 3 log CFU/g cells. The combination of BV with ampicillin or penicillin yielded an inhibitory concentration index ranging from 0.631 to 1.002, indicating a partial and indifferent synergistic effect. Compared to ampicillin or penicillin, both MRSA strains were more susceptible to the combination of BV with gentamicin or vancomycin. The expression of atl gene was increased in MRSA 3366 treated with BV. These results suggest that BV exhibited antibacterial activity and antibiotic-enhancing effects against MRSA strains. The atl gene was increased in MRSA exposed to BV, suggesting that cell division was interrupted. BV warrants further investigation as a natural antimicrobial agent and synergist of antibiotic activity.

  20. Pressing Issues of Rational Antibiotic Therapy for Inflammatory Diseases of the Lower Respiratory Tract in Pediatric Practice

    Directory of Open Access Journals (Sweden)

    Ye.N. Okhotnikova

    2015-03-01

    Full Text Available Over the past 30 years, high incidence of acute lower respiratory tract infections of bacterial origin, primarily pneumonia and bronchitis, treatment of which under the spread of antibiotic resistance is often a difficult task, cause alarm. Bronchitis — one of the most common respiratory diseases in childhood after acute respiratory viral infections. Application of antibiotics for acute bronchitis in children is not recommended, but they are prescribed for severe intoxication and prolonged hyperthermia (over 3 days, especially in infants, children with poor premorbid background and high risk of pneumonia. Antibiotic therapy is considered as the only science-based treatment of pneumonia. Taking into account the broad spectrum of modern antibiotics, monotherapy is most suitable. If it is necessary to extend their effect, combination of amoxicillin/clavulanate with macrolides, to which all the major respiratory pathogens are sensitive, is preferred.

  1. Changes of Proteases, Antiproteases, and Pathogens in Cystic Fibrosis Patients’ Upper and Lower Airways after IV-Antibiotic Therapy

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    Ulrike Müller

    2015-01-01

    Full Text Available Background. In cystic fibrosis (CF the upper (UAW and lower airways (LAW are reservoirs for pathogens like Pseudomonas aeruginosa. The consecutive hosts’ release of proteolytic enzymes contributes to inflammation and progressive pulmonary destruction. Objectives were to assess dynamics of protease : antiprotease ratios and pathogens in CF-UAW and LAW sampled by nasal lavage (NL and sputum before and after intravenous- (IV- antibiotic therapy. Methods. From 19 IV-antibiotic courses of 17 CF patients NL (10 mL/nostril and sputum were collected before and after treatment. Microbiological colonization and concentrations of NE/SLPI/CTSS (ELISA and MMP-9/TIMP-1 (multiplex bead array were determined. Additionally, changes of sinonasal symptoms were assessed (SNOT-20. Results. IV-antibiotic treatment had more pronounced effects on inflammatory markers in LAW, whereas trends to decrease were also found in UAW. Ratios of MMP-9/TIMP-1 were higher in sputum, and ratios of NE/SLPI were higher in NL. Remarkably, NE/SLPI ratio was 10-fold higher in NL compared to healthy controls. SNOT-20 scores decreased significantly during therapy (P=0.001. Conclusion. For the first time, changes in microbiological patterns in UAW and LAW after IV-antibiotic treatments were assessed, together with changes of protease/antiprotease imbalances. Delayed responses of proteases and antiproteases to IV-antibiotic therapy were found in UAW compared to LAW.

  2. Comparing short to standard duration of antibiotic therapy for patients hospitalized with cellulitis (DANCE): study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    Cranendonk, Duncan R.; Opmeer, Brent C.; Prins, Jan M.; Wiersinga, W. Joost

    2014-01-01

    Recommended therapy duration for patients hospitalized with cellulitis is 10-14 days. Unnecessary use of antibiotics is one of the key factors driving resistance. Recent studies have shown that antibiotic therapy for cellulitis in outpatients can safely be shortened, despite residual inflammation.

  3. REAL TIME PCR IDENTIFICATION FOR TARGET ADJUNCTIVE ANTIBIOTIC THERAPY OF SEVERE CHRONIC PERIODONTITIS. PART II - MICROBIOLOGICAL EFFECTIVENESS.

    Directory of Open Access Journals (Sweden)

    Kamen Kotsilkov

    2014-10-01

    Full Text Available INTRODUCTION: Antibiotic use in chronic periodontitis may result in improvement in periodontal status, although many questions regarding the indications for this therapy remain unanswered. The polymicrobial etiology of the periodontal infection hinders the choice of the proper antibiotic agent. Furthermore the indiscriminate use of antibiotics could lead to high levels of resistance and to various adverse reactions. In the recent years a various molecular diagnostics protocols were proposed in order to facilitate the decision for adjunctive antibiotic administration. OBJECTIVE: The aim of this study is to compare the microbiological effectiveness of adjunctive antibiotic administration with the mechanical periodontal therapy. METHODS: 30 patients with severe chronic periodontitis were enrolled in this study and were divided in 3 groups: Control group – with mechanical debridement only. Test group 1 – with combined adjunctive antibiotic administration using Amoxicillin+ Metronidazole. Test group 2 – with target antibiotic administration according to the resuts from the Real Time PCR identification. RESULTS: The prevalence of all the isolated microorganisms (exept. E.nodatum and C.gingivalis in Test Group 2 demonstrates statistically significant reduction compared with the other treatment approaches. Almost complete elimination was registered for the consensus pathogens from the red and orange complexes (above 99% and 100% for P.intemedia. CONCLUSION: The adjunct antibiotic treatment targeted with Real-Time PCR identification demonstrates almost complete elimination of the putative periodontal pathogens in the deep periodontal pockets in patients with severe chronic periodontitis. This result suggests slower recolonisation of these habitats thus limiting the risk for progression of the periodontal destruction.

  4. Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial.

    Science.gov (United States)

    Sippola, S; Grönroos, J; Tuominen, R; Paajanen, H; Rautio, T; Nordström, P; Aarnio, M; Rantanen, T; Hurme, S; Salminen, P

    2017-09-01

    An increasing amount of evidence supports antibiotic therapy for treating uncomplicated acute appendicitis. The objective of this study was to compare the costs of antibiotics alone versus appendicectomy in treating uncomplicated acute appendicitis within the randomized controlled APPAC (APPendicitis ACuta) trial. The APPAC multicentre, non-inferiority RCT was conducted on patients with CT-confirmed uncomplicated acute appendicitis. Patients were assigned randomly to appendicectomy or antibiotic treatment. All costs were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis during the 1-year follow-up. The cost estimates were based on cost levels for the year 2012. Some 273 patients were assigned to the appendicectomy group and 257 to antibiotic treatment. Most patients randomized to antibiotic treatment did not require appendicectomy during the 1-year follow-up. In the operative group, overall societal costs (€5989·2, 95 per cent c.i. 5787·3 to 6191·1) were 1·6 times higher (€2244·8, 1940·5 to 2549·1) than those in the antibiotic group (€3744·4, 3514·6 to 3974·2). In both groups, productivity losses represented a slightly higher proportion of overall societal costs than all treatment costs together, with diagnostics and medicines having a minor role. Those in the operative group were prescribed significantly more sick leave than those in the antibiotic group (mean(s.d.) 17·0(8·3) (95 per cent c.i. 16·0 to 18·0) versus 9·2(6·9) (8·3 to 10·0) days respectively; P antibiotic therapy for uncomplicated appendicitis incurred lower costs than those who had surgery. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  5. Decision and cost analysis of empirical antibiotic therapy of acute sinusitis in the era of increasing antimicrobial resistance: do we have an additional tool for antibiotic policy decisions?

    Science.gov (United States)

    Babela, Robert; Jarcuska, Pavol; Uraz, Vladimir; Krčméry, Vladimír; Jadud, Branislav; Stevlik, Jan; Gould, Ian M

    2017-11-01

    No previous analyses have attempted to determine optimal therapy for upper respiratory tract infections on the basis of cost-minimization models and the prevalence of antimicrobial resistance among respiratory pathogens in Slovakia. This investigation compares macrolides and cephalosporines for empirical therapy and look at this new tool from the aspect of potential antibiotic policy decision-making process. We employed a decision tree model to determine the threshold level of macrolides and cephalosporines resistance among community respiratory pathogens that would make cephalosporines or macrolides cost-minimising. To obtain information on clinical outcomes and cost of URTIs, a systematic review of the literature was performed. The cost-minimization model of upper respiratory tract infections (URTIs) treatment was derived from the review of literature and published models. We found that the mean cost of empirical treatment with macrolides for an URTIs was €93.27 when the percentage of resistant Streptococcus pneumoniae in the community was 0%; at 5%, the mean cost was €96.45; at 10%, €99.63; at 20%, €105.99, and at 30%, €112.36. Our model demonstrated that when the percentage of macrolide resistant Streptococcus pneumoniae exceeds 13.8%, use of empirical cephalosporines rather than macrolides minimizes the treatment cost of URTIs. Empirical macrolide therapy is less expensive than cephalosporines therapy for URTIs unless macrolide resistance exceeds 13.8% in the community. Results have important antibiotic policy implications, since presented model can be use as an additional decision-making tool for new guidelines and reimbursement processes by local authorities in the era of continual increase in antibiotic resistance.

  6. Urinary tract infection (UTI) multi-bacteria multi-antibiotic testing using surface enhanced Raman spectroscopy (SERS)

    Science.gov (United States)

    Hadjigeorgiou, Katerina; Kastanos, Evdokia; Pitris, Costas

    2013-02-01

    Antibiotic resistance is a major health care problem mostly caused by the inappropriate use of antibiotics. At the root of the problem lies the current method for determination of bacterial susceptibility to antibiotics which requires overnight cultures. Physicians suspecting an infection usually prescribe an antibiotic without waiting for the results. This practice aggravates the problem of bacterial resistance. In this work, a rapid method of diagnosis and antibiogram for a bacterial infection was developed using Surface Enhanced Raman Spectroscopy (SERS) with silver nanoparticles. SERS spectra of three species of gram negative bacteria, Escherichia coli, Proteus spp., and Klebsiella spp. were obtained after 0 and 4 hour exposure to the seven different antibiotics. Even though the concentration of bacteria was low (2x105 cfu/ml), species classification was achieved with 94% accuracy using spectra obtained at 0 hours. Sensitivity or resistance to antibiotics was predicted with 81%-100% accuracy from spectra obtained after 4 hours of exposure to the different antibiotics. With the enhancement provided by SERS, the technique can be applied directly to urine or blood samples, bypassing the need for overnight cultures. This technology can lead to the development of rapid methods of diagnosis and antibiogram for a variety of bacterial infections.

  7. Efficacy of Antibiotic Suppressive Therapy in Patients with a Prosthetic Joint Infection.

    Science.gov (United States)

    Wouthuyzen-Bakker, Marjan; Nijman, Jasperina M; Kampinga, Greetje A; van Assen, Sander; Jutte, Paul C

    2017-01-01

    Introduction: For chronic prosthetic joint infections (PJI), complete removal of the infected prosthesis is necessary in order to cure the infection. Unfortunately, a subgroup of patients is not able to undergo a revision surgery due to high surgical risk. Alternatively, these patients can be treated with antibiotic suppressive therapy (AST) to suppress the infection. Aim: To evaluate the efficacy and tolerability of AST. Methods: We retrospectively collected data (period 2009-2015) from patients with a PJI (of hip, knee or shoulder) who were treated with AST at the University Medical Center Groningen, the Netherlands. AST was defined as antibiotic treatment for PJI that was started after the usual 3 months of antibiotic treatment. The time of follow-up was defined from the time point AST was started. Treatment was considered as failed, when the patient still experienced joint pain, when surgical intervention (debridement, removal, arthrodesis or amputation) was needed to control the infection and/or when death occurred due to the infection. Results: We included 21 patients with a median age of 67 years (range 21 - 88) and with a median follow-up of 21 months (range 3 - 81). Coagulase negative staphylococci (CNS) (n=6), S. aureus (n=6) and polymicrobial flora (n=4) were the most frequently found causative pathogens. Most patients with CNS and S. aureus were treated with minocycline (67%) and clindamycin (83%) as AST, respectively. Overall, treatment was successful in 67% of patients. Failure was due to persistent joint pain (n=1), surgical intervention because of an uncontrolled infection (n=3), and death due the infection (n=3). We observed a treatment success of 90% in patients with a 'standard' prosthesis (n=11), compared to only 50% in patients with a tumor-prosthesis (n=10). Also, treatment was successful in 83% of patients with a CNS as causative microorganism for the infection, compared to 50% in patients with a S. aureus . Patients who failed on AST had a

  8. Use of nasopharyngeal culture to determine appropriateness of antibiotic therapy in acute bacterial rhinosinusitis.

    Science.gov (United States)

    Lee, Stella; Woodbury, Kristin; Ferguson, Berrylin J

    2013-04-01

    Rhinosinusitis is one of the top 5 diagnoses for which an antibiotic is prescribed, often without a clear bacterial etiology. This study evaluated whether nasopharyngeal culture and gram stain could serve as a surrogate for endoscopically obtained middle meatal cultures in directing appropriate therapy for acute bacterial rhinosinusitis (ABRS). This study also investigated the utility of a rapid sinus test screen in differentiating bacterial from nonbacterial rhinosinusitis. Thirty-one adult patients met inclusion criteria for ABRS. Samples were obtained from both the middle meatus and nasopharynx for Gram stain and culture. Nasal mucous samples were tested with a rapid sinus test strip measuring pH, levels of protein, nitrites, and leukocyte esterase. Sixty-one percent (61%) of nasopharyngeal and 48% of middle meatal samples grew pathogenic bacteria. The concordance rate was 84% between the 2 sites (p = 0.0006). The following pathogenic organisms were detected: Moraxella catarrhalis, Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Staphylococcus aureus. For nasopharyngeal samples, reliance on Gram stain alone exhibited a sensitivity of 31% and specificity of 100% and, similarly, for middle meatus samples, 47% and 93%, respectively. The rapid sinus test revealed a sensitivity of 83% and specificity of 7%. Nasopharyngeal and middle meatal cultures exhibited high concordance for pathogenic bacteria. Gram stain exhibited moderate sensitivity and excellent specificity. Nasopharyngeal cultures could provide a viable method, especially in a primary care setting, for determining the appropriateness of antibiotic therapy. The rapid sinus test's lack of specificity precluded its utility in the differentiation between bacterial and nonbacterial rhinosinusitis. © 2013 ARS-AAOA, LLC.

  9. Neonatal Escherichia coli Bloodstream Infections: Clinical Outcomes and Impact of Initial Antibiotic Therapy.

    Science.gov (United States)

    Bergin, Stephen P; Thaden, Joshua T; Ericson, Jessica E; Cross, Heather; Messina, Julia; Clark, Reese H; Fowler, Vance G; Benjamin, Daniel K; Hornik, Christoph P; Smith, P Brian

    2015-09-01

    Escherichia coli is a common cause of bloodstream infections (BSIs) in infants and is associated with high mortality and morbidity among survivors. The clinical significance of antibiotic resistance and timing of appropriate antimicrobial therapy in this population is poorly understood. We identified all infants with E. coli BSIs discharged from 77 neonatal intensive care units managed by the Pediatrix Medical Group in 2012. We used multivariable logistic regression to evaluate the association between 30-day mortality and ampicillin-resistant E. coli BSI, as well as the number of active empiric antimicrobial agents administered, controlling for gestational age, small-for-gestational age status, early-onset versus late-onset BSI, oxygen requirement, ventilator support and inotropic support on the day of the first positive blood culture. We identified 258 episodes of E. coli BSI, including 123 (48%) ampicillin-resistant isolates. Unadjusted 30-day mortality did not significantly differ between infants with ampicillin-resistant versus ampicillin-susceptible E. coli BSI [11 of 123 (9%) vs. 7 of 135 (5%); P = 0.33; adjusted odds ratio = 1.37 (95% confidence interval: 0.39, 4.77)]. Among ampicillin-resistant E. coli BSIs, 30-day mortality was not significantly lower for infants treated with at least one empiric antimicrobial active against ampicillin-resistant E. coli versus infants receiving no active empiric agent [adjusted odds ratio = 1.50 (0.07, 33.6)]. In this population of infants with E. coli BSI, ampicillin resistance was not associated with significantly increased mortality. Among the subset of infants with ampicillin-resistant E. coli, appropriate empirical antibiotic therapy was not associated with lower mortality.

  10. Cycling empirical antibiotic therapy in hospitals: meta-analysis and models.

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    Pia Abel zur Wiesch

    2014-06-01

    Full Text Available The rise of resistance together with the shortage of new broad-spectrum antibiotics underlines the urgency of optimizing the use of available drugs to minimize disease burden. Theoretical studies suggest that coordinating empirical usage of antibiotics in a hospital ward can contain the spread of resistance. However, theoretical and clinical studies came to different conclusions regarding the usefulness of rotating first-line therapy (cycling. Here, we performed a quantitative pathogen-specific meta-analysis of clinical studies comparing cycling to standard practice. We searched PubMed and Google Scholar and identified 46 clinical studies addressing the effect of cycling on nosocomial infections, of which 11 met our selection criteria. We employed a method for multivariate meta-analysis using incidence rates as endpoints and find that cycling reduced the incidence rate/1000 patient days of both total infections by 4.95 [9.43-0.48] and resistant infections by 7.2 [14.00-0.44]. This positive effect was observed in most pathogens despite a large variance between individual species. Our findings remain robust in uni- and multivariate metaregressions. We used theoretical models that reflect various infections and hospital settings to compare cycling to random assignment to different drugs (mixing. We make the realistic assumption that therapy is changed when first line treatment is ineffective, which we call "adjustable cycling/mixing". In concordance with earlier theoretical studies, we find that in strict regimens, cycling is detrimental. However, in adjustable regimens single resistance is suppressed and cycling is successful in most settings. Both a meta-regression and our theoretical model indicate that "adjustable cycling" is especially useful to suppress emergence of multiple resistance. While our model predicts that cycling periods of one month perform well, we expect that too long cycling periods are detrimental. Our results suggest that

  11. Experimental Simulation of the Effects of an Initial Antibiotic Treatment on a Subsequent Treatment after Initial Therapy Failure

    NARCIS (Netherlands)

    Feng, Yanfang; Händel, Nadine; de Groot, Marnix H. P.; Brul, Stanley; Schultsz, Constance; ter Kuile, Benno H.

    2014-01-01

    Therapy failure of empirical antibiotic treatments prescribed by primary care physicians occurs commonly. The effect of such a treatment on the susceptibility to second line antimicrobial drugs is unknown. Resistance to amoxicillin was rapidly induced or selected in E. coli at concentrations

  12. Antibiotic Potency against E. coli Is Enhanced by Channel-Forming Alkyl Lariat Ethers.

    Science.gov (United States)

    Negin, Saeedeh; Patel, Mohit B; Gokel, Michael R; Meisel, Joseph W; Gokel, George W

    2016-11-17

    Several N,N'-bis(n-alkyl-4,13-diaza[18]crown-6) lariat ethers were found to significantly enhance the potency of rifampicin and tetracycline, but not erythromycin and kanamycin, against the non-pathogenic DH5α and K-12 strains of Escherichia coli when administered at levels below their minimum inhibitory concentrations (MICs). The enhancements in antibiotic potency observed for the lariat ethers ranged from three- to 20-fold, depending on the strain of E. coli, the antibiotic, and the lengths of the alkyl chains attached at the macroring nitrogen atoms. The dialkyl lariat ethers, previously thought to only be cation carriers, formed well-behaved, ion-conducting pores in soybean asolectin membranes, as judged by planar bilayer conductance measurements. The ability of lariat ethers to form stable pores, which appeared to be aggregated, depended in part on alkyl chain length and in part on the composition of the bilayer membrane in which they were studied. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Cefditoren and ceftriaxone enhance complement-mediated immunity in the presence of specific antibodies against antibiotic-resistant pneumococcal strains.

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    Elisa Ramos-Sevillano

    Full Text Available BACKGROUND: Specific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health. METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry was used to determine whether complement-mediated immunity against three antibiotic-resistant S. pneumoniae clinical isolates is enhanced in the presence of sub-inhibitory concentrations of cefditoren and ceftriaxone. The binding of acute phase proteins such as C-reactive protein and serum amyloid P component, and of complement component C1q, to pneumococci was enhanced in the presence of serum plus either of these antibiotics. Both antibiotics therefore trigger the activation of the classical complement pathway against S. pneumoniae. C3b deposition was also increased in the presence of specific anti-pneumococcal antibodies and sub-inhibitory concentrations of cefditoren and ceftriaxone confirming that the presence of these antibiotics enhances complement-mediated immunity to S. pneumoniae. CONCLUSIONS/SIGNIFICANCE: Using cefditoren and ceftriaxone to promote the binding of acute phase proteins and C1q to pneumococci, and to increase C3b deposition, when anti-pneumococcal antibodies are present, might help reduce the impact of antibiotic resistance in S. pneumoniae infections.

  14. Sequential (as Opposed to Simultaneous) Antibiotic Therapy Improves Helicobacter pylori Eradication in the Pediatric Population: A Meta-Analysis.

    Science.gov (United States)

    Lau, Christine S M; Ward, Amanda; Chamberlain, Ronald S

    2016-06-01

    Helicobacter pylori is a common infection associated with many gastrointestinal diseases. Triple or quadruple therapy is the current recommendation for H pylori eradication in children but is associated with success rates as low as 50%. Recent studies have demonstrated that a 10-day sequential therapy regimen, rather than simultaneous antibiotic administration, achieved eradication rates of nearly 95%. This meta-analysis found that sequential therapy increased eradication rates by 14.2% (relative risk [RR] = 1.142; 95% confidence interval [CI] = 1.082-1.207; P sequential therapy significantly improved H pylori eradication rates compared to the 7-day standard therapy (RR = 1.182; 95% CI = 1.102-1.269; p sequential therapy is associated with increased H pylori eradication rates in children compared to standard therapy of equal or shorter duration. © The Author(s) 2015.

  15. Procalcitonin guided antibiotic therapy and hospitalization in patients with lower respiratory tract infections: a prospective, multicenter, randomized controlled trial

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    Henzen Christoph

    2007-07-01

    Full Text Available Abstract Background: Lower respiratory tract infections like acute bronchitis, exacerbated chronic obstructive pulmonary disease and community-acquired pneumonia are often unnecessarily treated with antibiotics, mainly because of physicians' difficulties to distinguish viral from bacterial cause and to estimate disease-severity. The goal of this trial is to compare medical outcomes, use of antibiotics and hospital resources in a strategy based on enforced evidence-based guidelines versus procalcitonin guided antibiotic therapy in patients with lower respiratory tract infections. Methods and design: We describe a prospective randomized controlled non-inferiority trial with an open intervention. We aim to randomize over a fixed recruitment period of 18 months a minimal number of 1002 patients from 6 hospitals in Switzerland. Patients must be >18 years of age with a lower respiratory tract infections Discussion: Use of and prolonged exposure to antibiotics in lower respiratory tract infections is high. The proposed trial investigates whether procalcitonin-guidance may safely reduce antibiotic consumption along with reductions in hospitalization costs and antibiotic resistance. It will additionally generate insights for improved prognostic assessment of patients with lower respiratory tract infections. Trial registration: ISRCTN95122877

  16. The use of inhaled antibiotic therapy in the treatment of ventilator-associated pneumonia and tracheobronchitis: a systematic review.

    Science.gov (United States)

    Russell, Christopher J; Shiroishi, Mark S; Siantz, Elizabeth; Wu, Brian W; Patino, Cecilia M

    2016-03-08

    Ventilator-associated respiratory infections (tracheobronchitis, pneumonia) contribute significant morbidity and mortality to adults receiving care in intensive care units (ICU). Administration of broad-spectrum intravenous antibiotics, the current standard of care, may have systemic adverse effects. The efficacy of aerosolized antibiotics for treatment of ventilator-associated respiratory infections remains unclear. Our objective was to conduct a systematic review of the efficacy of aerosolized antibiotics in the treatment of ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT), using the Cochrane Collaboration guidelines. We conducted a search of three databases (PubMed, Web of Knowledge and the Cochrane Collaboration) for randomized, controlled trials studying the use of nebulized antibiotics in VAP and VAT that measured clinical cure (e.g., change in Clinical Pulmonary Infection Score) as an outcome measurement. We augmented the electronic searches with hand searches of the references for any narrative review articles as well as any article included in the systematic review. Included studies were examined for risk of bias using the Cochrane Handbook's "Risk of Bias" assessment tool. Six studies met full inclusion criteria. For the systemic review's primary outcome (clinical cure), two studies found clinically and statistically significant improvements in measures of VAP cure while four found no statistically significant difference in measurements of cure. No studies found inferiority of aerosolized antibiotics. The included studies had various degrees of biases, particularly in the performance and detection bias domains. Given that outcome measures of clinical cure were not uniform, we were unable to conduct a meta-analysis. There is insufficient evidence for the use of inhaled antibiotic therapy as primary or adjuvant treatment of VAP or VAT. Additional, better-powered randomized-controlled trials are needed to assess the efficacy of inhaled

  17. [Adequacy of antibiotic therapy for urinary tract infection in a Medical Department from the university hospital of Lille: A retrospective cohort study].

    Science.gov (United States)

    Deconinck, L; Maillard, H; Lemaitre, M; Barbottin, E; Bakhache, E; Galperine, T; Puisieux, F; Hatron, P-Y; Lambert, M

    2015-11-01

    The main objective of the study was to assess the adequacy of antibiotic therapy for urinary tract infections (UTI) in a French hospital medical department. The secondary objective was to identify factors associated with inadequacy of the antibiotic therapy. A retrospective single centre cohort study was performed in the Post-Emergency Medicine Department (PEMD) of the university hospital of Lille. All patients presenting with an UTI from May 2012 to April 2014 were included. Adequacy of antibiotic therapy was assessed with reference to local guidelines. Factors associated with inadequacy of antibiotic prescription were determined using a multivariate logistic regression model. Two hundred and twenty-eight patients were included. The antibiotic prescription was fully adequate in 173 patients (76%) with appropriate use of a single or a combination antibiotic therapy in 96%, appropriate drug in 80%, appropriate dosage in 89% and appropriate route of administration in 95%. The risk for antibiotic inadequacy was significantly higher in patients with cystitis than in those with pyelonephritis (OR 12.01; 95% CI 4.17-34.65), when antibiotics were prescribed in the Emergency Department (OR 6.84; 95% CI 2.29-20.47) or before hospital admission (OR 382.46; 95% CI 19.61≥999.99) compared to when antibiotics were first administered in the PEMD, and in patients with severe UTI (OR 19.55; 95% CI 2.79-137.01). Adequacy of antibiotic therapy for UTI is relatively high in our study, reflecting the effective dissemination of antibiotic guidelines. However, antibiotic therapy is still inappropriate in cystitis, severe UTI and in case of prescription before the admission in the PEMD. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  18. Antibiotic resistance

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    Marianne Frieri

    2017-07-01

    Full Text Available Summary: Antimicrobial resistance in bacterial pathogens is a challenge that is associated with high morbidity and mortality. Multidrug resistance patterns in Gram-positive and -negative bacteria are difficult to treat and may even be untreatable with conventional antibiotics. There is currently a shortage of effective therapies, lack of successful prevention measures, and only a few new antibiotics, which require development of novel treatment options and alternative antimicrobial therapies. Biofilms are involved in multidrug resistance and can present challenges for infection control. Virulence, Staphylococcus aureus, Clostridium difficile infection, vancomycin-resistant enterococci, and control in the Emergency Department are also discussed. Keywords: Antibiotic resistance, Biofilms, Infections, Public health, Emergency Department

  19. Nano-antibiotics in chronic lung infection therapy against Pseudomonas aeruginosa.

    Science.gov (United States)

    Hadinoto, Kunn; Cheow, Wean Sin

    2014-04-01

    Antibiotic encapsulation into nanoparticle carriers has emerged as a promising inhaled antibiotic formulation for treatment of chronic Pseudomonas aeruginosa lung infection prevalent in chronic obstructive pulmonary diseases. Attributed to their prolonged lung retention, sustained antibiotic release, and mucus penetrating ability, antibiotic nanoparticles, or nano-antibiotics in short, can address the principal weakness of inhaled antibiotic solution, i.e. low antibiotic exposure in the vicinity of P. aeruginosa biofilm colonies resulting in diminished anti-pseudomonal efficacy after repeated uses. This review details the current state of development and limitations of the two most widely studied forms of nano-antibiotics, i.e. liposomes and polymer nanoparticles. Factors in their formulation that influence the anti-pseudomonal efficacy in vitro and in vivo, such as liposome's membrane rigidity, surface charge, size, and polymer hydrophobicity, are discussed. This review reveals that the superior anti-pseudomonal efficacy of liposomal antibiotics to free antibiotics has been clearly established when they are correctly formulated, with several liposomal antibiotic formulations are currently undergoing clinical trials. Liposomal antibiotics, nevertheless, are not without limitation due to their weak physicochemical stability. In contrast, only mucus penetrating ability of the more stable polymeric nano-antibiotics has been established, while their anti-pseudomonal efficacy has only been examined in vitro from which their superiority to free antibiotics has not been ascertained. Lastly, future research needs to bring liposome and polymer-based nano-antibiotics closer to their clinical realization are identified. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial).

    Science.gov (United States)

    Paajanen, Hannu; Grönroos, Juha M; Rautio, Tero; Nordström, Pia; Aarnio, Markku; Rantanen, Tuomo; Hurme, Saija; Dean, Kirsti; Jartti, Airi; Mecklin, Jukka-Pekka; Sand, Juhani; Salminen, Paulina

    2013-02-08

    Although the standard treatment of acute appendicitis (AA) consists of an early appendectomy, there has recently been both an interest and an increase in the use of antibiotic therapy as the primary treatment for uncomplicated AA. However, the use of antibiotic therapy in the treatment of uncomplicated AA is still controversial. The APPAC trial is a randomized prospective controlled, open label, non-inferiority multicenter trial designed to compare antibiotic therapy (ertapenem) with emergency appendectomy in the treatment of uncomplicated AA. The primary endpoint of the study is the success of the randomized treatment. In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year (treatment efficacy). Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100%. Secondary endpoints are post-intervention complications, overall morbidity and mortality, the length of hospital stay and sick leave, treatment costs and pain scores (VAS, visual analoque scale). A maximum of 610 adult patients (aged 18-60 years) with a CT scan confirmed uncomplicated AA will be enrolled from six hospitals and randomized by a closed envelope method in a 1:1 ratio either to undergo emergency appendectomy or to receive ertapenem (1 g per day) for three days continued by oral levofloxacin (500 mg per day) plus metronidazole (1.5 g per day) for seven days. Follow-up by a telephone interview will be at 1 week, 2 months and 1, 3, 5 and 10 years; the primary and secondary endpoints of the trial will be evaluated at each time point. The APPAC trial aims to provide level I evidence to support the hypothesis that approximately 75-85% of patients with uncomplicated AA can be treated with effective antibiotic therapy avoiding unnecessary appendectomies and the related operative morbidity, also resulting

  1. Enhancing Immune Checkpoint Inhibitor Therapy in Kidney Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0141 TITLE: Enhancing Immune Checkpoint Inhibitor therapy in Kidney Cancer PRINCIPAL INVESTIGATOR: Hans-Joerg Hammers...SUBTITLE Enhancing Immune Checkpoint Inhibitor therapy in Kidney Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH- 15-1-0141 5c. PROGRAM ELEMENT NUMBER...immune checkpoint inhibition in kidney cancer . The work is designed to test different strategies to induce or enhance the abscopal in a kidney cancer

  2. Systemic antibiotics in periodontics.

    Science.gov (United States)

    Slots, Jørgen

    2004-11-01

    This position paper addresses the role of systemic antibiotics in the treatment of periodontal disease. Topical antibiotic therapy is not discussed here. The paper was prepared by the Research, Science and Therapy Committee of the American Academy of Periodontology. The document consists of three sections: 1) concept of antibiotic periodontal therapy; 2) efficacy of antibiotic periodontal therapy; and 3) practical aspects of antibiotic periodontal therapy. The conclusions drawn in this paper represent the position of the American Academy of Periodontology and are intended for the information of the dental profession.

  3. Antibiotic susceptibility of Gram-negatives isolated from bacteremia in children with cancer. Implications for empirical therapy of febrile neutropenia.

    Science.gov (United States)

    Castagnola, Elio; Caviglia, Ilaria; Pescetto, Luisa; Bagnasco, Francesca; Haupt, Riccardo; Bandettini, Roberto

    2015-01-01

    Monotherapy is recommended as the first choice for initial empirical therapy of febrile neutropenia, but local epidemiological and antibiotic susceptibility data are now considered pivotal to design a correct management strategy. To evaluate the proportion of Gram-negative rods isolated in bloodstream infections in children with cancer resistant to antibiotics recommended for this indication. The in vitro susceptibility to ceftazidime, piperacillin-tazobactam, meropenem and amikacin of Gram-negatives isolated in bacteremic episodes in children with cancer followed at the Istituto "Giannina Gaslini", Genoa, Italy in the period of 2001-2013 was retrospectively analyzed using the definitions recommended by EUCAST in 2014. Data were analyzed for any single drug and to the combination of amikacin with each β-lactam. The combination was considered effective in absence of concomitant resistance to both drugs, and not evaluated by means of in vitro analysis of antibiotic combinations (e.g., checkerboard). A total of 263 strains were evaluated: 27% were resistant to piperacillin-tazobactam, 23% to ceftazidime, 12% to meropenem and 13% to amikacin. Concomitant resistance to β-lactam and amikacin was detected in 6% of strains for piperacillin-tazobactam, 5% for ceftazidime and 5% for meropenem. During the study period there was a nonsignificant increase in the proportions of strains resistant to β-lactams indicated for monotherapy, and also increase in the resistance to combined therapies. in an era of increasing resistance to antibiotics guideline-recommended monotherapy could be not appropriate for initial empirical therapy of febrile neutropenia. Strict local survey on etiology and antibiotic susceptibility is mandatory for a correct management of this complication in cancer patients.

  4. Clinical and economic consequences of failure of initial antibiotic therapy for patients with community-onset complicated intra-abdominal infections.

    Directory of Open Access Journals (Sweden)

    Yong Pil Chong

    Full Text Available Complicated intra-abdominal infection (cIAI is infection that extends beyond the hollow viscus of origin into the peritoneal space, and is associated with either abscess formation or peritonitis. There are few studies that have assessed the actual costs and outcomes associated with failure of initial antibiotic therapy for cIAI. The aims of this study were to evaluate risk factors and impact on costs and outcomes of failure of initial antibiotic therapy for community-onset cIAI.A retrospective study was performed at eleven tertiary-care hospitals. Hospitalized adults with community-onset cIAI who underwent an appropriate source control procedure between August 2008 and September 2011 were included. Failure of initial antibiotic therapy was defined as a change of antibiotics due to a lack of improvement of the clinical symptoms and signs associated with cIAI in the first week.A total of 514 patients hospitalized for community-onset cIAI were included in the analysis. The mean age of the patients was 53.3 ± 17.6 years, 72 patients (14% had health care-associated infection, and 48 (9% experienced failure of initial antibiotic therapy. Failure of initial antibiotic therapy was associated with increased costs and morbidity. After adjustment for covariates, patients with unsuccessful initial therapy received an additional 2.9 days of parenteral antibiotic therapy, were hospitalized for an additional 5.3 days, and incurred $3,287 in additional inpatient charges. Independent risk factors for failure of initial antibiotic therapy were health care-associated infection, solid cancer, and APACHE II ≥13.To improve outcomes and costs in patients with community-onset cIAI, rapid assessment of health care-associated risk factors and severity of disease, selection of an appropriate antibiotic regimen accordingly, and early infection source control should be performed.

  5. Antibiotic resistance pattern and empirical therapy for urinary tract infections in children

    International Nuclear Information System (INIS)

    Al-Harthi, Abdulla A.; Al-Fifi, Suliman H.

    2008-01-01

    Objective was to study the type of bacterial pathogen causing urinary tract infection in children at Aseer Central Hospital, southwestern Saudi Arabia and their antimicrobial resistance patterns. A retrospective study of all the urine cultures carried out on the children in the period from January 2003 to December 2006, for a total of 4 years were reviewed at the bacteriology laboratory, Aseer Central Hospital, southwestern region of Saudi Arabia. Their antimicrobial resistances as well as sensitivities were also analyzed. A total of 464 urine cultures were identified. Escherichia coli constitutes the most common pathogen isolated 37.3%, followed by Klebsiella 16.4% and Pseudomonas species 15.7%. In general, there was a significant increase in the resistance rates of different bacterial pathogens to different antibiotics. In spite of an increase in the resistance rates of bacterial pathogens causing UTI, ceftriaxone, imipenem and to some extent Azactam are appropriate for initial empirical intravenous therapy in UTI. In patients with uncomplicated UTI not requiring hospitalization, Nalidixic acid and Nitrofurantoin can be used as oral treatment. (author)

  6. Changes in Bacterial Resistance Patterns of Pediatric Urinary Tract Infections and Rationale for Empirical Antibiotic Therapy

    OpenAIRE

    İbrahim Gökçe; Neslihan Çiçek; Serçin Güven; Ülger Altuntaş; Neşe Bıyıklı; Nurdan Yıldız; Harika Alpay

    2017-01-01

    Background: The causative agent spectrum and resistance patterns of urinary tract infections in children are affected by many factors. Aims: To demonstrate antibiotic resistance in urinary tract infections and changing ratio in antibiotic resistance by years. Study Design: Retrospective cross-sectional study. Methods: We analysed antibiotic resistance patterns of isolated Gram (-) bacteria during the years 2011-2014 (study period 2) in children with urinary tract infections. We...

  7. Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

    Directory of Open Access Journals (Sweden)

    Tatiane eCoelho

    2015-04-01

    Full Text Available Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA to study single combinations between antituberculosis drugs and efflux inhibitors (EIs against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates.

  8. Anaerobic treatment of antibiotic production wastewater pretreated with enhanced hydrolysis: Simultaneous reduction of COD and ARGs.

    Science.gov (United States)

    Yi, Qizhen; Zhang, Yu; Gao, Yingxin; Tian, Zhe; Yang, Min

    2017-03-01

    The presence of high concentration antibiotics in wastewater can disturb the stability of biological wastewater treatment systems and promote generation of antibiotic resistance genes (ARGs) during the treatment. To solve this problem, a pilot system consisting of enhanced hydrolysis pretreatment and an up-flow anaerobic sludge bed (UASB) reactor in succession was constructed for treating oxytetracycline production wastewater, and the performance was evaluated in a pharmaceutical factory in comparison with a full-scale anaerobic system operated in parallel. After enhanced hydrolysis under conditions of pH 7 and 85 °C for 6 h, oxytetracycline production wastewater with an influent chemical oxygen demand (COD) of 11,086 ± 602 mg L -1 was directly introduced into the pilot UASB reactor. With the effective removal of oxytetracycline and its antibacterial potency (from 874 mg L -1 to less than 0.61 mg L -1 and from 900 mg L -1 to less than 0.84 mg L -1 , respectively) by the enhanced hydrolysis pretreatment, an average COD removal rate of 83.2%, 78.5% and 68.9% was achieved at an organic loading rate of 3.3, 4.8 and 5.9 kg COD m -3  d -1 , respectively. At the same time, the relative abundances of the total tetracycline (tet) genes and a mobile element (Class 1 integron (intI1)) in anaerobic sludge on day 96 were one order of magnitude lower than those in inoculated sludge on day 0 (P anaerobic system treating oxytetracycline production wastewater with an influent COD of 3720 ± 128 mg L -1 after dilution exhibited a COD removal of 51 ± 4% at an organic loading rate (OLR) 1.2 ± 0.2 kg m -3  d -1 , and a total tet gene abundance in sludge was five times higher than the pilot-scale system (P anaerobic treatment of oxytetracycline production wastewater containing high concentrations of oxytetracycline with significantly lower generation of ARGs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. A CRISPR-Cas system enhances envelope integrity mediating antibiotic resistance and inflammasome evasion.

    Science.gov (United States)

    Sampson, Timothy R; Napier, Brooke A; Schroeder, Max R; Louwen, Rogier; Zhao, Jinshi; Chin, Chui-Yoke; Ratner, Hannah K; Llewellyn, Anna C; Jones, Crystal L; Laroui, Hamed; Merlin, Didier; Zhou, Pei; Endtz, Hubert P; Weiss, David S

    2014-07-29

    Clustered, regularly interspaced, short palindromic repeats-CRISPR associated (CRISPR-Cas) systems defend bacteria against foreign nucleic acids, such as during bacteriophage infection and transformation, processes which cause envelope stress. It is unclear if these machineries enhance membrane integrity to combat this stress. Here, we show that the Cas9-dependent CRISPR-Cas system of the intracellular bacterial pathogen Francisella novicida is involved in enhancing envelope integrity through the regulation of a bacterial lipoprotein. This action ultimately provides increased resistance to numerous membrane stressors, including antibiotics. We further find that this previously unappreciated function of Cas9 is critical during infection, as it promotes evasion of the host innate immune absent in melanoma 2/apoptosis associated speck-like protein containing a CARD (AIM2/ASC) inflammasome. Interestingly, the attenuation of the cas9 mutant is complemented only in mice lacking both the AIM2/ASC inflammasome and the bacterial lipoprotein sensor Toll-like receptor 2, but not in single knockout mice, demonstrating that Cas9 is essential for evasion of both pathways. These data represent a paradigm shift in our understanding of the function of CRISPR-Cas systems as regulators of bacterial physiology and provide a framework with which to investigate the roles of these systems in myriad bacteria, including pathogens and commensals.

  10. On the Enhanced Antibacterial Activity of Antibiotics Mixed with Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Shantrokha AN

    2009-01-01

    Full Text Available Abstract The bacterial action of gentamicin and that of a mixture of gentamicin and 15-nm colloidal-gold particles onEscherichia coliK12 was examined by the agar-well-diffusion method, enumeration of colony-forming units, and turbidimetry. Addition of gentamicin to colloidal gold changed the gold color and extinction spectrum. Within the experimental errors, there were no significant differences in antibacterial activity between pure gentamicin and its mixture with gold nanoparticles (NPs. Atomic absorption spectroscopy showed that upon application of the gentamicin-particle mixture, there were no gold NPs in the zone of bacterial-growth suppression in agar. Yet, free NPs diffused into the agar. These facts are in conflict with the earlier findings indicating an enhancement of the bacterial activity of similar gentamicin–gold nanoparticle mixtures. The possible causes for these discrepancies are discussed, and the suggestion is made that a necessary condition for enhancement of antibacterial activity is the preparation of stable conjugates of NPs coated with the antibiotic molecules.

  11. The effects of enhanced access to antiretroviral therapy: a qualitative ...

    African Journals Online (AJOL)

    The effects of enhanced access to antiretroviral therapy: a qualitative study of community perceptions in ... Twenty FGDs comprising of 190 participants and 12 KI interviews were conducted. ... All data was tape recorded with consent from

  12. [Impact of pharmaceutical interventions on antibiotic therapy of urinary tract infections in rehabilitation center].

    Science.gov (United States)

    Rochefolle, A; Maison, O; Chazaud, C; Rioufol, C; Rode, G; Luaute, J; Jacquin-Courtois, S; Guinet-Lacoste, A; Carré, E

    2017-06-01

    The aim of this study was to assess the impact of medico-pharmaceutical partnership on the quality of antibiotic treatment in urinary tract infection (UTI) within rehabilitation center. All antibiotic prescriptions were validated by the pharmacist at the start of treatment and twice a week. All patients with symptomatic urinary tract infection between January 1, 2014 to December 31, 2015 were included in this study. Addition to awareness among specifiers to promoting the appropriate use of antibiotics, the pharmacist suggested pharmaceutical interventions (PI) in order to improve the quality of antibiotic treatments. At the same time, 3 quality indicators (QI) were followed: duration, dosage, antibiotic susceptibility. The compliance rates of this 3 QI allowed to assess the quality of the antibiotic treatment in urinary tract infection. The study population included 154 patients corresponding to 252 UTI. Sixty-eight PI were made by pharmacist about urinary tract infection treatment (overdosage or under-dosing, duration unknown, inadequate route of administration). These QI achieved 96.4% compliance with duration, 98.8% compliance with dosage and 99.2% with the antibiotic susceptibility. This study allowed showing the medico-pharmaceutical impact on the quality of antibiotic treatments in UTI. The awareness among specifiers with a daily validation of prescription by the pharmacist allowed to improve urinary tract infections care in rehabilitation center. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Challenges of Empirical Antibiotic Therapy for Community-Acquired Pneumonia in Children

    Directory of Open Access Journals (Sweden)

    Charlene M.C. Rodrigues, MBChB, MRCPCH

    2017-01-01

    Conclusions: Effective and timely treatment is required for CAP and empirical antibiotics are evidence-based and appropriate in most settings. However, better diagnostics and education to target treatment may help to prevent antibiotic resistance. Ensuring the secure financing of clean food and water, sanitation, and public health infrastructure are also required to reduce the burden of disease in children in developing countries.

  14. Relationship Enhancement Therapy: A Case Study for Treating Vaginismus.

    Science.gov (United States)

    Harman, Marsha J.; And Others

    1994-01-01

    A case study of Relationship Enhancement (RE) therapy with a couple, in which the woman was identified as having vaginismus, is presented including excerpts of transcripts from the therapy sessions. RE's effectiveness at improving communication skills and providing structure in which the couple could discuss the intimate issues affecting the…

  15. Time dependent enhanced resistance against antibiotics & metal salts by planktonic & biofilm form of Acinetobacter haemolyticus MMC 8 clinical isolate

    Directory of Open Access Journals (Sweden)

    Sharvari Vijaykumar Gaidhani

    2014-01-01

    Full Text Available Background & objectives: Available literature shows paucity of reports describing antibiotic and metal resistance profile of biofilm forming clinical isolates of Acinetobacter haemolyticus. The present study was undertaken to evaluate the antibiotic and metal resistance profile of Indian clinical isolate of A. haemolyticus MMC 8 isolated from human pus sample in planktonic and biofilm form. Methods: Antibiotic susceptibility and minimum inhibitory concentration were determined employing broth and agar dilution techniques. Biofilm formation was evaluated quantitatively by microtiter plate method and variation in complex architecture was determined by scanning electron microscopy. Minimum biofilm inhibiting concentration was checked by Calgary biofilm device. Results: Planktonic A. haemolyticus MMC 8 was sensitive to 14 antibiotics, AgNO 3 and HgC1 2 resistant to streptomycin and intermediately resistant to netilmycin and kanamycin. MMC 8 exhibited temporal variation in amount and structure of biofilm. There was 32 - 4000 and 4 - 256 fold increase in antibiotic and metal salt concentration, respectively to inhibit biofilm over a period of 72 h as against susceptible planktonic counterparts. Total viable count in the range of 10 5 -10 6 cfu / ml was observed on plating minimum biofilm inhibiting concentration on Muller-Hinton Agar plate without antimicrobial agents. Biofilm forming cells were several folds more resistant to antibiotics and metal salts in comparison to planktonic cells. Presence of unaffected residual cell population indicated presence of persister cells. Interpretation & conclusions: The results indicate that biofilm formation causes enhanced resistance against antibiotics and metal salts in otherwise susceptible planktonic A. haemolyticus MMC 8.

  16. A response regulator from a soil metagenome enhances resistance to the β-lactam antibiotic carbenicillin in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Heather K Allen

    Full Text Available Functional metagenomic analysis of soil metagenomes is a method for uncovering as-yet unidentified mechanisms for antibiotic resistance. Here we report an unconventional mode by which a response regulator derived from a soil metagenome confers resistance to the β-lactam antibiotic carbenicillin in Escherichia coli. A recombinant clone (βlr16 harboring a 5,169 bp DNA insert was selected from a metagenomic library previously constructed from a remote Alaskan soil. The βlr16 clone conferred specific resistance to carbenicillin, with limited increases in resistance to other tested antibiotics, including other β-lactams (penicillins and cephalosporins, rifampin, ciprofloxacin, erythromycin, chloramphenicol, nalidixic acid, fusidic acid, and gentamicin. Resistance was more pronounced at 24°C than at 37°C. Zone-of-inhibition assays suggested that the mechanism of carbenicillin resistance was not due to antibiotic inactivation. The DNA insert did not encode any genes known to confer antibiotic resistance, but did have two putative open reading frames (ORFs that were annotated as a metallopeptidase and a two-component response regulator. Transposon mutagenesis and subcloning of the two ORFs followed by phenotypic assays showed that the response regulator gene was necessary and sufficient to confer the resistance phenotype. Quantitative reverse transcriptase PCR showed that the response regulator suppressed expression of the ompF porin gene, independently of the small RNA regulator micF, and enhanced expression of the acrD, mdtA, and mdtB efflux pump genes. This work demonstrates that antibiotic resistance can be achieved by the modulation of gene regulation by heterologous DNA. Functional analyses such as these can be important for making discoveries in antibiotic resistance gene biology and ecology.

  17. Prolonged suppressive antibiotic therapy for prosthetic joint infection in the elderly: a national multicentre cohort study.

    Science.gov (United States)

    Prendki, V; Ferry, T; Sergent, P; Oziol, E; Forestier, E; Fraisse, T; Tounes, S; Ansart, S; Gaillat, J; Bayle, S; Ruyer, O; Borlot, F; Le Falher, G; Simorre, B; Dauchy, F-A; Greffe, S; Bauer, T; Bell, E N; Martha, B; Martinot, M; Froidure, M; Buisson, M; Waldner, A; Lemaire, X; Bosseray, A; Maillet, M; Charvet, V; Barrelet, A; Wyplosz, B; Noaillon, M; Denes, E; Beretti, E; Berlioz-Thibal, M; Meyssonnier, V; Fourniols, E; Tliba, L; Eden, A; Jean, M; Arvieux, C; Guignery-Kadri, K; Ronde-Oustau, C; Hansmann, Y; Belkacem, A; Bouchand, F; Gavazzi, G; Herrmann, F; Stirnemann, J; Dinh, A

    2017-09-01

    During prosthetic joint infection (PJI), optimal surgical management with exchange of the device is sometimes impossible, especially in the elderly population. Thus, prolonged suppressive antibiotic therapy (PSAT) is the only option to prevent acute sepsis, but little is known about this strategy. We aimed to describe the characteristics, outcome and tolerance of PSAT in elderly patients with PJI. We performed a national cross-sectional cohort study of patients >75 years old and treated with PSAT for PJI. We evaluated the occurrence of events, which were defined as: (i) local or systemic progression of the infection (failure), (ii) death and (iii) discontinuation or switch of PSAT. A total of 136 patients were included, with a median age of 83 years [interquartile range (IQR) 81-88]. The predominant pathogen involved was Staphylococcus (62.1%) (Staphylococcus aureus in 41.7%). A single antimicrobial drug was prescribed in 96 cases (70.6%). There were 46 (33.8%) patients with an event: 25 (18%) with an adverse drug reaction leading to definitive discontinuation or switch of PSAT, 8 (5.9%) with progression of sepsis and 13 died (9.6%). Among patients under follow-up, the survival rate without an event at 2 years was 61% [95% confidence interval (CI): 51;74]. In the multivariate Cox analysis, patients with higher World Health Organization (WHO) score had an increased risk of an event [hazard ratio (HR) = 1.5, p = 0.014], whereas patients treated with beta-lactams are associated with less risk of events occurring (HR = 0.5, p = 0.048). In our cohort, PSAT could be an effective and safe option for PJI in the elderly.

  18. Duration of oral tetracycline-class antibiotic therapy and use of topical retinoids for the treatment of acne among general practitioners (GP): A retrospective cohort study.

    Science.gov (United States)

    Barbieri, John S; Hoffstad, Ole; Margolis, David J

    2016-12-01

    Guidelines recommend limiting the duration of oral antibiotic therapy in acne to 3 to 6 months and prescribing concomitant topical retinoids for all patients. We sought to evaluate the duration of therapy with oral tetracyclines and the use of topical retinoids among patients with acne treated primarily by general practitioners in the United Kingdom. We conducted a retrospective cohort study using the Health Improvement Network database. The mean duration of therapy was 175.1 days. Of antibiotic courses, 62% were not associated with a topical retinoid; 29% exceeded 6 months in duration. If all regions were to achieve uses similar to the region with the shortest mean duration of therapy, approximately 3.3 million antibiotic days per year could be avoided in the United Kingdom. The Health Improvement Network does not include information on acne severity and clinical outcomes. Prescribing behavior for oral antibiotics in the treatment of acne among general practitioners is not aligned with current guideline recommendations. Increasing the use of topical retinoids and considering alternative agents to oral antibiotics when appropriate represent opportunities to reduce antibiotic exposure and associated complications such as antibiotic resistance and to improve outcomes in patients treated for acne. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  19. Does D-cycloserine enhance exposure therapy for anxiety disorders in humans? A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Helga Rodrigues

    Full Text Available The treatment of anxiety is on the edge of a new era of combinations of pharmacologic and psychosocial interventions. A new wave of translational research has focused on the use of pharmacological agents as psychotherapy adjuvants using neurobiological insights into the mechanism of the action of certain psychological treatments such as exposure therapy. Recently, d-cycloserine (DCS an antibiotic used to treat tuberculosis has been applied to enhance exposure-based treatment for anxiety and has proved to be a promising, but as yet unproven intervention. The present study aimed to evaluate the efficacy of DCS in the enhancement of exposure therapy in anxiety disorders. A systematic review/meta-analysis was conducted. Electronic searches were conducted in the databases ISI-Web of Science, Pubmed and PsycINFO. We included only randomized, double-blind, placebo-controlled trials with humans, focusing on the role of DCS in enhancing the action of exposure therapy for anxiety disorders. We identified 328 references, 13 studies were included in our final sample: 4 on obsessive-compulsive disorder, 2 on panic disorder, 2 on social anxiety disorder, 2 on posttraumatic stress disorder, one on acrophobia, and 2 on snake phobia. The results of the present meta-analysis show that DCS enhances exposure therapy in the treatment of anxiety disorders (Cohen d =  -0.34; CI: -0.54 to -0.14, facilitating the specific process of extinction of fear. DCS seems to be effective when administered at a time close to the exposure therapy, at low doses and a limited number of times. DCS emerges as a potential new therapeutic approach for patients with refractory anxiety disorders that are unresponsive to the conventional treatments available. When administered correctly, DCS is a promising strategy for augmentation of CBT and could reduce health care costs, drop-out rates and bring faster relief to patients.

  20. [Systemic therapy with anti-infective agents. Principles of rational use of systemic antibiotics in dermatology].

    Science.gov (United States)

    Sunderkötter, C; Brehler, R; Becker, K

    2014-02-01

    Antibiotics are frequently prescribed and extremely valuable drugs, because they are curative. However, their often incorrect use is the main reason for the increase of multiresistant pathogens. Inappropriate prescription of broad spectrum antibiotics for skin and soft tissue infections favors the selection and spread of multiresistant bacteria not only in the skin, but also in remote visceral organs (e.g. in the intestines), due to their systemic distribution and effects in the body (so-called collateral damage). For this reason basic knowledge and special prudence when using antibiotics are just as desirable as an awareness of responsibility for the public welfare. This article intends to convey basic knowledge on the indications and selection of suitable antibiotics as well as on the development of bacterial resistance and it gives recommendations for allergological procedures when patients report alleged drug reactions to antibiotics. Systemic antibiotics for soft tissue infections are indicated when the infection spreads within the tissue so that it is no longer accessible for local antiseptics. In addition to the clinical symptoms, important parameters are high blood sedimentation rates (BSR) and high levels of C-reactive protein (CRP), leukocytosis with neutrophilia and fever (not always present in elderly or immunosuppressed patients). Certain constellations, such as the presence of severe underlying diseases, perfusion disorders or a particular localization (e.g. infection of the face) may necessitate early or parenteral administration. There is no need for systemic administration of antibiotics for uncomplicated wounds without soft tissue infections. Due to their curative effects, the decisive criterion for the use of antibiotics is their sufficient antimicrobial efficacy at the site of infection. An inappropriate administration increases both the selection pressure and costs of treatment and can have fatal consequences in serious situations. In

  1. A Spiral in the Heart: Mitral Valve Endocarditis with Unusual Vegetation Shape Potentially Affecting Effectiveness of Antibiotic Therapy

    Directory of Open Access Journals (Sweden)

    Veronica Fibbi

    2015-01-01

    Full Text Available We report an unusual case of infective endocarditis (IE in an 88-year-old woman, occurring on a prolapsing mitral valve and characterized by an atypical vegetation shape resembling a spiral-like appearance. After the patient refused surgical correction, persistent IE despite prolonged antibiotic therapy was observed, resulting in an ischemic stroke probably secondary to septic embolus. The importance of vegetation shape in the management of patients with IE was classically related to the increased risk of embolization associated with pedunculated, irregular, and multilobed masses. We hypothesize that the unusual spiral-like vegetation shape in our patient may have favored IE persistence by two mechanisms, namely, a decrease of the exposed vegetation surface with creation of an internal core where the penetration of antimicrobial agents was obstacled and the creation of blood turbulence within the vegetation preventing a prolonged contact with circulating antibiotics. These considerations suggest that vegetation shape might be considered of importance in patients with IE not only because of its classical association with embolization risk, but also because of its potential effect on the efficacy of antibiotic therapy.

  2. X-ray therapy with enhanced effectiveness

    International Nuclear Information System (INIS)

    Silberbauer, F.

    1989-01-01

    The introduction of iodine atoms into a malignant tumor by intravenous injection of a contrast medium that is excreted by way of the kidneys selectively increases the tumor's capacity for the absorption of X-ray photons. This effect is exploited in CCT, but in high-voltage X-ray therapy it leads to an elevated focal dose while the incident dose remains the same. (orig.) [de

  3. Data on gut metagenomes of the patients with Helicobacter pylori infection before and after the antibiotic therapy

    Directory of Open Access Journals (Sweden)

    Oksana E. Glushchenko

    2017-04-01

    Full Text Available Antibiotic therapy can lead to the disruption of gut microbiota community with possible negative outcomes for human health. One of the diseases for which the treatment scheme commonly included antibiotic intake is Helicobacter pylori infection. The changes in taxonomic and functional composition of microbiota in patients can be assessed using “shotgun” metagenomic sequencing. Ten stool samples were collected from 4 patients with Helicobacter pylori infection before and directly after the H. pylori eradication course. Additionally, for two of the subjects, the samples were collected 1 month after the end of the treatment. The samples were subject to “shotgun” (whole-genome metagenomic sequencing using Illumina HiSeq platform. The reads are deposited in the ENA (project ID: PRJEB18265.

  4. Antibiotic combination therapy can select for broad-spectrum multidrug resistance in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Paulander, Wilhelm; Marvig, Rasmus L.

    2016-01-01

    with the resistance evolved after single-drug exposure. Combination therapy selected for mutants that displayed broad-spectrum resistance, and a major resistance mechanism was mutational inactivation of the repressor gene mexR that regulates the multidrug efflux operon mexAB–oprM. Deregulation of this operon led...... to a broad-spectrum resistance phenotype that decreased susceptibility to the combination of drugs applied during selection as well as to unrelated antibiotic classes. Mutants isolated after single-drug exposure displayed narrow-spectrum resistance and carried mutations in the MexCD–OprJ efflux pump...... regulator gene nfxB conferring ciprofloxacin resistance, or in the gene encoding the non-essential penicillin-binding protein DacB conferring ceftazidime resistance. Reconstruction of resistance mutations by allelic replacement and in vitro fitness assays revealed that in contrast to single antibiotic use...

  5. Antibiotic prescribing for endodontic therapies: a comparative survey between general dental practitioners and final year Bachelor of Dental Surgery students in Cardiff, UK.

    Science.gov (United States)

    Al Masan, A A; Dummer, P M H; Farnell, D J J; Vianna, M E

    2018-07-01

    To evaluate the views of final year dental surgery students (BDS; G1) at Cardiff University and general dental practitioners (GDPs; G2) within the geographic area of Cardiff, Wales, on antibiotic prescribing for endodontic conditions, and investigate the potential differences between the two groups. A cross-sectional online questionnaire-based survey of 12 qualitative and quantitative questions was distributed to 76 final year BDS Cardiff University students and 55 dental practices within Cardiff, UK. Six questions recorded general information, and the remaining questions included a series of hypothetical clinical scenarios, where the participants were asked to state whether they would or would not prescribe antibiotics. The data were analysed using spss version 23 to produce descriptive statistics, contingency tables and to run chi-square (χ²) tests, Fisher's exact tests and relative risk calculations. The response rate was 60% (n = 79). All G1 participants were aware of the consequences of antibiotic overuse. Approximately 60% of responders were aware of guidelines for antibiotic use in endodontic therapies, and 83% would only use antibiotics for a limited selection of patients (e.g. patients with systemic complications). G1 responses to clinical scenarios indicated overall that they were comparable to the ideal answers except for acute apical abscess (64% believed that antibiotics were indicated). The majority of G2 were aware of the consequences of antibiotic overuse. Only 28% of G2 were aware of guidelines for antibiotic use in endodontic therapies. Overall responses revealed that antibiotics would be prescribed for: systemic complications (78%), acute apical abscess (72%) and symptomatic apical periodontitis (28%). The clinical scenarios revealed G1 were more likely to prescribe antibiotics compared to G2 for cases of necrotic pulp with symptomatic apical periodontitis without systemic complications (incorrect answer) and less likely to other clinical

  6. Combination therapy of menstrual derived mesenchymal stem cells and antibiotics ameliorates survival in sepsis.

    Science.gov (United States)

    Alcayaga-Miranda, Francisca; Cuenca, Jimena; Martin, Aldo; Contreras, Luis; Figueroa, Fernando E; Khoury, Maroun

    2015-10-16

    Sepsis is a clinical syndrome associated with a severe systemic inflammation induced by infection. Although different anti-microbial drugs have been used as treatments, morbidity and mortality rates remain high. Mesenchymal stem cells (MSCs) derived from the bone marrow have demonstrated a partial protective effect in sepsis. Menstrual derived MSCs (MenSCs) emerge as an attractive candidate because they present important advantages over other sources, including improved proliferation rates and paracrine response under specific stress conditions. Here, we evaluate their therapeutic effect in a polymicrobial severe sepsis model. The antimicrobial activity of MenSCs was determined in vitro through direct and indirect bacterial growth assays and the measurement of the expression levels of different antimicrobial peptides (AMPs) by quantitative reverse transcription-polymerase chain reaction. The therapeutic effect of MenSCs was determined in the cecal ligation and puncture (CLP) mouse model. Mice were then treated with antibiotics (AB) or MenSCs alone or in combination. The survival rates and histological and biochemical parameters were evaluated, and the systemic levels of pro- and anti-inflammatory cytokines as well as the response of specific lymphocyte subsets were determined by flow cytometry. MenSCs exerted an important antimicrobial effect in vitro, mediated by a higher expression of the AMP-hepcidin. In the CLP mouse model, MenSCs in synergy with AB (a) improved the survival rate (95 %) in comparison with saline (6 %), AB (73 %), and MenSCs alone (48 %) groups; (b) enhanced bacterial clearance in the peritoneal fluids and blood; (c) reduced organ injuries evaluated by lower concentrations of the liver enzymes alanine aminotransferase and aspartate aminotransferase; and (d) modulated the inflammatory response through reduction of pro- and anti-inflammatory cytokines without significant loss of T and B lymphocytes. We conclude that MenSCs in combination with AB

  7. Role of outpatient parenteral antibiotic therapy in the treatment of community acquired skin and soft tissue infections in Singapore.

    Science.gov (United States)

    Chan, Monica; Ooi, Chee Kheong; Wong, Joshua; Zhong, Lihua; Lye, David

    2017-07-06

    Treatment of community acquired skin and soft tissue infections (SSTIs) is a common indication for outpatient parenteral antibiotic therapy (OPAT) in USA, UK and Australasia, however data from Asia are lacking. OPAT is well established within the Singapore healthcare since 2002, however, systematic use of OPAT for the treatment of SSTIs remains infrequent. In this report, we describe the treatment and outcome of patients with SSTIs referred directly from Emergency Department (ED) to OPAT for continuation of intravenous (IV) antibiotics in Singapore, thus avoiding potential hospital admission. This is a single center university hospital retrospective study of patients with SSTIs presenting to ED who were assessed to require IV antibiotics and accepted to the OPAT clinic for continuation of IV treatment. Exclusion criteria were: haemodynamic instability, uncontrolled or serious underlying co-morbidities, necessity for inpatient surgical drainage, facial cellulitis and cephalosporin allergy. Patients returned daily to the hospital’s OPAT clinic for administration of IV antibiotics and review, then switched to oral antibiotics on improvement. From 7 February 2012 to 31 July 2015, 120 patients with SSTIs were treated in OPAT. Median age was 56 years and 63% were male. Lower limbs were affected in 91%. Diabetes was present in 20%. Sixty-seven (56%) had been treated with oral antibiotics for a median duration of 3 days prior to OPAT treatment. Common symptoms were erythema (100%), swelling (96%), pain (88%) and fever (55%). Antibiotics administered were IV cefazolin with oral probenecid (71%) or IV ceftriaxone (29%) for median 3 days then oral cloxacillin (85%) for median 7 days. Clinical improvement occurred in 90%. Twelve patients (10%) were hospitalized for worsening cellulitis, with 4 patients requiring surgical drainage of abscess. Microbiological cultures from 2 patients with drained abscess grew methicillin sensitive Staphylococcus aureus (MSSA) and Klebsiella

  8. The Loss and Recovery of Erotic Intimacy in Primary Relationships: Narrative Therapy and Relationship Enhancement Therapy.

    Science.gov (United States)

    Snyder, Maryhelen

    2000-01-01

    Therapists working with intimate relationships are frequently confronted with issues regarding the loss of erotic intimacy, differences in levels of sexual desire, and the existence of intimate relationships outside the primary. Proposes that an approach derived from an integration of narrative therapy and relationship enhancement therapy can be…

  9. Limits to human enhancement: nature, disease, therapy or betterment?

    Science.gov (United States)

    Hofmann, Bjørn

    2017-10-10

    New technologies facilitate the enhancement of a wide range of human dispositions, capacities, or abilities. While it is argued that we need to set limits to human enhancement, it is unclear where we should find resources to set such limits. Traditional routes for setting limits, such as referring to nature, the therapy-enhancement distinction, and the health-disease distinction, turn out to have some shortcomings. However, upon closer scrutiny the concept of enhancement is based on vague conceptions of what is to be enhanced. Explaining why it is better to become older, stronger, and more intelligent presupposes a clear conception of goodness, which is seldom provided. In particular, the qualitative better is frequently confused with the quantitative more. We may therefore not need "external" measures for setting its limits - they are available in the concept of enhancement itself. While there may be shortcomings in traditional sources of limit setting to human enhancement, such as nature, therapy, and disease, such approaches may not be necessary. The specification-of-betterment problem inherent in the conception of human enhancement itself provides means to restrict its unwarranted proliferation. We only need to demand clear, sustainable, obtainable goals for enhancement that are based on evidence, and not on lofty speculations, hypes, analogies, or weak associations. Human enhancements that specify what will become better, and provide adequate evidence, are good and should be pursued. Others should not be accepted.

  10. Febrile neutropenia in paediatric peripheral blood stem cell transplantation, in vitro sensitivity data and clinical response to empirical antibiotic therapy

    International Nuclear Information System (INIS)

    Ansari, S.H.; Nasim, S.; Ahmed, A.; Irfan, M.; Ishaque, A.; Farzana, T.; Panjwani, V.K.; Taj, M.; Shamsi, T.S.

    2006-01-01

    To find the in-vitro sensitivity data and clinical response in order to determine the changes required in empiric antibiotic therapy for management of febrile neutropenia in paediatric patients undergoing peripheral blood stem cell transplantation. All patients were treated according to institutional protocol for febrile neutropenia. Empirical antibiotics include Ceftriaxone and Amikacin. In non-responders, changes made included Imipenem and Amikacin, Piperacillin Tazobactum/Tiecoplanin or Vancomycin/Cloxacilin/Ceftazidime. In non-responders, amphotaracin was added until recovery. Out of 52 patients, 5 did not develop any fever; in the remaining 47 patients there were 57 episodes of febrile neutropenia. The mean days of febrile episodes were 4.71 (range 3-8). Fever of unknown origin (FUO) occurred in 31 (54.3%) episodes. Microbiologically documented infection (MDI) occurred in 17 (29.8%) episodes of fever. Clinically documented infection (CDI) occurred in 9 (15.7%) episodes. Gram-negative organisms were isolated in 10 while gram-positive organisms in 7. Klebseilla, S. aureus were the most common isolates. Empirical therapy was effective in 12 of the 33 (36%) episodes. Out of 28, 26 (92%) responded to Imipenem/Amikacin as second line therapy while those who received any other second line combination, only 11 out of 22 (50%) showed response. Systemic Amphotericin was used in 4 patients, 2 responded. Infection related mortality rate was 4%. (author)

  11. Duration of oral antibiotic therapy for the treatment of adult acne: a retrospective analysis investigating adherence to guideline recommendations and opportunities for cost-savings.

    Science.gov (United States)

    Straight, Chelsey E; Lee, Young H; Liu, Guodong; Kirby, Joslyn S

    2015-05-01

    The duration of oral antibiotic acne therapy for adolescents compared with guidelines was recently investigated; however it was uncertain if duration of antibiotics for adult acne therapy differed. This study aimed to evaluate duration of oral antibiotics for adult acne compared with guidelines and determine possible cost-savings. This was a retrospective cohort study of MarketScan Commercial Claims and Encounters database that incorporated claims data to determine duration and costs of antibiotic treatment among adults ages 21 years and older. Of 17,448 courses, 84.5% (14,737) aligned with duration guidelines, although 12,040 (69.0%) courses did not include concomitant topical retinoid therapy. Mean savings of $592.26 per person could result if prolonged courses met guidelines. Mean (median) costs of generic and branded formulations for the most frequent course duration (90-179 days) were $103.77 ($54.27) and $1421.61 ($1462.25), respectively. Actual patient prescription adherence is uncertain and database lacks information regarding acne severity, patient physical characteristics, and clinical outcomes. The majority of oral antibiotic course durations follow guidelines, although topical retinoids are underused. Costs of antibiotic therapy were lower for shorter courses and those using generic medications; the cost-effectiveness of these modifications has not been investigated. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. Reducing Vibrio load in Artemia nauplii using antimicrobial photodynamic therapy: a promising strategy to reduce antibiotic application in shrimp larviculture

    Science.gov (United States)

    Asok, Aparna; Arshad, Esha; Jasmin, C.; Somnath Pai, S.; Bright Singh, I. S.; Mohandas, A.; Anas, Abdulaziz

    2012-01-01

    Summary We propose antimicrobial photodynamic therapy (aPDT) as an alternative strategy to reduce the use of antibiotics in shrimp larviculture systems. The growth of a multiple antibiotic resistant Vibrio harveyi strain was effectively controlled by treating the cells with Rose Bengal and photosensitizing for 30 min using a halogen lamp. This resulted in the death of > 50% of the cells within the first 10 min of exposure and the 50% reduction in the cell wall integrity after 30 min could be attributed to the destruction of outer membrane protein of V. harveyi by reactive oxygen intermediates produced during the photosensitization. Further, mesocosm experiments with V. harveyi and Artemia nauplii demonstrated that in 30 min, the aPDT could kill 78.9% and 91.2% of heterotrophic bacterial and Vibrio population respectively. In conclusion, the study demonstrated that aPDT with its rapid action and as yet unreported resistance development possibilities could be a propitious strategy to reduce the use of antibiotics in shrimp larviculture systems and thereby, avoid their hazardous effects on human health and the ecosystem at large. PMID:21951316

  13. Tamsulosin Monotherapy versus Combination Therapy with Antibiotics or Anti-Inflammatory Agents in the Treatment of Chronic Pelvic Pain Syndrome

    Directory of Open Access Journals (Sweden)

    Tae Hyo Kim

    2011-06-01

    Full Text Available Purpose Chronic pelvic pain syndrome (CPPS is treated by use of various protocols. We compared tamsulosin monotherapy with tamsulosin in combination with antibiotics or anti-inflammatory agents and evaluated the efficacy of these treatments in patients with CPPS. Methods Patients (n=107 who were younger than 55 years and diagnosed with CPPS were randomly assigned to treatment with tamsulosin at 0.2 mg (group A, tamsulosin at 0.2 mg plus anti-inflammatory drugs (group B or tamsulosin at 0.2 mg plus antibiotics (group C daily. We applied the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI and the International Prostate Symptom Score (IPSS to evaluate 100 patients who were treated for 12 weeks (7 withdrew. Scores of the three groups were compared by analysis of variance and we also evaluated subscores, which included pain, voiding and quality of life (QoL. Results All three groups showed statistically significant decreases in NIH-CPSI score, IPSS and subscore scores (P<0.05. There were no statistically significant differences between the groups except for the QoL domain of the IPSS (group A vs. C; P<0.01. Conclusions Tamsulosin monotherapy for 12 weeks was effective for treating patients with CPPS, compared with combination therapy with antibiotics or anti-inflammatory drugs.

  14. A procalcitonin-based algorithm to guide antibiotic therapy in secondary peritonitis following emergency surgery: a prospective study with propensity score matching analysis.

    Science.gov (United States)

    Huang, Ting-Shuo; Huang, Shie-Shian; Shyu, Yu-Chiau; Lee, Chun-Hui; Jwo, Shyh-Chuan; Chen, Pei-Jer; Chen, Huang-Yang

    2014-01-01

    Procalcitonin (PCT)-based algorithms have been used to guide antibiotic therapy in several clinical settings. However, evidence supporting PCT-based algorithms for secondary peritonitis after emergency surgery is scanty. In this study, we aimed to investigate whether a PCT-based algorithm could safely reduce antibiotic exposure in this population. From April 2012 to March 2013, patients that had secondary peritonitis diagnosed at the emergency department and underwent emergency surgery were screened for eligibility. PCT levels were obtained pre-operatively, on post-operative days 1, 3, 5, and 7, and on subsequent days if needed. Antibiotics were discontinued if PCT was Advanced age, coexisting pulmonary diseases, and higher severity of illness were significantly associated with longer durations of antibiotic use. The PCT-based algorithm safely reduces antibiotic exposure in this study. Further randomized trials are needed to confirm our findings and incorporate cost-effectiveness analysis. Australian New Zealand Clinical Trials Registry ACTRN12612000601831.

  15. Organic acids enhance bioavailability of tetracycline in water to Escherichia coli for uptake and expression of antibiotic resistance.

    Science.gov (United States)

    Zhang, Yingjie; Boyd, Stephen A; Teppen, Brian J; Tiedje, James M; Li, Hui

    2014-11-15

    Tetracyclines are a large class of antimicrobials used most extensively in livestock feeding operations. A large portion of tetracyclines administered to livestock is excreted in manure and urine which is collected in waste lagoons. Subsequent land application of these wastes introduces tetracyclines into the soil environment, where they could exert selective pressure for the development of antibiotic resistance genes in bacteria. Tetracyclines form metal-complexes in natural waters, which could reduce their bioavailability for bacterial uptake. We hypothesized that many naturally-occurring organic acids could effectively compete with tetracyclines as ligands for metal cations, hence altering the bioavailability of tetracyclines to bacteria in a manner that could enhance the selective pressure. In this study, we investigated the influence of acetic acid, succinic acid, malonic acid, oxalic acid and citric acid on tetracycline uptake from water by Escherichia coli bioreporter construct containing a tetracycline resistance gene which induces the emission of green fluorescence when activated. The presence of the added organic acid ligands altered tetracycline speciation in a manner that enhanced tetracycline uptake by E. coli. Increased bacterial uptake of tetracycline and concomitant enhanced antibiotic resistance response were quantified, and shown to be positively related to the degree of organic acid ligand complexation of metal cations in the order of citric acid > oxalic acid > malonic acid > succinic acid > acetic acid. The magnitude of the bioresponse increased with increasing aqueous organic acid concentration. Apparent positive relation between intracellular tetracycline concentration and zwitterionic tetracycline species in aqueous solution indicates that (net) neutral tetracycline is the species which most readily enters E. coli cells. Understanding how naturally-occurring organic acid ligands affect tetracycline speciation in solution, and how speciation

  16. Antibiotic therapy as an adjunct to scaling and root planing in smokers: a systematic review and meta-analysis.

    Science.gov (United States)

    Assem, Naida Zanini; Alves, Márcio Luiz Ferro; Lopes, Alessandra Barreto; Gualberto, Erivan Clementino; Garcia, Valdir Gouveia; Theodoro, Letícia Helena

    2017-07-03

    The aim of this study was to perform a systematic review and meta-analysis to examine the effect of systemic antibiotics in the periodontal treatment of smokers. The selection criteria were as follows: controlled randomized clinical trials; studies published in English; studies with smoker patients diagnosed with chronic periodontitis; patients without systemic diseases; studies that used systemic antibiotic therapy associated with periodontal treatment; studies that presented results for the test and control groups and assessments of clinical periodontal parameters, such as probing depth (PD), bleeding on probing (BOP), and clinical attachment level (CAL). The differences in average weights were calculated with a confidence interval (CI) of 95% for PD reduction, CAL gain and BOP. The means of the periodontal clinical parameters were compared between the baseline and post-treatment periods between the test groups and the control groups. The heterogeneity was assessed using the Cochran Q test (Q (df = 3), α = 5%). A total of 67 articles were found, and after the selection process, three randomized controlled trials were included in the meta-analysis. The results indicate that SRP associated with systemic antibiotics promoted additional benefits when compared to SRP alone, with a greater reduction of PD (p = 0.0359, CI = -0.42, -0.01) and a gain of CAL (p = 0.0161, CI = -0.39, -0.04). There was a modest PD reduction (PD, DM -0.21) and a modest CAL gain (CAL, DM -0.22). The results of our meta-analysis reveal the clinical benefits of systemic antibiotics as an adjunct to the non-surgical periodontal treatment of smokers. These clinical improvements, although statistically significant, appeared to be of little clinical relevance.

  17. Antibiotic therapy as an adjunct to scaling and root planing in smokers: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Naida Zanini ASSEM

    2017-07-01

    Full Text Available Abstract The aim of this study was to perform a systematic review and meta-analysis to examine the effect of systemic antibiotics in the periodontal treatment of smokers. The selection criteria were as follows: controlled randomized clinical trials; studies published in English; studies with smoker patients diagnosed with chronic periodontitis; patients without systemic diseases; studies that used systemic antibiotic therapy associated with periodontal treatment; studies that presented results for the test and control groups and assessments of clinical periodontal parameters, such as probing depth (PD, bleeding on probing (BOP, and clinical attachment level (CAL. The differences in average weights were calculated with a confidence interval (CI of 95% for PD reduction, CAL gain and BOP. The means of the periodontal clinical parameters were compared between the baseline and post-treatment periods between the test groups and the control groups. The heterogeneity was assessed using the Cochran Q test (Q (df = 3, α = 5%. A total of 67 articles were found, and after the selection process, three randomized controlled trials were included in the meta-analysis. The results indicate that SRP associated with systemic antibiotics promoted additional benefits when compared to SRP alone, with a greater reduction of PD (p = 0.0359, CI = -0.42, -0.01 and a gain of CAL (p = 0.0161, CI = -0.39, -0.04. There was a modest PD reduction (PD, DM -0.21 and a modest CAL gain (CAL, DM -0.22. The results of our meta-analysis reveal the clinical benefits of systemic antibiotics as an adjunct to the non-surgical periodontal treatment of smokers. These clinical improvements, although statistically significant, appeared to be of little clinical relevance.

  18. 5-aminolevulinic acid-mediated photodynamic therapy and its strain-dependent combined effect with antibiotics on Staphylococcus aureus biofilm.

    Directory of Open Access Journals (Sweden)

    Qing-Zhao Zhang

    Full Text Available Staphylococcus aureus (S. aureus is hard to be eradicated, not only due to the emergence of antibiotic resistant strains but also because of its ability to form biofilm. Antibiotics are the major approach to treating biofilm infections, but their effects are unsatisfactory. One of the potential alternative treatments for controlling biofilm infections is photodynamic therapy (PDT, which requires the administration of photosensitizer, followed by light activation. 5-aminolevulinic acid (ALA, a natural photosensitizer prodrug, presents favorable characteristics, such as easy penetration and rapid clearance. These advantages enable ALA-based PDT (ALA-PDT to be well-tolerated by patients and it can be repeatedly applied without cumulative toxicity or serious side effects. ALA-PDT has been proven to be an effective treatment for multidrug resistant pathogens; however, the study of its effect on S. aureus biofilm is limited. Here, we established our PDT system based on the utilization of ALA and a light-emitting diode, and we tested the effect of ALA-PDT on S. aureus biofilm as well as the combined effect of ALA-PDT and antibiotics on S. aureus biofilm. Our results showed that ALA-PDT has a strong antibacterial effect on S. aureus biofilm, which was confirmed by the confocal laser scanning microscope. We also found that lethal photosensitization occurred predominantly in the upper layer of the biofilm, while the residual live bacteria were located in the lower layer of the biofilm. In addition, the improved bactericidal effect was observed in the combined treatment group but in a strain-dependent manner. Our results suggest that ALA-PDT is a potential alternative approach for future clinical use to treat S. aureus biofilm-associated infections, and some patients may benefit from the combined treatment of ALA-PDT and antibiotics, but drug sensitivity testing should be performed in advance.

  19. Effect of a Standardized Protocol of Antibiotic Therapy on Surgical Site Infection after Laparoscopic Surgery for Complicated Appendicitis.

    Science.gov (United States)

    Park, Hyoung-Chul; Kim, Min Jeong; Lee, Bong Hwa

    Although it is accepted that complicated appendicitis requires antibiotic therapy to prevent post-operative surgical infections, consensus protocols on the duration and regimens of treatment are not well established. This study aimed to compare the outcome of post-operative infectious complications in patients receiving old non-standardized and new standard antibiotic protocols, involving either 5 or 10 days of treatment, respectively. We enrolled 1,343 patients who underwent laparoscopic surgery for complicated appendicitis between January 2009 and December 2014. At the beginning of the new protocol, the patients were divided into two groups; 10 days of various antibiotic regimens (between January 2009 and June 2012, called the non-standardized protocol; n = 730) and five days of cefuroxime and metronidazole regimen (between July 2012 and December 2014; standardized protocol; n = 613). We compared the clinical outcomes, including surgical site infection (SSI) (superficial and deep organ/space infections) in the two groups. The standardized protocol group had a slightly shorter operative time (67 vs. 69 min), a shorter hospital stay (5 vs. 5.4 d), and lower medical cost (US$1,564 vs. US$1,654). Otherwise, there was no difference between the groups. No differences were found in the non-standardized and standard protocol groups with regard to the rate of superficial infection (10.3% vs. 12.7%; p = 0.488) or deep organ/space infection (2.3% vs. 2.1%; p = 0.797). In patients undergoing laparoscopic surgery for complicated appendicitis, five days of cefuroxime and metronidazole did not lead to more SSIs, and it decreased the medical costs compared with non-standardized antibiotic regimens.

  20. Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies.

    Science.gov (United States)

    Tepekule, Burcu; Uecker, Hildegard; Derungs, Isabel; Frenoy, Antoine; Bonhoeffer, Sebastian

    2017-09-01

    Multiple treatment strategies are available for empiric antibiotic therapy in hospitals, but neither clinical studies nor theoretical investigations have yielded a clear picture when which strategy is optimal and why. Extending earlier work of others and us, we present a mathematical model capturing treatment strategies using two drugs, i.e the multi-drug therapies referred to as cycling, mixing, and combination therapy, as well as monotherapy with either drug. We randomly sample a large parameter space to determine the conditions determining success or failure of these strategies. We find that combination therapy tends to outperform the other treatment strategies. By using linear discriminant analysis and particle swarm optimization, we find that the most important parameters determining success or failure of combination therapy relative to the other treatment strategies are the de novo rate of emergence of double resistance in patients infected with sensitive bacteria and the fitness costs associated with double resistance. The rate at which double resistance is imported into the hospital via patients admitted from the outside community has little influence, as all treatment strategies are affected equally. The parameter sets for which combination therapy fails tend to fall into areas with low biological plausibility as they are characterised by very high rates of de novo emergence of resistance to both drugs compared to a single drug, and the cost of double resistance is considerably smaller than the sum of the costs of single resistance.

  1. Developments and strategies for inhaled antibiotic drugs in tuberculosis therapy : A critical evaluation

    NARCIS (Netherlands)

    Hoppentocht, M; Hagedoorn, P; Frijlink, H W; de Boer, A H

    2014-01-01

    Inhaled antibiotics have been a valuable tool in treating pulmonary infections in cystic fibrosis patients for decades, and the pulmonary route is now becoming increasingly interesting for other infectious diseases like tuberculosis too. Especially with multidrug and extensively drug-resistant

  2. Differential effects of antibiotic therapy on the structure and function of human gut microbiota.

    Directory of Open Access Journals (Sweden)

    Ana Elena Pérez-Cobas

    Full Text Available The human intestinal microbiota performs many essential functions for the host. Antimicrobial agents, such as antibiotics (AB, are also known to disturb microbial community equilibrium, thereby having an impact on human physiology. While an increasing number of studies investigate the effects of AB usage on changes in human gut microbiota biodiversity, its functional effects are still poorly understood. We performed a follow-up study to explore the effect of ABs with different modes of action on human gut microbiota composition and function. Four individuals were treated with different antibiotics and samples were taken before, during and after the AB course for all of them. Changes in the total and in the active (growing microbiota as well as the functional changes were addressed by 16S rRNA gene and metagenomic 454-based pyrosequencing approaches. We have found that the class of antibiotic, particularly its antimicrobial effect and mode of action, played an important role in modulating the gut microbiota composition and function. Furthermore, analysis of the resistome suggested that oscillatory dynamics are not only due to antibiotic-target resistance, but also to fluctuations in the surviving bacterial community. Our results indicated that the effect of AB on the human gut microbiota relates to the interaction of several factors, principally the properties of the antimicrobial agent, and the structure, functions and resistance genes of the microbial community.

  3. No. 233-Antibiotic Therapy in Preterm Premature Rupture of the Membranes.

    Science.gov (United States)

    Yudin, Mark H; van Schalkwyk, Julie; Van Eyk, Nancy

    2017-09-01

    To review the evidence and provide recommendations on the use of antibiotics in preterm premature rupture of the membranes (PPROM). Outcomes evaluated include the effect of antibiotic treatment on maternal infection, chorioamnionitis, and neonatal morbidity and mortality. Published literature was retrieved through searches of Medline, EMBASE, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary and key words (PPROM, infection, and antibiotics). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and new material incorporated in the guideline to July 2008. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Guideline implementation should assist the practitioner in developing an approach to the use of antibiotics in women with PPROM. Patients will benefit from appropriate management of this condition. This guideline has been reviewed and approved by the Infectious Diseases Committee and the Maternal Fetal Medicine Committee of the SOGC, and approved by the Executive and Council of the SOGC. The Society of Obstetricians and Gynaecologists of Canada. Copyright © 2017. Published by Elsevier Inc.

  4. The sensitivities to first-line antibiotic therapy of the common urinary ...

    African Journals Online (AJOL)

    Background: Urinary tract infections (UTIs) are among the most common human infections. Many urinary tract bacteria are capable of expressing drug resistance. Resistant bacteria may be present from the commencement of the infection or may develop during treatment. This study focused on the problem of antibiotic ...

  5. Towards a compatible probiotic-antibiotic combination therapy: assessment of antimicrobial resistance in the Japanese probiotics.

    Science.gov (United States)

    Hammad, A M; Shimamoto, T

    2010-10-01

    To determine the antimicrobial resistance of the Japanese probiotics available in the market without a pharmacist's supervision. A total of 43 isolates were obtained from 40 samples of probiotics (30 dairy products and 10 products in tablet form). Isolates were identified using 16S rRNA gene sequencing and tested for their susceptibility to 14 antimicrobials. They were screened using PCR for some antibiotic resistance genes. Inactivation of cefepime, clarithromycin and vancomycin by different inocula of 11 strains was evaluated using the antibiotic inactivation bioassay. None of the dairy probiotics showed a level of constitutive resistance or carried inducible resistance genes, making them suitable to be administrated with macrolides. Among the probiotics in tablet form only Enterococcus faecium strains carrying the msrC gene showed an MIC(90) of 4 μg ml(-1). Extended-spectrum β-lactams, tetracyclines and ampicillin exhibited powerful germicidal activity against the vast majority of the probiotic strains. There is a limited choice of the Japanese probiotics that can be administered with clinically used antibiotics. Japanese probiotics are widely distributed all over the world. Through the findings of our study, we have attempted to provide guidance for clinicians interested in using the Japanese probiotics in combination with antibiotics. © 2010 The Authors. Journal compilation © 2010 The Society for Applied Microbiology.

  6. Berberine Enhances the Antibacterial Activity of Selected Antibiotics against Coagulase-Negative Staphylococcus Strains in Vitro

    Directory of Open Access Journals (Sweden)

    Robert D. Wojtyczka

    2014-05-01

    Full Text Available Synergistic interactions between commonly used antibiotics and natural bioactive compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has proven efficacy against a broad spectrum of microorganisms. The aim of the presented work was to assess the antibacterial activity of berberine chloride in light of the effect exerted by common antibiotics on fourteen reference strains of Staphylococccus spp., and to evaluate the magnitude of interactions of berberine with these antistaphylococcal antibiotics. In our study minimum inhibitory concentrations (MIC of berberine chloride against CoNS ranged from 16 to 512 µg/mL. The most noticeable effects were observed for S. haemolyticus ATCC 29970, S. epidermidis ATCC 12228, S. capitis subsp. capitis ATCC 35661, S. galinarium ATCC 700401, S. hominis subsp. hominis ATCC 27844, S. intermedius ATCC 29663 and S. lugdunensis ATCC 49576. The most significant synergistic effect was noticed for berberine in combination with linezolid, cefoxitin and erythromycin. The synergy between berberine and antibiotics demonstrates the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections.

  7. Berberine enhances the antibacterial activity of selected antibiotics against coagulase-negative Staphylococcus strains in vitro.

    Science.gov (United States)

    Wojtyczka, Robert D; Dziedzic, Arkadiusz; Kępa, Małgorzata; Kubina, Robert; Kabała-Dzik, Agata; Mularz, Tomasz; Idzik, Danuta

    2014-05-22

    Synergistic interactions between commonly used antibiotics and natural bioactive compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has proven efficacy against a broad spectrum of microorganisms. The aim of the presented work was to assess the antibacterial activity of berberine chloride in light of the effect exerted by common antibiotics on fourteen reference strains of Staphylococccus spp., and to evaluate the magnitude of interactions of berberine with these antistaphylococcal antibiotics. In our study minimum inhibitory concentrations (MIC) of berberine chloride against CoNS ranged from 16 to 512 µg/mL. The most noticeable effects were observed for S. haemolyticus ATCC 29970, S. epidermidis ATCC 12228, S. capitis subsp. capitis ATCC 35661, S. galinarium ATCC 700401, S. hominis subsp. hominis ATCC 27844, S. intermedius ATCC 29663 and S. lugdunensis ATCC 49576. The most significant synergistic effect was noticed for berberine in combination with linezolid, cefoxitin and erythromycin. The synergy between berberine and antibiotics demonstrates the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections.

  8. Pharmaco-economic evaluation of antibiotic therapy strategies in DRG-based healthcare systems - a new approach

    Directory of Open Access Journals (Sweden)

    Wilke MH

    2010-11-01

    Full Text Available Abstract The cost of treatments especially in conditions where multiresistant bacteria are involved are a major issue in times where in most developed countries in the world payment systems based on diagnoses-related-groups (DRG are in place. There is great evidence that especially the length of stay in hospital (LOS, the time in the intensive care unit (ICU-days and the hours of mechanical ventilation (HMV are major cost drivers. While established methods of pharmacoeconomical analyses focus on the efficiency of drugs from healthcare system perspective, these data are often not sufficient for improving treatment strategies in a given hospital context. We developed a system that allows the analysis of patients with severe infections on the basis of routine data that is also used for reimbursement. These data contain a lot of information concerning the clinical conditions. By using the ICD-coding we developed an algorithm which allows the detection of patients with infections and gives information on the potential financial outcome of these patients. By using the analysis it is possible to identify subsets of infections and the patient records that had a potentially negative DRG-result, i.e. the costs are higher than the reimbursement. When identified the patient records undergo a peer review, where the clinical situation and the antibiotic therapy are reviewed by medical experts. In case simulations it is possible to find out if a different therapeutic approach, e.g. by different choices in initial (empirical antibiotic treatment would have caused other outcomes. Data driven analyses together with peer reviews of patient records are a useful tool to examine antibiotic treatment strategies and to establish changes that again can be reviewed on a regular basis. Doing this a continous improvement process can be established in hospitals which can lead to a better balance of clinical and economical outcomes in patients with severe infections

  9. A retrospective analysis of the duration of oral antibiotic therapy for the treatment of acne among adolescents: investigating practice gaps and potential cost-savings.

    Science.gov (United States)

    Lee, Young H; Liu, Guodong; Thiboutot, Diane M; Leslie, Douglas L; Kirby, Joslyn S

    2014-07-01

    Duration of oral antibiotic therapy in acne has not been widely studied. Recent guidelines suggest it should be limited to 3 to 6 months. We sought to compare the duration of oral antibiotic use with recent guidelines and determine the potential cost-savings related to shortened durations. This is a retrospective cohort study from the MarketScan Commercial Claims and Encounters database. Claims data were used to determine duration and costs of antibiotic therapy. The mean course duration was 129 days. The majority (93%) of courses were less than 9 months. Among the 31,634 courses, 18,280 (57.8%) did not include concomitant topical retinoid therapy. The mean (95% confidence interval) duration with and without topical retinoid use was 133 (131.5-134.7) days and 127 (125.4-127.9) days, respectively. The mean excess direct cost of antibiotic treatment for longer than 6 months was $580.99/person. Claims cannot be attributed to a specific diagnosis or provider. The database does not provide information on acne severity. Duration of antibiotic use is decreasing when compared with previous data. However, 5547 (17.53%) courses exceeded 6 months, highlighting an opportunity for reduced antibiotic use. If courses greater than 6 months were shortened to 6 months, savings would be $580.99/person. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  10. Mastitis therapy and antimicrobial susceptibility: a multispecies review with a focus on antibiotic treatment of mastitis in dairy cattle.

    Science.gov (United States)

    Barlow, John

    2011-12-01

    Mastitis occurs in numerous species. Antimicrobial agents are used for treatment of infectious mastitis in dairy cattle, other livestock, companion animals, and humans. Mastitis is an economically important disease of dairy cattle and most mastitis research has focused on epidemiology and control of bovine mastitis. Antibiotic treatment of clinical and subclinical mastitis in dairy cattle is an established component of mastitis control programs. Research on the treatment of clinical and subclinical mastitis in other dairy species such as sheep and goats has been less frequent, although the general principles of mastitis therapy in small ruminants are similar to those of dairy cattle. Research on treatment of clinical mastitis in humans is limited and as for other species empirical treatment of mastitis appears to be common. While antimicrobial susceptibility testing is recommended to direct treatment decisions in many clinical settings, the use of susceptibility testing for antibiotic selection for mastitis treatments of dairy cattle has been challenged in a number of publications. The principle objective of this review is to summarize the literature evaluating the question, "Does antimicrobial susceptibility predict treatment outcome for intramammary infections caused by common bacterial pathogens?" This review also addresses current issues related to antimicrobial use and treatment decisions for mastitis in dairy cattle. Information on treatment of mastitis in other species, including humans, is included although research appears to be limited. Issues related to study design, gaps in current knowledge and opportunities for future research are identified for bovine mastitis therapy.

  11. Nasal methicillin-resistant Staphylococcus aureus polymerase chain reaction: a potential use in guiding antibiotic therapy for pneumonia.

    Science.gov (United States)

    Johnson, Jennifer A; Wright, Michael E; Sheperd, Lyndsay A; Musher, Daniel M; Dang, Bich N

    2015-01-01

    The role at admission of nasal polymerase chain reaction (PCR) for patients with methicillin-resistant Staphylococcus aureus (MRSA) in guiding antibiotic therapy for lower respiratory tract infection is unknown. To determine whether nasal MRSA PCR at admission can predict the absence of MRSA in lower respiratory tract secretions. We performed a retrospective study of adult patients admitted to a large urban hospital. Patients had a nasal MRSA PCR test and a lower respiratory tract culture obtained within 48 hours of admission and the culture yielded S aureus. Sensitivity, specificity, and positive and negative predictive values. Our results showed high sensitivity (93.3%) and negative predictive value (95.2%) of nasal PCR for MRSA in the lower respiratory tract. With its high sensitivity and negative predictive value, a nasal MRSA PCR test performed within 48 hours of hospital admission could help guide the discontinuation of MRSA-directed empiric antibiotic therapy in patients who are unlikely to be infected with this organism. A prospective study is needed to confirm these findings.

  12. Menadione (vitamin K enhances the antibiotic activity of drugs by cell membrane permeabilization mechanism

    Directory of Open Access Journals (Sweden)

    Jacqueline C. Andrade

    2017-01-01

    Full Text Available Menadione, vitamin K3, belongs to the class of lipid-soluble vitamins and lipophilic substances as menadione cause disturbances in the bacterial membrane, resulting in damage to the fundamental elements for the integrity of the membrane, thus allowing increased permeability. Accordingly, the aim of this study was to evaluate in vitro the antibiotic-modifying activity of menadione in multiresistant strains of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, with a gradual increase in its subinhibitory concentration. In addition, menadione was compared with cholesterol and ergosterol for similarity in mechanism of drug modulatory action. Antibiotic-modifying activity and antibacterial effect were determined by the broth microdilution assay. Menadione, cholesterol and ergosterol showed modulatory activity at clinically relevant concentrations, characterizing them as modifiers of bacterial drug resistance, since they lowered the MIC of the antibiotics tested. This is the first report of the antibacterial activity of menadione and its potentiation of aminoglycosides against multiresistant bacteria.

  13. Antibiotic stability related to temperature variations in elastomeric pumps used for outpatient parenteral antimicrobial therapy (OPAT).

    Science.gov (United States)

    Voumard, Rachel; Van Neyghem, Niklas; Cochet, Camille; Gardiol, Céline; Decosterd, Laurent; Buclin, Thierry; de Valliere, Serge

    2017-05-01

    Elastomeric pumps can be used for the continuous administration of antimicrobials in the outpatient setting. A potentially limiting factor in their use is the stability of antimicrobials. To investigate under real-life conditions the temperature variations of antibiotic solutions contained in elastomeric pumps, and to examine under such conditions the stability of five antibiotics. Healthy volunteers carried the elastomeric pumps in carry pouches during their daily activities. A thermologger measured the temperatures every 15 min over 24 h. Antibiotic concentrations were measured by HPLC coupled to tandem MS. During daytime, the temperature of solutions in the pumps increased steadily, warming to >30°C. During the night, when the pumps were kept attached to the waist, the temperatures reached up to 33°C. The use of white carry pouches avoided excessive temperature increases. Over seven experiments, cefazolin, cefepime, piperacillin and tazobactam were found to be stable over 24 h. Flucloxacillin showed a mean decrease in concentration of 11% ( P  = 0.001). Real-life situations can cause significant temperature rises in elastomeric pumps, thereby potentially increasing the risk of antibiotic degradation. Patients should be instructed to avoid situations causing excessive temperature increases. Despite these temperature variations, cefazolin, cefepime, piperacillin and tazobactam were found to be stable over 24 h. A moderate degradation was noticed for flucloxacillin, albeit most probably not to an extent that might impair anti-infective efficacy. © 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.

  14. Efficacy of two non-antibiotic therapies, oxytocin and topical liniment, against bovine staphylococcal mastitis.

    Science.gov (United States)

    Knight, C H; Fitzpatrick, J L; Logue, D N; Platt, D J

    2000-03-11

    Eight cows were challenged by a single quarter intramammary infusion of a relatively low-virulence strain of Staphylococcus aureus on four occasions five weeks apart and, after each challenge, each cow received one of four treatments, according to a duplicated Latin-square design. The treatments were massage alone (negative control), massage with a proprietary liniment, oxytocin, and a single course of a proprietary intramammary antibiotic. The massage treatments were applied at every milking for three weeks, oxytocin was given for one week, and the antibiotic was given after three successive milkings. Milk samples were collected immediately before and for three weeks after each challenge, and a scoring system was used to quantify the presence of bacteria during the whole of the period. None of the treatments completely eliminated bacteria from all the cows. Relative to the negative control, the liniment had no significant effect, but both oxytocin and the antibiotic reduced the numbers of bacteria significantly and did not differ significantly in efficacy.

  15. Succession in the gut microbiome following antibiotic and antibody therapies for Clostridium difficile.

    Science.gov (United States)

    Peterfreund, Gregory L; Vandivier, Lee E; Sinha, Rohini; Marozsan, Andre J; Olson, William C; Zhu, Jun; Bushman, Frederic D

    2012-01-01

    Antibiotic disruption of the intestinal microbiota may cause susceptibility to pathogens that is resolved by progressive bacterial outgrowth and colonization. Succession is central to ecological theory but not widely documented in studies of the vertebrate microbiome. Here, we study succession in the hamster gut after treatment with antibiotics and exposure to Clostridium difficile. C. difficile infection is typically lethal in hamsters, but protection can be conferred with neutralizing antibodies against the A and B toxins. We compare treatment with neutralizing monoclonal antibodies (mAb) to treatment with vancomycin, which prolongs the lives of animals but ultimately fails to protect them from death. We carried out longitudinal deep sequencing analysis and found distinctive waves of succession associated with each form of treatment. Clindamycin sensitization prior to infection was associated with the temporary suppression of the previously dominant Bacteroidales and the fungus Saccinobaculus in favor of Proteobacteria. In mAb-treated animals, C. difficile proliferated before joining Proteobacteria in giving way to re-expanding Bacteroidales and the fungus Wickerhamomyces. However, the Bacteroidales lineages returning by day 7 were different from those that were present initially, and they persisted for the duration of the experiment. Animals treated with vancomycin showed a different set of late-stage lineages that were dominated by Proteobacteria as well as increased disparity between the tissue-associated and luminal cecal communities. The control animals showed no change in their gut microbiota. These data thus suggest different patterns of ecological succession following antibiotic treatment and C. difficile infection.

  16. Succession in the gut microbiome following antibiotic and antibody therapies for Clostridium difficile.

    Directory of Open Access Journals (Sweden)

    Gregory L Peterfreund

    Full Text Available Antibiotic disruption of the intestinal microbiota may cause susceptibility to pathogens that is resolved by progressive bacterial outgrowth and colonization. Succession is central to ecological theory but not widely documented in studies of the vertebrate microbiome. Here, we study succession in the hamster gut after treatment with antibiotics and exposure to Clostridium difficile. C. difficile infection is typically lethal in hamsters, but protection can be conferred with neutralizing antibodies against the A and B toxins. We compare treatment with neutralizing monoclonal antibodies (mAb to treatment with vancomycin, which prolongs the lives of animals but ultimately fails to protect them from death. We carried out longitudinal deep sequencing analysis and found distinctive waves of succession associated with each form of treatment. Clindamycin sensitization prior to infection was associated with the temporary suppression of the previously dominant Bacteroidales and the fungus Saccinobaculus in favor of Proteobacteria. In mAb-treated animals, C. difficile proliferated before joining Proteobacteria in giving way to re-expanding Bacteroidales and the fungus Wickerhamomyces. However, the Bacteroidales lineages returning by day 7 were different from those that were present initially, and they persisted for the duration of the experiment. Animals treated with vancomycin showed a different set of late-stage lineages that were dominated by Proteobacteria as well as increased disparity between the tissue-associated and luminal cecal communities. The control animals showed no change in their gut microbiota. These data thus suggest different patterns of ecological succession following antibiotic treatment and C. difficile infection.

  17. Medical-grade honey enriched with antimicrobial peptides has enhanced activity against antibiotic-resistant pathogens

    NARCIS (Netherlands)

    Kwakman, P. H. S.; de Boer, L.; Ruyter-Spira, C. P.; Creemers-Molenaar, T.; Helsper, J. P. F. G.; Vandenbroucke-Grauls, C. M. J. E.; Zaat, S. A. J.; te Velde, A. A.

    2011-01-01

    Honey has potent activity against both antibiotic-sensitive and -resistant bacteria, and is an interesting agent for topical antimicrobial application to wounds. As honey is diluted by wound exudate, rapid bactericidal activity up to high dilution is a prerequisite for its successful application. We

  18. Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in non surgical wounds.

    Science.gov (United States)

    Gurusamy, Kurinchi Selvan; Koti, Rahul; Toon, Clare D; Wilson, Peter; Davidson, Brian R

    2013-11-18

    Non surgical wounds include chronic ulcers (pressure or decubitus ulcers, venous ulcers, diabetic ulcers, ischaemic ulcers), burns and traumatic wounds. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonisation (i.e. presence of MRSA in the absence of clinical features of infection such as redness or pus discharge) or infection in chronic ulcers varies between 7% and 30%. MRSA colonisation or infection of non surgical wounds can result in MRSA bacteraemia (infection of the blood) which is associated with a 30-day mortality of about 28% to 38% and a one-year mortality of about 55%. People with non surgical wounds colonised or infected with MRSA may be reservoirs of MRSA, so it is important to treat them, however, we do not know the optimal antibiotic regimen to use in these cases. To compare the benefits (such as decreased mortality and improved quality of life) and harms (such as adverse events related to antibiotic use) of all antibiotic treatments in people with non surgical wounds with established colonisation or infection caused by MRSA. We searched the following databases: The Cochrane Wounds Group Specialised Register (searched 13 March 2013); The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2); Database of Abstracts of Reviews of Effects (2013, Issue 2); NHS Economic Evaluation Database (2013, Issue 2); Ovid MEDLINE (1946 to February Week 4 2013); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, March 12, 2013); Ovid EMBASE (1974 to 2013 Week 10); EBSCO CINAHL (1982 to 8 March 2013). We included only randomised controlled trials (RCTs) comparing antibiotic treatment with no antibiotic treatment or with another antibiotic regimen for the treatment of MRSA-infected non surgical wounds. We included all relevant RCTs in the analysis, irrespective of language, publication status, publication year, or sample size. Two review authors independently identified the trials, and extracted data from the trial reports. We

  19. Infectious olecranon and patellar bursitis: short-course adjuvant antibiotic therapy is not a risk factor for recurrence in adult hospitalized patients.

    Science.gov (United States)

    Perez, Cédric; Huttner, Angela; Assal, Mathieu; Bernard, Louis; Lew, Daniel; Hoffmeyer, Pierre; Uçkay, Ilker

    2010-05-01

    No evidence-based recommendations exist for the management of infectious bursitis. We examined epidemiology and risk factors for recurrence of septic bursitis. Specifically, we compared outcome in patients receiving bursectomy plus short-course adjuvant antibiotic therapy (7 days). Retrospective study of adult patients with infectious olecranon and patellar bursitis requiring hospitalization at Geneva University Hospital from January 1996 to March 2009. We identified 343 episodes of infectious bursitis (237 olecranon and 106 patellar). Staphylococcus aureus predominated among the 256 cases with an identifiable pathogen (85%). Three hundred and twelve cases (91%) were treated surgically; 142 (41%) with one-stage bursectomy and closure and 146 with two-stage bursectomy. All received antibiotics for a median duration of 13 days with a median intravenous component of 3 days. Cure was achieved in 293 (85%) episodes. Total duration of antibiotic therapy [odds ratio (OR) 0.9; 95% confidence interval (95% CI) 0.8-1.1] showed no association with cure. In multivariate analysis, only immunosuppression was linked to recurrence (OR 5.6; 95% CI 1.9-18.4). Compared with 14 days of antibiotic treatment (OR 0.9; 95% CI 0.1-10.7) was equivalent, as was the intravenous component (OR 1.1; 95% CI 1.0-1.3). In severe infectious bursitis requiring hospitalization, adjuvant antibiotic therapy might be limited to 7 days in non-immunosuppressed patients.

  20. Antibiotic-Enhanced Phagocytosis of ’Borrelia recurrentis’ by Blood Polymorphonuclear Leukocytes.

    Science.gov (United States)

    1979-11-30

    hours after Butler 7 institution of antibiotic treatment. Polymorphonuclear leukocytes are known to release endogenous pyrogen after phagocytosis of...other bacteria (6), and endogenous pyrogen may be one of the mediators of the rigor and temperature rise in the Jarisch-Herxheimer reaction (2). Release...the pathogenesis of fever. XII. The effect of phagocytosis on the release of endogenous pyrogen by polymorphonuclear leukocytes. J. Exp. Med. 119:715

  1. Lumbosacral multiradiculopathy responsive to antibiotic therapy: description of four patients with lumbar spondylosis and a superimposed Lyme disease.

    Science.gov (United States)

    Luigetti, Marco; Vollaro, Stefano; Corbetto, Marzia; Salomone, Gaetano; Dicuonzo, Giordano; Scoppettuolo, Giancarlo; Di Lazzaro, Vincenzo

    2014-12-01

    Lyme disease is a diffuse zoonosis caused by spirochaetes of the Borrelia burgdorferi species complex. Neurological manifestations of the disease, involving central or peripheral nervous system, are common. This study describes four consecutive patients with an MRI-proven lumbosacral spondylosis, who complained of progressive worsening of symptoms in the last months in which serological evaluation suggested a superimposed B. Burgdorferi infection. Four patients, all from the Lazio region, were admitted to the Department of Neurology. Extensive laboratory studies and clinical, anamnestic and neurophysiological evaluation were performed in all cases. In all cases, anamnesis revealed a previous diagnosis of lumbosacral foraminal stenosis. Clinical and neurophysiological findings were consistent with a lumbosacral multiradiculopathy. Considering serological evaluation suggestive of a superimposed B. burgdorferi infection a proper antibiotic therapy was started. All cases showed a marked improvement of symptoms. Clinicians should be aware that in all cases of lumbosacral multiradiculopathy, even if a mechanical cause is documented, B. burgdorferi may be a simply treatable condition.

  2. Proceedings of scientific instructional conference on local antibiotic therapy on prevention and treatment of infections in orthopaedics and traumatology.

    Science.gov (United States)

    Okapa, Robert; Marczyński, Wojciech; Kolbuszewski, Andrzej

    2013-06-13

    Proceedings of scientific instructional conference which was held on 7th July 2012 in Józefów near Warsaw. Dring the Conference the cectures were presented by leading experts - Dr. David Jenkins, clinical microbiology consultant from the University Hospital in Leicester, Professor Harald Knaepler, head of the Department of Trauma and Orthopaedics in Wetzlar, Germany, Dr. David Jahoda, head of the department of orthopedic infections, Motol University Hospital, Prague, and Professor Wojciech Marczyński, head of the Department of Orthopaedics, The Centre of Postgraduate Medical Education, Professor Adam Gruca Teaching Hospital in Otwock, who was also the Conference moderator. The meeting was the opportunity to clarify the indications and contraindications to the use of local antibiotic therapy in the treatment of infectious complications after surgical procedures  and focus on practical aspects of clinical microbiology and its important contribution to the identification and resolution of problems with infectious complications in orthopedics and traumatology.  

  3. Comparison of Procalcitonin Guidance-Administered Antibiotics with Standard Guidelines on Antibiotic Therapy in Children with Lower Respiratory Tract Infections: A Retrospective Study in China.

    Science.gov (United States)

    Wu, Guo; Wu, Gao; Wu, Shuxie; Wu, Hanbin

    2017-01-01

    To establish the efficacy of an algorithm based on the biomarker procalcitonin (PCT) to reduce antibiotic exposure in pediatric patients with lower respiratory tract infection (LRTI). The clinical data of 357 patients (standard group (n = 174) using SAS 9.1.3 software. The overall adverse effect rates were similar in both the PCT and standard groups: 42 (22.95%) and 51 (29.31%), respectively. The length of hospital stay was not significantly different between the PCT (9.96 ± 5.81 days) and standard groups (10.58 ± 4.24 days) (difference: -0.62%; 95% CI: -1.68 to 0.43). Antibiotic prescribing rates were significantly different in the PCT group compared to the standard group: 54.64% versus 83.91% (difference: -29.26%; 95% CI: -38.31, -20.22; p = 0.23). Mean duration of antibiotic exposure in the PCT group (3.98 ± 2.17 days) was lower than the standard groups (6.66 ± 5.59 days) (difference: -2.68%; 95% CI: -3.21 to -2.16). This study showed that PCT guidance of antibiotic treatment in children and adolescents with LRTI reduced the duration of antibiotic exposure and antibiotic prescribing rates, but did not affect the adverse effect rate and length of hospital stay. © 2017 S. Karger AG, Basel.

  4. Empirical mono- versus combination antibiotic therapy in adult intensive care patients with severe sepsis – A systematic review with meta-analysis and trial sequential analysis

    DEFF Research Database (Denmark)

    Sjövall, Karl Fredrik Lennart; Perner, Anders; Hylander Møller, Morten

    2017-01-01

    assessment and trial sequential analysis (TSA). We included randomised clinical trials (RCT) assessing empirical mono-antibiotic therapy versus a combination of two or more antibiotics in adult ICU patients with severe sepsis. We exclusively assessed patient-important outcomes, including mortality. Two...... reviewers independently evaluated studies for inclusion, extracted data, and assessed risk of bias. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated and the risk of random errors was assessed by TSA. Results Thirteen RCTs (n = 2633) were included; all were judged as having high risk...... of bias. Carbapenems were the most frequently used mono-antibiotic (8 of 13 trials). There was no difference in mortality (RR 1.11, 95% CI 0.95–1.29; p = 0.19) or in any other patient-important outcomes between mono- vs. combination therapy. In TSA of mortality, the Z-curve reached the futility area...

  5. Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die on basis of high IL-6 levels.

    Science.gov (United States)

    Vyas, Dinesh; Javadi, Pardis; Dipasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-10-01

    Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 h after cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 h after septic insult. Our first aim was to see whether earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die on the basis of high IL-6 levels. Mice (n = 184) were subjected to CLP, had IL-6 levels drawn 6 h later, and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning 6 or 12 h postoperatively. Overall 1-wk survival improved from 25.5 to 35.9% with earlier administration of antibiotics (P 14,000 pg/ml, 25% survived if imipenem was started at 6 h, whereas none survived if antibiotics were started later (P 14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6.

  6. Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die based upon high IL-6 levels

    Science.gov (United States)

    Vyas, Dinesh; Javadi, Pardis; DiPasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-01-01

    Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 hours following cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 hours after the septic insult. The first aim of this study was to see if earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die based upon high IL-6 levels. Mice (n=184) were subjected to CLP, had IL-6 levels drawn six hours later and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning six or twelve hours post-operatively. Overall one-week survival improved from 25.5% to 35.9% with earlier administration of antibiotics (p14,000 pg/ml, 25% survived if imipenem was started at 6 hours, while none survived if antibiotics were started later (p14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6. PMID:15947070

  7. The role of procalcitonin as a guide for the diagnosis, prognosis, and decision of antibiotic therapy for lower respiratory tract infections

    Directory of Open Access Journals (Sweden)

    Amal Abd El-Azeem

    2013-10-01

    Conclusion: Serum PCT level could be used as a novel marker of lower respiratory tract bacterial infections for diagnosis, prognosis and follow up of therapy. This reduces side-effects of an unnecessary antibiotic use, lowers costs, and in the long-term, leads to diminishing drug resistance.

  8. Antibiotic therapy and Clostridium difficile infection – primum non nocere – first do no harm

    Directory of Open Access Journals (Sweden)

    Crowther GS

    2015-09-01

    Full Text Available Grace S Crowther,1 Mark H Wilcox1,2 1Faculty of Medicine and Health, University of Leeds, Leeds, UK; 2Department of Microbiology, Leeds Teaching Hospitals Trust, Leeds, UK Abstract: Treatment options for Clostridium difficile infection (CDI remain limited despite this usually nosocomial infection posing an urgent threat to public health. A major paradox of the management of CDI is the use of antimicrobial agents to treat infection, which runs the risk of prolonged gut microbiota perturbation and so recurrence of infection. Here, we explore alternative CDI treatment and prevention options currently available or in development. Notably, strategies that aim to reduce the negative effects of antibiotics on gut microbiota offer the potential to alter current antimicrobial stewardship approaches to preventing CDI. Keywords: treatment, prevention, CDI, SYN-004, vaccine, beta-lactams

  9. Delay in diagnosis of malaria because of improper effects of antibiotic therapy

    International Nuclear Information System (INIS)

    Jalali Tabatabai, M.; Vosough, P.; Samadpour, H.; Yousefi, Sh.

    2000-01-01

    Although most parts of Iran is free of malaria owing to appreciable struggle against this disease by the Ministry of Public Health, in every case of fever of unknown origin possibility of malaria should not be neglected. Unjustified administration of antibiotics can delay the diagnosis because of diminishing effect in number of malaria parasites in peripheral blood. For this reason frequent peripheral blood smears may be necessary to establish the diagnosis. In this article, 10 cases of malaria (age ranged from 2 mo. to 12 r) were diagnosed at Hazart Ali Asghar Hospital, Mostly referred to as fever of unknown origin with possible diagnosis of malignancy, within the last 10 years (1986-1996)

  10. Antimicrobial and enhancement of the antibiotic activity by phenolic compounds: Gallic acid, caffeic acid and pyrogallol.

    Science.gov (United States)

    Lima, Valéria N; Oliveira-Tintino, Cícera D M; Santos, Enaide S; Morais, Luís P; Tintino, Saulo R; Freitas, Thiago S; Geraldo, Yuri S; Pereira, Raimundo L S; Cruz, Rafael P; Menezes, Irwin R A; Coutinho, Henrique D M

    2016-10-01

    The indiscriminate use of antimicrobial drugs has increased the spectrum of exposure of these organisms. In our studies, these phenolic compounds were evaluated: gallic acid, caffeic acid and pyrogallol. The antibacterial, antifungal and modulatory of antibiotic activities of these compounds were assayed using microdilution method of Minimum Inhibitory Concentration (MIC) to bacteria and Minimum Fungicide Concentration (MFC) to fungi. The modulation was made by comparisons of the MIC and MFC of the compounds alone and combined with drugs against bacteria and fungi respectively, using a sub-inhibitory concentration of 128 μg/mL of substances (MIC/8). All substances not demonstrated clinically relevant antibacterial activity with a MIC above ≥1024 μg/mL. As a result, we observed that the caffeic acid presented a potentiating antibacterial effect over the 3 groups of bacteria studied. Pyrogallol showed a synergistic effect with two of the antibiotics tested, but only against Staphylococcus aureus. In general, caffeic acid was the substance that presented with the greatest number of antibiotics and with the greatest number of bacteria. In relation to the antifungal activity of all the compounds, the verified results were ≥1024 μg/mL, not demonstrating significant activity. Regarding potentiation of the effect of fluconazole, was observed synergistic effect only when assayed against Candida tropicalis, with all substances. Therefore, as can be seen, the compounds presented as substances that can be promising potentiating agents of antimicrobial drugs, even though they do not have direct antibacterial and antifungal action. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Effectiveness of Dry Cow Therapy Comprising Antibiotic Treatment, Internal Teat Sealant, and α-Tocopherol Against New Intramammary Infections in Cows

    Directory of Open Access Journals (Sweden)

    Cengiz Mehmet

    2015-04-01

    Full Text Available The aim of this study was to evaluate the preventive effectiveness of dry cow therapy based on antibiotic, internal teat sealant, and α-tocopherol administered separately or in various combinations at drying-off The study was performed on 322 uninfected quarters of 95 cows originating from three dairy herds. The new intramammary infection rates after calving were measured to evaluate the effectiveness. The quarters were divided into six groups differing in treatment, namely: control group (group C, n = 40 and five treatment groups. Treatment groups were arranged as follows: group A (antibiotic alone, n = 81, group AS (antibiotic + sealant, n = 40, group AST (antibiotic + sealant + α-tocopherol, n = 40, group T (α-tocopherol alone, n = 40, group S (sealant alone, n = 81. New infection rate amounted to 47.5% in group C. The treatment in group AST significantly prevented from the occurrence of new intramammary infections (12.5%, P 0.05, although the use of the sealant alone (group S decreased the risk of new infection (24.7%, P 0.05. Increased α-tocopherol level (P < 0.05 was detected after calving in the quarters from cows that received α-tocopherol injections. In conclusion, the combination of antibiotic, internal teat sealant, and α-tocopherol used in dry cow therapy showed a significantly better preventive effect against new intramammary infections, than the therapeutics administered separately.

  12. A Biosurfactant-Sophorolipid Acts in Synergy with Antibiotics to Enhance Their Efficiency

    Directory of Open Access Journals (Sweden)

    Kasturi Joshi-Navare

    2013-01-01

    Full Text Available Sophorolipids (SLs, biosurfactants with antimicrobial properties, have been tried to address the problem of antibiotic resistance. The synergistic action of SL and antibiotics was checked using standard microdilution and spread plate methods. With Staphylococcus aureus, SL-tetracycline combination achieved total inhibition before 4 h of exposure while tetracycline alone couldnot achieve total inhibition till the end of 6 h. The inhibition caused by exposure of bacterium to SL-tetracycline mixture was ~25% more as compared to SL alone. In spite of known robustness of gram-negative bacteria, SL-cefaclor mixture proved to be efficient against Escherichia coli which showed ~48% more inhibition within 2 h of exposure as compared to cefaclor alone. Scanning electron microscopy of the cells treated with mixture revealed bacterial cell membrane damage and pore formation. Moreover, SLs being a type of asymmetric bola, they are expected to form self-assemblies with unique functionality. This led to the speculation that SLs being amphiphilic in nature can span through the structurally alike cell membrane and facilitate the entry of drug molecules.

  13. Good practice recommendations for paediatric outpatient parenteral antibiotic therapy (p-OPAT) in the UK: a consensus statement.

    Science.gov (United States)

    Patel, Sanjay; Abrahamson, Ed; Goldring, Stephen; Green, Helen; Wickens, Hayley; Laundy, Matt

    2015-02-01

    There is compelling evidence to support the rationale for managing children on intravenous antimicrobial therapy at home whenever possible, including parent and patient satisfaction, psychological well-being, return to school/employment, reductions in healthcare-associated infection and cost savings. As a joint collaboration between the BSAC and the British Paediatric Allergy, Immunity and Infection Group, we have developed good practice recommendations to highlight good clinical practice and governance within paediatric outpatient parenteral antibiotic therapy (p-OPAT) services across the UK. These guidelines provide a practical approach for safely delivering a p-OPAT service in both secondary care and tertiary care settings, in terms of the roles and responsibilities of members of the p-OPAT team, the structure required to deliver the service, identifying patients and pathologies that are suitable for p-OPAT, ensuring appropriate vascular access, antimicrobial choice and delivery and the clinical governance aspects of delivering a p-OPAT service. The process of writing a business case to support the introduction of a p-OPAT service is also addressed. © 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.

  14. Chronic bacterial prostatitis: efficacy of short-lasting antibiotic therapy with prulifloxacin (Unidrox®) in association with saw palmetto extract, lactobacillus sporogens and arbutin (Lactorepens®).

    Science.gov (United States)

    Busetto, Gian Maria; Giovannone, Riccardo; Ferro, Matteo; Tricarico, Stefano; Del Giudice, Francesco; Matei, Deliu Victor; De Cobelli, Ottavio; Gentile, Vincenzo; De Berardinis, Ettore

    2014-07-19

    Bacterial prostatitis (BP) is a common condition accounting responsible for about 5-10% of all prostatitis cases; chronic bacterial prostatitis (CBP) classified as type II, are less common but is a condition that significantly hampers the quality of life, (QoL) because not only is it a physical condition but also a psychological distress. Commonly patients are treated with antibiotics alone, and in particular fluoroquinolones are suggested by the European Urology guidelines. This approach, although recommended, may not be enough. Thus, a multimodal approach to the prolonged antibiotic therapy may be helpful. 210 patients affected by chronic bacterial prostatitis were enrolled in the study. All patients were positive to Meares-Stamey test and symptoms duration was > 3 months. The purpose of the study was to evaluate the efficacy of a long lasting therapy with a fluoroquinolone in association with a nutraceutical supplement (prulifloxacin 600 mg for 21 days and an association of Serenoa repens 320 mg, Lactobacillus Sporogens 200 mg, Arbutin 100 mg for 30 days). Patients were randomized in two groups (A and B) receiving respectively antibiotic alone and an association of antibiotic plus supplement. Biological recurrence at 2 months in Group A was observed in 21 patients (27.6%) and in Group B in 6 patients (7.8%). Uropathogens found at the first follow-up were for the majority Gram - (E. coli and Enterobacter spp.). A statistically significant difference was found at the time of the follow-up between Group A and B in the NIH-CPSI questionnaire score, symptoms evidence and serum PSA. Broad band, short-lasting antibiotic therapy in association with a nutritional supplement (serenoa repens, lactobacillus sporogens and arbutin) show better control and recurrence rate on patients affected by chronic bacterial prostatitits in comparison with antibiotic treatment alone. NCT02130713. Date of trial Registration: 30/04/2014.

  15. Biodegradable magnesium nanoparticle-enhanced laser hyperthermia therapy

    Directory of Open Access Journals (Sweden)

    Wang Q

    2012-08-01

    Full Text Available Qian Wang,1 Liping Xie,1 Zhizhu He,2 Derui Di,2 Jing Liu1,21Department of Biomedical Engineering, School of Medicine, Tsinghua University, 2Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, People's Republic of ChinaBackground: Recently, nanoparticles have been demonstrated to have tremendous merit in terms of improving the treatment specificity and thermal ablation effect on tumors. However, the potential toxicity and long-term side effects caused by the introduced nanoparticles and by expelling them out of the body following surgery remain a significant challenge. Here, we propose for the first time to directly adopt magnesium nanoparticles as the heating enhancer in laser thermal ablation to avoid these problems by making full use of the perfect biodegradable properties of this specific material.Methods: To better understand the new nano “green” hyperthermia modality, we evaluated the effects of magnesium nanoparticles on the temperature transients inside the human body subject to laser interstitial heating. Further, we experimentally investigated the heating enhancement effects of magnesium nanoparticles on a group of biological samples: oil, egg white, egg yolk, in vitro pig tissues, and the in vivo hind leg of rabbit when subjected to laser irradiation.Results: Both the theoretical simulations and experimental measurements demonstrated that the target tissues injected with magnesium nanoparticles reached much higher temperatures than tissues without magnesium nanoparticles. This revealed the enhancing behavior of the new nanohyperthermia method.Conclusion: Given the unique features of magnesium nanoparticles – their complete biological safety and ability to enhance heating – which most other advanced metal nanoparticles do not possess, the use of magnesium nanoparticles in hyperthermia therapy offers an important “green” nanomedicine modality for treating tumors

  16. Assessment of empirical antibiotic therapy optimisation in six hospitals: an observational cohort study.

    Science.gov (United States)

    Braykov, Nikolay P; Morgan, Daniel J; Schweizer, Marin L; Uslan, Daniel Z; Kelesidis, Theodoros; Weisenberg, Scott A; Johannsson, Birgir; Young, Heather; Cantey, Joseph; Srinivasan, Arjun; Perencevich, Eli; Septimus, Edward; Laxminarayan, Ramanan

    2014-12-01

    Modification of empirical antimicrobials when warranted by culture results or clinical signs is recommended to control antimicrobial overuse and resistance. We aimed to assess the frequency with which patients were started on empirical antimicrobials, characteristics of the empirical regimen and the clinical characteristics of patients at the time of starting antimicrobials, patterns of changes to empirical therapy at different timepoints, and modifiable factors associated with changes to the initial empirical regimen in the first 5 days of therapy. We did a chart review of adult inpatients receiving one or more antimicrobials in six US hospitals on 4 days during 2009 and 2010. Our primary outcome was the modification of antimicrobial regimen on or before the 5th day of empirical therapy, analysed as a three-category variable. Bivariate analyses were used to establish demographic and clinical variables associated with the outcome. Variables with p values below 0·1 were included in a multivariable generalised linear latent and mixed model with multinomial logit link to adjust for clustering within hospitals and accommodate a non-binary outcome variable. Across the six study sites, 4119 (60%) of 6812 inpatients received antimicrobials. Of 1200 randomly selected patients with active antimicrobials, 730 (61%) met inclusion criteria. At the start of therapy, 220 (30%) patients were afebrile and had normal white blood cell counts. Appropriate cultures were collected from 432 (59%) patients, and 250 (58%) were negative. By the 5th day of therapy, 12·5% of empirical antimicrobials were escalated, 21·5% were narrowed or discontinued, and 66·4% were unchanged. Narrowing or discontinuation was more likely when cultures were collected at the start of therapy (adjusted OR 1·68, 95% CI 1·05-2·70) and no infection was noted on an initial radiological study (1·76, 1·11-2·79). Escalation was associated with multiple infection sites (2·54, 1·34-4·83) and a positive

  17. Enhancing Brief Cognitive Behavioral Therapy with Motivational Enhancement Techniques in Cocaine Users

    Science.gov (United States)

    McKee, Sherry A.; Carroll, Kathleen M.; Sinha, Rajita; Robinson, Jane E.; Nich, Charla; Cavallo, Dana; O’Malley, Stephanie

    2008-01-01

    Background We investigated the impact of enhancing brief cognitive behavioral therapy with motivational interviewing techniques for cocaine abuse or dependence, using a focused intervention paradigm. Methods Participants (n=74) who met current criteria for cocaine abuse or dependence were randomized to 3-session cognitive behavioral therapy (CBT) or 3-session enhanced CBT (MET + CBT), which included an initial session of motivational enhancement therapy (MET). Outcome measures included treatment retention, process measures (e.g., commitment to abstinence, satisfaction with treatment), and cocaine use. Results Participants who received the MET+CBT intervention attended more drug treatment sessions following the study interventions, reported significantly greater desire for abstinence and expectation of success, and they expected greater difficulty in maintaining abstinence compared to the CBT condition. There were no differences across treatment conditions on cocaine use. Conclusions These findings offer mixed support for the addition of MET as an adjunctive approach to CBT for cocaine users. In addition, the study provides evidence for the feasibility of using short-term studies to test the effects of specific treatment components or refinements on measures of therapy process and outcome. PMID:17573205

  18. PIRATE project: point-of-care, informatics-based randomised controlled trial for decreasing overuse of antibiotic therapy in Gram-negative bacteraemia.

    Science.gov (United States)

    Huttner, Angela; Albrich, Werner C; Bochud, Pierre-Yves; Gayet-Ageron, Angèle; Rossel, Anne; Dach, Elodie von; Harbarth, Stephan; Kaiser, Laurent

    2017-07-13

    Antibiotic overuse drives antibiotic resistance. The optimal duration of antibiotic therapy for Gram-negative bacteraemia (GNB), a common community and hospital-associated infection, remains unknown and unstudied via randomised controlled trials (RCTs). This investigator-initiated, multicentre, non-inferiority, informatics-based point-of-care RCT will randomly assign adult hospitalised patients receiving microbiologically efficacious antibiotic(s) for GNB to (1) 14 days of antibiotic therapy, (2) 7 days of therapy or (3) an individualised duration determined by clinical response and 75% reduction in peak C reactive protein (CRP) values. The randomisation will occur in equal proportions (1:1:1) on day 5 (±1) of efficacious antibiotic therapy as determined by antibiogram; patients, their physicians and study investigators will be blind to treatment duration allocation until the day of antibiotic discontinuation. Immunosuppressed patients and those with GNB due to complicated infections (endocarditis, osteomyelitis, etc) and/or non-fermenting bacilli ( Acinetobacter spp, Burkholderia spp, Pseudomonas spp) Brucella spp, Fusobacterium spp or polymicrobial growth with Gram-positive organisms will be ineligible. The primary outcome is incidence of clinical failure at day 30; secondary outcomes include clinical failure, all-cause mortality and incidence of Clostridiumdifficile infection in the 90-day study period. An interim safety analysis will be performed after the first 150 patients have been followed for ≤30 days. Given a chosen margin of 10%, the required sample size to determine non-inferiority is roughly 500 patients. Analyses will be performed on both intention-to-treat and per-protocol populations. Ethics approval was obtained from the cantonal ethics committees of all three participating sites. Results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal. This trial is registered at www

  19. Management of colonic diverticular disease with poorly absorbed antibiotics and other therapies

    Science.gov (United States)

    Sopeña, Federico; Lanas, Angel

    2011-01-01

    Colonic diverticular disease is common in Western countries and its prevalence increases with age. The large majority of patients (80–85%) will remain entirely asymptomatic throughout their life. In symptomatic cases, most patients will have diverticulosis without inflammation while the remainder will have diverticulitis with or without complications. About 1–2% will require hospitalization and 0.5% will require surgery. Factors predicting the development of symptoms remain to be identified. However, it is generally recognized that diverticular disease is probably related to complex interactions between colon structure, intestinal motility, diet, and genetic features. Epidemiologic studies have demonstrated an association between diverticulosis and diets that are low in fiber and high in refined carbohydrates. Although the causes of symptom development are still unclear, it is thought that previous episodes of intestinal inflammation may play a role. Changes in intestinal microflora could be one of the putative mechanisms responsible for low-grade inflammation. In patients with uncomplicated diverticulosis, a diet abundant in fruit and vegetables is recommended. The current therapeutic approaches in preventing recurrence of symptoms are based on nonabsorbable antibiotics, mesalazine, and/or probiotics. Cyclic rifaximin administration seems to be an adequate approach to relieving symptoms and preventing acute diverticulitis in patients with symptomatic diverticulosis. PMID:22043229

  20. Fate of antibiotic resistance genes in mesophilic and thermophilic anaerobic digestion of chemically enhanced primary treatment (CEPT) sludge.

    Science.gov (United States)

    Jang, Hyun Min; Shin, Jingyeong; Choi, Sangki; Shin, Seung Gu; Park, Ki Young; Cho, Jinwoo; Kim, Young Mo

    2017-11-01

    Anaerobic digestion (AD) of chemically enhanced primary treatment (CEPT) sludge and non-CEPT (conventional sedimentation) sludge were comparatively operated under mesophilic and thermophilic conditions. The highest methane yield (692.46±0.46mL CH 4 /g VS removed in CEPT sludge) was observed in mesophilic AD of CEPT sludge. Meanwhile, thermophilic conditions were more favorable for the removal of total antibiotic resistance genes (ARGs). In this study, no measurable difference in the fates and removal of ARGs and class 1 integrin-integrase gene (intI1) was observed between treated non-CEPT and CEPT sludge. However, redundancy analysis indicated that shifts in bacterial community were primarily accountable for the variations in ARGs and intI1. Network analysis further revealed potential host bacteria for ARGs and intI1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Enhancing Cold Atmospheric Plasma Treatment Efficiency for Cancer Therapy

    Science.gov (United States)

    Cheng, Xiaoqian

    To improve efficiency and safety of anti-cancer therapies the researchers and clinicians alike are prompted to develop targeted combined therapies that especially minimize damage to healthy tissues while eradicating the body of cancerous tissues. Previous research in cold atmospheric plasma (CAP) and cancer cell interaction has repeatedly proven that cold plasma induced cell death. In this study, we seek to integrate the medical application of CAP. We proposed and implemented 3 novel ideas to enhance efficacy and selectivity of cancer therapy. It is postulated that the reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a major role in the CAP cancer therapy. We determined a mechanism of CAP therapy on glioblastoma cells (U87) through an understanding of the composition of CAP, including output voltage, treatment time, and gas flow-rate. We varied the characteristics of the cold plasma in order to obtain different major species (such as O, OH, N2+, and N2 lines). "plasma dosage" D ~ Q * V * t. is defined, where D is the entire "plasma dosage"; Q is the flow rate of feeding gas; V is output voltage; t is treatment time. The proper CAP dosage caused 3-fold cell death in the U87 cells compared to the normal human astrocytes E6/E7 cells. We demonstrated there is a synergy between AuNPS and CAP in cancer therapy. Specifically, the concentration of AuNPs plays an important role on plasma therapy. At an optimal concentration, gold nanoparticles can significantly induce U87 cell death up to a 30% overall increase compared to the control group with the same plasma dosage but no AuNPs applied. The ROS intensity of the corresponding conditions has a reversed trend compared to cell viability. This matches with the theory that intracellular ROS accumulation results in oxidative stress, which further changes the intracellular pathways, causing damage to the proteins, lipids and DNA. Our results show that this synergy has great potential in improving the

  2. Study of the use of probiotic foods as a complement of the conventional antibiotic-therapy for the treatment of Helicobacter pylori infection in children and it's use as a prophylactic therapy in the reinfection by this pathogen

    International Nuclear Information System (INIS)

    Zubillaga, M.; Goldman, C.; Caro, R.; Boccio, J.; Weill, R.; Postaire, E.

    2000-01-01

    Helicobacter pylori infection is very frequent in children in developing countries. Studies on eradication regimens and its complications are not well documented. The European Helicobacter pylori Study Group strongly recommends that treatment should be with proton pump inhibitor based triple therapy, consisting of a proton pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin in various combinations. Recent advances in probiotic research show much promise in a new product development of functional foods based on milk. Among the reported beneficial effects of consuming certain strains of cultures or their metabolites, or both are control of ulcers related to Helicobacter pylori. Kefir seems to be a potential probiotic to control Helicobacter pylori infection. In this study 2 groups of 10 children each which demonstrate to be Helicobacter pylori positive will be treated as follows: Group 1: antibiotic treatment + placebo (fluid milk) and Group 2: antibiotic treatment + kefir. The Triple Therapy consists in the combination of two antibiotics (amoxycillin and clarithromycin) with a proton pump inhibitor (Lansoprazole). In all the cases, the post-treatment control will be performed by the 13 C UBT 2 months after the end of the treatment. Once the infection is eradicated, the group who received the antibiotic-therapy with milk (placebo) as well as the group who received the antibiotic-therapy with the probiotic under study will continue with the administration of the milk and/or probiotic food during one year. During this period, the children will be submitted to post-treatment controls performed by the 13 C UBT every three months. We expect to find that the group that received the triple therapy in combination with the probiotic food (kefir) would have less recidiva rates for the Helicobacter pylori infection than the group that received the triple therapy with the placebo (fluid milk). (author)

  3. Study of the use of probiotic foods as a complement of the conventional antibiotic-therapy for the treatment of Helicobacter pylori infection in children and it's use as a prophylactic therapy in the reinfection by this pathogen

    Energy Technology Data Exchange (ETDEWEB)

    Zubillaga, M; Goldman, C; Caro, R; Boccio, J [Laboratorio de Radioisotopos, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires (Argentina); Weill, R [Departamento de Industrias Agrarias, Facultad de Agronomia, Universidad de Moron, Buenos Aires (Argentina); Postaire, E [Research International Center Daniel Carasso (France)

    2000-07-01

    Helicobacter pylori infection is very frequent in children in developing countries. Studies on eradication regimens and its complications are not well documented. The European Helicobacter pylori Study Group strongly recommends that treatment should be with proton pump inhibitor based triple therapy, consisting of a proton pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin in various combinations. Recent advances in probiotic research show much promise in a new product development of functional foods based on milk. Among the reported beneficial effects of consuming certain strains of cultures or their metabolites, or both are control of ulcers related to Helicobacter pylori. Kefir seems to be a potential probiotic to control Helicobacter pylori infection. In this study 2 groups of 10 children each which demonstrate to be Helicobacter pylori positive will be treated as follows: Group 1: antibiotic treatment + placebo (fluid milk) and Group 2: antibiotic treatment + kefir. The Triple Therapy consists in the combination of two antibiotics (amoxycillin and clarithromycin) with a proton pump inhibitor (Lansoprazole). In all the cases, the post-treatment control will be performed by the {sup 13}C UBT 2 months after the end of the treatment. Once the infection is eradicated, the group who received the antibiotic-therapy with milk (placebo) as well as the group who received the antibiotic-therapy with the probiotic under study will continue with the administration of the milk and/or probiotic food during one year. During this period, the children will be submitted to post-treatment controls performed by the {sup 13}C UBT every three months. We expect to find that the group that received the triple therapy in combination with the probiotic food (kefir) would have less recidiva rates for the Helicobacter pylori infection than the group that received the triple therapy with the placebo (fluid milk). (author)

  4. The use of genes for performance enhancement: doping or therapy?

    Directory of Open Access Journals (Sweden)

    R.S. Oliveira

    2011-12-01

    Full Text Available Recent biotechnological advances have permitted the manipulation of genetic sequences to treat several diseases in a process called gene therapy. However, the advance of gene therapy has opened the door to the possibility of using genetic manipulation (GM to enhance athletic performance. In such ‘gene doping’, exogenous genetic sequences are inserted into a specific tissue, altering cellular gene activity or leading to the expression of a protein product. The exogenous genes most likely to be utilized for gene doping include erythropoietin (EPO, vascular endothelial growth factor (VEGF, insulin-like growth factor type 1 (IGF-1, myostatin antagonists, and endorphin. However, many other genes could also be used, such as those involved in glucose metabolic pathways. Because gene doping would be very difficult to detect, it is inherently very attractive for those involved in sports who are prepared to cheat. Moreover, the field of gene therapy is constantly and rapidly progressing, and this is likely to generate many new possibilities for gene doping. Thus, as part of the general fight against all forms of doping, it will be necessary to develop and continually improve means of detecting exogenous gene sequences (or their products in athletes. Nevertheless, some bioethicists have argued for a liberal approach to gene doping.

  5. The use of genes for performance enhancement: doping or therapy?

    Science.gov (United States)

    Oliveira, R S; Collares, T F; Smith, K R; Collares, T V; Seixas, F K

    2011-12-01

    Recent biotechnological advances have permitted the manipulation of genetic sequences to treat several diseases in a process called gene therapy. However, the advance of gene therapy has opened the door to the possibility of using genetic manipulation (GM) to enhance athletic performance. In such 'gene doping', exogenous genetic sequences are inserted into a specific tissue, altering cellular gene activity or leading to the expression of a protein product. The exogenous genes most likely to be utilized for gene doping include erythropoietin (EPO), vascular endothelial growth factor (VEGF), insulin-like growth factor type 1 (IGF-1), myostatin antagonists, and endorphin. However, many other genes could also be used, such as those involved in glucose metabolic pathways. Because gene doping would be very difficult to detect, it is inherently very attractive for those involved in sports who are prepared to cheat. Moreover, the field of gene therapy is constantly and rapidly progressing, and this is likely to generate many new possibilities for gene doping. Thus, as part of the general fight against all forms of doping, it will be necessary to develop and continually improve means of detecting exogenous gene sequences (or their products) in athletes. Nevertheless, some bioethicists have argued for a liberal approach to gene doping.

  6. The relationship between antibiotic therapy in early childhood and the symptoms of allergy in children aged 6-8 years - the questionnaire study results.

    Science.gov (United States)

    Raciborski, Filip; Tomaszewska, Aneta; Komorowski, Jarosław; Samel-Kowalik, Piotr; Białoszewski, Artur Z; Walkiewicz, Artur; Lusawa, Adam; Szymański, Jakub; Opoczyńska, Dagmara; Drużba, Michał; Borowicz, Jacek; Lipiec, Agnieszka; Kapalczynski, Wojciech J; Samoliński, Bolesław

    2012-09-01

    Studies based on the ISAAC questionnaire suggest a correlation between the use of antibiotics and the prevalence of asthma and allergy in children aged 6-7 years. The number of courses of antibiotic therapy is an important factor. To investigate the relationship between the use of antibiotics during the first years of life and the prevalence of allergy and asthma among children (aged 6-8 years) in the urban population of Poland. A survey-based study with a self-completed questionnaire. The respondents were parents of children aged 6-8 years living in Warszawa, Poland. 1461 completed questionnaires were collected. Asthma was declared in 4.3% of the children. Wheezing and/or sibilant rhonchi within 12 months before the study was observed in 13.5% of the cases. Asthma medication was taken by 21.8% of the children. Allergic rhinitis was declared in 18.7% of the children. Problems with sneezing, rhinorrhea, and nasal congestion not associated with cold or fever were observed in 40.7% of the children. The analysis of the odds ratios between the use of antibiotics and the symptoms of allergic diseases revealed a clear correlation. The highest odds ratio was observed between the completion of over three courses of antibiotic therapy prior to the age of 12 months and the declaration of one of the following: asthma (OR = 5.59, 95% CI: 2.6-12.01), wheezing and/or sibilant rhonchi (OR = 4.68, 95% CI: 3.01-7.27) and taking medicines for breathlessness (OR = 5.12, 95% CI: 3.42-7.68). There is a direct relationship between antibiotic use in the first 3 years of life and asthma and allergy symptoms in children aged 6-8 years old.

  7. Vancomycin-Rifampin Combination Therapy Has Enhanced Efficacy against an Experimental Staphylococcus aureus Prosthetic Joint Infection

    Science.gov (United States)

    Niska, Jared A.; Shahbazian, Jonathan H.; Ramos, Romela Irene; Francis, Kevin P.; Bernthal, Nicholas M.

    2013-01-01

    Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects. PMID:23917317

  8. [Clinical and pharmacological aspects of rifaximin, local antibiotic therapy in intestinal disorders].

    Science.gov (United States)

    Gasztonyi, Beáta; Hunyady, Béla

    2004-10-24

    The authors report pharmacokinetics and indications of rifaximin and the results of clinical studies. Rifaximin has a large antibacterial spectrum with a good therapeutic effect on both gram positive and gram negative aerob and anaerob bacteria. Practically there is no absorption (< 1%) following oral administration with a high concentration in gastrointestinal mucosa (8000 microg/g). No increase in absorption can be detected in intestinal damage caused by inflammatory bowel disease. The remarkable safety profile of rifaximin is due to its negligible quality of absorption. According to the clinical studies rifaximin could be an adequate therapeutic approach in all gastrointestinal diseases and interventions when antibacterial therapy is needed.

  9. A prospective randomized cohort study evaluating 3 weeks vs 6 weeks of oral antibiotic treatment in the setting of "maximal medical therapy" for chronic rhinosinusitis.

    Science.gov (United States)

    Sreenath, Satyan B; Taylor, Robert J; Miller, Justin D; Ambrose, Emily C; Rawal, Rounak B; Ebert, Charles S; Senior, Brent A; Zanation, Adam M

    2015-09-01

    Surprisingly, little literature exists evaluating the optimal duration of antibiotic treatment in "maximal medical therapy" for chronic rhinosinusitis (CRS). As such, we investigated whether 3 weeks vs 6 weeks of antibiotic therapy resulted in significant differences in clinical response. A prospective, randomized cohort study was performed with patients assigned to 3-week or 6-week cohorts. Our primary outcome was failure of "maximal medical therapy" and surgical recommendation. Secondary outcomes included changes in pretherapy and posttherapy scores for the Rhinosinusitis Disability Index (RSDI), Chronic Sinusitis Survey (CSS), and computed tomography (CT)-based Lund-Mackay (LM) evaluation. Analyses were substratified based on presence of nasal polyps. Forty patients were randomized to the 3-week or 6-week treatment cohorts, with near-complete clinical follow-up achieved. No significant difference was found between the proportion of patients who failed medical therapy and were deemed surgical candidates between the 2 cohorts (71% vs 68%, p = 1.000). No significant difference was found in the change of RSDI or CSS scores in the 3 vs 6 weeks of treatment groups (mean ± standard error of the mean [SEM]; RSDI: 9.62 ± 4.14 vs 1.53 ± 4.01, p = 0.868; CSS: 5.75 ± 4.36 vs 9.65 ± 5.34, p = 0.573). Last, no significant difference was found in the change of LM scores (3.35 ± 1.11 vs 1.53 ± 0.81, p = 0.829). Based on this data, there is little difference in clinical outcomes between 3 weeks vs 6 weeks of antibiotic treatment as part of "maximal medical therapy" for CRS. Increased duration of antibiotic treatment theoretically may increase risk from side effects and creates higher healthcare costs. © 2015 ARS-AAOA, LLC.

  10. Gold Nanoparticles and Their Alternatives for Radiation Therapy Enhancement

    Directory of Open Access Journals (Sweden)

    Daniel R. Cooper

    2014-10-01

    Full Text Available Radiation therapy is one of the most commonly used treatments for cancer. The dose of delivered ionizing radiation can be amplified by the presence of high-Z materials via an enhancement of the photoelectric effect; the most widely studied material is gold (atomic number 79. However, a large amount is needed to obtain a significant dose enhancement, presenting a challenge for delivery. In order to make this technique of broader applicability, the gold must be targeted, or alternative formulations developed that do not rely solely on the photoelectric effect. One possible approach is to excite scintillating nanoparticles with ionizing radiation, and then exploit energy transfer between these particles and attached dyes in a manner analogous to photodynamic therapy. Doped rare-earth halides and semiconductor quantum dots have been investigated for this purpose. However, although the spectrum of emitted light after radiation excitation is usually similar to that seen with light excitation, the yield is not. Measurement of scintillation yields is challenging, and in many cases has been done only for bulk materials, with little understanding of how the principles translate to the nanoscale. Another alternative is to use local heating using gold or iron, followed by application of ionizing radiation. Hyperthermia pre-sensitizes the tumors, leading to an improved response. Another approach is to use chemotherapeutic drugs that can radiosensitize tumors. Drugs may be attached to high-Z nanoparticles or encapsulated. This article discusses each of these techniques, giving an overview of the current state of nanoparticle-assisted radiation therapy and future directions.

  11. The effect of systemic antibiotics administered during the active phase of non-surgical periodontal therapy or after the healing phase: a systematic review

    Directory of Open Access Journals (Sweden)

    Aretuza FRITOLI

    2015-06-01

    Full Text Available Objective The aim of this systematic review was to compare the clinical effectiveness of systemic antibiotics administered in the active stage of periodontal treatment or after the healing phase. Material and Methods An electronic search was performed in the databases EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA statement. A manual search of the reference list of selected studies and of review articles was also performed up to November 2013. Randomized Clinical Trials (RCT that evaluated the systemic administration of antibiotics as adjuvants to scaling and root planning (SRP at different phases of periodontal treatment were included. Systematic reviews and studies that evaluated subjects with systemic diseases and those that used subantimicrobial doses of antibiotics were excluded. Results The initial search identified 1,039 articles, of which seven were selected, and only one met the inclusion criteria. This study showed that subjects taking metronidazole and amoxicillin at the initial phase of treatment exhibited statistically significantly greater reduction in pocket depth and gain in clinical attachment level in initially deep sites (PD≥7 mm than subjects taking antibiotics after healing (p<0.05. This comparison was conducted 2 months after antibiotic intake, at the healing phase. Conclusion To date, only one short-term RCT has directly compared different moments of systemic antibiotics administration, as adjuncts to SRP, in the treatment of periodontitis. Although the results of this study suggested some benefits for antibiotics intake during the active phase of therapy, these findings need to be confirmed by larger placebo-controlled randomized clinical trials with longer follow-up periods.

  12. A CRISPR-Cas system enhances envelope integrity mediating antibiotic resistance and inflammasome evasion

    NARCIS (Netherlands)

    T.R. Sampson (Timothy); B.A. Napier (Brooke); M.R. Schroeder (Max); J. Zhao (Jingshi); R.P.L. Louwen (Rogier); C.-Y. Chin (Chui-Yoke); H.K. Ratner (Hannah); A.C. Llewellyn (Anna); C.L. Jones (Crystal); H. Laroui (Hamed); D. Merlin (Didier); P. Zhou (Pei); H.P. Endtz (Hubert); D.S. Weiss (David)

    2014-01-01

    textabstractClustered, regularly interspaced, short palindromic repeats-CRISPR associated (CRISPR-Cas) systems defend bacteria against foreign nucleic acids, such as during bacteriophage infection and transformation, processes which cause envelope stress. It is unclear if these machineries enhance

  13. Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy.

    Directory of Open Access Journals (Sweden)

    Massimo Conese

    Full Text Available In seeking more specific biomarkers of the cystic fibrosis (CF lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibiotic treatment. Genes involved in neutrophil-mediated inflammation, i.e. chemotaxis, respiratory burst, apoptosis, and granule exocytosis, were the targets of this study. Microarray analysis was carried out in blood and airway neutrophils from CF patients and in control subjects. A fold change (log threshold of 1.4 and a cut-off of p<0.05 were utilized to identify significant genes. Community networks and principal component analysis were used to distinguish the groups of controls, pre- and post-therapy patients. Control subjects and CF patients before therapy were readily separated, whereas a clear distinction between patients before and after antibiotic therapy was not possible. Blood neutrophils before therapy presented 269 genes down-regulated and 56 up-regulated as compared with control subjects. Comparison between the same patients before and after therapy showed instead 44 genes down-regulated and 72 up-regulated. Three genes appeared to be sensitive to therapy and returned to "healthy" condition: phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, hydrogen voltage-gated channel 1 (HVCN1, and β-arrestin 1 (ARRB1. The up-regulation of these genes after therapy were confirmed by real time PCR. In airway neutrophils, 1029 genes were differentially expressed post- vs pre-therapy. Of these, 30 genes were up-regulated and 75 down-regulated following antibiotic treatment. However, biological plausibility determined that only down-regulated genes belonged to the gene classes studied for blood neutrophils. Finally, it was observed that commonly expressed genes showed a greater variability in airway neutrophils than that found in blood neutrophils

  14. Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy.

    Science.gov (United States)

    Conese, Massimo; Castellani, Stefano; Lepore, Silvia; Palumbo, Orazio; Manca, Antonio; Santostasi, Teresa; Polizzi, Angela Maria; Copetti, Massimiliano; Di Gioia, Sante; Casavola, Valeria; Guerra, Lorenzo; Diana, Anna; Montemurro, Pasqualina; Mariggiò, Maria Addolorata; Gallo, Crescenzio; Maffione, Angela Bruna; Carella, Massimo

    2014-01-01

    In seeking more specific biomarkers of the cystic fibrosis (CF) lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibiotic treatment. Genes involved in neutrophil-mediated inflammation, i.e. chemotaxis, respiratory burst, apoptosis, and granule exocytosis, were the targets of this study. Microarray analysis was carried out in blood and airway neutrophils from CF patients and in control subjects. A fold change (log) threshold of 1.4 and a cut-off of p<0.05 were utilized to identify significant genes. Community networks and principal component analysis were used to distinguish the groups of controls, pre- and post-therapy patients. Control subjects and CF patients before therapy were readily separated, whereas a clear distinction between patients before and after antibiotic therapy was not possible. Blood neutrophils before therapy presented 269 genes down-regulated and 56 up-regulated as compared with control subjects. Comparison between the same patients before and after therapy showed instead 44 genes down-regulated and 72 up-regulated. Three genes appeared to be sensitive to therapy and returned to "healthy" condition: phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), hydrogen voltage-gated channel 1 (HVCN1), and β-arrestin 1 (ARRB1). The up-regulation of these genes after therapy were confirmed by real time PCR. In airway neutrophils, 1029 genes were differentially expressed post- vs pre-therapy. Of these, 30 genes were up-regulated and 75 down-regulated following antibiotic treatment. However, biological plausibility determined that only down-regulated genes belonged to the gene classes studied for blood neutrophils. Finally, it was observed that commonly expressed genes showed a greater variability in airway neutrophils than that found in blood neutrophils, both before and

  15. Do we treat our patients or rather periodontal microbes with adjunctive antibiotics in periodontal therapy? A 16S rDNA microbial community analysis.

    Science.gov (United States)

    Hagenfeld, Daniel; Koch, Raphael; Jünemann, Sebastian; Prior, Karola; Harks, Inga; Eickholz, Peter; Hoffmann, Thomas; Kim, Ti-Sun; Kocher, Thomas; Meyle, Jörg; Kaner, Doğan; Schlagenhauf, Ulrich; Ehmke, Benjamin; Harmsen, Dag

    2018-01-01

    Empiric antibiotics are often used in combination with mechanical debridement to treat patients suffering from periodontitis and to eliminate disease-associated pathogens. Until now, only a few next generation sequencing 16S rDNA amplicon based publications with rather small sample sizes studied the effect of those interventions on the subgingival microbiome. Therefore, we studied subgingival samples of 89 patients with chronic periodontitis (solely non-smokers) before and two months after therapy. Forty-seven patients received mechanical periodontal therapy only, whereas 42 patients additionally received oral administered amoxicillin plus metronidazole (500 and 400 mg, respectively; 3x/day for 7 days). Samples were sequenced with Illumina MiSeq 300 base pairs paired end technology (V3 and V4 hypervariable regions of the 16S rDNA). Inter-group differences before and after therapy of clinical variables (percentage of sites with pocket depth ≥ 5mm, percentage of sites with bleeding on probing) and microbiome variables (diversity, richness, evenness, and dissimilarity) were calculated, a principal coordinate analysis (PCoA) was conducted, and differential abundance of agglomerated ribosomal sequence variants (aRSVs) classified on genus level was calculated using a negative binomial regression model. We found statistically noticeable decreased richness, and increased dissimilarity in the antibiotic, but not in the placebo group after therapy. The PCoA revealed a clear compositional separation of microbiomes after therapy in the antibiotic group, which could not be seen in the group receiving mechanical therapy only. This difference was even more pronounced on aRSV level. Here, adjunctive antibiotics were able to induce a microbiome shift by statistically noticeably reducing aRSVs belonging to genera containing disease-associated species, e.g., Porphyromonas, Tannerella, Treponema, and Aggregatibacter, and by noticeably increasing genera containing health

  16. Evaluation of the Antimicrobial Activity of Different Antibiotics Enhanced with Silver-Doped Hydroxyapatite Thin Films

    Directory of Open Access Journals (Sweden)

    Daniela Predoi

    2016-09-01

    Full Text Available The inhibitory and antimicrobial effects of silver particles have been known since ancient times. In the last few years, a major health problem has arisen due to pathogenic bacteria resistance to antimicrobial agents. The antibacterial activities of new materials including hydroxyapatite (HAp, silver-doped hydroxyapatite (Ag:HAp and various types of antibiotics such as tetracycline (T-HAp and T-Ag:HAp or ciprofloxacin (C-HAp and C-Ag:HAp have not been studied so far. In this study we reported, for the first time, the preparation and characterization of various thin films based on hydroxyapatite and silver-doped hydroxyapatite combined with tetracycline or ciprofloxacin. The structural and chemical characterization of hydroxyapatite and silver-doped hydroxyapatite thin films has been evaluated by X-ray diffraction (XRD and Fourier transform infrared spectroscopy (FTIR. The morphological studies of the HAp, Ag:HAp, T-HAp, T-Ag:HAp, C-HAp and C-Ag:HAp thin solid films were performed using scanning electron microscopy (SEM. In order to study the chemical composition of the coatings, energy dispersive X-ray analysis (EDX and glow discharge optical emission spectroscopy (GDOES measurements have been used, obtaining information on the distribution of the elements throughout the film. These studies have confirmed the purity of the prepared hydroxyapatite and silver-doped hydroxyapatite thin films obtained from composite targets containing Ca10−xAgx(PO46(OH2 with xAg = 0 (HAp and xAg = 0.2 (Ag:HAp. On the other hand, the major aim of this study was the evaluation of the antibacterial activities of ciprofloxacin and tetracycline in the presence of HAp and Ag:HAp thin layers against Staphylococcus aureus and Escherichia coli strains. The antibacterial activities of ciprofloxacin and tetracycline against Staphylococcus aureus and Escherichia coli test strains increased in the presence of HAp and Ag:HAp thin layers.

  17. Analysis of Acinetobacter baumannii resistance patterns in patients with chronic obstructive pulmonary disease (COPD in terms of choice of effective empiric antibiotic therapy

    Directory of Open Access Journals (Sweden)

    Aneta Grochowalska

    2017-06-01

    In the performed study, the infections caused by multi-resistant Acinetobacter baumannii, were observed in COPD, which should be taken into consideration in choosing empirical antibiotic therapy. Simultaneously, the local resistance patterns of multi-drug-resistant (MDR Gram-negative strains co-infecting COPD should be considered in empirical treatment. Moreover, both additional clinical complication and co-infections contribute to a more severe course of diseases. In this study, the mortality percent exceeded 29%.

  18. Circulating cytokines and procalcitonin in acute Q fever granulomatous hepatitis with poor response to antibiotic and short-course steroid therapy: a case report

    Directory of Open Access Journals (Sweden)

    Chang Lin-Li

    2010-07-01

    Full Text Available Abstract Background Q fever is a zoonosis distributed worldwide that is caused by Coxiella burnetii infection and the defervescence usually occurs within few days of appropriate antibiotic therapy. Whether the changes of cytokine levels are associated with acute Q fever with persistent fever despite antibiotic therapy had not been investigated before. Case Presentation We report a rare case of acute Q fever granulomatous hepatitis remained pyrexia despite several antibiotic therapy and 6-day course of oral prednisolone. During the 18-month follow-up, the investigation of the serum cytokines profile and procalcitonin (PCT revealed that initially elevated levels of interleukin-2 (IL-2, IL-8, IL-10, and PCT decreased gradually, but the IL-6 remained in low titer. No evidence of chronic Q fever was identified by examinations of serum antibodies against C. burnetii and echocardiography. Conclusions The changes of cytokine levels may be associated with acute Q fever with poor response to treatment and PCT may be an indicator for monitoring the response to treatment.

  19. Local dose enhancement in radiation therapy: Monte Carlo simulation study

    International Nuclear Information System (INIS)

    Silva, Laura E. da; Nicolucci, Patricia

    2014-01-01

    The development of nanotechnology has boosted the use of nanoparticles in radiation therapy in order to achieve greater therapeutic ratio between tumor and healthy tissues. Gold has been shown to be most suitable to this task due to the high biocompatibility and high atomic number, which contributes to a better in vivo distribution and for the local energy deposition. As a result, this study proposes to study, nanoparticle in the tumor cell. At a range of 11 nm from the nanoparticle surface, results have shown an absorbed dose 141 times higher for the medium with the gold nanoparticle compared to the water for an incident energy spectrum with maximum photon energy of 50 keV. It was also noted that when only scattered radiation is interacting with the gold nanoparticles, the dose was 134 times higher compared to enhanced local dose that remained significant even for scattered radiation. (author)

  20. A Comparison of Hospital Versus Outpatient Parenteral Antibiotic Therapy at Home for Pyelonephritis and Meningitis.

    Science.gov (United States)

    Hensey, Conor C; Sett, Arun; Connell, Tom G; Bryant, Penelope A

    2017-09-01

    Despite the benefits of home treatment with outpatient parenteral antimicrobial therapy (OPAT), children with pyelonephritis and meningitis are rarely included. We aimed to compare clinical characteristics and outcomes between hospital and home treatment for these conditions and to identify factors influencing home treatment. Children admitted to the hospital with pyelonephritis or proven and presumed bacterial meningitis from January 1, 2012, to December 31, 2013 were identified retrospectively. Patients who received any OPAT (home group) received daily visits via our Hospital-in-the-Home (HITH) program; inpatients (hospital group) received standard care. Clinical and demographic features, length of stay, readmission rate and cost were compared between hospital and home groups. One hundred thirty-nine children with pyelonephritis and 70 with meningitis were identified, of which 127 and 44 were potentially suitable for OPAT, respectively. Of these, 12 (9%) with pyelonephritis received OPAT, contrasting with 29 (66%) with meningitis. Clinical features did not differ between hospital- and home-treated patients for either condition. Patients with meningitis in the hospital group were younger than those transferred to HITH (1 vs. 2 months; P = 0.01). All patients were afebrile before transfer to HITH. Admissions for pyelonephritis were brief with inpatients having a shorter length of stay than home patients (median: 3 vs. 4.5 days; P = 0.002). Unplanned readmission rates were comparable across all groups. Transfer to HITH resulted in a saving of AU$178,180. Children with pyelonephritis and meningitis can feasibly receive OPAT. Age, treatment duration and fever influence this decision. None of these should be barriers to OPAT, and the cost savings support change in practice.

  1. First Report of a Case of Pneumococcal Meningitis Which Did Not Respond to the Ceftriaxone Therapy despite the Isolated Organism Being Sensitive to This Antibiotic In Vitro

    Directory of Open Access Journals (Sweden)

    Maryam Mojtabavi

    2011-01-01

    Full Text Available A 60-year-old man presented with pneumococcal meningitis which did not respond to the ceftriaxone therapy, in spite of in-vitro susceptibility (minimal inhibitory concentration of 0.016 μg/dLit of the isolated organism to this antibacterial agent, although ceftriaxone is still the drug of choice for such pneumococcal meningitis. Review of published articles revealed no report of clinical resistance in organisms which were susceptible to the same antimicrobial agent in vitro. This alarming emergence of isolates with in vivo resistance should be considered and even could lead to a shift in the empirical antibiotic therapy for pneumococcal infections.

  2. Antibiotics and Antibiotic Resistance

    Science.gov (United States)

    ... all that ails you. Antibiotics, also known as antimicrobial drugs, are drugs that fight infections caused by bacteria. ... Information for Consumers and Health Professionals Information by drug class Antimicrobial Resistance Animal and Veterinary Related Resources Further information ...

  3. Home intravenous antibiotic therapy in children with cystic fibrosis: clinical outcome, quality of life and economic benefit

    OpenAIRE

    Chrysochoou, EA; Hatziagorou, E; Kirvassilis, F; Tsanakas, J

    2016-01-01

    Background: Pediatric home care has improved therapeutic options for children with chronic disease. Home intravenous (IV) antibiotic treatment against Pseudomonas aeruginosa (PsA) in cystic fibrosis (CF) patients has offered increased flexibility to these patients and family life. A prospective clinical study was conducted to compare safety, efficacy, and cost benefits of home versus hospital IV antibiotic treatment among CF children and adolescents.

  4. Rational Antibiotic Therapy for BHSA-Infection as a Factor of Prevention of Primary and Secondary Acute Rheumatic Fever

    Directory of Open Access Journals (Sweden)

    V.V. Bugeruk

    2014-03-01

    Full Text Available The article discusses the choice of antibiotic agent to treat infections caused by beta-hemolytic streptococcus group A (BHSA. There are given antibiotic regimens in different variants — carriage of BHSA, BHSA-pharyngitis in patients with and without allergy on penicillin, in acute rheumatic fever.

  5. The effect of systemic antibiotics administered during the active phase of non-surgical periodontal therapy or after the healing phase: a systematic review.

    Science.gov (United States)

    Fritoli, Aretuza; Gonçalves, Cristiane; Faveri, Marcelo; Figueiredo, Luciene Cristina; Pérez-Chaparro, Paula Juliana; Fermiano, Daiane; Feres, Magda

    2015-01-01

    The aim of this systematic review was to compare the clinical effectiveness of systemic antibiotics administered in the active stage of periodontal treatment or after the healing phase. An electronic search was performed in the databases EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL), in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A manual search of the reference list of selected studies and of review articles was also performed up to November 2013. Randomized Clinical Trials (RCT) that evaluated the systemic administration of antibiotics as adjuvants to scaling and root planning (SRP) at different phases of periodontal treatment were included. Systematic reviews and studies that evaluated subjects with systemic diseases and those that used subantimicrobial doses of antibiotics were excluded. The initial search identified 1,039 articles, of which seven were selected, and only one met the inclusion criteria. This study showed that subjects taking metronidazole and amoxicillin at the initial phase of treatment exhibited statistically significantly greater reduction in pocket depth and gain in clinical attachment level in initially deep sites (PD≥7 mm) than subjects taking antibiotics after healing (pantibiotic intake, at the healing phase. To date, only one short-term RCT has directly compared different moments of systemic antibiotics administration, as adjuncts to SRP, in the treatment of periodontitis. Although the results of this study suggested some benefits for antibiotics intake during the active phase of therapy, these findings need to be confirmed by larger placebo-controlled randomized clinical trials with longer follow-up periods.

  6. The effect of systemic antibiotics administered during the active phase of non-surgical periodontal therapy or after the healing phase: a systematic review

    Science.gov (United States)

    FRITOLI, Aretuza; GONÇALVES, Cristiane; FAVERI, Marcelo; FIGUEIREDO, Luciene Cristina; PÉREZ-CHAPARRO, Paula Juliana; FERMIANO, Daiane; FERES, Magda

    2015-01-01

    Objective The aim of this systematic review was to compare the clinical effectiveness of systemic antibiotics administered in the active stage of periodontal treatment or after the healing phase. Material and Methods An electronic search was performed in the databases EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL), in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A manual search of the reference list of selected studies and of review articles was also performed up to November 2013. Randomized Clinical Trials (RCT) that evaluated the systemic administration of antibiotics as adjuvants to scaling and root planning (SRP) at different phases of periodontal treatment were included. Systematic reviews and studies that evaluated subjects with systemic diseases and those that used subantimicrobial doses of antibiotics were excluded. Results The initial search identified 1,039 articles, of which seven were selected, and only one met the inclusion criteria. This study showed that subjects taking metronidazole and amoxicillin at the initial phase of treatment exhibited statistically significantly greater reduction in pocket depth and gain in clinical attachment level in initially deep sites (PD≥7 mm) than subjects taking antibiotics after healing (pantibiotic intake, at the healing phase. Conclusion To date, only one short-term RCT has directly compared different moments of systemic antibiotics administration, as adjuncts to SRP, in the treatment of periodontitis. Although the results of this study suggested some benefits for antibiotics intake during the active phase of therapy, these findings need to be confirmed by larger placebo-controlled randomized clinical trials with longer follow-up periods. PMID:26221918

  7. Chicken egg yolk antibodies (IgY) as non-antibiotic production enhancers for use in swine production: a review

    OpenAIRE

    Li, Xiaoyu; Wang, Lili; Zhen, Yuhong; Li, Shuying; Xu, Yongping

    2015-01-01

    In recent years, the use of in-feed antibiotics for growth and disease prevention in livestock production has been under severe scrutiny. The use and misuse of in-feed antibiotics has led to problems with drug residues in animal products and increased bacterial resistance. Chicken egg yolk antibodies (IgY) have attracted considerable attention as an alternative to antibiotics to maintain swine health and performance. Oral administration of IgY possesses many advantages over mammalian IgG such...

  8. Preparation and characterization of flexible nanoliposomes loaded with daptomycin, a novel antibiotic, for topical skin therapy

    Directory of Open Access Journals (Sweden)

    Li C

    2013-03-01

    Full Text Available Chong Li, Xiaolin Zhang, Xinliang Huang, Xiaoying Wang, Guojian Liao, Zhangbao ChenCollege of Pharmaceutical Sciences, Southwest University, Chongqing, People’s Republic of ChinaAbstract: The purpose of this study was to investigate flexible nanoliposomes for mediating topical delivery of daptomycin, and to document permeation rates and bacteriostatic activity towards skin infections. Response surface methodology was used to optimize the daptomycin-loaded flexible nanoliposomes (DAP-FL, and the amount of drug loaded into the particles was evaluated as the investigation index. The optimal lipid ratio was lecithin to sodium cholate 17:1 (w/w and the lipid to drug ratio was 14:1 (w/w. The hydration temperature was set at 37°C and the duration of treatment with ultrasound was 20 minutes. The DAP-FL obtained had a small mean particle size (55.4 nm with a narrow size distribution (polydispersity index 0.15. The mean entrapment efficiency was 87.85% ± 2.15% and the mean percent drug loading was 5.61% ± 0.14%. Using skin mounted between the donor and receptor compartments of a modified Franz diffusion cell, the percentage and quantity of cumulative daptomycin permeation from DAP-FL within 12 hours were measured at 96.28% ± 0.70% and (132.23 ± 17.73 µg/cm2 *5 = 661.15 ± 88.65 µg/cm2, directly, showing rapid and efficient antibacterial activity against Staphylococcus aureus. Following local administration of DAP-FL, daptomycin was detected in multilayer tissues within the skin and underlying structures in the dorsal skin of the mouse. Effective therapeutic concentrations were maintained for several hours, and significantly inhibited bacterial growth and injury-induced biofilms. These results demonstrate that the DAP-FL can enhance the ability of daptomycin to permeate the skin efficiently, where it has a powerful antibacterial action and activity against biofilms. This novel formulation of daptomycin has potential as a new approach in the

  9. Nosocomial extended-spectrum beta-lactamase-producing Klebsiella pneumoniae bacteremia in hemodialysis patients and the implications for antibiotic therapy.

    Science.gov (United States)

    Yang, Chih-Chao; Wu, Chien-Hsing; Lee, Chien-Te; Liu, Han-Tsung; Chen, Jin-Bor; Chiu, Chien-Hua; Chen, Chih-Hung; Chuang, Feng-Rong

    2014-11-01

    In the face of increasing treatment options for extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-Kp) hemodialysis (HD) access-related bacteremia, the difference in clinical effectiveness between ertapenem and flomoxef remains unclear. We conducted this retrospective study to determine their efficacies and treatment outcomes. Patients on maintenance HD with fistula-, graft-, or catheter-related ESBL-Kp bacteremia were enrolled. Data related to clinical features and antibiotic treatments were collected. Outcome was determined by mortality resulting from bacteremia during the 14-day period after the collection of the first positive blood culture for flomoxef-susceptible ESBL-Kp. The 64 patients studied had severe septicemia as determined by the Pitt bacteremia score; 50% (32/64) were in the intensive care unit (ICU) at the time of bacteremia. Old age (>65 years; 57.8%), malnutrition (albumin30 days; 75%) were also highly prevalent. The study population comprised nine fistula-, 10 graft-, and 45 HD catheter-related bacteremia cases, and the mortality rate was high (38/64, 59.4%). The mortality rate was significantly higher in the flomoxef treatment group than in the ertapenem treatment group (22/30, 73% vs. 16/34, 47%, pflomoxef use (odds ratio (OR) 2.52, 95% confidence interval (CI) 1.34-35.17) and Pitt bacteremia score (OR 4.37, 95% CI 1.28-5.26) were independently associated with mortality. In accordance with our previous study, our results have demonstrated the inferiority of flomoxef to carbapenems in the treatment of HD access-related ESBL-Kp bacteremia and provide an insight into the possibility of using ertapenem rather than flomoxef as an initial or de-escalating therapy for infections caused by ESBL-producing bacteria.

  10. Dynamic energy budget approach to evaluate antibiotic effects on biofilms

    Science.gov (United States)

    Birnir, Bjorn; Carpio, Ana; Cebrián, Elena; Vidal, Perfecto

    2018-01-01

    Quantifying the action of antibiotics on biofilms is essential to devise therapies against chronic infections. Biofilms are bacterial communities attached to moist surfaces, sheltered from external aggressions by a polymeric matrix. Coupling a dynamic energy budget based description of cell metabolism to surrounding concentration fields, we are able to approximate survival curves measured for different antibiotics. We reproduce numerically stratified distributions of cell types within the biofilm and introduce ways to incorporate different resistance mechanisms. Qualitative predictions follow that are in agreement with experimental observations, such as higher survival rates of cells close to the substratum when employing antibiotics targeting active cells or enhanced polymer production when antibiotics are administered. The current computational model enables validation and hypothesis testing when developing therapies.

  11. Rapid identification and susceptibility testing of uropathogenic microbes via immunosorbent ATP-bioluminescence assay on a microfluidic simulator for antibiotic therapy.

    Science.gov (United States)

    Dong, Tao; Zhao, Xinyan

    2015-02-17

    The incorporation of pathogen identification with antimicrobial susceptibility testing (AST) was implemented on a concept microfluidic simulator, which is well suited for personalizing antibiotic treatment of urinary tract infections (UTIs). The microfluidic device employs a fiberglass membrane sandwiched between two polypropylene components, with capture antibodies immobilized on the membrane. The chambers in the microfluidic device share the same geometric distribution as the wells in a standard 384-well microplate, resulting in compatibility with common microplate readers. Thirteen types of common uropathogenic microbes were selected as the analytes in this study. The microbes can be specifically captured by various capture antibodies and then quantified via an ATP bioluminescence assay (ATP-BLA) either directly or after a variety of follow-up tests, including urine culture, antibiotic treatment, and personalized antibiotic therapy simulation. Owing to the design of the microfluidic device, as well as the antibody specificity and the ATP-BLA sensitivity, the simulator was proven to be able to identify UTI pathogen species in artificial urine samples within 20 min and to reliably and simultaneously verify the antiseptic effects of eight antibiotic drugs within 3-6 h. The measurement range of the device spreads from 1 × 10(3) to 1 × 10(5) cells/mL in urine samples. We envision that the medical simulator might be broadly employed in UTI treatment and could serve as a model for the diagnosis and treatment of other diseases.

  12. Antibiotic Conjugated Fluorescent Carbon Dots as a Theranostic Agent for Controlled Drug Release, Bioimaging, and Enhanced Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Mukeshchand Thakur

    2014-01-01

    Full Text Available A novel report on microwave assisted synthesis of bright carbon dots (C-dots using gum arabic (GA and its use as molecular vehicle to ferry ciprofloxacin hydrochloride, a broad spectrum antibiotic, is reported in the present work. Density gradient centrifugation (DGC was used to separate different types of C-dots. After careful analysis of the fractions obtained after centrifugation, ciprofloxacin was attached to synthesize ciprofloxacin conjugated with C-dots (Cipro@C-dots conjugate. Release of ciprofloxacin was found to be extremely regulated under physiological conditions. Cipro@C-dots were found to be biocompatible on Vero cells as compared to free ciprofloxacin (1.2 mM even at very high concentrations. Bare C-dots (∼13 mg mL−1 were used for microbial imaging of the simplest eukaryotic model—Saccharomyces cerevisiae (yeast. Bright green fluorescent was obtained when live imaging was performed to view yeast cells under fluorescent microscope suggesting C-dots incorporation inside the cells. Cipro@C-dots conjugate also showed enhanced antimicrobial activity against both model gram positive and gram negative microorganisms. Thus, the Cipro@C-dots conjugate paves not only a way for bioimaging but also an efficient new nanocarrier for controlled drug release with high antimicrobial activity, thereby serving potential tool for theranostics.

  13. Clinicians’ Views and Experiences of Interventions to Enhance the Quality of Antibiotic Prescribing for Acute Respiratory Tract Infections

    NARCIS (Netherlands)

    Anthierens, Sibyl; Tonkin-Crine, Sarah; Cals, Jochen W.; Coenen, Samuel; Yardley, Lucy; Brookes-Howell, Lucy; Fernandez-Vandellos, Patricia; Krawczyk, Jaroslaw; Godycki-Cwirko, Maciek; Llor, Carl; Butler, Christopher C.; Verheij, Theo; Goossens, Herman; Little, Paul; Francis, Nick A.

    2015-01-01

    BACKGROUND: Evidence shows a high rate of unnecessary antibiotic prescriptions in primary care in Europe and the United States. Given the costs of widespread use and associated antibiotic resistance, reducing inappropriate use is a public health priority. OBJECTIVE: We aimed to explore clinicians’

  14. Risk factors associated with bacteriological cure, new infection, and incidence of clinical mastitis after dry cow therapy with three different antibiotics.

    Science.gov (United States)

    Gundelach, Yasmin; Kalscheuer, Elke; Hamann, Henning; Hoedemaker, Martina

    2011-09-01

    Factors affecting bacteriological cure rates (BCR) and new intramammary infections (IMI) during the dry period as well as clinical mastitis (CM) during early lactation were investigated in 414 German Holstein dairy cows receiving dry cow therapy. Cows were treated with either benethamine benzylpenicillin (300,000 IU), penethamate hydriodide (100,000 IU), and framycetin sulphate (100 mg, n = 136), or cefquinome (150 mg, n = 135), or benzathine cloxacillin (1,280 mg, n = 143). Overall BCR, IMI, and CM at parturition were 86.4%, 20.7%, and 4.3%, respectively. The three antibiotic treatments differed only in BCR, with cloxacillin yielding better results than the others. Udder quarters from cows with > 4 lactations had a higher risk of IMI and CM at calving. Chronic changes in udder tissues were linked to a lower BCR and were associated with a higher risk of CM during early lactation. The risk of CM at calving was higher in udder quarters with unspecific or subclinical mastitis before drying off. In conclusion, with antibiotic dry cow therapy, age and health status of the udder appear to be major determinants of IMI and CM during the dry period and early lactation, while BCR was associated with the antibiotic type and udder tissue status.

  15. Anti-Rhodotorula activity of mycophenolic acid enhanced in the presence of polyene antibiotic nystatin.

    Science.gov (United States)

    Kinoshita, H; Wongsuntornpoj, S; Ihara, F; Nihira, T

    2017-02-01

    Rhodotorula species are opportunistic pathogens, which cause not only systemic fungaemia but also other localized infections. Despite serious side effects such as nephrotoxicity and hypokalemia, amphotericin B (a polyene antifungal) has been commonly prescribed for Rhodotorula infection because Rhodotorula species are resistant against a candin family of antifungal agents. In this study, novel active compounds against Rhodotorula species were screened from the extracts of entomopathogenic fungi based on the synergistic effect of polyene nystatin (NYS), which causes efficient targeting of compounds due to increased permeability through the fungal cell membrane. Around 37% of culture extracts from 31 entomopathogenic fungal strains showed anti-Rhodotorula activity in the synergistic bioassay system, suggesting that the coexistence assay with NYS enhanced the discovery of anti-Rhodotorula compounds. Judging from various physicochemical data, the active component from strain HF763 was identified as an immunosuppressant drug, mycophenolic acid (MPA). The minimum inhibitory concentration of MPA against three pathogenic Rhodotorula strains was determined, focusing on the synergistic effect with NYS. The results revealed that the values decreased by at least 87% in the presence of NYS, indicating that MPA showed a synergistic effect with NYS. This study aimed to screen active compounds against Rhodotorula species that are resistant to a candin family of antifungal agents, from entomopathogenic fungi. Assuming that most of the latent antifungal compounds do not exert their activity due to their inability to penetrate the membrane, we took advantage of polyene nystatin in the screening to increase permeability through the fungal cell membrane. The result of the screening revealed hidden antifungal activity of mycophenolic acid, demonstrating that the method applied in this study unlocks the potentials of bioresources, and proposes a new remedy for mycosis. © 2016 The

  16. Appropriateness of antibiotic prescription for targeted therapy of infections caused by multidrug-resistant bacteria: assessment of the most common improper uses in a tertiary hospital in southern Italy.

    Science.gov (United States)

    Viceconte, Giulio; Maraolo, Alberto Enrico; Iula, Vita Dora; Catania, Maria Rosaria; Tosone, Grazia; Orlando, Raffaele

    2017-09-01

    A huge proportion of antibiotic therapies for infections caused by multidrug-resistant bacteria (MDR) are inappropriate. In this study, we described the most common causes of inappropriateness of definitive antibiotic regimes in a large university hospital in southern Italy and we evaluated the impact on microbial eradication, length of stay, 30-day readmission and mortality. We retrospectively assessed 45 patients who received a definitive antibiotic therapy after isolation of multidrug-resistant Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. strains between 2014 and 2015. From the literature, we set a series of criteria to retrospectively determine the appropriateness of the therapy. In all, 61% of the prescribed antibiotic regimes were found to be inappropriate, especially due to incorrect drug dosage. It emerged that meropenem was the antibiotic most frequently inappropriately used. In 46% of infections caused by MDR but not extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenems were inappropriately administered. Microbial eradication was achieved in 87% of the appropriate therapy group compared to 31% of the inappropriate therapy group (chi-square=6.750, p<0.027). No statistically significant association was found between inappropriate therapy and the length of stay (chi-square=3.084, p=0.101) and 30-day readmission (p=0.103). Definitive antibiotic therapy in infections caused by multidrug-resistant bacteria in a large university hospital is often inappropriate, especially due to the drug dosing regimen, particularly in the case of meropenem and colistin. This inappropriateness has a significant impact on post-treatment microbial eradication in specimens collected after antibiotic therapy.

  17. Efficacy of antibiotic treatment of implant-associated Staphylococcus aureus infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: an animal study.

    Science.gov (United States)

    Greimel, Felix; Scheuerer, Christine; Gessner, Andre; Simon, Michaela; Kalteis, Thomas; Grifka, Joachim; Benditz, Achim; Springorum, Hans-Robert; Schaumburger, Jens

    2017-01-01

    The efficacy of antibiotic monotherapy and combination therapy in the treatment of implant-associated infection by Staphylococcus aureus was evaluated in an animal study. The femoral medullary cavity of 66 male Wistar rats was contaminated with S. aureus (ATCC 29213) and a metal device was implanted, of which 61 could be evaluated. Six treatment groups were studied: flucloxacillin, flucloxacillin in combination with rifampin, moxifloxacin, moxifloxacin in combination with rifampin, rifampin, and a control group with aqua. The treatment was applied for 14 days. After euthanasia, the bacterial counts in the periprosthetic bone, the soft tissue, and the implant-associated biofilm were measured. Both antibiotic combination treatments (moxifloxacin plus rifampin and flucloxacillin plus rifampin) achieved a highly significant decrease in microbial counts in the bone and soft tissue and in the biofilm. Mono-antibiotic treatments with either moxifloxacin or flucloxacillin were unable to achieve a significant decrease in microbial counts in bone and soft tissue or the biofilm, whilst rifampin was able to reduce the counts significantly only in the biofilm. Antibiotic resistance was measured in 1/3 of the cases in the rifampin group, whereas no resistance was measured in all other groups. The results show that combinations of both moxifloxacin and flucloxacillin plus rifampin are adequate for the treatment of periprosthetic infections due to infections with S. aureus , whereas monotherapies are not effective or not applicable due to the rapid development of antibiotic resistance. Therefore, moxifloxacin is an effective alternative in combination with rifampin for the treatment of implant-associated infections.

  18. Efficacy of antibiotic treatment of implant-associated Staphylococcus aureus infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: an animal study

    Directory of Open Access Journals (Sweden)

    Greimel F

    2017-06-01

    Full Text Available Felix Greimel,1 Christine Scheuerer,1 Andre Gessner,2 Michaela Simon,2 Thomas Kalteis,1 Joachim Grifka,1 Achim Benditz,1 Hans-Robert Springorum,1 Jens Schaumburger1 1Department of Orthopedics, University Medical Center Regensburg, Asklepios Klinikum Bad Abbach, Bad Abbach, 2Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, Regensburg, Bavaria, Germany Abstract: The efficacy of antibiotic monotherapy and combination therapy in the treatment of implant-associated infection by Staphylococcus aureus was evaluated in an animal study. The femoral medullary cavity of 66 male Wistar rats was contaminated with S. aureus (ATCC 29213 and a metal device was implanted, of which 61 could be evaluated. Six treatment groups were studied: flucloxacillin, flucloxacillin in combination with rifampin, moxifloxacin, moxifloxacin in combination with rifampin, rifampin, and a control group with aqua. The treatment was applied for 14 days. After euthanasia, the bacterial counts in the periprosthetic bone, the soft tissue, and the implant-associated biofilm were measured. Both antibiotic combination treatments (moxifloxacin plus rifampin and flucloxacillin plus rifampin achieved a highly significant decrease in microbial counts in the bone and soft tissue and in the biofilm. Mono-antibiotic treatments with either moxifloxacin or flucloxacillin were unable to achieve a significant decrease in microbial counts in bone and soft tissue or the biofilm, whilst rifampin was able to reduce the counts significantly only in the biofilm. Antibiotic resistance was measured in 1/3 of the cases in the rifampin group, whereas no resistance was measured in all other groups. The results show that combinations of both moxifloxacin and flucloxacillin plus rifampin are adequate for the treatment of periprosthetic infections due to infections with S. aureus, whereas monotherapies are not effective or not applicable due to the rapid development of

  19. Enhancing the Therapy Experience Using Principles of Video Game Design.

    Science.gov (United States)

    Folkins, John Wm; Brackenbury, Tim; Krause, Miriam; Haviland, Allison

    2016-02-01

    This article considers the potential benefits that applying design principles from contemporary video games may have on enhancing therapy experiences. Six principles of video game design are presented, and their relevance for enriching clinical experiences is discussed. The motivational and learning benefits of each design principle have been discussed in the education literature as having positive impacts on student motivation and learning and are related here to aspects of clinical practice. The essential experience principle suggests connecting all aspects of the experience around a central emotion or cognitive connection. The discovery principle promotes indirect learning in focused environments. The risk-taking principle addresses the uncertainties clients face when attempting newly learned skills in novel situations. The generalization principle encourages multiple opportunities for skill transfer. The reward system principle directly relates to the scaffolding of frequent and varied feedback in treatment. Last, the identity principle can assist clients in using their newly learned communication skills to redefine self-perceptions. These principles highlight areas for research and interventions that may be used to reinforce or advance current practice.

  20. Parent-Child Interaction Therapy: Enhancing Parent-Child Relationships

    Directory of Open Access Journals (Sweden)

    Anthony J. Urquiza

    2012-07-01

    Full Text Available Disruptive child behavior problems are common problems for parents and can be associated with serious delinquent behaviors and aggressive/violent behaviors in adolescence and adulthood. Parenting interventions to address disruptive child behavior problems has gained widespread acceptance. One of these parenting interventions is Parent-Child Interaction Therapy (PCIT. PCIT is a 14- to 20-week, founded on social learning and attachment theories, designed for children between 2 and 7 years of age with disruptive, or externalizing, behavior problems. This article will provide a brief review of the history of PCIT, a description of the basic components of PCIT, and an overview of recent developments that highlight the promise of PCIT with maltreating parent-child relationships, traumatized children, and in developing resilience in young children. In addressing the three basic treatment objectives for PCIT (i.e., reduction in child behavior problems, improving parenting skills, enhancing the quality of parent-child relationships, there is an abundance of research demonstrating very strong treatment effects and therefore, its value to the field. Recent research has also demonstrated the value of PCIT in reducing trauma symptoms in young children.

  1. Sore throat: effective communication delivers improved diagnosis, enhanced self-care and more rational use of antibiotics.

    Science.gov (United States)

    van der Velden, A W; Bell, J; Sessa, A; Duerden, M; Altiner, A

    2013-11-01

    The majority of throat infections are of viral origin and resolve without antibiotic treatment. Despite this, antibiotic use for sore throat infections remains high, partly because it is difficult to determine when antibiotics may be useful, on the basis of physical findings alone. Antibiotics may be beneficial in bacterial throat infections under certain clinical and epidemiological circumstances; however, even many of those infections in which bacteria play a role do resolve just as quickly without antibiotics. Furthermore, non-medical factors such as patient expectations and patient pressure are also important drivers of antibiotic use. To address these issues, a behavioural change is required that can be facilitated by improved communication between primary healthcare providers and patients. In this article, we provide doctors, nurses and pharmacy staff, working in primary care or in the community, with a structured approach to sore throat management, with the aim of educating and empowering patients to self-manage their condition. The first component of this approach involves identifying and addressing patients' expectations and concerns with regard to their sore throat and eliciting their opinion on antibiotics. The second part is dedicated to a pragmatic assessment of the severity of the condition, with attention to red-flag symptoms and risk factors for serious complications. Rather than just focusing on the cause (bacterial or viral) of the upper respiratory tract infections as a rationale for antibiotic use, healthcare providers should instead consider the severity of the patient's condition and whether they are at high risk of complications. The third part involves counselling patients on effective self-management options and providing information on the expected clinical course. Such a structured approach to sore throat management, using empathetic, non-paternalistic language, combined with written patient information, will help to drive patient

  2. Multiple Genetic Analysis System-Based Antibiotic Susceptibility Testing in Helicobacter pylori and High Eradication Rate With Phenotypic Resistance-Guided Quadruple Therapy.

    Science.gov (United States)

    Dong, Fangyuan; Ji, Danian; Huang, Renxiang; Zhang, Fan; Huang, Yiqin; Xiang, Ping; Kong, Mimi; Nan, Li; Zeng, Xianping; Wu, Yong; Bao, Zhijun

    2015-11-01

    Antibiotics resistance in Helicobacter pylori (H. pylori) is the major factor for eradication failure. Molecular tests including fluorescence in situ hybridization, PCR-restriction fragment length polymorphism, and dual priming oligonucleotide-PCR (DPO-PCR) play critical roles in the detection of antibiotic susceptibility; however, limited knowledge is known about application of multiple genetic analysis system (MGAS) in the area of H. pylori identification and antibiotics resistance detection.The aim of this study is to determine the antibiotics resistance using different molecular tests and evaluate the treatment outcomes of E-test-based genotypic resistance.A total of 297 patients with dyspepsia complaint were recruited for gastroscopies. Ninety patients with H. pylori culture positive were randomly divided into 2 groups (test group and control group). E-test, general PCR, and MGAS assay were performed in test group. Patients in control group were treated with empirical therapy (rabeprazole + bismuth potassium citrate + amoxicillin [AMX] + clarithromycin [CLR]), whereas patients in test group received quadruple therapy based on E-test results twice daily for 14 consecutive days. The eradication effect of H. pylori was confirmed by C-urea breath test after at least 4 weeks when treatment was finished.Rapid urease test showed 46.5% (128/297) patients with H. pylori infection, whereas 30.3% (90/297) patients were H. pylori culture positive. E-test showed that H. pylori primary resistance rate to CLR, AMX, metronidazole, tetracycline, and levofloxacin (LVX) was 40.0% (18/45), 4.4% (2/45), 53.3% (24/45), 0% (0/45), and 55.6% (25/45), respectively. In addition, there are many multidrug resistant (MDR) phenotypes, and the MDR strains have higher minimum inhibitory concentration than their single-drug resistant counterparts. Considering E-test as the reference test, the sensitivities of general PCR and MGAS in detecting CLR resistance were 83.3% (15/18) and 94.4% (17

  3. Cognitive deficits in marijuana users: effects on motivational enhancement therapy plus cognitive behavioral therapy treatment outcome

    Science.gov (United States)

    Aharonovich, Efrat; Brooks, Adam C; Nunes, Edward V; Hasin, Deborah S

    2008-01-01

    Clinical variables that affect treatment outcome for marijuana dependent individuals are not yet well understood, including the effects of cognitive functioning. To address this, level of cognitive functioning and treatment outcome were investigated. Twenty marijuana-dependent outpatients were administered a neuropsychological battery at treatment entry. All patients received 12 weekly individual sessions of combined motivational enhancement therapy and cognitive behavioral therapy. The Wilcoxon Exact Test was used to compare cognitive functioning test scores between completers and dropouts, and the Fisher Exact Test was used to compare proportion of negative urines between those with higher and lower scores on the cognitive tests. Marijuana abstinence was unrelated to cognitive functioning. However, dropouts scored significantly lower than completers on measures of abstract reasoning and processing accuracy, providing initial evidence that cognitive functioning plays a role in treatment retention of adult marijuana dependent patients. If supported by further studies, the findings may help inform the development of interventions tailored for cognitively impaired marijuana dependent patients. PMID:18329188

  4. Study of the use of probiotic foods as a complement of the conventional antibiotic-therapy for the treatment of Helicobacter pylori infection in children and its use as a prophylactic therapy in the reinfection by this pathogen

    Energy Technology Data Exchange (ETDEWEB)

    Zubillaga, M; Goldman, C; Salgueiro, J; Boccio, H [Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires (Argentina); [Laboratory of Stable Isotopes Applied to Biology and Medicine, School of Pharmacy and Biochemistry, University of Buenos Aires (Argentina); Balcarce, N; Cueto Rua, E [Children' s Hospital ' Sor Maria Ludovica' , Buenos Aires (Argentina); Oshiro, M [Health Centre ' Di Matteo' , Buenos Aires (Argentina); Lujan Calcagno, M [Mathemathics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires (Argentina); Martinez Sarrasague, M; Barrado, A [Laboratory of Stable Isotopes Applied to Biology and Medicine, School of Pharmacy and Biochemistry, University of Buenos Aires (Argentina); Weill, R [Agrarian Industries Department, School of Agronomy, University of Moron, Buenos Aires (Argentina)

    2004-07-01

    Heliocobacter pylori is a major etiologic factor in the development of chronic gastritis and peptic ulcer disease. Management of H. pylori infection in children was deeply discussed. Current recommended treatment includes a proton pump inhibitor in combination with antibiotics. Research on the use of probiotic foods as a treatment or as a complement of antibiotic treatment for H. pylori infection, showed promising results. Based on that evidence, the aims of our study were: To evaluate the prevalence of H. pylori infection in symptomatic children by means of a nuclear technique (13 C-UBT); To assess H. pylori eradication in the studied population by the administration of antibiotic triple therapy and probiotic foods; To evaluate H. pylori reinfection after 3 months of treatment with probiotics; and to evaluate symptoms improvement in the children after the end of the treatment. 137 children who assisted to the gastroenterologic visit were evaluated for H. pylori infection by the 13C-Urea Breath Test. Then 24 positive children were included in this study. The patients were separated into 2 groups. Group 1 received antibiotic treatment and placebo, and Group 2 received antibiotic treatment and probiotic food. The antibiotic treatment consisted of the combination of two antibiotics (amoxycillin and clarithromycin) with a proton pump inhibitor (omeprazole). After the end of antibiotic treatment both groups continued with the milk or probiotic food intake for three months. Post treatment controls by the 13C-UBT and a clinical evaluation were performed 1 and 3 months after the end of the antibiotic treatment. We found that prevalence of H. pylori infection in our population was 32.12% . Rates of eradication were 55% and 46% in Groups 1 and 2 respectively. No reinfection was found after three months of eradication. No significant difference in H. pylori eradication and symptoms improvement were observed between the children that consumed probiotics and the ones that

  5. Rhinosinusitis associated with post-dental extraction chronic oroantral fistula: outcomes of non-surgical management comprising antibiotics and local decongestion therapy.

    Science.gov (United States)

    Mishra, A K; Sinha, V R; Nilakantan, A; Singh, D K

    2016-06-01

    A non-surgical approach for managing rhinosinusitis associated with chronic oroantral fistula resulting from tooth extraction was evaluated. Twenty-six consecutive patients (15 males and 11 females) aged 28-72 years (mean, 49.81 years) were administered local decongestion therapy for 2 weeks and antibiotics for 10 days. Patients showing a reduction in Sino-Nasal Outcome Test 22 scores after two weeks continued to receive local decongestion therapy weekly for up to six weeks, while those not showing any improvement underwent surgical management. At 2 weeks, 17 patients (65.38 per cent) showed an improvement in rhinosinusitis (33.39 per cent mean reduction in Sino-Nasal Outcome Test 22 scores). The primary determinant of response was fistula size. At 6 weeks, sinusitis resolved completely in all 17 patients, and the fistula closed in 16 of these. Final Sino-Nasal Outcome Test 22 and Lund-Mackay scores showed no significant difference between the surgically treated and non-surgically treated groups. Local decongestion therapy along with antibiotics may promote resolution in this subset of rhinosinusitis patients.

  6. The Motivational Enhancement Therapy and Cognitive Behavioral Therapy Supplement: 7 Sessions of Cognitive Behavioral Therapy for Adolescent Cannabis Users, Cannabis Youth Treatment (CYT) Series, Volume 2.

    Science.gov (United States)

    Webb, Charles; Scudder, Meleney; Kaminer, Yifrah; Kaden, Ron

    This manual, a supplement to "Motivational Enhancement Therapy and Cognitive Behavioral Therapy for Adolescent Cannabis Users: 5 Sessions, Cannabis Youth Treatment (CYT) Series, Volume 1", presents a seven-session cognitive behavioral treatment (CBT7) approach designed especially for adolescent cannabis users. It addresses the implementation and…

  7. Selection of hyperproduction of AmpC and SME-1 in a carbapenem-resistant Serratia marcescens isolate during antibiotic therapy.

    Science.gov (United States)

    Hemarajata, Peera; Amick, Thomas; Yang, Shangxin; Gregson, Aric; Holzmeyer, Cameron; Bush, Karen; Humphries, Romney M

    2018-02-19

    Antibiotic selective pressure may result in changes to antimicrobial susceptibility throughout the course of infection, especially for organisms that harbour chromosomally encoded AmpC β-lactamases, notably Enterobacter spp., in which hyperexpression of ampC may be induced following treatment with cephalosporins. In this study, we document a case of bacteraemia caused by a blaSME-1-harbouring Serratia marcescens that subsequently developed resistance to expanded-spectrum cephalosporins, piperacillin/tazobactam and fluoroquinolones, over the course of several months of treatment with piperacillin/tazobactam and ciprofloxacin. Susceptibility testing and WGS were performed on three S. marcescens isolates from the patient. β-Lactamase activity in the presence or absence of induction by imipenem was measured by nitrocefin hydrolysis assays. Expression of ampC and blaSME-1 under the same conditions was determined by real-time PCR. WGS demonstrated accumulation of missense and nonsense mutations in ampD associated with stable derepression of AmpC. Gene expression and β-lactamase activity of both AmpC and SME-1 were inducible in the initial susceptible isolate, but were constitutively high in the resistant isolate, in which total β-lactamase activity was increased by 128-fold. Although development of such in vitro resistance due to selective pressure imposed by antibiotics is reportedly low in S. marcescens, our findings highlight the need to evaluate isolates on a regular basis during long-term antibiotic therapy.

  8. Environmental pollution by antibiotics and by antibiotic resistance determinants

    International Nuclear Information System (INIS)

    Martinez, Jose Luis

    2009-01-01

    Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations. - The article reviews the current knowledge on the effects that pollution by antibiotics and antibiotic resistance genes may have for the microbiosphere.

  9. Environmental pollution by antibiotics and by antibiotic resistance determinants

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Jose Luis, E-mail: jlmtnez@cnb.csic.e [Departamento de Biotecnologia Microbiana, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Darwin 3, Cantoblanco, 28049 Madrid, and CIBERESP (Spain)

    2009-11-15

    Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations. - The article reviews the current knowledge on the effects that pollution by antibiotics and antibiotic resistance genes may have for the microbiosphere.

  10. [Antibiotics: present and future].

    Science.gov (United States)

    Bérdy, János

    2013-04-14

    The author discuss the up to date interpretation of the concept of antibiotics and antibiotic research, as well as the present role of various natural, semisynthetic and synthetic antibiotic compounds in various areas of the human therapy. The origin and the total number of all antibiotics and applied antibiotics in the practice, as well as the bioactive microbial metabolites (antibiotics) in other therapeutical, non-antibiotic fields (including agriculture) are also reviewed. The author discusses main problems, such as increasing (poly)resistance, virulence of pathogens and the non-scientific factors (such as a decline of research efforts and their sociological, economic, financial and regulatory reasons). A short summary of the history of Hungarian antibiotic research is also provided. The author briefly discusses the prospects in the future and the general advantages of the natural products over synthetic compounds. It is concluded that new approaches for the investigation of the unlimited possibilities of the living world are necessary. The discovery of new types or simply neglected (micro)organisms and their biosynthetic capabilities, the introduction of new biotechnological and genetic methods (genomics, metagenom, genome mining) are absolutely required in the future.

  11. Antibiotics for methicillin-resistant Staphylococcus aureus skin and soft tissue infections: the challenge of outpatient therapy.

    Science.gov (United States)

    Pate, Amy J; Terribilini, Reno Giovonni; Ghobadi, Farzaneh; Azhir, Alaleh; Barber, Andre; Pearson, Julie Marie; Kalantari, Hossein; Hassen, Getaw W

    2014-02-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections are becoming increasingly prevalent in both community and hospital settings. Certain strains are notorious for causing skin and soft tissue infections in patients with no established risk factors. In this article, we report our findings on the dynamic antibiotic resistance pattern of MRSA and outpatient prescription trend for skin and soft tissue infections within our community. We conducted a retrospective medical record review of 1876 patients evaluated in the emergency department of an urban community hospital from 2003 to 2012. Data regarding culture isolates and associated antimicrobial resistance, antibiotic treatment, site of specimen collection, age, race, and sex were collected and analyzed. Analysis of 1879 culture specimens yielded 2193 isolates. In some cases, a single specimen yielded polymicrobial growth. Staphylococcus aureus represented 996 isolates (45.4%); 463 were methicillin-susceptible (21.1%) and 533 (24.3%) were methicillin-resistant. Most patients were prescribed a single- or poly-drug regimen of trimethoprim/sulfamethoxazole, cephalexin, and clindamycin. Antimicrobial resistance analysis indicated that MRSA became increasingly resistant to the aforementioned antibiotics over time: 10% and 6% in 2012 vs 3.5% and 3.4% in 2007 for clindamycin and trimethoprim/sulfamethoxazole, respectively. Methicillin-resistant Staphylococcus aureus is a particularly virulent, rapidly adaptive pathogen that is becoming increasingly difficult to combat with existing antibiotics. Care must be taken to ensure appropriate treatment and follow-up of patients with known MRSA infections. © 2013.

  12. Decreased antibiotic susceptibility and enhanced probiotic production potential of goat milk fermented curd in comparison with cow and buffalo milk

    Directory of Open Access Journals (Sweden)

    Jyoti Lakhanpal

    2017-07-01

    Full Text Available The present study was carried out to characterize and compare the production potential and antibiotic susceptibility of probiotics isolated from goat, cow and buffalo milk. The probiotics isolated from milk fermented curd were compared with regard to their number, morphology, gram staining, motility, bile salt tolerance, pH-resistance, catalase activity, oxidase production and antibiotic resistance. We demonstrated that the probiotics isolated from milk fermented curd of all three species were gram positive, motile, catalase negative, and oxidase negative and were able to produce lactic acid. Further, we observed that buffalo milk is more potent in forming curd with the highest count of probiotics per ml (3.53 × 10!5 as compared to cow (5.8 × 10!6 and goat milk (7×10!7; moreover, goat milk bacterial isolates were more tolerant to acidic pH but were less bile-salt tolerant than cow milk. Also, probiotics isolated from goat milk curd were more resistant to antibiotics (resistant to 12 out of 15 screened antibiotics than those from cow and buffalo milk (resistant to 8-9 antibiotics. This report shows that goat milk fermented products possess the highest antibacterial potential and are highly acid-tolerant.

  13. Costs, quality of life and treatment compliance associated with antibiotic therapies in patients with cystic fibrosis: a review of the literature.

    Science.gov (United States)

    Weiner, Jennifer R; Toy, Edmond L; Sacco, Patricia; Duh, Mei Sheng

    2008-04-01

    Cystic fibrosis is the most common incurable hereditary disease in the US. Persistent respiratory infection is the leading cause of morbidity and mortality in cystic fibrosis patients. This study aimed to review the literature on economic and quality of life outcomes and treatment compliance associated with antibiotic therapies for cystic fibrosis patients. A systematic literature review was conducted using keyword searches of the MEDLINE database and selected conference abstracts. The review covered studies published between January 1990 and May 2007. Evidence suggests that inhaled tobramycin, a key chronic suppressive therapy, can reduce other healthcare costs. The main determinants of the cost of care include disease severity and respiratory infection. Costs vary widely by country. There is evidence that inhaled tobramycin and oral azithromycin improve quality of life and that treatment setting and patient convenience may also impact on quality of life. Antibiotic treatment compliance varied significantly and depended on the method of measurement, with more subjective measures tending to be higher. This review concludes by offering directions for future research.

  14. Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocollitis in forumula-fed newborn preterm pigs

    DEFF Research Database (Denmark)

    Birck, Malene M; Nguyen, Duc Ninh; Cilieborg, Malene Skovsted

    2016-01-01

    , relative to CON pigs (P pigs were intermediate with few affected parameters (reduced lactic acid levels and density and adherence of Gram-positive bacteria, relative to CON pigs, P antimicrobial resistance following the treatments. We......Preterm infants are susceptible to infection and necrotizing enterocolitis (NEC) and are often treated with antibiotics. Simultaneous administration of enteral and parenteral antibiotics during the first days after preterm birth prevents formula-induced NEC lesions in pigs, but it is unknown which...... administration route is most effective. We hypothesized that only enteral antibiotics suppress gut bacterial colonization and NEC progression in formula-fed preterm pigs. Caesarean-delivered preterm pigs (90–92% of gestation) were fed increasing amounts of infant formula from birth to day 5 and given saline (CON...

  15. The ability of selected plant essential oils to enhance the action of recommended antibiotics against pathogenic wound bacteria.

    Science.gov (United States)

    Sienkiewicz, Monika; Łysakowska, Monika; Kowalczyk, Edward; Szymańska, Grażyna; Kochan, Ewa; Krukowska, Jolanta; Olszewski, Jurek; Zielińska-Bliźniewska, Hanna

    2017-03-01

    The aim of this work was to characterize the ability of essential oils to support antibiotics against pathogenic bacteria in wounds. Gram-positive and Gram-negative bacteria obtained from wound infections were identified according to standard microbiological methods. Essential oils were analysed by GC-FID-MS. The susceptibility of bacteria to antibiotics, essential oils and their combination was assessed using the disc-diffusion method. The Minimal Inhibitory Concentration and Minimum Bactericidal Concentration of the essential oils were established by the micro-dilution broth method. Although cinnamon, clove, thyme and lavender essential oils were found to have the greatest antibacterial activity when used alone, the greatest additive and synergistic effects against pathogenic wound bacteria in combination with recommended antibiotics were demonstrated by basil, clary sage and rosemary oils. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  16. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

    International Nuclear Information System (INIS)

    Szkudlarek-Mikho, Maria; Saunders, Rudel A.; Yap, Sook Fan; Ngeow, Yun Fong; Chin, Khew-Voon

    2012-01-01

    Highlights: ► Salinomycin inhibits preadipocyte differentiation into adipocytes. ► Salinomycin inhibits transcriptional regulation of adipogenesis. ► Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor γ. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

  17. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Szkudlarek-Mikho, Maria; Saunders, Rudel A. [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States); Yap, Sook Fan [Faculty of Medicine and Health Sciences, Department of Pre-Clinical Sciences, University of Tunku Abdul Rahman (Malaysia); Ngeow, Yun Fong [Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603 (Malaysia); Chin, Khew-Voon, E-mail: khew-voon.chin@utoledo.edu [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States)

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer Salinomycin inhibits preadipocyte differentiation into adipocytes. Black-Right-Pointing-Pointer Salinomycin inhibits transcriptional regulation of adipogenesis. Black-Right-Pointing-Pointer Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor {gamma}. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

  18. Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial.

    Science.gov (United States)

    Mir, Fatima; Nisar, Imran; Tikmani, Shiyam S; Baloch, Benazir; Shakoor, Sadia; Jehan, Fyezah; Ahmed, Imran; Cousens, Simon; Zaidi, Anita K M

    2017-02-01

    Parenteral antibiotic therapy for young infants (aged 0-59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection. We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0-59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429. Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and

  19. A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

    Science.gov (United States)

    2015-10-01

    spectrum disorders , and assessing the efficacy of this approach in comparison to an active Enriched Supportive Therapy (EST) intervention . Major...This project is focused on conducting the first randomized-controlled trial of Cognitive Enhancement Therapy (CET) in 54 verbal adults with autism ...of the neuroplastic effects of CET on brain function in support of cognitive enhancement in adult autism . Analyses of treatment effects to date

  20. Sustainability of Water Reclamation: Long-Term Recharge with Reclaimed Wastewater Does Not Enhance Antibiotic Resistance in Sediment Bacteria

    Directory of Open Access Journals (Sweden)

    Jean E. McLain

    2014-03-01

    Full Text Available Wastewater reclamation for municipal irrigation is an increasingly attractive option for extending water supplies. However, public health concerns include the potential for development of antibiotic resistance (AR in environmental bacteria after exposure to residual pharmaceuticals in reclaimed water. Though scientific studies have reported high levels of AR in soils irrigated with wastewater, these works often fail to address the soil resistome, or the natural occurrence of AR. This study compared AR patterns in sediment Enterococcus isolated from water storage basins containing either reclaimed water or groundwater in central Arizona. Resistance to 16 antibiotics was quantified in isolates to a depth of 30 cm. Results reveal high levels of resistance to certain antibiotics, including lincomycin, ciprofloxacin, and erythromycin, exists in sediments regardless of the water source (groundwater, reclaimed water, and higher AR was not detectable in reclaimed water sediments. Furthermore, multiple-antibiotic-resistance (MAR was substantially reduced in isolates from reclaimed water sediments, compared to freshwater sediment isolates. Comparing the development of AR in sediment bacteria at these two sites will increase awareness of the environmental and public health impacts of using reclaimed water for irrigation of municipal areas, and illustrates the necessity for control sites in studies examining AR development in environmental microbiota.

  1. Autologous Immune Enhancement Therapy for Cancer - Our experience since 2004

    Directory of Open Access Journals (Sweden)

    Hiroshi Terunuma

    2012-01-01

    Full Text Available Cancer, the major killer disease of the century requires a multi-pronged approach and among the latest modalities of treatments, Immunotherapy occupies a promising role. Immunotherapy for cancer was first started to be practised in the NIH and cell based immunotherapy for cancer is in practice for the past three decades. [1, 2] There are several literatures from various countries on the successful application of cell based Immunotherapies for various solid tumours and haematological malignancies. [3-8] Our team’s association with immune cells started when I was working on RNA transcriptome analysis to understand the immune system in HIV carriers which in turn required in vitro expansion of human Natural Killer (NK cells. [9] This led to the customization of protocols which has resulted in successful in vitro expansion, activation of NK cells and T cells for Immunotherapy. The purpose of Biotherapy institute of Japan (BIJ is to support research and clinical application of immune cells like NK cells, γδT cells, αβT cells, Cytotoxic T lymphocytes (CTL and Dendritic cells (DC for application as Autologous Immune Enhancement Therapy (AIET to fight against cancer. AIET using NK cells, CTLs, DCs etc have been administered for more than 5000 patients since 2004 till date by BIJ. Principle of AIET: For AIET using NK cells, the process involves separation of lymphocytes from the peripheral blood of the patient followed by selective NK cell expansion using the expansion kit (BINKIT, BIJ, JAPAN without feeder layers and then infusion of the expanded-activated NK cells. [10,11] As reports suggest that the activity of peripheral blood NK cells are lower in cancer patients compared to normal individuals [12] and as in vitro expansion of NK cells increases the cytotoxic ability 5 to 10 fold, [13] the NK cells are expanded in vivo and then infused to the patient in AIET. We are also working on combination immunotherapy using NK cells and CTLs and also NK

  2. Candida albicans and bacterial microbiota interactions in the cecum during recolonization following broad-spectrum antibiotic therapy.

    Science.gov (United States)

    Mason, Katie L; Erb Downward, John R; Mason, Kelly D; Falkowski, Nicole R; Eaton, Kathryn A; Kao, John Y; Young, Vincent B; Huffnagle, Gary B

    2012-10-01

    Candida albicans is a normal member of the gastrointestinal (GI) tract microbiota of healthy humans, but during host immunosuppression or alterations in the bacterial microbiota, C. albicans can disseminate and cause life-threatening illness. The bacterial microbiome of the GI tract, including lactic acid bacteria (LAB), plays a vital role in preventing fungal invasion. However, little is known about the role of C. albicans in shaping the bacterial microbiota during antibiotic recovery. We investigated the fungal burdens in the GI tracts of germfree mice and mice with a disturbed microbiome to demonstrate the role of the microbiota in preventing C. albicans colonization. Histological analysis demonstrated that colonization with C. albicans during antibiotic treatment does not trigger overt inflammation in the murine cecum. Bacterial diversity is reduced long term following cefoperazone treatment, but the presence of C. albicans during antibiotic recovery promoted the recovery of bacterial diversity. Cefoperazone diminishes Bacteroidetes populations long term in the ceca of mice, but the presence of C. albicans during cefoperazone recovery promoted Bacteroidetes population recovery. However, the presence of C. albicans resulted in a long-term reduction in Lactobacillus spp. and promoted Enterococcus faecalis populations. Previous studies have focused on the ability of bacteria to alter C. albicans; this study addresses the ability of C. albicans to alter the bacterial microbiota during nonpathogenic colonization.

  3. Effect of pH on the microstructure of β-Ga2O3 and its enhanced photocatalytic activity for antibiotic degradation.

    Science.gov (United States)

    Liu, Jin; Lu, Wei; Zhong, Qian; Wu, Hongzhang; Li, Yunlin; Li, Lili; Wang, Zhenling

    2018-06-01

    Semiconductor photocatalysis has become the focus of recent research on antibiotic treatment because it is a green and efficient technology. In this study, α-GaOOH with several novel microstructures has been synthesized at a low temperature and its subsequent thermal transformation. The influence of pH on the synthesis of α-GaOOH is studied, and the results indicate that pH played an important role in the microstructures of α-GaOOH and β-Ga 2 O 3 . All Ga 2 O 3 samples possess macro-mesoporous network structures and exhibits a remarkable photocatalytic activity for antibiotic degradation. The photoelectron chemical tests show that the separation efficiency of photogenerated charge carriers of Ga 2 O 3 -7.0 is higher than that of other Ga 2 O 3 . The enhanced photocatalytic activity of Ga 2 O 3 -7.0 is mainly ascribed to its morphology and oxygen vacancy. The active species trapping and photoluminescence measurement experiments indicate that OH and O 2 - are the major active species contributing to the photocatalytic process. This study will bring about the potential application in treatment of the antibiotic pollutants. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Quinacrine enhances carmustine therapy of experimental rat glioma.

    Science.gov (United States)

    Reyes, S; Herrera, L A; Ostrosky, P; Sotelo, J

    2001-10-01

    The high rate of mutagenesis in malignant cells has been considered to be a primary factor in the appearance of chemotherapy-resistant cell clones in glioblastomas. Quinacrine binds strongly to deoxyribonucleic acid, preventing mutagenesis. We investigated whether quinacrine could improve carmustine therapy in C6 cell cultures and in C6 malignant gliomas implanted subcutaneously into Wistar rats. A potential chemopreventive effect of quinacrine on acquired resistance to carmustine therapy was studied in vitro and in vivo. Deoxyribonucleic acid damage was measured in cultured C6 cells by using the micronucleus test. Wistar rats with subcutaneously implanted C6 gliomas were treated with carmustine, quinacrine, or carmustine plus quinacrine, using pharmacological schemes similar to those used for human patients. The addition of quinacrine to cultured C6 cells did not modify carmustine-induced cytotoxicity; however, the deoxyribonucleic acid damage in surviving cells was minor, as indicated by the frequency of micronucleated cells. The surviving cells continued to be susceptible to a second exposure to carmustine, in contrast to non-quinacrine-treated control cells, which developed resistance to carmustine in a subsequent exposure (P < 0.05). The rate of tumor remission was higher for glioma-bearing rats treated with quinacrine plus carmustine, compared with rats treated with carmustine alone (P < 0.01). The addition of quinacrine to carmustine therapy increases the antineoplastic effect of the carmustine therapy. Our results suggest that chemical inhibition of mutagenesis in malignant glial cells during chemotherapy prevents the appearance of resistant clones.

  5. A clinical decision support system algorithm for intravenous to oral antibiotic switch therapy: validity, clinical relevance and usefulness in a three-step evaluation study.

    Science.gov (United States)

    Akhloufi, H; Hulscher, M; van der Hoeven, C P; Prins, J M; van der Sijs, H; Melles, D C; Verbon, A

    2018-04-26

    To evaluate a clinical decision support system (CDSS) based on consensus-based intravenous to oral switch criteria, which identifies intravenous to oral switch candidates. A three-step evaluation study of a stand-alone CDSS with electronic health record interoperability was performed at the Erasmus University Medical Centre in the Netherlands. During the first step, we performed a technical validation. During the second step, we determined the sensitivity, specificity, negative predictive value and positive predictive value in a retrospective cohort of all hospitalized adult patients starting at least one therapeutic antibacterial drug between 1 and 16 May 2013. ICU, paediatric and psychiatric wards were excluded. During the last step the clinical relevance and usefulness was prospectively assessed by reports to infectious disease specialists. An alert was considered clinically relevant if antibiotics could be discontinued or switched to oral therapy at the time of the alert. During the first step, one technical error was found. The second step yielded a positive predictive value of 76.6% and a negative predictive value of 99.1%. The third step showed that alerts were clinically relevant in 53.5% of patients. For 43.4% it had already been decided to discontinue or switch the intravenous antibiotics by the treating physician. In 10.1%, the alert resulted in advice to change antibiotic policy and was considered useful. This prospective cohort study shows that the alerts were clinically relevant in >50% (n = 449) and useful in 10% (n = 85). The CDSS needs to be evaluated in hospitals with varying activity of infectious disease consultancy services as this probably influences usefulness.

  6. Fate of antibiotic resistance bacteria and genes during enhanced anaerobic digestion of sewage sludge by microwave pretreatment.

    Science.gov (United States)

    Tong, Juan; Liu, Jibao; Zheng, Xiang; Zhang, Junya; Ni, Xiaotang; Chen, Meixue; Wei, Yuansong

    2016-10-01

    The fate of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) were investigated during the sludge anaerobic digestion (AD) with microwave-acid (MW-H), microwave (MW) and microwave-H2O2-alkaline (MW-H2O2) pretreatments. Results showed that combined MW pretreatment especially for the MW-H pretreatment could efficiently reduce the ARB concentration, and most ARG concentrations tended to attenuate during the pretreatment. The subsequent AD showed evident removal of the ARB, but most ARGs were enriched after AD. Only the concentration of tetX kept continuous declination during the whole sludge treatment. The total ARGs concentration showed significant correlation with 16S rRNA during the pretreatment and AD. Compared with unpretreated sludge, the AD of MW and MW-H2O2 pretreated sludge presented slightly better ARB and ARGs reduction efficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Analysis of Acinetobacter baumannii resistance patterns in patients with chronic obstructive pulmonary disease (COPD) in terms of choice of effective empiric antibiotic therapy.

    Science.gov (United States)

    Grochowalska, Aneta; Kozioł-Montewka, Maria; Sobieszczańska, Anna

    2017-06-12

    Introduction. Multi-resistant Acinetobacter baumannii isolated from patients has become one of the most hazardous pathogens in health care settings. The aim of the study was to analyze pneumonia caused by Acinetobacter baumannii in patients hospitalized because of exacerbation of chronic obstructive pulmonary diseases (COPD), who were admitted to the Pulmonology Ward of the Masovian Specialistic Hospital in Radom (MSS). The incidence and drug sensitivity of these non-fermenting rods were evaluated, and compliance with antimicrobial procedure with the algorithm of the guidelines in applicable recommendations, was estimated. This should result in determining the local patterns of resistance and verifying therapeutic procedures in accordance with the assumptions of hospital antibiotic policy. In addition, the study examined the effectiveness of empiric and targeted therapy according to the clinical condition of the patient, and the eradication of A. baumannii, in comparison with the aggravating factors of the patient. Materials and Method. The retrospective study included 90 patients with exacerbation of COPD whose etiological factor of infection was A. baumannii, hospitalized in the Department of Pulmonology (MSS) in 2012-2016. Results. Studies were conducted on 90 patients with COPD exacerbation from which A. baumannii was isolated. Co-infections with other bacterial species among 41 patients were additionally noted. The majority of A. baumannii strains showed a high resistance (90%) to fluoroquinolones, ceftazidime, piperacillin/tazobactam. For strains causing a co-infection, drug resistance was successively 44-56%, 44%, 44%. All of patients received empirical therapy. The most commonly used drug was amoxicillin with a clavulanic acid, often combined with fluoroquinolone. This type of therapy was effective among 10% of patients. The mortality in this group was determined at 29%. Among 79% of patients with COPD, a targeted therapy was performed which proved to be

  8. Enhanced adsorption of ionizable antibiotics on activated carbon fiber under electrochemical assistance in continuous-flow modes.

    Science.gov (United States)

    Wang, Sitan; Li, Xiaona; Zhao, Huimin; Quan, Xie; Chen, Shuo; Yu, Hongtao

    2018-05-01

    Ionizable antibiotics have attracted serious concerns because of their variable dissociation forms and thereby rendering unique toxicity and microorganism resistance. Developing an efficient and environmentally friendly method for removing these micropollutants from environmental media remains very challenging. Here, electro-assisted adsorption onto activated carbon fiber in continuous-flow mode was used to remove three ionizable antibiotics, sulfadimethoxine (SDM), ciprofloxacin (CIP), and clarithromycin (CLA), from water. Benefiting from strengthened electrostatic interactions, the adsorption capacities for the target antibiotics (10 mg/L) in flow mode (70.9-202.2 mg/g) increased by ∼5 times under a potential of 1.0 V (SDM) or -1.0 V (CIP and CLA) relative to those of open circuit (OC) adsorption. Meanwhile, effluent concentration decreased from >100 μg/L to 9.6 μg/L with removal efficiency increasing from 99.0% to 99.9%. Moreover, high recovery efficiency of ACF up to 96.35 ± 0.65% was achieved by imposing a reverse potential (-1.0 V) relative to that used for SDM adsorption. In addition, trace levels of antibiotics (364-580 ng/L) in surface water could be removed effectively to achieve low effluent concentration (0.4-1.2 ng/L) and high removal efficiency (99.9%) upon treating up to ∼1560 bed volumes (BVs), demonstrating the potential of electro-assisted adsorption for practical application in water treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Surfactant therapy and antibiotics in neonates with meconium aspiration syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Natarajan, C K; Sankar, M J; Jain, K; Agarwal, R; Paul, V K

    2016-05-01

    Meconium aspiration syndrome (MAS), a common cause of respiratory failure in neonates, is associated with high mortality and morbidity. The objectives of this review were to evaluate the effects of administration of (a) surfactant-either as lung lavage (SLL) or bolus surfactant (BS) and (b) antibiotics on mortality and severe morbidities in neonates with MAS. We searched the following databases: MEDLINE via PubMed, Cochrane CENTRAL, WHOLIS and CABI using sensitive search strategies. We included eight studies on use of surfactant and three studies on use of antibiotics. Neither SLL nor BS reduced the risk of mortality in neonates with MAS (relative risk (RR) 0.38, 95% confidence interval (CI) 0.09 to 1.57; and RR 0.80, 95% CI 0.39 to 1.66, respectively). Both SLL and BS reduced the duration of hospital stay (mean difference -2.0, 95% CI -3.66 to -0.34; and RR -4.68, 95% CI -7.11 to -2.24 days, respectively) and duration of mechanical ventilation (mean difference -1.31, 95% CI -1.91 to -0.72; and mean difference 5.4, 95% CI -9.76 to -1.03 days). Neonates who received BS needed extracorporeal membrane oxygenation (ECMO) less often than the controls (RR 0.64, 95% CI 0.46 to 0.91). Use of antibiotics for MAS did not result in significant reduction in the risk of mortality, sepsis or duration of hospital stay. Surfactant administration either as SLL or BS for MAS was found to reduce the duration of mechanical ventilation and hospital stay; BS also reduced the need for ECMO. Administration of antibiotics did not show any significant clinical benefits in neonates with MAS and no evidence of sepsis. Given the limited number of studies and small number of neonates enrolled, there is an urgent need to generate more evidence on the efficacy and cost-effectiveness of these two treatment modalities before recommending them in routine clinical practice.

  10. Aspectos a tener en cuenta antes de aplicar una antibioticoterapia Aspects to be taken into account before applying an antibiotic therapy

    Directory of Open Access Journals (Sweden)

    Moisés Morejón García

    2005-04-01

    Full Text Available Se presenta una revisión sobre los aspectos que debe tener en cuenta el facultativo antes de aplicar una antibioticoterapia, como son: la procedencia del paciente, la localización y el tipo de la sepsis, los factores del huésped, la determinación del germen posible, la selección del antibiótico, la vía de administración y sus dosis e intervalos, la duración del tratamiento antimicrobiano, los efectos adversos y el costo del medicamento. Además se abordan las combinaciones de antimicrobianos, la quimioprofilaxis antimicrobiana y el uso inadecuado de los antimicrobianos.A review of the aspects the physician should take into consideration before applying an antibiotic therapy is made. The origin of the patient, the location and type of sepsis, the factors of the guest, the determination of the possible germ, the selection of the antibiotic, the route of administration and its doses and intervals, the duration of the antimicrobial treatment, the adverse effects and the cost of the drug are among these aspects. The combination of antimicrobials, the antimicrobial chemoprophylaxis and the inadequate use of antimicrobials are also exposed.

  11. A Novel Murine Model of Established Staphylococcal Bone Infection in the Presence of a Fracture Fixation Plate to Study Therapies Utilizing Antibiotic-laden Spacers after Revision Surgery

    Science.gov (United States)

    Inzana, Jason A.; Schwarz, Edward M.; Kates, Stephen L.; Awad, Hani A.

    2014-01-01

    local or systemic vancomycin did not display gross pathology at the end of the study. While localized vancomycin delivery alone tended to decrease the bacterial burden and osteolysis, these effects were only significant when combined with systemic antibiotic therapy. This novel mouse model replicates key features of implant-associated osteomyelitis that make treatment extremely difficult, such as biofilm formation and osteolysis, and imitates the clinical practice of placing an antibiotic-laden spacer after infected tissue debridement. In addition, the model demonstrates the limitations of current PMMA spacers and could be an invaluable tool for evaluating alternative antimicrobial treatments for implant-associated bone infection. PMID:25459073

  12. [Diagnostic value of serum procalcitonin in identifying the etiology of non-responding community-acquired pneumonia after initial antibiotic therapy].

    Science.gov (United States)

    Wang, Zheng; Zhang, Xiaoju; Wu, Jizhen; Zhang, Wenping; Kuang, Hongyan; Li, Xiao; Xuan, Weixia; Wang, Kai; Ma, Lijun

    2014-11-01

    This study was to investigate the diagnostic value of serum procalcitonin(PCT) in identifying the etiology of non-responding community-acquired pneumonia (CAP) after initial antibiotic therapy. A retrospective analysis was performed for 232 hospitalized CAP patients admitted to the People's Hospital of Zhengzhou University during June 2013 and January 2014. Early treatment failure was defined as the presence of persistent fever (>38 °C) and/or clinical symptoms (malaise, cough, expectoration, dyspnea) or deterioration after at least 72 h of initial antimicrobial treatment, or development of respiratory failure requiring mechanical ventilation, or septic shock. Bronchoscopy or transthoracic lung biopsy was performed in case of early treatment failure when indicated. Serum level of PCT was detected by double antibody sandwich method. The differences between 2 or more groups were compared using 2-independent student t test, one-way ANOVA; Mann-Whitney U test, Kruskal-Wallis rank sum test, or χ(2) test. Risk factors and odds ratios for nonresponsiveness were analyzed by setting up a Logistic regression model. The diagnostic values of PCT were determined by receiver operating characteristic curves (ROC curves). Of the 232 CAP patients enrolled, 124 were male and 108 were female, with an average age of (46 ± 20) years. Thirty-six patients failed to respond to the initial antibiotic therapy. As shown by Logistic regression analysis, the risk factors for treatment failure included hypoalbuminemia, type 2 diabetes, previous history of splenectomy , PSI 4-5 grade, and lung infiltration ≥ 3 lobes. The most common causes of non-responsiveness were antimicrobial insufficiency (n = 23), and misdiagnosis of noninfectious mimics of pneumonia (n = 11), with 2 cases of unidentified etiology. The serum PCT level in admission was 0.19 (0.07-0.66) µg/L in the antimicrobial insufficiency subgroup, which was significantly higher than that in the misdiagnosis subgroup [0

  13. Antibiotic prescribing for acute bronchitis

    DEFF Research Database (Denmark)

    Llor, Carl; Bjerrum, Lars

    2016-01-01

    INTRODUCTION: Acute bronchitis is a self-limiting infectious disease characterized by acute cough with or without sputum but without signs of pneumonia. About 90% of cases are caused by viruses. AREAS COVERED: Antibiotics for acute bronchitis have been associated with an approximately half......-day reduction in duration of cough. However, at follow-up there are no significant differences in overall clinical improvement inpatients treated with antibiotics compared with those receiving placebo. Despite this, antibiotics are administered to approximately two thirds of these patients. This review...... discusses the reason for this antibiotic overprescription. Other therapies targeted to control symptoms have also demonstrated a marginal or no effect. EXPERT COMMENTARY: Clinicians should be aware of the marginal effectiveness of antibiotic therapy. Some strategies like the use of rapid tests, delayed...

  14. Brain-specific enhancers for cell-based therapy

    Science.gov (United States)

    Visel, Axel; Rubenstein, John L.R.; Chen, Ying-Jiun; Pennacchio, Len A.; Vogt, Daniel; Nicholas, Cory; Kriegstein, Arnold

    2018-04-24

    Herein are described a set of novel specific human enhancers for specific forebrain cell types used to study and select for human neural progenitor cells. This approach enables the ability to generate interneurons from human ES, iPS and iN cells, making them available for human transplantation and for molecular/cellular analyzes. These approaches are also directly applicable to generating other neuronal cell types, such as cortical and striatal projection neurons, which have implications for many human diseases.

  15. Successful Intra-peritoneal Antibiotic Therapy for Primary Abdominal Nocardiosis in an Immunocompetent Young Female Masquerading as Carcinoma Ovary

    Directory of Open Access Journals (Sweden)

    Ravi N Patil

    2012-01-01

    Full Text Available Nocardiosis is a common opportunistic infection in the immunocompromised and in patients with chronic debilitating diseases,e.g continuous ambulatory peritoneal dialysis (CAPD patients. Primary abdominal nocardiosis is rare and is indeed a very rare infection in immunocompetent persons. Only two cases have been reported in immunocompetent patients so far and this may be third case to the best of our knowledge and first in India. About 11 cases have been reported in CAPD patients and AIDS patients.We report a case of Nocardiosis in an immunocompetent young female who presented with an abdomino-pelvic mass masquerading as carcinoma ovary.After initial resistance to various antibiotics, she responded to intraperitoneal and oral linezolid and oral ciprofloxacin.

  16. Antibiotic Policies in the Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Nese Saltoglu

    2003-08-01

    Full Text Available The antimicrobial management of patients in the Intensive Care Units are complex. Antimicrobial resistance is an increasing problem. Effective strategies for the prevention of antimicrobial resistance in ICUs have focused on limiting the unnecessary use of antibiotics and increasing compliance with infection control practices. Antibiotic policies have been implemented to modify antibiotic use, including national or regional formulary manipulations, antibiotic restriction forms, care plans, antibiotic cycling and computer assigned antimicrobial therapy. Moreover, infectious diseases consultation is a simple way to limit antibiotic use in ICU units. To improve rational antimicrobial using a multidisiplinary approach is suggested. [Archives Medical Review Journal 2003; 12(4.000: 299-309

  17. [Endoprosthesis Infections - Guidelines for Antibiotic Therapy Common Guidelines of the Czech Society for Orthopaedics and Traumatology and the Society for Infectious Diseases of the Czech Medical Association of J. E. Purkyně].

    Science.gov (United States)

    Musil, D; Balejová, M; Horníková, M; Chrdle, A; Mallátová, N; Nyč, O; Chmelík, V; Gallo, J; Jahoda, D; Stehlík, J

    2017-01-01

    PURPOSE OF THE STUDY This study aims to articulate regional guidelines for curative and suppressive antibiotic therapy of total joint replacement infections. MATERIAL AND METHODS When developing the standard, used as source materials were the published foreign guidelines for antibiotic therapy of prosthetic joint infections, the analysis of resistance of bacterial strains conducted in the Hospital in České Budějovice, a.s. and the assessment of strain resistance for the Czech Republic published by the European Antimicrobial Resistance Surveillance Network (EARS-Net). Considered was also the availability of individual antibiotics in the Czech Republic and restricted prescription according to the Summary of Product Characteristics as specified in the State Institute for Drug Control marketing authorisation. The expert group composed of orthopaedists, microbiologists and infectious disease specialists elaborated the basic antibiotic guideline for choosing an appropriate antibiotic/antifungal drug based on the usual susceptibility, its dose and dosage interval for initial and continuation therapy. The comments of individual specialists were gradually incorporated therein and in case of doubts majority rule was applied. The drafted document was sent for peer reviews to clinical orthopaedic, infectious disease and microbiological centres, whose comments were also incorporated and the finalised document was submitted for evaluation to specialised medical societies. RESULTS The outcome is the submitted guideline for antibiotic curative and suppressive therapy suitable for managing the prosthetic joint infections, which was approved by the committee of the Czech Society for Orthopaedics and Traumatology andthe Society for Infectious Diseases of the Czech Medical Association of J. E. Purkyně. DISCUSION Curative therapy of total joint replacement infections consists primarily in surgical treatment and has to be accompanied by adequate antibiotic therapy administered

  18. Genetic engineering of stem cells for enhanced therapy.

    Science.gov (United States)

    Nowakowski, Adam; Andrzejewska, Anna; Janowski, Miroslaw; Walczak, Piotr; Lukomska, Barbara

    2013-01-01

    Stem cell therapy is a promising strategy for overcoming the limitations of current treatment methods. The modification of stem cell properties may be necessary to fully exploit their potential. Genetic engineering, with an abundance of methodology to induce gene expression in a precise and well-controllable manner, is particularly attractive for this purpose. There are virus-based and non-viral methods of genetic manipulation. Genome-integrating viral vectors are usually characterized by highly efficient and long-term transgene expression, at a cost of safety. Non-integrating viruses are also highly efficient in transduction, and, while safer, offer only a limited duration of transgene expression. There is a great diversity of transfectable forms of nucleic acids; however, for efficient shuttling across cell membranes, additional manipulation is required. Both physical and chemical methods have been employed for this purpose. Stem cell engineering for clinical applications is still in its infancy and requires further research. There are two main strategies for inducing transgene expression in therapeutic cells: transient and permanent expression. In many cases, including stem cell trafficking and using cell therapy for the treatment of rapid-onset disease with a short healing process, transient transgene expression may be a sufficient and optimal approach. For that purpose, mRNA-based methods seem ideally suited, as they are characterized by a rapid, highly efficient transfection, with outstanding safety. Permanent transgene expression is primarily based on the application of viral vectors, and, due to safety concerns, these methods are more challenging. There is active, ongoing research toward the development of non-viral methods that would induce permanent expression, such as transposons and mammalian artificial chromosomes.

  19. Stimulation of dendritic cells enhances immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.

    2009-02-01

    Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

  20. Forgotten antibiotics

    DEFF Research Database (Denmark)

    Pulcini, Céline; Bush, Karen; Craig, William A

    2012-01-01

    In view of the alarming spread of antimicrobial resistance in the absence of new antibiotics, this study aimed at assessing the availability of potentially useful older antibiotics. A survey was performed in 38 countries among experts including hospital pharmacists, microbiologists, and infectious...

  1. A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

    Science.gov (United States)

    2012-10-01

    life for more able individuals with autism or Asperger syndrome. Autism , 4(1), 63-83. Kanner, L. (1971). Follow-up study of eleven autistic...Enhancement Therapy for Adults with Autism Spectrum Disorders PRINCIPAL INVESTIGATOR: Nancy J. Minshew, M.D. & Shaun M. Each, Ph.D...Therapy for Adults with Autism Spectrum Disorders 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0665 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

  2. HDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: where do we stand?

    OpenAIRE

    Whittle, Nigel; Singewald, Nicolas

    2014-01-01

    A novel strategy to treat anxiety and fear-related disorders such as phobias, panic and PTSD (post-traumatic stress disorder) is combining CBT (cognitive behavioural therapy), including extinction-based exposure therapy, with cognitive enhancers. By targeting and boosting mechanisms underlying learning, drug development in this field aims at designing CBT-augmenting compounds that help to overcome extinction learning deficits, promote long-term fear inhibition and thus support relapse prevent...

  3. Salinomycin, A Polyether Ionophoric Antibiotic, Inhibits Adipogenesis

    Science.gov (United States)

    Szkudlarek-Mikho, Maria; Saunders, Rudel A.; Yap, Sook Fan; Ngeow, Yun Fong; Chin, Khew-Voon

    2012-01-01

    The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor γ. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy. PMID:23123626

  4. Nosocomial extended-spectrum beta-lactamase-producing Klebsiella pneumoniae bacteremia in hemodialysis patients and the implications for antibiotic therapy

    Directory of Open Access Journals (Sweden)

    Chih-Chao Yang

    2014-11-01

    Conclusions: In accordance with our previous study, our results have demonstrated the inferiority of flomoxef to carbapenems in the treatment of HD access-related ESBL-Kp bacteremia and provide an insight into the possibility of using ertapenem rather than flomoxef as an initial or de-escalating therapy for infections caused by ESBL-producing bacteria.

  5. Utilization of a lateral flow colloidal gold immunoassay strip based on surface-enhanced Raman spectroscopy for ultrasensitive detection of antibiotics in milk

    Science.gov (United States)

    Shi, Qiaoqiao; Huang, Jie; Sun, Yaning; Yin, Mengqi; Hu, Mei; Hu, Xiaofei; Zhang, Zhijun; Zhang, Gaiping

    2018-05-01

    An ultrasensitive method for the detection of antibiotics in milk is developed based on inexpensive, simple, rapid and portable lateral flow immunoassay (LFI) strip, in combination with high sensitivity surface-enhanced Raman spectroscopy (SERS). In our strategy, an immunoprobe was prepared from colloidal gold (AuNPs) conjugated with both a monoclonal antibody against neomycin (NEO-mAb) and a Raman probe molecule 4-aminothiophenol (PATP). The competitive interaction with immunoprobe between free NEO and the coated antigen (NEO-OVA) resulted in the change of the amount of the immobilized immunoprobe on the paper substrate. The LFI procedure was completed within 15 min. The Raman intensity of PATP on the test line of the LFI strip was measured for the quantitative determination of NEO. The IC50 and the limit of detection (LOD) of this assay are 0.04 ng/mL and 0.216 pg/mL of NEO, respectively. There is no cross-reactivity (CR) of the assay with other compounds, showing high specificity of the assay. The recoveries for milk samples with added NEO are in the range of 89.7%-105.6% with the relative standard deviations (RSD) of 2.4%-5.3% (n = 3). The result reveals that this method possesses high specificity, sensitivity, reproducibility and stability, and can be used to detect a variety of antibiotic residues in milk samples.

  6. Comparative Outcome Analysis of Penicillin-Based Versus Fluoroquinolone-Based Antibiotic Therapy for Community-Acquired Pneumonia

    Science.gov (United States)

    Wang, Chi-Chuan; Lin, Chia-Hui; Lin, Kuan-Yin; Chuang, Yu-Chung; Sheng, Wang-Huei

    2016-01-01

    Abstract Community-acquired pneumonia (CAP) is a common but potentially life-threatening condition, but limited information exists on the effectiveness of fluoroquinolones compared to β-lactams in outpatient settings. We aimed to compare the effectiveness and outcomes of penicillins versus respiratory fluoroquinolones for CAP at outpatient clinics. This was a claim-based retrospective cohort study. Patients aged 20 years or older with at least 1 new pneumonia treatment episode were included, and the index penicillin or respiratory fluoroquinolone therapies for a pneumonia episode were at least 5 days in duration. The 2 groups were matched by propensity scores. Cox proportional hazard models were used to compare the rates of hospitalizations/emergence service visits and 30-day mortality. A logistic model was used to compare the likelihood of treatment failure between the 2 groups. After propensity score matching, 2622 matched pairs were included in the final model. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy (adjusted odds ratio [AOR], 0.88; 95% confidence interval [95%CI], 0.77–0.99), but no differences were found in hospitalization/emergence service (ES) visits (adjusted hazard ratio [HR], 1.27; 95% CI, 0.92–1.74) and 30-day mortality (adjusted HR, 0.69; 95% CI, 0.30–1.62) between the 2 groups. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy for CAP on an outpatient clinic basis. However, this effect may be marginal. Further investigation into the comparative effectiveness of these 2 treatment options is warranted. PMID:26871827

  7. Prescription appropriateness of empiric antibiotic therapy: survey in the internal medicine departments of the Emilia Romagna region

    Directory of Open Access Journals (Sweden)

    Giovanni Pedretti

    2014-05-01

    Full Text Available The article reports the results of an observational study conducted in 53 internal medicine departments of the Emilia Romagna region based on the answers to 54 questions administered in a questionnaire, submitted electronically, based on the type of center (large >250 beds, small <250 beds, laboratory equipment, management aspects, pharmacological and clinical/economic aspects and use of antibiotics in the empirical treatment of severe infections. The result is a snapshot of the existing situation which shows a substantial availability of resources and a good level of expertise in the field of infectious disease management, despite some areas still need improvement. It also highlights some differences in terms of procedures amongst large hospitals, where infectious diseases are treated by an ad hoc specialized staff, and the small ones, where the internist is generally involved, being responsible for both direct management of severe infections and giving advice to other departments (emergency or surgery. It emerged that, both in small and large hospitals, more discussion and continuous assessment are needed to apply the appropriate protocols based on reference checklists.

  8. Use of a culture-independent on-farm algorithm to guide the use of selective dry-cow antibiotic therapy.

    Science.gov (United States)

    Vasquez, A K; Nydam, D V; Foditsch, C; Wieland, M; Lynch, R; Eicker, S; Virkler, P D

    2018-06-01

    An algorithm using only computer-based records to guide selective dry-cow therapy was evaluated at a New York State dairy farm via a randomized field trial. DairyComp 305 (Valley Ag Software, Tulare, CA) and Dairy Herd Improvement Association test-day data were used to identify cows as low risk (cows that might not benefit from dry-cow antibiotics) or high risk (cows that will likely benefit). Low-risk cows were those that had all of the following: somatic cell count (SCC) ≤200,000 cells/mL at last test, an average SCC ≤200,000 cells/mL over the last 3 tests, no signs of clinical mastitis at dry-off, and no more than 1 clinical mastitis event in the current lactation. Low-risk cows were randomly assigned to receive intramammary antibiotics and external teat sealant (ABXTS) or external teat sealant only (TS) at dry-off. Using pre-dry-off and postcalving quarter-level culture results, low-risk quarters were assessed for microbiological cure risk and new infection risk. Groups were also assessed for differences in first-test milk yield and linear scores, individual milk weights for the first 30 d, and culling and mastitis events before 30 d in milk. A total of 304 cows and 1,040 quarters in the ABXTS group and 307 cows and 1,058 quarters in the TS group were enrolled. Among cows to be dried, the proportion of cows that met low-risk criteria was 64% (n = 611/953). Of cultures eligible for bacteriological cure analysis (n = 171), 93% of ABXTS cured, whereas 88% of TS cured. Of the non-cures, 95% were contributed by the minor pathogens coagulase-negative staphylococci (n = 19/20). These organisms also accounted for 57.5% of new infections (n = 77/134). We found no statistical differences between treatment groups for new infection risk (TS = 7.3% quarters experiencing new infections; ABXTS = 5.5%), milk production (ABXTS = 40.5 kg; TS = 41.2 kg), linear scores (ABXTS = 2.5; TS = 2.7), culling events (ABXTS, n = 18; TS, n = 15), or clinical mastitis events (ABXTS, n

  9. Supplementation of standard antibiotic therapy with oral probiotics for bacterial vaginosis and aerobic vaginitis: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Heczko, Piotr B; Tomusiak, Anna; Adamski, Paweł; Jakimiuk, Artur J; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena; Strus, Magdalena

    2015-12-03

    This multicentre, randomised, double-blind, placebo-controlled trial was performed to determine whether the use of oral probiotic preparation (prOVag®) containing three Lactobacillus strains together with standard metronidazole treatment and also targeted antibiotic treatment (following the failure of metronidazole therapy) could reduce the recurrence rates of bacterial vaginosis (BV) and aerobic vaginitis (AV). Patients at private gynaecological clinics in Poland with histories of recurrent BV/AV and current symptoms were randomly allocated to receive metronidazole and probiotic or placebo, and assessed monthly on visits II and III-V. The total number of study visits was 5-6 (I, II, II bis - if applicable, III, IV, V). One probiotic or placebo capsule was administered with metronidazole/targeted antibiotic twice daily for 10 days; during follow up, patients took one capsule daily for 10 days perimenstrually. Clinical examination and vaginal swabbing were performed at each visit. Primary outcomes were clinical or microbiological BV/AV recurrence and probiotic safety. Secondary outcomes were vaginal pH, Nugent score, and Lactobacillus counts in the vaginal microbiota. Safety analysis was performed in 578 (probiotic, n = 285; placebo, n = 293) 18-50-year-old women who were randomised. BV/AV was confirmed microbiologically in 241 (probiotic, n = 118; placebo, n = 123) participants, who continued the trial. Data from 154 (probiotic, n = 73; placebo, n = 81) participants who completed the study were analysed to determine the efficacy of prOVag. Additional analyses included 37 (probiotic, n = 22; placebo, n = 15) participants who received targeted antibiotics and probiotics or placebo. prOVag lengthened the time to clinical relapse of BV/AV symptoms up to 51 % (p vaginal pH and Nugent score, and increased vaginal Lactobacillus counts following standard treatment. This study demonstrated that oral probiotics lengthened remission in

  10. Enhanced removal of sulfonamide antibiotics by KOH-activated anthracite coal: Batch and fixed-bed studies.

    Science.gov (United States)

    Zuo, Linzi; Ai, Jing; Fu, Heyun; Chen, Wei; Zheng, Shourong; Xu, Zhaoyi; Zhu, Dongqiang

    2016-04-01

    The presence of sulfonamide antibiotics in aquatic environments poses potential risks to human health and ecosystems. In the present study, a highly porous activated carbon was prepared by KOH activation of an anthracite coal (Anth-KOH), and its adsorption properties toward two sulfonamides (sulfamethoxazole and sulfapyridine) and three smaller-sized monoaromatics (phenol, 4-nitrophenol and 1,3-dinitrobenzene) were examined in both batch and fixed-bed adsorption experiments to probe the interplay between adsorbate molecular size and adsorbent pore structure. A commercial powder microporous activated carbon (PAC) and a commercial mesoporous carbon (CMK-3) possessing distinct pore properties were included as comparative adsorbents. Among the three adsorbents Anth-KOH exhibited the largest adsorption capacities for all test adsorbates (especially the two sulfonamides) in both batch mode and fixed-bed mode. After being normalized by the adsorbent surface area, the batch adsorption isotherms of sulfonamides on PAC and Anth-KOH were displaced upward relative to the isotherms on CMK-3, likely due to the micropore-filling effect facilitated by the microporosity of adsorbents. In the fixed-bed mode, the surface area-normalized adsorption capacities of Anth-KOH for sulfonamides were close to that of CMK-3, and higher than that of PAC. The irregular, closed micropores of PAC might impede the diffusion of the relatively large-sized sulfonamide molecules and in turn led to lowered fixed-bed adsorption capacities. The overall superior adsorption of sulfonamides on Anth-KOH can be attributed to its large specific surface area (2514 m(2)/g), high pore volume (1.23 cm(3)/g) and large micropore sizes (centered at 2.0 nm). These findings imply that KOH-activated anthracite coal is a promising adsorbent for the removal of sulfonamide antibiotics from aqueous solution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Monte Carlo and analytic simulations in nanoparticle-enhanced radiation therapy

    Directory of Open Access Journals (Sweden)

    Paro AD

    2016-09-01

    Full Text Available Autumn D Paro,1 Mainul Hossain,2 Thomas J Webster,1,3,4 Ming Su1,4 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2NanoScience Technology Center and School of Electrical Engineering and Computer Science, University of Central Florida, Orlando, Florida, USA; 3Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia; 4Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Science, Wenzhou Medical University, Zhejiang, People’s Republic of China Abstract: Analytical and Monte Carlo simulations have been used to predict dose enhancement factors in nanoparticle-enhanced X-ray radiation therapy. Both simulations predict an increase in dose enhancement in the presence of nanoparticles, but the two methods predict different levels of enhancement over the studied energy, nanoparticle materials, and concentration regime for several reasons. The Monte Carlo simulation calculates energy deposited by electrons and photons, while the analytical one only calculates energy deposited by source photons and photoelectrons; the Monte Carlo simulation accounts for electron–hole recombination, while the analytical one does not; and the Monte Carlo simulation randomly samples photon or electron path and accounts for particle interactions, while the analytical simulation assumes a linear trajectory. This study demonstrates that the Monte Carlo simulation will be a better choice to evaluate dose enhancement with nanoparticles in radiation therapy. Keywords: nanoparticle, dose enhancement, Monte Carlo simulation, analytical simulation, radiation therapy, tumor cell, X-ray 

  12. Enhancing attention in neurodegenerative diseases: current therapies and future directions

    Directory of Open Access Journals (Sweden)

    Sharma Kanchan

    2016-01-01

    Full Text Available We all experience at least occasional lapses in attention but in some neurological conditions, loss of attention is pervasive and debilitating. Treating deficits in attention first requires an understanding of the neurobiology of attention, which we now understand to be a set of different cognitive processes. Cholinesterase inhibitors are already established as effective attentional enhancers used in the treatment of certain dementias. Other stimulant agents such as modafanil, amphetamine and methylphenidate have demonstrated limited success in healthy individuals where attention is already optimal and clinical trials in patients with neurological disease are sparse. Dietary and lifestyle changes are gaining increasing prominence, as are experimental treatments such as deep brain stimulation and transcranial magnetic stimulation. As the therapeutic arsenal widens, clinicians will be able to match specific treatments to selective deficits in attention, giving patients a tailored management plan. Here we review common diseases that impair attention and emphasise how an understanding of attentional processing within the brain might lead to improved therapeutic strategies.

  13. Enhanced tumor responses through therapies combining CCNU, MISO and radiation

    International Nuclear Information System (INIS)

    Siemann, D.W.; Hill, S.A.

    1984-01-01

    Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). In initial experiments KHT sarcoma-bearing mice were injected with 1.0 mg/g of MISO simultaneously with a 20 mg/kg dose of CCNU 30-40 min prior to irradiation (1500 rad). With this treatment protocol approximately 60% of the mice were found to be tumor-free 100 days post treatment. By comparison all 2 agent combinations led to 0% cures. To evaluate the relative importance of chemopotentiation versus radiosensitization in the 3 agent protocol, tumors were treated with MISO plus one anti-tumor agent (either radiation of CCNU) and then at times ranging from 0 to 24 hr later exposed to the other agent. When the time between treatments was 0 to 6 hr, a 60 to 80% tumor control rate was achieved for both MISO plus radiation followed by CCNU and MISO plus CCNU followed by radiation. However if the time interval was increased to 18 or 24 hr, the cure rate in the former treatment regimen dropped to 10% while that of the latter remained high at 40%. The data therefore indicate that (1) improved tumor responses may be achieved when MISO is added to a radiation-chemotherapy combination and (2) MISO may be more effective in such a protocol when utilized as a chemopotentiator

  14. Nano-engineered titanium for enhanced bone therapy

    Science.gov (United States)

    Gulati, Karan; Atkins, Gerald J.; Findlay, David M.; Losic, Dusan

    2013-09-01

    Current treatment of a number of orthopaedic conditions, for example fractures, bone infection, joint replacement and bone cancers, could be improved if mechanical support could be combined with drug delivery. A very challenging example is that of infection following joint replacement, which is very difficult to treat, can require multiple surgeries and compromises both the implant and the patient's wellbeing. An implant capable of providing appropriate biomechanics and releasing drugs/proteins locally might ensure improved healing of the traumatized bone. We propose fabrication of nanoengineered titanium bone implants using bioinert titanium wires in order to achieve this goal. Titanium in the form of flat foils and wires were modified by fabrication of titania nanotubes (TNTs), which are hollow self-ordered cylindrical tubes capable of accommodating substantial drug amounts and releasing them locally. To further control the release of drug to over a period of months, a thin layer of biodegradable polymer PLGA poly(lactic-coglycolic acid) was coated onto the drug loaded TNTs. This delayed release of drug and additionally the polymer enhanced bone cell adhesion and proliferation.

  15. Agency over Phantom Limb Enhanced by Short-Term Mirror Therapy.

    Science.gov (United States)

    Imaizumi, Shu; Asai, Tomohisa; Koyama, Shinichi

    2017-01-01

    Most amputees experience phantom limb, whereby they feel that the amputated limb is still present. In some cases, these experiences include pain that can be alleviated by "mirror therapy." Mirror therapy consists of superimposing a mirrored image of the moving intact limb onto the phantom limb. This therapy provides a closed loop between the motor command to the amputated limb and its predicted visual feedback. This loop is also involved in the sense of agency, a feeling of controlling one's own body. However, it is unclear how mirror therapy is related to the sense of agency over a phantom limb. Using mirror therapy, we investigated phantom limb pain and the senses of agency and ownership (i.e., a feeling of having one's own body) of the phantom limb. Nine upper-limb amputees, five of whom reported recent phantom limb pain, underwent a single 15-min trial of mirror therapy. Before and after the trial, the participants completed a questionnaire regarding agency, ownership, and pain related to their phantom limb. They reported that the sense of agency over the phantom limb increased following the mirror therapy trial, while the ownership slightly increased but not as much as did the agency. The reported pain did not change; that is, it was comparably mild before and after the trial. These results suggest that short-term mirror therapy can, at least transiently, selectively enhance the sense of agency over a phantom limb, but may not alleviate phantom limb pain.

  16. Celecoxib-Induced Self-Assembly of Smart Albumin-Doxorubicin Conjugate for Enhanced Cancer Therapy.

    Science.gov (United States)

    Shi, Leilei; Xu, Li; Wu, Chenwei; Xue, Bai; Jin, Xin; Yang, Jiapei; Zhu, Xinyuan

    2018-03-14

    Recent years have witnessed the great contributions that drug combination therapy has made for enhanced cancer therapy. However, because of the complicated pharmacokinetics of combined drug formulations, the majority of combination strategies show severe adverse effects at high dosage and poor biodistribution in vivo. To overcome these deficiencies and achieve enhanced cancer therapy, we put forward a method to construct a smart albumin-based nanoplatform, denoted as K237-HSA-DC, for codelivery of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) and chemotherapeutic agent (doxorubicin, DOX). Both in vitro and in vivo studies indicate that K237-HSA-DC exhibits the best therapeutic efficacy on tumor cells compared with all the other formulations. Moreover, K237-HSA-DC shows fewer side effects on normal organs in contrast to other formulations. To understand the reasons behind the improved drug efficacy in depth, we performed a cell metabonomics-based mechanism study and found that celecoxib could enhance the inhibitory effect of DOX on the transport of glucose into cells and then lead to subsequent significant energy metabolism inhibition. Considering the above-mentioned advantages of K237-HSA-DC, we believe the smart albumin-based nanoplatform can serve as a promising drug delivery system for enhanced cancer therapy.

  17. Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorder: Results of an 18-Month Feasibility Study

    Science.gov (United States)

    Eack, Shaun M.; Greenwald, Deborah P.; Hogarty, Susan S.; Bahorik, Amber L.; Litschge, Maralee Y.; Mazefsky, Carla A.; Minshew, Nancy J.

    2013-01-01

    Adults with autism experience significant impairments in social and non-social information processing for which few treatments have been developed. This study conducted an 18-month uncontrolled trial of Cognitive Enhancement Therapy (CET), a comprehensive cognitive rehabilitation intervention, in 14 verbal adults with autism spectrum disorder to…

  18. Alcohol Treatment and Cognitive-Behavioral Therapy: Enhancing Effectiveness by Incorporating Spirituality and Religion

    Science.gov (United States)

    Hodge, David R.

    2011-01-01

    Cognitive-behavioral therapy (CBT) is an effective modality for the treatment of alcoholism. Given widespread interest in incorporating spirituality into professional treatment, this article orients practitioners to spiritually modified CBT, an approach that may enhance outcomes with some spiritually motivated clients. More specifically, by…

  19. Bacteraemia due to AmpC β-lactamase-producing Escherichia coli in hospitalized cancer patients: risk factors, antibiotic therapy, and outcomes.

    Science.gov (United States)

    Zhang, Qing; Zhang, Wenfang; Li, Zheng; Bai, Changsen; Li, Ding; Zheng, Shan; Zhang, Peng; Zhang, Sihe

    2017-07-01

    AmpC β-lactamase-producing Escherichia coli (AmpC-EC) is one of the main antimicrobial resistant pathogens in patients with cancer. A cohort study was performed to evaluate the risk factors, antibiotic therapy, and outcomes of AmpC-EC bacteraemia in hospitalized cancer patients from September 2012 through December 2015. Two hundred forty-eight cases of E. coli bacteraemia were documented in cancer patients, 51 (20.6%) were caused by AmpC-EC and 197 (79.4%) were caused with non-AmpC-EC. Prior exposure to cephalosporins (OR 2.786; 95% CI: 1.094-7.091; P=0.032), carbapenems (OR 2.296; 95% CI: 1.054-5.004; P=0.036), and invasive procedures (OR 4.237; 95% CI: 1.731-10.37; P=0.002) were identified as independent risk factors for AmpC-EC. The time to positivity (TTP) of patients with AmpC-EC bacteraemia tended to be significantly shorter than that of non-AmpC-EC (8.33±2.18h versus 9.48±3.82h; P=0.006), and had a higher 30-day mortality rate in AmpC-EC compared with non-AmpC-EC (25.5% versus 12.2%; P=0.018). Metastasis (OR=2.778, 95% CI: 1.078-7.162; P=0.034), the presence of septic shock (OR=4.983, 95% CI: 1.761-14.10; P=0.002), and organ failure (OR=24.51 95% CI: 9.884-60.81; P<0.001) were independently associated with the overall mortality. The mortality rate showed a gradual increase when appropriate antibiotic therapy (AAT) was delayed more than 48h as determined by the trend test (P<0.001). In conclusion, this study showed that prevalence of AmpC-EC was high in hospitalized cancer patients of our area. Thus, it is necessary to apply appropriate therapeutic approaches and improve outcomes based on the analysis of risk factors for the acquisition of AmpC-EC. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Mitochondria-targeted cationic porphyrin-triphenylamine hybrids for enhanced two-photon photodynamic therapy.

    Science.gov (United States)

    Hammerer, Fabien; Poyer, Florent; Fourmois, Laura; Chen, Su; Garcia, Guillaume; Teulade-Fichou, Marie-Paule; Maillard, Philippe; Mahuteau-Betzer, Florence

    2018-01-01

    The proof of concept for two-photon activated photodynamic therapy has already been achieved for cancer treatment but the efficiency of this approach still heavily relies on the availability of photosensitizers combining high two-photon absorption and biocompatibility. In this line we recently reported on a series of porphyrin-triphenylamine hybrids which exhibit high singlet oxygen production quantum yield as well as high two-photon absorption cross-sections but with a very poor cellular internalization. We present herein new photosensitizers of the same porphyrin-triphenylamine hybrid series but bearing cationic charges which led to strongly enhanced water solubility and thus cellular penetration. In addition the new compounds have been found localized in mitochondria that are preferential target organelles for photodynamic therapy. Altogether the strongly improved properties of the new series combined with their specific mitochondrial localization lead to a significantly enhanced two-photon activated photodynamic therapy efficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Enhanced removal of sulfonamide antibiotics by KOH-activated anthracite coal: Batch and fixed-bed studies

    International Nuclear Information System (INIS)

    Zuo, Linzi; Ai, Jing; Fu, Heyun; Chen, Wei; Zheng, Shourong; Xu, Zhaoyi; Zhu, Dongqiang

    2016-01-01

    The presence of sulfonamide antibiotics in aquatic environments poses potential risks to human health and ecosystems. In the present study, a highly porous activated carbon was prepared by KOH activation of an anthracite coal (Anth-KOH), and its adsorption properties toward two sulfonamides (sulfamethoxazole and sulfapyridine) and three smaller-sized monoaromatics (phenol, 4-nitrophenol and 1,3-dinitrobenzene) were examined in both batch and fixed-bed adsorption experiments to probe the interplay between adsorbate molecular size and adsorbent pore structure. A commercial powder microporous activated carbon (PAC) and a commercial mesoporous carbon (CMK-3) possessing distinct pore properties were included as comparative adsorbents. Among the three adsorbents Anth-KOH exhibited the largest adsorption capacities for all test adsorbates (especially the two sulfonamides) in both batch mode and fixed-bed mode. After being normalized by the adsorbent surface area, the batch adsorption isotherms of sulfonamides on PAC and Anth-KOH were displaced upward relative to the isotherms on CMK-3, likely due to the micropore-filling effect facilitated by the microporosity of adsorbents. In the fixed-bed mode, the surface area-normalized adsorption capacities of Anth-KOH for sulfonamides were close to that of CMK-3, and higher than that of PAC. The irregular, closed micropores of PAC might impede the diffusion of the relatively large-sized sulfonamide molecules and in turn led to lowered fixed-bed adsorption capacities. The overall superior adsorption of sulfonamides on Anth-KOH can be attributed to its large specific surface area (2514 m"2/g), high pore volume (1.23 cm"3/g) and large micropore sizes (centered at 2.0 nm). These findings imply that KOH-activated anthracite coal is a promising adsorbent for the removal of sulfonamide antibiotics from aqueous solution. - Highlights: • A high efficiency adsorbent for sulfonamide removal is prepared from anthracite. • Effects of

  2. Treatment of periodontitis in smokers with multiple sessions of antimicrobial photodynamic therapy or systemic antibiotics: A randomized clinical trial.

    Science.gov (United States)

    Theodoro, Letícia Helena; Assem, Naida Zanini; Longo, Mariéllen; Alves, Márcio Luiz Ferro; Duque, Cristiane; Stipp, Rafael Nobrega; Vizoto, Natália Leal; Garcia, Valdir Gouveia

    2018-06-01

    The aim of this study was to evaluate the effects of non-surgical periodontal therapies on smokers with chronic periodontitis, involving multiple adjunctive applications of antimicrobial photodynamic therapy (aPDT), and systemic metronidazole (MTZ) with amoxicillin (AMX). All participants were treated with scaling and root planing (SRP). Seventeen patients received 400 mg of MTZ and 500 mg of AMX three times per day for 7 days (MTZ + AMX). Additionally, 17 patients received a placebo, and 17 patients were treated with three applications of aPDT (immediately, 48 h and 96 h after SRP). Clinical and microbiological examinations were performed at baseline and at 90 and 180 days post-therapy. Subgingival samples were analyzed using real-time polymerase chain reaction. After 180 days, the patients in groups MTZ + AMX and aPDT had significantly lower mean probing depths, more clinical attachment level gains and less bleeding on probing. At 180 days, in the moderate pocket there was a reduction in the levels of Porphyromonas gingivalis and Prevotella nigrescens in the MTZ + AMX group, while group aPDT showed a reduction in Prevotella nigrescens. Furthermore, at 180 days, in the deep pocket a reduction in Porphyromonas gingivalis, Prevotella intermedia and Prevotella nigrescens was observed in group MTZ + AMX, as well as a reduction in the levels of Prevotella intermedia and Prevotella nigrescens in group aPDT. In smokers with periodontitis, the MTZ + AMX and aPDT treatments significantly improved the effects of SRP. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Antibiotics for acute bronchitis.

    Science.gov (United States)

    Smith, Susan M; Fahey, Tom; Smucny, John; Becker, Lorne A

    2017-06-19

    The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care. To assess the effects of antibiotics in improving outcomes and to assess adverse effects of antibiotic therapy for people with a clinical diagnosis of acute bronchitis. We searched CENTRAL 2016, Issue 11 (accessed 13 January 2017), MEDLINE (1966 to January week 1, 2017), Embase (1974 to 13 January 2017), and LILACS (1982 to 13 January 2017). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 5 April 2017. Randomised controlled trials comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in people without underlying pulmonary disease. At least two review authors extracted data and assessed trial quality. We did not identify any new trials for inclusion in this 2017 update. We included 17 trials with 5099 participants in the primary analysis. The quality of trials was generally good. At follow-up there was no difference in participants described as being clinically improved between the antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15). Participants given antibiotics were less likely to have a cough (4 studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) 6) and a night cough (4 studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7). Participants given antibiotics had a shorter mean cough duration (7 studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated participants were more likely to be improved according to clinician's global assessment (6 studies

  4. Formulation of a Novel Nano emulsion System for Enhanced Solubility of a Sparingly Water Soluble Antibiotic, Clarithromycin

    International Nuclear Information System (INIS)

    Vatsraj, S.; Pathak, H.; Chauhan, K.

    2014-01-01

    The sparingly water soluble property of majority of medicinally significant drugs acts as a potential barrier towards its utilization for therapeutic purpose. The present study was thus aimed at development of a novel oil-in-water (o/w) nano emulsion (NE) system having ability to function as carrier for poorly soluble drugs with clarithromycin as a model antibiotic. The therapeutically effective concentration of clarithromycin, 5 mg/mL, was achieved using polysorbate 80 combined with olive oil as lipophilic counterion. A three-level three-factorial central composite experimental design was utilized to conduct the experiments. The effects of selected variables, polysorbate 80 and olive oil content and concentration of polyvinyl alcohol, were investigated. The particle size of clarithromycin for the optimized formulation was observed to be 30 nm. The morphology of the nano emulsion was explored using transmission electron microscopy (TEM). The emulsions prepared with the optimized formula demonstrated good physical stability during storage at room temperature. Antibacterial activity was conducted with the optimized nano emulsion NESH 01 and compared with free clarithromycin. Zone of inhibition was larger for NESH 01 as compared to that with free clarithromycin. This implies that the solubility and hence the bioavailability of clarithromycin has increased in the formulated nano emulsion system.

  5. Immunomodulatory effects of macrolide antibiotics - part 2: advantages and disadvantages of long-term, low-dose macrolide therapy.

    Science.gov (United States)

    Altenburg, J; de Graaff, C S; van der Werf, T S; Boersma, W G

    2011-01-01

    The available evidence for long-term, low-dose treatment with 14- and 15-membered ring macrolides in non-cystic fibrosis (CF) bronchiectasis, COPD, chronic sinusitis, and asthma is reviewed with special attention to possible adverse effects and the emergence of resistance during long-term macrolide treatment. Macrolide maintenance therapy has been proven to be of benefit in diffuse panbronchiolitis and CF, presumably due to an anti-inflammatory mechanism of action in addition to its direct antimicrobial effect. Solid evidence to justify this treatment regimen for non-CF bronchiectasis, asthma, or sinusitis is still lacking, although a beneficial effect of long-term macrolide therapy has been found in small clinical trials on these subjects. Data from randomized trials of long-term macrolide treatment in COPD are conflicting. A sufficiently long duration of treatment and the careful selection of patients appears to be crucial. Aside from its beneficial effects, possible side effects of macrolide treatment should be taken into account, the most important of these being gastrointestinal upset and cardiac arrhythmias. Development of macrolide resistance among respiratory pathogens is very common during long-term macrolide treatment. Whether this finding is clinically significant is a matter of debate. Copyright © 2010 S. Karger AG, Basel.

  6. Enhancing Photodynamyc Therapy Efficacy by Combination Therapy: Dated, Current and Oncoming Strategies

    International Nuclear Information System (INIS)

    Postiglione, Ilaria; Chiaviello, Angela; Palumbo, Giuseppe

    2011-01-01

    Combination therapy is a common practice in many medical disciplines. It is defined as the use of more than one drug to treat the same disease. Sometimes this expression describes the simultaneous use of therapeutic approaches that target different cellular/molecular pathways, increasing the chances of killing the diseased cell. This short review is concerned with therapeutic combinations in which PDT (Photodynamyc Therapy) is the core therapeutic partner. Besides the description of the principal methods used to assess the efficacy attained by combinations in respect to monotherapy, this review describes experimental results in which PDT was combined with conventional drugs in different experimental conditions. This inventory is far from exhaustive, as the number of photosensitizers used in combination with different drugs is very large. Reports cited in this work have been selected because considered representative. The combinations we have reviewed include the association of PDT with anti-oxidants, chemotherapeutics, drugs targeting topoisomerases I and II, antimetabolites and others. Some paragraphs are dedicated to PDT and immuno-modulation, others to associations of PDT with angiogenesis inhibitors, receptor inhibitors, radiotherapy and more. Finally, a look is dedicated to combinations involving the use of natural compounds and, as new entries, drugs that act as proteasome inhibitors

  7. Enhanced cognitive behaviour therapy for adolescents with anorexia nervosa: An alternative to family therapy?

    Science.gov (United States)

    Dalle Grave, Riccardo; Calugi, Simona; Doll, Helen A.; Fairburn, Christopher G.

    2013-01-01

    A specific form of family therapy (family-based treatment) is the leading treatment for adolescents with anorexia nervosa. As this treatment has certain limitations, alternative approaches are needed. “Enhanced” cognitive behaviour therapy (CBT-E) is a potential candidate given its utility as a treatment for adults with eating disorder psychopathology. The aim of the present study was to establish, in a representative cohort of patients with marked anorexia nervosa, the immediate and longer term outcome following CBT-E. Forty-nine adolescent patients were recruited from consecutive referrals to a community-based eating disorder clinic. Each was offered 40 sessions of CBT-E over 40 weeks from a single therapist. Two-thirds completed the full treatment with no additional input. In these patients there was a substantial increase in weight together with a marked decrease in eating disorder psychopathology. Over the 60-week post-treatment follow-up period there was little change despite minimal subsequent treatment. These findings suggest that CBT-E may prove to be a cost-effective alternative to family-based treatment. PMID:23123081

  8. [Antibiotics in the critically ill].

    Science.gov (United States)

    Kolak, Radmila R

    2010-01-01

    Antibiotics are one the most common therapies administered in the intensive care unit setting. This review outlines the strategy for optimal use of antimicrobial agents in the critically ill. In severely ill patients, empirical antimicrobial therapy should be used when a suspected infection may impair the outcome. It is necessary to collect microbiological documentation before initiating empirical antimicrobial therapy. In addition to antimicrobial therapy, it is recommended to control a focus of infection and to modify factors that promote microbial growth or impair the host's antimicrobial defence. A judicious choice of antimicrobial therapy should be based on the host characteristics, the site of injection, the local ecology, and the pharmacokinetics/pharmacodynamics of antibiotics. This means treating empirically with broad-spectrum antimicrobials as soon as possible and narrowing the spectrum once the organism is identified (de-escalation), and limiting duration of therapy to the minimum effective period. Despite theoretical advantages, a combined antibiotic therapy is nor more effective than a mono-therapy in curing infections in most clinical trials involving intensive care patients. Nevertheless, textbooks and guidelines recommend a combination for specific pathogens and for infections commonly caused by these pathogens. Avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will improve patient outcomes while minimizing risks for the development of bacterial resistance. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilisation and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use be evaluated at the local level.

  9. Phonatory vocal tract stability in stuttering children before and after fluency--enhancing therapy.

    Science.gov (United States)

    Dehqan, A; Ali Dashti, G; Mirzadeh, M

    2010-01-01

    Stuttering is a complex disorder. Essentially, it is a neuromuscular disorder whose core consists of tiny lags and disruptions in the timing of the complicated movements required for speech. The purpose of the current study was to collec and comparg jitters and shimmer values in children who stutter before and after fluency--enhancing therapy. Subjects consisted of 15 Iranian preschool girls with stutterg, and 15 Iranial preschool girls without afflictions, matched according to age. Vocal jittering and shimmer measurements of thesphonation of the children were compared before and after therapy. Each subject phonated vowels nine times in a random order. Each phonation was sustained for at least five seconds and was recorded. The middle three-second portion of each recorded vowel phonation was subjected to jitter and shimmer analysis. On shimmer measures between pre-treatment and post treatment, significant differences were found in all sustained vowels of persons who stutter group and means of shimmer in post therapy were significantly lower than pre-treatment. Differences in jitter measurements were not significant between pre-treatment and post-treatment statuses and this parameter did not change after therapy. The findings showed that therapy resulted in decreaseg irregularity in the amplitude of vibrations (shimmer). In other words, the therapy increases the steady-state of the laryngeal system. Moreover, this parameter may be used as an index for the effectiveness of therapy.

  10. Self-medication with antibiotics in the Republic of Srpska community pharmacies: pharmacy staff behavior.

    Science.gov (United States)

    Marković-Peković, Vanda; Grubiša, Nataša

    2012-10-01

    Self-medication with antibiotics adds to the global risk of increased spread of bacterial resistance. Attitudes and behavior of health professionals also may reinforce self-medication with antibiotics. The aim of this study was to determine whether self-medication with antibiotics is possible in our community pharmacies and to what extent, and to evaluate the behavior and service of pharmacy health professionals regarding non-prescription antibiotic dispensation. An observational, cross-section study was conducted, and pseudo-patient methodology was used to establish the kind of professional service provided in case of patient's explicit demand to buy an antibiotic for treatment of self-diagnosed upper respiratory tract infection. Of the total 318 community pharmacies, 131 (41%) were visited and included in the study. Non-prescription antibiotics were dispensed in 76 (58%) pharmacies. Counseling and symptomatic therapy was offered in 88 (67%) pharmacies. In 25% of pharmacies, no symptomatic therapy was offered; instead, only an antibiotic was sold. Amoxicillin was sold in 85% of cases and, mostly, the one of 1.30 Euro per pack. Both oral and written use instructions were given in 78% cases, whereas none was given in 3% of cases. Self-medication with antibiotics occurs in our community pharmacies, despite being illegal. Pharmacy staff behavior can be a factor that puts patients at risk for self-medication with antibiotics. Community pharmacies are failing their tasks in enhancing rational use of antibiotics. Such a practice may be a consequence of weak enforcement and control over the legislation and professional standards. Copyright © 2012 John Wiley & Sons, Ltd.

  11. SU-E-T-56: Brain Metastasis Treatment Plans for Contrast-Enhanced Synchrotron Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Obeid, L; Adam, J [Grenoble Institut des Neurosciences, La Tronche, Rhone-Alpes (France); Tessier, A [Centre Hospitalier Universitaire, La Tronche, Rhone-Alpes (France); Vautrin, M; Benkebil, M [DOSIsoft, Cachan, Ile de France (France); Sihanath, R [Centre Hospitalier Universitaire, La Tronche, Rhone- Alpes (France)

    2014-06-01

    Purpose: Iodine-enhanced radiotherapy is an innovative treatment combining the selective accumulation of an iodinated contrast agent in brain tumors with irradiations using monochromatic medium energy x-rays. The aim of this study is to compare dynamic stereotactic arc-therapy and iodineenhanced SSRT. Methods: Five patients bearing brain metastasis received a standard helical 3D-scan without iodine. A second scan was acquired 13 min after an 80 g iodine infusion. Two SSRT treatment plans (with/without iodine) were performed for each patient using a dedicated Monte Carlo (MC) treatment planning system (TPS) based on the ISOgray TPS. Ten coplanar beams (6×6 cm2, shaped with collimator) were simulated. MC statistical error objective was less than 5% in the 50% isodose. The dynamic arc-therapy plan was achieved on the Iplan Brainlab TPS. The treatment plan validation criteria were fixed such that 100% of the prescribed dose is delivered at the beam isocentre and the 70% isodose contains the whole target volume. The comparison elements were the 70% isodose volume, the average and maximum doses delivered to organs at risk (OAR): brainstem, optical nerves, chiasma, eyes, skull bone and healthy brain parenchyma. Results: The stereotactic dynamic arc-therapy remains the best technique in terms of dose conformation. Iodine-enhanced SSRT presents similar performances to dynamic arc-therapy with increased brainstem and brain parenchyma sparing. One disadvantage of SSRT is the high dose to the skull bone. Iodine accumulation in metastasis may increase the dose by 20–30%, allowing a normal tissue sparing effect at constant prescribed dose. Treatment without any iodine enhancement (medium-energy stereotactic radiotherapy) is not relevant with degraded HDVs (brain, parenchyma and skull bone) comparing to stereotactic dynamic arc-therapy. Conclusion: Iodine-enhanced SSRT exhibits a good potential for brain metastasis treatment regarding the dose distribution and OAR criteria.

  12. Antibiotic Resistance

    DEFF Research Database (Denmark)

    Munck, Christian

    morbidity and mortality as well as an increase in the cost of treatment. Understanding how bacteria respond to antibiotic exposure gives the foundations for a rational approach to counteract antimicrobial resistance. In the work presented in this thesis, I explore the two fundamental sources...... of antimicrobial resistance: (1) adaptive mutations and (2) horizontal acquisition of resistance genes from antibiotic gene reservoirs. By studying the geno- and phenotypic changes of E. coli in response to single and drug-pair exposures, I uncover the evolutionary trajectories leading to adaptive resistance. I...... to rationally design drug combinations that limit the evolution of antibiotic resistance due to counteracting evolutionary trajectories. My results highlight that an in-depth knowledge about the genetic responses to the individual antimicrobial compounds enables the prediction of responses to drug combinations...

  13. Massage Therapy of the Back Using a Real-Time Haptic-Enhanced Telerehabilitation System

    Directory of Open Access Journals (Sweden)

    Cristina Ramírez-Fernández

    2017-01-01

    Full Text Available We present the usability evaluation of a haptic-enhanced telerehabilitation system for massage therapy of the back using the Vybe haptic gaming pad and the gesture sensor LEAP motion controller. The evaluated system includes features that allow for (i administering online therapy programs, (ii providing self-adjustable and safety treatment of back massages using a virtual environment, and (iii saving and replaying massage sessions according to a patient’s therapy program. The usability evaluation with 25 older adults and 10 specialists suggests that the haptic telerehabilitation system is perceived with high usability and pleasurable user experience, while providing personalized intensity of haptic therapy in a supervised, real-time, and secure way to treat the patient. Moreover, the specialists totally agree that the system design features, such as save and play, and delimiting therapy zones are the most important for back massage therapy, while the features of regulating feedback intensity and providing/receiving a massage remotely are also important. Finally, based on their comments, five design insights aiming at improving the current version of the system were generated.

  14. Antibiotics for mastitis in breastfeeding women

    Directory of Open Access Journals (Sweden)

    Shayesteh Jahanfar

    Full Text Available ABSTRACT: BACKGROUND: Mastitis can be caused by ineffective positioning of the baby at the breast or restricted feeding. Infective mastitis is commonly caused by Staphylococcus aureus . The prevalence of mastitis in breastfeeding women may reach 33%. Effective milk removal, pain medication and antibiotic therapy have been the mainstays of treatment. OBJECTIVES: This review aims to examine the effectiveness of antibiotic therapies in relieving symptoms for breastfeeding women with mastitis with or without laboratory investigation. METHODS: Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2012, contacted investigators and other content experts known to us for unpublished trials and scanned the reference lists of retrieved articles. Selection criteria: We selected randomised controlled trials (RCTs and quasi-RCTs comparing the effectiveness of various types of antibiotic therapies or antibiotic therapy versus alternative therapies for the treatment of mastitis. Data collection and analysis: Two review authors independently assessed trial quality and extracted data. When in dispute, we consulted a third author. MAIN RESULTS: Two trials met the inclusion criteria. One small trial (n = 25 compared amoxicillin with cephradine and found no significant difference between the two antibiotics in terms of symptom relief and abscess formation. Another, older study compared breast emptying alone as 'supportive therapy' versus antibiotic therapy plus supportive therapy, and no therapy. The findings of the latter study suggested faster clearance of symptoms for women using antibiotics, although the study design was problematic. AUTHORS CONCLUSIONS: There is insufficient evidence to confirm or refute the effectiveness of antibiotic therapy for the treatment of lactational mastitis. There is an urgent need to conduct high-quality, double-blinded RCTs to determine whether antibiotics should be used in this

  15. Antibiotics and oral contraceptives.

    Science.gov (United States)

    DeRossi, Scott S; Hersh, Elliot V

    2002-10-01

    With the exception of rifampin-like drugs, there is a lack of scientific evidence supporting the ability of commonly prescribed antibiotics, including all those routinely employed in outpatient dentistry, to either reduce blood levels and/or the effectiveness of oral contraceptives. To date, all clinical trials studying the effects of concomitant antibiotic therapy (with the exception of rifampin and rifabutin) have failed to demonstrate an interaction. Like all drugs, oral contraceptives are not 100% effective with the failure rate in the typical United States population reported to be as high as 3%. It is thus possible that the case reports of unintended pregnancies during antibiotic therapy may simply represent the normal failure rate of these drugs. Considering that both drug classes are prescribed frequently to women of childbearing potential, one would expect a much higher rate of oral contraceptive failure in this group of patients if a true drug:drug interaction existed. On the other hand, if the interaction does exist but is a relatively rare event, occurring in, say, 1 in 5000 women, clinical studies such as those described in this article would not detect the interaction. The pharmacokinetic studies of simultaneous antibiotic and oral contraceptive ingestion, and the retrospective studies of pregnancy rates among oral contraceptive users exposed to antibiotics, all suffer from one potential common weakness, i.e., their relatively small sample size. Sample sizes in the pharmacokinetic trials ranged from 7 to 24 participants, whereas the largest retrospective study of pregnancy rates still evaluated less than 800 total contraceptive users. Still, the incidence of such a rare interaction would not differ from the accepted normal failure rate of oral contraceptive therapy. The medico-legal ramifications of what looks like at best a rare interaction remains somewhat "murky." On one hand, we have medico-legal experts advising the profession to exercise caution

  16. Local ablation therapy with contrast-enhanced ultrasonography for hepatocellular carcinoma: a practical review

    Directory of Open Access Journals (Sweden)

    Tae Kyoung Kim

    2015-10-01

    Full Text Available A successful program for local ablation therapy for hepatocellular carcinoma (HCC requires extensive imaging support for diagnosis and localization of HCC, imaging guidance for the ablation procedures, and post-treatment monitoring. Contrast-enhanced ultrasonography (CEUS has several advantages over computed tomography/magnetic resonance imaging (CT/MRI, including real-time imaging capability, sensitive detection of arterial-phase hypervascularity and washout, no renal excretion, no ionizing radiation, repeatability, excellent patient compliance, and relatively low cost. CEUS is useful for image guidance for isoechoic lesions. While contrast-enhanced CT/MRI is the standard method for the diagnosis of HCC and post-ablation monitoring, CEUS is useful when CT/MRI findings are indeterminate or CT/MRI is contraindicated. This article provides a practical review of the role of CEUS in imaging algorithms for pre- and post-ablation therapy for HCC.

  17. Pharmacological Targeting of the Host-Pathogen Interaction: Alternatives to Classical Antibiotics to Combat Drug-Resistant Superbugs.

    Science.gov (United States)

    Munguia, Jason; Nizet, Victor

    2017-05-01

    The rise of multidrug-resistant pathogens and the dearth of new antibiotic development place an existential strain on successful infectious disease therapy. Breakthrough strategies that go beyond classical antibiotic mechanisms are needed to combat this looming public health catastrophe. Reconceptualizing antibiotic therapy in the richer context of the host-pathogen interaction is required for innovative solutions. By defining specific virulence factors, the essence of a pathogen, and pharmacologically neutralizing their activities, one can block disease progression and sensitize microbes to immune clearance. Likewise, host-directed strategies to boost phagocyte bactericidal activity, enhance leukocyte recruitment, or reverse pathogen-induced immunosuppression seek to replicate the success of cancer immunotherapy in the field of infectious diseases. The answer to the threat of multidrug-resistant pathogens lies 'outside the box' of current antibiotic paradigms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Robot Enhanced Therapy for Children with Autism (DREAM): A Social Model of Autism

    OpenAIRE

    Richardson, Kathleen; Coecklebergh, M; Wakunuma, Kutoma; Billing, Erik; Ziemke, Tom; Gomez, P; Vanderborght, Bram; Belpaeme, Tony

    2017-01-01

    Development of Robot-enhanced Therapy for Children with Autism Spectrum Disorders The development of social robots for children with autism has been a growth field in the last 15 years. This paper reviews studies in robots and autism as a neurodevelopmental disorder that impacts on social-communication development and the way in which social robots could help children with autism develop social skills. Drawing on the ethics research from the EU funded DREAM project (framework 7), based on ...

  19. Synthetic biology era: Improving antibiotic's world.

    Science.gov (United States)

    Guzmán-Trampe, Silvia; Ceapa, Corina D; Manzo-Ruiz, Monserrat; Sánchez, Sergio

    2017-06-15

    The emergence of antibiotic-resistant pathogen microorganisms is problematic in the context of the current spectrum of available medication. The poor specificity and the high toxicity of some available molecules have made imperative the search for new strategies to improve the specificity and to pursue the discovery of novel compounds with increased bioactivity. Using living cells as platforms, synthetic biology has counteracted this problem by offering novel pathways to create synthetic systems with improved and desired functions. Among many other biotechnological approaches, the advances in synthetic biology have made it possible to design and construct novel biological systems in order to look for new drugs with increased bioactivity. Advancements have also been made in the redesigning of RNA and DNA molecules in order to engineer antibiotic clusters for antibiotic overexpression. As for the production of these antibacterial compounds, yeasts and filamentous fungi as well as gene therapy are utilized to enhance protein solubility. Specific delivery is achieved by creating chimeras using plant genes into bacterial hosts. Some of these synthetic systems are currently in clinical trials, proving the proficiency of synthetic biology in terms of both pharmacological activities as well as an increase in the biosafety of treatments. It is possible that we may just be seeing the tip of the iceberg, and synthetic biology applications will overpass expectations beyond our present knowledge. Copyright © 2017. Published by Elsevier Inc.

  20. Combating Antibiotic Resistance

    Science.gov (United States)

    ... Bacteria Phasing Out Certain Antibiotic Use in Farm Animals FDA: Cutting-Edge Technology Sheds Light on Antibiotic Resistance For More Information Antibiotics and Antibiotic Resistance Antimicrobial Resistance Information for Consumers and Health Professionals CDC: ...

  1. A dynamical systems model for combinatorial cancer therapy enhances oncolytic adenovirus efficacy by MEK-inhibition.

    Science.gov (United States)

    Bagheri, Neda; Shiina, Marisa; Lauffenburger, Douglas A; Korn, W Michael

    2011-02-01

    Oncolytic adenoviruses, such as ONYX-015, have been tested in clinical trials for currently untreatable tumors, but have yet to demonstrate adequate therapeutic efficacy. The extent to which viruses infect targeted cells determines the efficacy of this approach but many tumors down-regulate the Coxsackievirus and Adenovirus Receptor (CAR), rendering them less susceptible to infection. Disrupting MAPK pathway signaling by pharmacological inhibition of MEK up-regulates CAR expression, offering possible enhanced adenovirus infection. MEK inhibition, however, interferes with adenovirus replication due to resulting G1-phase cell cycle arrest. Therefore, enhanced efficacy will depend on treatment protocols that productively balance these competing effects. Predictive understanding of how to attain and enhance therapeutic efficacy of combinatorial treatment is difficult since the effects of MEK inhibitors, in conjunction with adenovirus/cell interactions, are complex nonlinear dynamic processes. We investigated combinatorial treatment strategies using a mathematical model that predicts the impact of MEK inhibition on tumor cell proliferation, ONYX-015 infection, and oncolysis. Specifically, we fit a nonlinear differential equation system to dedicated experimental data and analyzed the resulting simulations for favorable treatment strategies. Simulations predicted enhanced combinatorial therapy when both treatments were applied simultaneously; we successfully validated these predictions in an ensuing explicit test study. Further analysis revealed that a CAR-independent mechanism may be responsible for amplified virus production and cell death. We conclude that integrated computational and experimental analysis of combinatorial therapy provides a useful means to identify treatment/infection protocols that yield clinically significant oncolysis. Enhanced oncolytic therapy has the potential to dramatically improve non-surgical cancer treatment, especially in locally advanced

  2. Utilizing a Modified Care Coordination Measurement Tool to Capture Value for a Pediatric Outpatient Parenteral and Prolonged Oral Antibiotic Therapy Program.

    Science.gov (United States)

    Vaz, Louise E; Farnstrom, Cindi L; Felder, Kimberly K; Guzman-Cottrill, Judith; Rosenberg, Hannah; Antonelli, Richard C

    2017-04-17

    Outpatient parenteral or prolonged oral antibiotic therapy (OPAT) programs reduce inpatient healthcare costs by shifting care to outpatient settings. Care coordination (CC) is a necessary component to successfully transition patients. Our objective was to assess outcomes of provider time spent on nonreimbursable CC activities in a pediatric OPAT program. We used a qualitative feasibility pilot design and modified the Care Coordination Measurement Tool. We captured nonreimbursable CC activity and associated outcome(s) among pediatric patients enrolled in OPAT from March 1 to April 30, 2015 (44 work days) at Doernbecher Children's Hospital. We generated summary statistics for this institutional review board-waived QI project. There were 154 nonreimbursable CC encounters conducted by 2 infectious diseases (ID) providers for 29 patients, ages 17 months-15 years, with complex infections. Total estimated time spent on CC was 54 hours, equivalent to at least 6 workdays. Five patients with complex social issues used 37% of total CC time. Of 129 phone events, 38% involved direct contact with families, pharmacies (13%), primary care providers (13%), and home health nursing (11%). Care coordination prevented 10 emergency room (ER) visits and 2 readmissions. Care coordination led to 16 additional, not previously scheduled subspecialist and 13 primary care visits. The OPAT providers billed for 32 clinic visits during the study period. Nonreimbursable CC work by OPAT providers prevented readmissions and ER visits and helped facilitate appropriate healthcare use. The value of pediatric OPAT involvement in patient care would have been underestimated based on reimbursable ID consultations and clinic visits alone. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Sodium Mercaptoethane Sulfonate Reduces Collagenolytic Degradation and Synergistically Enhances Antimicrobial Durability in an Antibiotic-Loaded Biopolymer Film for Prevention of Surgical-Site Infections

    Directory of Open Access Journals (Sweden)

    Joel Rosenblatt

    2017-01-01

    Full Text Available Implant-associated surgical-site infections can have significant clinical consequences. Previously we reported a method for prophylactically disinfecting implant surfaces in surgical pockets, where an antibiotic solution containing minocycline (M and rifampin (R was applied as a solid film in a crosslinked biopolymer matrix that partially liquefied in situ to provide extended prophylaxis. Here we studied the effect of adding sodium 2-mercaptoethane sulfonate (MeSNA on durability of prophylaxis in an in vitro model of implant-associated surgical-site infection. Adding MeSNA to the M/R biopolymer, antimicrobial film extended the duration for which biofilm formation by multidrug-resistant Pseudomonas aeruginosa (MDR-PA was prevented on silicone surfaces in the model. M/R films with and without MeSNA were effective in preventing colonization by methicillin-resistant Staphylococcus aureus. Independent experiments revealed that MeSNA directly inhibited proteolytic digestion of the biopolymer film and synergistically enhanced antimicrobial potency of M/R against MDR-PA. Incubation of the MeSNA containing films with L929 fibroblasts revealed no impairment of cellular metabolic activity or viability.

  4. [INHALED ANTIBIOTICS IN TREATMENT OF NOSOCOMIAL PNEUMONIA].

    Science.gov (United States)

    Kuzovlev, A N; Moroz, V V; Golubev, A M

    2015-01-01

    Nosocomial pneumonia is the most common infection in intensive care units. Currently the problem of resistance of noso-comial pathogens to miost of antibiotics is crucial. Using of inhaled antibiotics in combination with intravenous drugs is eff ective and safe method for treatment of nosocomial pneumonia. The literature review describes current opportunities of ihhaled antibiotic therapy of nosocomial pneumonia, descriptions of drugs, the advantages and disadvantages of this treatment. Special attention is paid for using inhaled aminoglycosides for nosocomial pneumonia.

  5. Newly approved antibiotics and antibiotics reserved for resistant infections: Implications for emergency medicine.

    Science.gov (United States)

    Mazer-Amirshahi, Maryann; Pourmand, Ali; May, Larissa

    2017-01-01

    Millions of patients are evaluated every year in the emergency department (ED) for bacterial infections. Emergency physicians often diagnose and prescribe initial antibiotic therapy for a variety of bacterial infections, ranging from simple urinary tract infections to severe sepsis. In life-threatening infections, inappropriate choice of initial antibiotic has been shown to increase morbidity and mortality. As such, initiation of appropriate antibiotic therapy on the part of the emergency physician is critical. Increasing rates of antibiotic resistance, drug allergies, and antibiotic shortages further complicates the choice of antibiotics. Patients may have a history of prior resistant infections or culture data indicating that common first-line antibiotics used in the ED may be ineffective. In recent years, there have been several new antibiotic approvals as well as renewed interest in second and third line antibiotics because of the aforementioned concerns. In addition, several newly approved antibiotics have the advantage of being administered once weekly or even as a single infusion, which has the potential to decrease hospitalizations and healthcare costs. This article reviews newly approved antibiotics and antibiotics used to treat resistant infections with a focus on implications for emergency medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Photoelectric-enhanced radiation therapy with quasi-monochromatic computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Jost, Gregor; Mensing, Tristan; Golfier, Sven; Lawaczeck, Ruediger; Pietsch, Hubertus; Huetter, Joachim; Cibik, Levent; Gerlach, Martin; Krumrey, Michael; Fratzscher, Daniel; Arkadiev, Vladimir; Wedell, Reiner; Haschke, Michael; Langhoff, Norbert; Wust, Peter; Luedemann, Lutz [TRG Diagnostic Imaging, Bayer Schering Pharma AG, 13353 Berlin (Germany); Department of Radiotherapy, Charite Medical Centre, 13353 Berlin (Germany); TRG Diagnostic Imaging, Bayer Schering Pharma AG, 13353 Berlin (Germany); Physikalisch-Technische Bundesanstalt, 10587 Berlin (Germany); Institute of Applied Photonics e.V., 12489 Berlin (Germany); Institute for Scientific Instruments GmbH, 12489 Berlin (Germany); Department of Radiotherapy, Charite Medical Centre, 13353 Berlin (Germany)

    2009-06-15

    Photoelectric-enhanced radiation therapy is a bimodal therapy, consisting of the administration of highly radiation-absorbing substances into the tumor area and localized regional irradiation with orthovoltage x-rays. Irradiation can be performed by a modified computed tomography (CT) unit equipped with an additional x-ray optical module which converts the polychromatic, fan-shaped CT beam into a monochromatized and focused beam for energy-tuned photoelectric-enhanced radiotherapy. A dedicated x-ray optical module designed for spatial collimation, focusing, and monochromatization was mounted at the exit of the x-ray tube of a clinical CT unit. Spectrally resolved measurements of the resulting beam were performed using an energy-dispersive detection system calibrated by synchrotron radiation. The spatial photon fluence was determined by film dosimetry. Depth-dose measurements were performed and compared to the polychromatic CT and a therapeutic 6 MV beam. The spatial dose distribution in phantoms using a rotating radiation source (quasi-monochromatic CT and 6 MV, respectively) was investigated by gel dosimetry. The photoelectric dose enhancement for an iodine fraction of 1% in tissue was calculated and verified experimentally. The x-ray optical module selectively filters the energy of the tungsten K{alpha} emission line with an FWHM of 5 keV. The relative photon fluence distribution demonstrates the focusing characteristic of the x-ray optical module. A beam width of about 3 mm was determined at the isocenter of the CT gantry. The depth-dose measurements resulted in a half-depth value of approximately 36 mm for the CT beams (quasi-monochromatic, polychromatic) compared to 154 mm for the 6 MV beam. The rotation of the radiation source leads to a steep dose gradient at the center of rotation; the gel dosimetry yields an entrance-to-peak dose ratio of 1:10.8 for the quasi-monochromatic CT and 1:37.3 for a 6 MV beam of the same size. The photoelectric dose enhancement

  7. Photoelectric-enhanced radiation therapy with quasi-monochromatic computed tomography.

    Science.gov (United States)

    Jost, Gregor; Mensing, Tristan; Golfier, Sven; Lawaczeck, Rüdiger; Pietsch, Hubertus; Hütter, Joachim; Cibik, Levent; Gerlach, Martin; Krumrey, Michael; Fratzscher, Daniel; Arkadiev, Vladimir; Wedell, Reiner; Haschke, Michael; Langhoff, Norbert; Wust, Peter; Lüdemann, Lutz

    2009-06-01

    Photoelectric-enhanced radiation therapy is a bimodal therapy, consisting of the administration of highly radiation-absorbing substances into the tumor area and localized regional irradiation with orthovoltage x-rays. Irradiation can be performed by a modified computed tomography (CT) unit equipped with an additional x-ray optical module which converts the polychromatic, fan-shaped CT beam into a monochromatized and focused beam for energy-tuned photoelectric-enhanced radiotherapy. A dedicated x-ray optical module designed for spatial collimation, focusing, and monochromatization was mounted at the exit of the x-ray tube of a clinical CT unit. Spectrally resolved measurements of the resulting beam were performed using an energy-dispersive detection system calibrated by synchrotron radiation. The spatial photon fluence was determined by film dosimetry. Depth-dose measurements were performed and compared to the polychromatic CT and a therapeutic 6 MV beam. The spatial dose distribution in phantoms using a rotating radiation source (quasimonochromatic CT and 6 MV, respectively) was investigated by gel dosimetry. The photoelectric dose enhancement for an iodine fraction of 1% in tissue was calculated and verified experimentally. The x-ray optical module selectively filters the energy of the tungsten Kalpha emission line with an FWHM of 5 keV. The relative photon fluence distribution demonstrates the focusing characteristic of the x-ray optical module. A beam width of about 3 mm was determined at the isocenter of the CT gantry. The depth-dose measurements resulted in a half-depth value of approximately 36 mm for the CT beams (quasi-monochromatic, polychromatic) compared to 154 mm for the 6 MV beam. The rotation of the radiation source leads to a steep dose gradient at the center of rotation; the gel dosimetry yields an entrance-to-peak dose ratio of 1:10.8 for the quasi-monochromatic CT and 1:37.3 for a 6 MV beam of the same size. The photoelectric dose enhancement

  8. Photoelectric-enhanced radiation therapy with quasi-monochromatic computed tomography

    International Nuclear Information System (INIS)

    Jost, Gregor; Mensing, Tristan; Golfier, Sven; Lawaczeck, Ruediger; Pietsch, Hubertus; Huetter, Joachim; Cibik, Levent; Gerlach, Martin; Krumrey, Michael; Fratzscher, Daniel; Arkadiev, Vladimir; Wedell, Reiner; Haschke, Michael; Langhoff, Norbert; Wust, Peter; Luedemann, Lutz

    2009-01-01

    Photoelectric-enhanced radiation therapy is a bimodal therapy, consisting of the administration of highly radiation-absorbing substances into the tumor area and localized regional irradiation with orthovoltage x-rays. Irradiation can be performed by a modified computed tomography (CT) unit equipped with an additional x-ray optical module which converts the polychromatic, fan-shaped CT beam into a monochromatized and focused beam for energy-tuned photoelectric-enhanced radiotherapy. A dedicated x-ray optical module designed for spatial collimation, focusing, and monochromatization was mounted at the exit of the x-ray tube of a clinical CT unit. Spectrally resolved measurements of the resulting beam were performed using an energy-dispersive detection system calibrated by synchrotron radiation. The spatial photon fluence was determined by film dosimetry. Depth-dose measurements were performed and compared to the polychromatic CT and a therapeutic 6 MV beam. The spatial dose distribution in phantoms using a rotating radiation source (quasi-monochromatic CT and 6 MV, respectively) was investigated by gel dosimetry. The photoelectric dose enhancement for an iodine fraction of 1% in tissue was calculated and verified experimentally. The x-ray optical module selectively filters the energy of the tungsten Kα emission line with an FWHM of 5 keV. The relative photon fluence distribution demonstrates the focusing characteristic of the x-ray optical module. A beam width of about 3 mm was determined at the isocenter of the CT gantry. The depth-dose measurements resulted in a half-depth value of approximately 36 mm for the CT beams (quasi-monochromatic, polychromatic) compared to 154 mm for the 6 MV beam. The rotation of the radiation source leads to a steep dose gradient at the center of rotation; the gel dosimetry yields an entrance-to-peak dose ratio of 1:10.8 for the quasi-monochromatic CT and 1:37.3 for a 6 MV beam of the same size. The photoelectric dose enhancement factor

  9. Antibiotics and inflammatory bowel diseases.

    Science.gov (United States)

    Scribano, Maria Lia; Prantera, Cosimo

    2013-01-01

    Inflammatory bowel diseases are characterized by an altered composition of gut microbiota (dysbiosis) that may contribute to their development. Antibiotics can alter the bacterial flora, and a link between antibiotic use and onset of Crohn's disease (CD), but not ulcerative colitis, has been reported. The hypothesis that Mycobacterium avium subspecies paratuberculosis (MAP) could be an etiologic agent of CD has not been confirmed by a large study on patients treated by an association of antibiotics active against MAP. The observations supporting a role of intestinal microbiota in CD pathogenesis provide the rationale for a therapeutic manipulation of the intestinal flora through the employment of antibiotics. However, current data do not strongly support a therapeutic benefit from antibiotics, and there is still controversy regarding their use as primary therapy for treatment of acute flares of CD, and for postoperative recurrence prevention. Nevertheless, clinical practice and some studies suggest that a subgroup of patients with colonic involvement, early disease, and abnormal laboratory test of inflammation may respond better to antibiotic treatment. Since their long-term use is frequently complicated by a high rate of side effects, the use of antibiotics that work locally appears to be promising.

  10. Inhaled Antibiotics in the Treatment of Nosocomial Pneumonia

    Directory of Open Access Journals (Sweden)

    A. N. Kuzovlev

    2013-01-01

    Full Text Available Nosocomial pneumonia is the most common nosocomial infection in intensive care units. Rational antibiotic therapy is the basis for the treatment of nosocomial pneumonia. There is currently a challenge of the pathogens of nosocomial pneumonia being resistant to most of the antibiotics recommended for its treatment. Inhaled antibiotics used in combination with systemic drugs are an effective and safe treatment for nosocomial pneumonia. This review of literature characterizes the current possibilities of inhaled antibiotic therapy for nosocomial pneumonia in detail and describes medicaments and the advantages and disadvantages of this treatment option. Despite insufficient evidence in circumstances where the microorganisms are polyresistant and where the design of novel antibiotics shows no promise, the use of inhaled antibiotics is an important alternative in the treatment of severe nosocomial pneumonia caused by polyresistant gram-negative bacteria. Key words: nosocomial pneumonia, antibiotic therapy, inhaled antibiotics, resistance.

  11. Prescribing Antibiotics

    DEFF Research Database (Denmark)

    Pedersen, Inge Kryger; Jepsen, Kim Sune

    2018-01-01

    The medical professions will lose an indispensable tool in clinical practice if even simple infections cannot be cured because antibiotics have lost effectiveness. This article presents results from an exploratory enquiry into “good doctoring” in the case of antibiotic prescribing at a time when...... the knowledge base in the healthcare field is shifting. Drawing on in-depth interviews about diagnosing and prescribing, the article demonstrates how the problem of antimicrobial resistance is understood and engaged with by Danish general practitioners. When general practitioners speak of managing “non......-medical issues,” they refer to routines, clinical expertise, experiences with their patients, and decision-making based more on contextual circumstances than molecular conditions—and on the fact that such conditions can be hard to assess. This article’s contribution to knowledge about how new and global health...

  12. A systematic review of randomized controlled trials on curative and health enhancement effects of forest therapy

    Directory of Open Access Journals (Sweden)

    Kamioka H

    2012-07-01

    Full Text Available Hiroharu Kamioka,1 Kiichiro Tsutani,2 Yoshiteru Mutoh,3 Takuya Honda,4 Nobuyoshi Shiozawa,5 Shinpei Okada,6 Sang-Jun Park,6 Jun Kitayuguchi,7 Masamitsu Kamada,8 Hiroyasu Okuizumi,9 Shuichi Handa91Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 3Todai Policy Alternatives Research Institute, The University of Tokyo, Tokyo, 4Japanese Society for the Promotion of Science, Tokyo, 5Food Labeling Division, Consumer Affairs Agency, Cabinet Office, Government of Japan, Tokyo, 6Physical Education and Medicine Research Foundation, Nagano, 7Physical Education and Medicine Research Center Unnan, Shimane, 8Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Shimane, 9Mimaki Onsen (Spa Clinic, Tomi City, Nagano, JapanObjective: To summarize the evidence for curative and health enhancement effects through forest therapy and to assess the quality of studies based on a review of randomized controlled trials (RCTs.Study design: A systematic review based on RCTs.Methods: Studies were eligible if they were RCTs. Studies included one treatment group in which forest therapy was applied. The following databases – from 1990 to November 9, 2010 – were searched: MEDLINE via PubMed, CINAHL, Web of Science, and Ichushi-Web. All Cochrane databases and Campbell Systematic Reviews were also searched up to November 9, 2010.Results: Two trials met all inclusion criteria. No specific diseases were evaluated, and both studies reported significant effectiveness in one or more outcomes for health enhancement. However, the results of evaluations with the CONSORT (Consolidated Standards of Reporting Trials 2010 and CLEAR NPT (A Checklist to Evaluate a Report of a Nonpharmacological Trial checklists generally showed a remarkable lack of description in the studies. Furthermore, there was a

  13. Design of a boron neutron capture enhanced fast neutron therapy assembly

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhonglu [Georgia Inst. of Technology, Atlanta, GA (United States)

    2006-12-01

    The use of boron neutron capture to boost tumor dose in fast neutron therapy has been investigated at several fast neutron therapy centers worldwide. This treatment is termed boron neutron capture enhanced fast neutron therapy (BNCEFNT). It is a combination of boron neutron capture therapy (BNCT) and fast neutron therapy (FNT). It is believed that BNCEFNT may be useful in the treatment of some radioresistant brain tumors, such as glioblastoma multiform (GBM). A boron neutron capture enhanced fast neutron therapy assembly has been designed for the Fermilab Neutron Therapy Facility (NTF). This assembly uses a tungsten filter and collimator near the patient's head, with a graphite reflector surrounding the head to significantly increase the dose due to boron neutron capture reactions. The assembly was designed using Monte Carlo radiation transport code MCNP version 5 for a standard 20x20 cm2 treatment beam. The calculated boron dose enhancement at 5.7-cm depth in a water-filled head phantom in the assembly with a 5x5 cm2 collimation was 21.9% per 100-ppm 10B for a 5.0-cm tungsten filter and 29.8% for a 8.5-cm tungsten filter. The corresponding dose rate for the 5.0-cm and 8.5-cm thick filters were 0.221 and 0.127 Gy/min, respectively; about 48.5% and 27.9% of the dose rate of the standard 10x10 cm2 fast neutron treatment beam. To validate the design calculations, a simplified BNCEFNT assembly was built using four lead bricks to form a 5x5 cm2 collimator. Five 1.0-cm thick 20x20 cm2 tungsten plates were used to obtain different filter thicknesses and graphite bricks/blocks were used to form a reflector. Measurements of the dose enhancement of the simplified assembly in a water-filled head phantom were performed using a pair of tissue-equivalent ion chambers. One of the ion chambers is loaded with 1000-ppm natural boron (184-ppm 10B) to measure dose due to boron neutron capture. The

  14. The combination of suicide gene therapy and radiation enhances the killing of nasopharyngeal carcinoma xenographs

    International Nuclear Information System (INIS)

    Xia Jiahui; Xia Kun; Feng Yong

    2004-01-01

    Nasopharyngeal carcinoma (NPC) is very common in Southern China and Southeast Asian countries. To explore a novel and more effective approach to NPC therapy, a combined strategy of suicide genes and radiation was designed in this study. Five suicide gene expression cassettes, yeast cytosine deaminase (CD), yeast CD/uracil phosphoribosyl-transferase (UPRT), and yeast CDglyTK gene controlled by CMV, and Egr-1 and a synthetic CMV-enhanced Egr-1 promoter (CE) were constructed in an expression vector p11MS. The expression of suicide genes in NPC CNE-2 cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. The cytotoxicity of suicide gene therapy and radiation were analyzed by MTT assay. An animal study in which yeast CD/UPRT-expressing CNE-2 tumors in nude mice were treated with 5-fluorocytosine (5-FC) and radiation was also developed. Our results revealed that p11MSCEyCD/UPRT and p11MSCEyCDglyTK are superior over three other constructs in the killing of NPC cells in vitro. We combined suicide gene-expressing tumors, 5-FC treatment, and radiation in vivo and found that the tumors greatly regressed, some disappeared completely in 3 nude mice in the yCD/UPRT group, and a significant difference of tumor volumes was observed between this group and the other four groups (p<0.05). Our results indicated that suicide gene therapy and radiation have a synergic effect on NPC therapy, and the combined strategy of radiogene therapy is of great potential as a substitute for the traditional method, radiation alone, in NPC therapies. (author)

  15. TH-E-BRD-01: Innovation in (gold) Nanoparticle-Enhanced Therapy

    International Nuclear Information System (INIS)

    Krishnan, S; Chithrani, B; Berbeco, R

    2014-01-01

    Radiation therapy relies on the concept of delivering high dose to tumor volumes whilst simultaneously aiming to minimize irradiation of healthy tissue. Gold and other metallic nanoparticles (GNPs) have the potential to greatly enhance dose depositions in their close proximity. While it was originally thought that this effect would only be significant for kV photon beams, it has been shown that GNPs also enhance dose and increase cell killing and survival fraction for MV photons as well as protons. GNPs have been shown to be preferentially taken up in tumors, depending on the GNP properties either internalized in the tumor cells or clustering in the tumor vasculature. Therefore GNPs offer an intriguing additional option to target the tumor while sparing healthy tissue. While a growing amount of research shows GNP induced enhancement factors in the order of 1.5 and higher, GNPs have not yet entered into clinical routine. In this symposium we will have three presentations discussing the current status of GNP based research, the potential to include GNPs in radiation therapy and the limitations and problems to use GNPs in the clinic. Physical and biological underpinnings of radiosensitization with gold nano particles An evolving body of recent literature alludes to the potential to sensitize tumors to radiation therapy using metallic nanoparticles. In preclinical studies, the techniques that hold promise for eventual clinical deployment are nanoparticle-assisted radiation dose enhancement and hyperthermic radiosensitization. To understand the underlying nanoparticle-radiation interactions, computational techniques offer an explanation for and predict the biophysical consequences at a nano-/meso-scopic scale. Nonetheless, there are persisting gaps in knowledge relating to the molecular mechanism of action of these radiosensitization approaches — some of these issues will be addressed. Since the literature relating to the diverse disciplines involved in these efforts

  16. TH-E-BRD-01: Innovation in (gold) Nanoparticle-Enhanced Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, S; Chithrani, B; Berbeco, R [Brigham and Women' s Hospital, Boston, MA (United States)

    2014-06-15

    Radiation therapy relies on the concept of delivering high dose to tumor volumes whilst simultaneously aiming to minimize irradiation of healthy tissue. Gold and other metallic nanoparticles (GNPs) have the potential to greatly enhance dose depositions in their close proximity. While it was originally thought that this effect would only be significant for kV photon beams, it has been shown that GNPs also enhance dose and increase cell killing and survival fraction for MV photons as well as protons. GNPs have been shown to be preferentially taken up in tumors, depending on the GNP properties either internalized in the tumor cells or clustering in the tumor vasculature. Therefore GNPs offer an intriguing additional option to target the tumor while sparing healthy tissue. While a growing amount of research shows GNP induced enhancement factors in the order of 1.5 and higher, GNPs have not yet entered into clinical routine. In this symposium we will have three presentations discussing the current status of GNP based research, the potential to include GNPs in radiation therapy and the limitations and problems to use GNPs in the clinic. Physical and biological underpinnings of radiosensitization with gold nano particles An evolving body of recent literature alludes to the potential to sensitize tumors to radiation therapy using metallic nanoparticles. In preclinical studies, the techniques that hold promise for eventual clinical deployment are nanoparticle-assisted radiation dose enhancement and hyperthermic radiosensitization. To understand the underlying nanoparticle-radiation interactions, computational techniques offer an explanation for and predict the biophysical consequences at a nano-/meso-scopic scale. Nonetheless, there are persisting gaps in knowledge relating to the molecular mechanism of action of these radiosensitization approaches — some of these issues will be addressed. Since the literature relating to the diverse disciplines involved in these efforts

  17. Polydopamine-coated gold nanostars for CT imaging and enhanced photothermal therapy of tumors

    Science.gov (United States)

    Li, Du; Shi, Xiangyang; Jin, Dayong

    2016-12-01

    The advancement of biocompatible nanoplatforms with dual functionalities of diagnosis and therapeutics is strongly demanded in biomedicine in recent years. In this work, we report the synthesis and characterization of polydopamine (pD)-coated gold nanostars (Au NSs) for computed tomography (CT) imaging and enhanced photothermal therapy (PTT) of tumors. Au NSs were firstly formed via a seed-mediated growth method and then stabilized with thiolated polyethyleneimine (PEI-SH), followed by deposition of pD on their surface. The formed pD-coated Au NSs (Au-PEI@pD NSs) were well characterized. We show that the Au-PEI@pD NSs are able to convert the absorbed near-infrared laser light into heat, and have strong X-ray attenuation property. Due to the co-existence of Au NSs and the pD, the light to heat conversion efficiency of the NSs can be significantly enhanced. These very interesting properties allow their uses as a powerful theranostic nanoplatform for efficient CT imaging and enhanced phtotothermal therapy of cancer cells in vitro and the xenografted tumor model in vivo. With the easy functionalization nature enabled by the coated pD shell, the developed pD-coated Au NSs may be developed as a versatile nanoplatform for targeted CT imaging and PTT of different types of cancer.

  18. Effects of an immuno-enhanced diet containing antioxidants in esophageal cancer surgery following neoadjuvant therapy.

    Science.gov (United States)

    Aiko, S; Kumano, I; Yamanaka, N; Tsujimoto, H; Takahata, R; Maehara, T

    2012-02-01

    Neoadjuvant therapy-induced immunological deterioration may be a key factor in postoperative morbidity in patients with esophageal cancer. This study aimed to determine the effects of perioperative feeding with an immuno-enhanced diet on immune competence in patients treated with neoadjuvant therapy followed by surgery. Because an immuno-enhanced diet that contained several antioxidants was used, perioperative oxidative stress and the effects of the immuno-enhanced diet on this stress were also investigated. Of 39 patients with esophageal cancer who underwent similar surgical procedures, 26 patients who received chemotherapy or chemoradiation therapy before surgery were randomly divided into two groups: group 1 (n= 14) was given an immuno-enhanced diet for 5 days before surgery, and group 2 (n= 12) received no enteral feeding products before surgery. Group 3 (n= 13) consisted of patients that did not receive neoadjuvant therapy and received no enteral feeding products before surgery. Several markers for coagulation and fibrinolysis were determined and immunological assessments were performed for each patient. To measure reactive oxygen metabolites and the total antioxidant capacity, diacron-reactive oxygen metabolites (d-ROMs) and OXY-adsorbent tests were performed using a free radical elective evaluator. Significant depression in lymphocyte numbers was observed in groups 1 and 2 before and early after surgery as compared to group 3. Numbers of B cells, CD4/CD8 ratio, and phytohemagglutinin-induced lymphocyte transformation tests were also significantly decreased in groups 1 and 2 on postoperative day 1. Fibrin and fibrinogen degradation products were significantly elevated in group 2 compared to group 1. d-ROMs and OXY-adsorbent test values were elevated before surgery and were decreased transiently early after surgery. Compared to groups 2 and 3, d-ROMs values were significantly lower in group 1 patients throughout the postoperative period, while OXY

  19. A Randomized Controlled Comparison of Integrative Cognitive-Affective Therapy and Cognitive-Behavioral Therapy-Enhanced for Bulimia Nervosa

    Science.gov (United States)

    Wonderlich, Stephen A.; Peterson, Carol B.; Crosby, Ross D.; Smith, Tracey L.; Klein, Marjorie H.; Mitchell, James E.; Crow, Scott J.

    2016-01-01

    Background The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa, Integrative Cognitive-Affective Therapy (ICAT), with an established treatment, Cognitive-Behavioral Therapy-Enhanced (CBT-E). Method Eighty adults with symptoms of bulimia nervosa were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination, were assessed at baseline, end of treatment, and 4-month follow-up. Treatment outcome, as measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety, and self-esteem, was determined using generalized estimating equations, logistic regression, and a general linear model (intent-to-treat). Results Both treatments were associated with significant improvement in bulimic symptoms as well as all measures of outcome, and no statistically significant differences were observed between the two conditions at end of treatment or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at end of treatment, 32.5% at follow-up) and CBT-E (22.5% at both end of treatment and follow-up) were not significantly different. Conclusions ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for bulimia nervosa suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study. PMID:23701891

  20. Costs of a motivational enhancement therapy coupled with cognitive behavioral therapy versus brief advice for pregnant substance users.

    Directory of Open Access Journals (Sweden)

    Xiao Xu

    Full Text Available To determine and compare costs of a nurse-administered behavioral intervention for pregnant substance users that integrated motivational enhancement therapy with cognitive behavioral therapy (MET-CBT to brief advice (BA administered by an obstetrical provider. Both interventions were provided concurrent with prenatal care.We conducted a micro-costing study that prospectively collected detailed resource utilization and unit cost data for each of the two intervention arms (MET-CBT and BA within the context of a randomized controlled trial. A three-step approach for identifying, measuring and valuing resource utilization was used. All cost estimates were inflation adjusted to 2011 U.S. dollars.A total of 82 participants received the MET-CBT intervention and 86 participants received BA. From the societal perspective, the total cost (including participants' time cost of the MET-CBT intervention was $120,483 or $1,469 per participant. In contrast, the total cost of the BA intervention was $27,199 or $316 per participant. Personnel costs (nurse therapists and obstetric providers for delivering the intervention sessions and supervising the program composed the largest share of the MET-CBT intervention costs. Program set up costs, especially intervention material design and training costs, also contributed substantially to the overall cost.Implementation of an MET-CBT program to promote drug abstinence in pregnant women is associated with modest costs. Future cost effectiveness and cost benefit analyses integrating costs with outcomes and benefits data will enable a more comprehensive understanding of the intervention in improving the care of substance abusing pregnant women.

  1. Enhanced generation of hydroxyl radicals on well-crystallized molybdenum trioxide/nano-graphite anode with sesame cake-like structure for degradation of bio-refractory antibiotic.

    Science.gov (United States)

    Tang, Bo; Du, Jiannan; Feng, Qingmao; Zhang, Jiaqi; Wu, Dan; Jiang, Xiankai; Dai, Ying; Zou, Jinlong

    2018-05-01

    Anodic electro-catalysis oxidation is a highly effective way to solve the pollution problem of antibiotics in wastewater and receiving water bodies. In this study, for the first time, molybdenum trioxide/Nano-graphite (MoO 3 /Nano-G) composites are synthesized as anodic catalysts by a surfactant-assisted solvothermal method followed by low-temperature calcination. The effects of the proportion of MoO 3 to Nano-G (10, 30 and 50%) on the properties of composites are investigated through structural characterizations and electrochemical measurements. Results indicate that MoO 3 (30)/Nano-G electrode displays the electro-catalysis degradation efficiency of 99.9% towards ceftazidime, which is much higher than those of Nano-G (46.7%) and dimensionally stable anode (69.2%). The degradation mechanism for ceftazidime is studied by investigating the yields and kinds of active species. Results show that all of the OH, O 2- and H 2 O 2 are responsible for the electro-catalytic degradation process, and the produced OH radicals are the major active species for ceftazidime degradation. The synergistic effects between MoO 3 and Nano-G greatly contribute to the activation of H 2 O molecules to produce OH, meanwhile the special sesame cake-like structure facilitates to the exposure of contaminants to OH on active sites to enhance the degradation efficiency. These results suggest that MoO 3 /Nano-G electrodes can be considered as the promising catalysts for treating bio-refractory organic wastewater. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Enhanced biodegradation of antibiotic combinations via the sequential treatment of the sludge resulting from pharmaceutical wastewater treatment using white-rot fungi Trametes versicolor and Bjerkandera adusta.

    Science.gov (United States)

    Aydin, Sevcan

    2016-07-01

    While anaerobic treatment is capable of treating pharmaceutical wastewater and removing antibiotics in liquid phases, solid phases may still contain significant amounts of antibiotics following this treatment. The main goal of this study was to evaluate the use of white-rot fungi to remove erythromycin, sulfamethoxazole, and tetracycline combinations from biosolids. The degradation potential of Trametes versicolor and Bjerkandera adusta was evaluated via the sequential treatment of anaerobic sludge. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analyses were used to identify competition between the autochthonous microbial communities and white-rot fungi. Solid-phase treatment using white-rot fungi substantially reduced antibiotic concentrations and toxicity in sludge. According to PCR-DGGE results, there is an association between species of fungus and antibiotic type as a result of the different transformation pathways of fungal strains. Fungal post-treatment of sludge represents a promising method of removing antibiotic combinations, therefore holding a significant promise as an environmentally friendly means of degrading the antibiotics present in sludge.

  3. Can tDCS enhance item-specific effects and generalization after linguistically motivated aphasia therapy for verbs?

    NARCIS (Netherlands)

    de Aguiar, Vania; Bastiaanse, Roelien; Capasso, Rita; Gandolfi, Marialuisa; Smania, Nicola; Rossi, Giorgio; Miceli, Gabriele

    2015-01-01

    Background: Aphasia therapy focusing on abstract properties of language promotes both item-specific effects and generalization to untreated materials. Neuromodulation with transcranial Direct Current Stimulation (tDCS) has been shown to enhance item-specific improvement, but its potential to enhance

  4. Impact of antibiotics on necrotizing enterocolitis and antibiotic-associated diarrhea

    Science.gov (United States)

    Silverman, Michael A.; Konnikova, Liza; Gerber, Jeffrey S.

    2017-01-01

    Summary Antibiotics induce changes or dysbiosis of the intestinal microbiome. These antibiotic-induce changes may contribute to the pathogenesis of necrotizing enterocolitis (NEC) and antibiotic-associated diarrhea (AAD). Studies are beginning to unravel the contribution of specific groups of microbes to these diseases—most notably Gammaproteobacteria for NEC and bile acid- and carbohydrate-metabolizing microbes for AAD. Antibiotic-associated diarrhea occurs when antibiotic treatment induces diarrhea by altering the metabolic function of the patient’s intestinal microbiota leading to either an osmotic or infectious diarrhea, most notably Clostridium difficile infection (CDI). Antibiotic therapy impairs the host microbiota’s ability to resist colonization or expansion of pathogenic bacteria. In the case of CDI, there is growing evidence that microbiota-mediated bile acid metabolism is critical in the pathogenesis of this infection. Probiotics or other microbiota-targeted therapies may provide effective strategies to prevent and treat NEC and AAD. PMID:28164853

  5. Synthetic membrane-targeted antibiotics.

    Science.gov (United States)

    Vooturi, S K; Firestine, S M

    2010-01-01

    Antimicrobial resistance continues to evolve and presents serious challenges in the therapy of both nosocomial and community-acquired infections. The rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant enterococci (VRE) suggests that antimicrobial resistance is an inevitable evolutionary response to antimicrobial use. This highlights the tremendous need for antibiotics against new bacterial targets. Agents that target the integrity of bacterial membrane are relatively novel in the clinical armamentarium. Daptomycin, a lipopeptide is a classical example of membrane-bound antibiotic. Nature has also utilized this tactic. Antimicrobial peptides (AMPs), which are found in all kingdoms, function primarily by permeabilizing the bacterial membrane. AMPs have several advantages over existing antibiotics including a broad spectrum of activity, rapid bactericidal activity, no cross-resistance with the existing antibiotics and a low probability for developing resistance. Currently, a small number of peptides have been developed for clinical use but therapeutic applications are limited because of poor bioavailability and high manufacturing cost. However, their broad specificity, potent activity and lower probability for resistance have spurred the search for synthetic mimetics of antimicrobial peptides as membrane-active antibiotics. In this review, we will discuss the different classes of synthetic membrane-bound antibiotics published since 2004.

  6. Hypoxia-targeted suicidal gene therapy system enhances antitumor effects of radiotherapy

    International Nuclear Information System (INIS)

    Liu Junye; Guo Yao; Guo Guozhen

    2006-01-01

    Objective: To explore the effects of hypoxia-targeted suicidal gene therapy system combined with radiotherapy on pancreatic cancer. Methods: The recombinant adenovirus Ad-5HRE/hCMVmp-BCD was constructed by DNA recombinant technique. Western blot was used to detect hypoxia-induced expression of bacterial cytosine deaminase (BCD). Cell growth inhibition assay was used to determine the sensitivity of human pancreatic cancer cells MIA-PACA2 to 5-fluorocytosine (5-FC). Tumor xenograft growth delay assays was used to evaluate the effects of Ad-5HRE/hCMVmp-BCD/5-FC combined with radiotherapy on pancreatic cancer. Results: Western blot analysis demonstrated that hypoxia-induced BCD protein expression was achieved in MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD. With hypoxia treatment, the sensitivity of MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD to 5-FC significantly increased. Administration of either Ad-5HRE/hCMVmp-BCD/5-FC or radiotherapy could inhibit the growth of MIA-PACA2 xenografts in nude mice. Moreover, combination of Ad-5HRE/hCMVmp-BCD/5-FC could significantly enhance suppressing effects of radiotherapy on MIA-PACA2 xenografts. Conclusion: Hypoxia-targeted suicidal gene therapy system Ad-5HRE/hCMVmp-BCD/5-FC could enhance antitumor effects of radiotherapy on pancreatic cancer and can be used as a powerful adjunct to conventional radiotherapy. (authors)

  7. Longitudinal functional brain imaging study in early course schizophrenia before and after cognitive enhancement therapy.

    Science.gov (United States)

    Keshavan, Matcheri S; Eack, Shaun M; Prasad, Konasale M; Haller, Chiara S; Cho, Raymond Y

    2017-05-01

    Schizophrenia is characterized by impaired -social and non social cognition both of which lead to functional deficits. These deficits may benefit from cognitive remediation, but the neural underpinnings of such improvements have not been clearly delineated. We conducted a functional magnetic resonance (fMRI) study in early course schizophrenia patients randomly assigned to cognitive enhancement therapy (CET) or enriched supportive therapy (EST) and treated for two years. Imaging data over three time points including fMRI blood oxygen level dependent (BOLD) data were acquired during performance of a cognitive control paradigm, the Preparing to Overcome Prepotency (POP) task, and functional connectivity data, were analyzed. During the two years of treatment, CET patients showed a continual increase in BOLD activity in the right dorsolateral prefrontal cortex (DLPFC), whereas EST patients tended to show no change in prefrontal brain function throughout treatment. Increases in right DLPFC activity were modestly associated with improved neurocognition (β = .14, p = .041), but not social cognition. Functional connectivity analyses showed reduced connectivity between the DLPFC and the anterior cingulate cortex (ACC) in CET compared to EST over the two years of treatment, which was associated with neurocognitive improvement. These findings suggest that CET leads to enhanced neural activity in brain regions mediating cognitive control and increased efficiency in prefrontal circuits; such changes may be related to the observed therapeutic effects of CET on neurocognitive function. Copyright © 2017. Published by Elsevier Inc.

  8. Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

    Science.gov (United States)

    Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

    2017-11-01

    Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Cognitive enhancement therapy for adult autism spectrum disorder: Results of an 18-month randomized clinical trial.

    Science.gov (United States)

    Eack, Shaun M; Hogarty, Susan S; Greenwald, Deborah P; Litschge, Maralee Y; Porton, Shannondora A; Mazefsky, Carla A; Minshew, Nancy J

    2018-03-01

    Cognitive remediation is a promising approach to treating core cognitive deficits in adults with autism, but rigorously controlled trials of comprehensive interventions that target both social and non-social cognition over a sufficient period of time to impact functioning are lacking. This study examined the efficacy of cognitive enhancement therapy (CET) for improving core cognitive and employment outcomes in adult autism. Verbal adult outpatients with autism spectrum disorder (N = 54) were randomized to an 18-month, single-blind trial of CET, a cognitive remediation approach that integrates computer-based neurocognitive training with group-based training in social cognition, or an active enriched supportive therapy (EST) comparison focused on psychoeducation and condition management. Primary outcomes were composite indexes of neurocognitive and social-cognitive change. Competitive employment was a secondary outcome. Intent-to-treat analyses indicated that CET produced significant differential increases in neurocognitive function relative to EST (d = .46, P = .013). Both CET and EST were associated with large social-cognitive improvements, with CET demonstrating an advantage at 9 (d = .58, P = 0.020), but not 18 months (d = .27, P = 0.298). Effects on employment indicated that participants treated with CET were significantly more likely to gain competitive employment than those in EST, OR = 6.21, P = 0.023, which was mediated by cognitive improvement. CET is a feasible and potentially effective treatment for core cognitive deficits in adult autism spectrum disorder. The treatment of cognitive impairments in this population can contribute to meaningful improvements in adult outcomes. Autism Res 2018, 11: 519-530. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Cognitive enhancement therapy (CET), an 18-month cognitive remediation intervention designed to improve thinking and social understanding, was

  10. Line-Enhanced Deformable Registration of Pulmonary Computed Tomography Images Before and After Radiation Therapy With Radiation-Induced Fibrosis

    Science.gov (United States)

    Sensakovic, William F.; Maxim, Peter; Diehn, Maximilian; Loo, Billy W.; Xing, Lei

    2018-01-01

    Purpose: The deformable registration of pulmonary computed tomography images before and after radiation therapy is challenging due to anatomic changes from radiation fibrosis. We hypothesize that a line-enhanced registration algorithm can reduce landmark error over the entire lung, including the irradiated regions, when compared to an intensity-based deformable registration algorithm. Materials: Two intensity-based B-spline deformable registration algorithms of pre-radiation therapy and post-radiation therapy images were compared. The first was a control intensity–based algorithm that utilized computed tomography images without modification. The second was a line enhancement algorithm that incorporated a Hessian-based line enhancement filter prior to deformable image registration. Registrations were evaluated based on the landmark error between user-identified landmark pairs and the overlap ratio. Results: Twenty-one patients with pre-radiation therapy and post-radiation therapy scans were included. The median time interval between scans was 1.2 years (range: 0.3-3.3 years). Median landmark errors for the line enhancement algorithm were significantly lower than those for the control algorithm over the entire lung (1.67 vs 1.83 mm; P 5 Gy (2.25 vs 3.31; P 5 Gy dose interval demonstrated a significant inverse relationship with post-radiation therapy fibrosis enhancement after line enhancement filtration (Pearson correlation coefficient = −0.48; P = .03). Conclusion: The line enhancement registration algorithm is a promising method for registering images before and after radiation therapy. PMID:29343206

  11. Approach to osteomyelitis treatment with antibiotic loaded PMMA.

    Science.gov (United States)

    Wentao, Zhang; Lei, Guangyu; Liu, Yang; Wang, Wei; Song, Tao; Fan, Jinzhu

    2017-01-01

    To reduce the incidence of osteomyelitis infection, local antibiotic impregnated delivery systems are commonly used as a promising and effective approach to deliver high antibiotic concentrations at the infection site. The objective of this review was to provide a literature review regarding approach to osteomyelitis treatment with antibiotic loaded PMMA. Literature study regarding osteomyelitis treatment with antibiotic loaded carriers using key terms Antibiotic, osteomyelitis, biodegradable PMMA through published articles. Hands searching of bibliographies of identified articles were also undertaken. We concluded that Antibiotic-impregnated PMMA beads are useful options for the treatment of osteomyelitis for prolonged drug therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. An Archaeosome-Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Significantly Enhances Protection from Murine Melanoma

    Directory of Open Access Journals (Sweden)

    Felicity C. Stark

    2017-10-01

    Full Text Available Archaeosomes constitute archaeal lipid vesicle vaccine adjuvants that evoke a strong CD8+ T cell response to antigenic cargo. Therapeutic treatment of murine B16-ovalbumin (B16-OVA melanoma with archaeosome-OVA eliminates small subcutaneous solid tumors; however, they eventually resurge despite an increased frequency of circulating and tumor infiltrating OVA-CD8+ T cells. Herein, a number of different approaches were evaluated to improve responses, including dose number, interval, and the combination of vaccine with checkpoint inhibitors. Firstly, we found that tumor protection could not be enhanced by repetitive and/or delayed boosting to maximize the CD8+ T cell number and/or phenotype. The in vivo cytotoxicity of vaccine-induced OVA-CD8+ T cells was impaired in tumor-bearing mice. Additionally, tumor-infiltrating OVA-CD8+ T cells had an increased expression of programmed cell death protein-1 (PD-1 compared to other organ compartments, suggesting impaired function. Combination therapy of tumor-bearing mice with the vaccine archaeosome-OVA, and α-CTLA-4 administered concurrently as well as α-PD-1 and an α-PD-L1 antibody administered starting 9 days after tumor challenge given on a Q3Dx4 schedule (days 9, 12, 15 and 18, significantly enhanced survival. Following multi-combination therapy ~70% of mice had rapid tumor recession, with no detectable tumor mass after >80 days in comparison to a median survival of 17–22 days for untreated or experimental groups receiving single therapies. Overall, archaeosomes offer a powerful platform for delivering cancer antigens when used in combination with checkpoint inhibitor immunotherapies.

  13. Results of ENHANCED Implantable Cardioverter Defibrillator Programming to Reduce Therapies and Improve Quality of Life (from the ENHANCED-ICD Study)

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H.; Pedersen, Susanne S.; van der Tweel, Ingeborg

    2016-01-01

    -reported outcomes. The "ENHANCED Implantable Cardioverter Defibrillator programming to reduce therapies and improve quality of life" study (ENHANCED-ICD study) was a prospective, safety-monitoring study enrolling 60 primary and secondary prevention patients at the University Medical Center Utrecht. Patients...... programming strategy, unnecessary ICD therapy was prevented in 10% of ENHANCED-ICD patients during a median follow-up period of 1.3 years. With respect to patient-reported outcomes, levels of distress were highest and perceived health status lowest at the time of implantation, which both gradually improved...... during follow-up. In conclusion, the ENHANCED-ICD study demonstrates that programming a NID 60/80 for VT/VF detection is safe for ICD patients and does not negatively impact their quality of life....

  14. Gene therapy and its implications in Periodontics

    Science.gov (United States)

    Mahale, Swapna; Dani, Nitin; Ansari, Shumaila S.; Kale, Triveni

    2009-01-01

    Gene therapy is a field of Biomedicine. With the advent of gene therapy in dentistry, significant progress has been made in the control of periodontal diseases and reconstruction of dento-alveolar apparatus. Implementation in periodontics include: -As a mode of tissue engineering with three approaches: cell, protein-based and gene delivery approach. -Genetic approach to Biofilm Antibiotic Resistance. Future strategies of gene therapy in preventing periodontal diseases: -Enhances host defense mechanism against infection by transfecting host cells with an antimicrobial peptide protein-encoding gene. -Periodontal vaccination. Gene therapy is one of the recent entrants and its applications in the field of periodontics are reviewed in general here. PMID:20376232

  15. A dual-targeting strategy for enhanced drug delivery and synergistic therapy based on thermosensitive nanoparticles.

    Science.gov (United States)

    Wang, Mingxin; You, Chaoqun; Gao, Zhiguo; Wu, Hongshuai; Sun, Baiwang; Zhu, Xiaoli; Chen, Renjie

    2018-08-01

    The functionalized nanoparticles have been widely studied and reported as carriers of drug transport recently. Furthermore, many groups have focused more on developing novel and efficient treatment methods, such as photodynamic therapy and photothermal therapy, since both therapies have shown inspiring potential in the application of antitumor. The mentioned treatments exhibited the superiority of cooperative manner and showed the ability to compensate for the adverse effects caused by conventional monotherapy in proposed strategies. In view of the above descriptions, we formulated a thermosensitive drug delivery system, which achieved the enhanced delivery of cisplatin and two photosensitizers (ICG and Ce6) by dual-targeting traction. Drawing on the thin film hydration method, cisplatin and photosensitizers were encapsulated inside nanoparticles. Meanwhile, the targeting peptide cRGD and targeting molecule folate can be modified on the surface of nanoparticles to realize the active identification of tumor cells. The measurements of dynamic light scattering showed that the prepared nanoparticles had an ideal dispersibility and uniform particle size of 102.6 nm. On the basis of the results observed from confocal laser scanning microscope, the modified nanoparticles were more efficient endocytosed by MCF-7 cells as a contrast to SGC-7901 cells. Photothermal conversion-triggered drug release and photo-therapies produced a significant apoptosis rate of 85.9% on MCF-7 cells. The distinguished results made it believed that the formulated delivery system had conducted great efforts and innovations for the realization of concise collaboration and provided a promising strategy for the treatment of breast cancer.

  16. Enhancing the Pediatric Drug Development Framework to Deliver Better Pediatric Therapies Tomorrow.

    Science.gov (United States)

    Bucci-Rechtweg, Christina

    2017-10-01

    Health care professionals involved in the clinical management of children have long appreciated the limited number of therapies suitably evaluated for their optimal use in the pediatric population. In the past century, advances in regulatory policy significantly evolved adult drug evaluation. The scarcity of available patient populations, practical complexities of drug development research, and minimal financial returns have hampered pharmaceutical investment in the study of therapies for children. More recently, pediatric policy and legislation in the United States and Europe have instituted a system of obligations and incentives to stimulate investment in pediatric drug development. These initiatives, in conjunction with a more sophisticated process of drug discovery and development, have led to significant advancements in the labeling of drugs for pediatric use. Facilitated by the emergence of new targets, precision medicine, and innovations in regulatory science, there is now a subtle shift in focus toward drug development research for children rather than simply in children. Although there has been an increase in pediatric studies of investigational agents and labeling of pediatric information for use, there have been unintended consequences of existing policies. As a result, limited progress has been made in certain therapeutic areas and for off-patent therapies. Future policy reform to enhance the availability and accessibility of pediatric medicines should not only reflect an understanding not only of the successes of existing policy and legislative initiatives but also constructively address failures and unintended consequences. Taken together, policy reform, global cooperation, and innovation in regulatory science will more ably deliver better pediatric therapies tomorrow. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  17. BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage.

    Directory of Open Access Journals (Sweden)

    Katja Storch

    Full Text Available Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease.

  18. HDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: where do we stand?

    Science.gov (United States)

    Whittle, Nigel; Singewald, Nicolas

    2014-04-01

    A novel strategy to treat anxiety and fear-related disorders such as phobias, panic and PTSD (post-traumatic stress disorder) is combining CBT (cognitive behavioural therapy), including extinction-based exposure therapy, with cognitive enhancers. By targeting and boosting mechanisms underlying learning, drug development in this field aims at designing CBT-augmenting compounds that help to overcome extinction learning deficits, promote long-term fear inhibition and thus support relapse prevention. Progress in revealing the role of epigenetic regulation of specific genes associated with extinction memory generation has opened new avenues in this direction. The present review examines recent evidence from pre-clinical studies showing that increasing histone acetylation, either via genetic or pharmacological inhibition of HDACs (histone deacetylases) by e.g. vorinostat/SAHA (suberoylanilide hydroxamic acid), entinostat/MS-275, sodium butyrate, TSA (trichostatin A) or VPA (valproic acid), or by targeting HATs (histone acetyltransferases), augments fear extinction and, importantly, generates a long-term extinction memory that can protect from return of fear phenomena. The molecular mechanisms and pathways involved including BDNF (brain-derived neurotrophic factor) and NMDA (N-methyl-D-aspartate) receptor signalling are just beginning to be revealed. First studies in healthy humans are in support of extinction-facilitating effects of HDAC inhibitors. Very recent evidence that HDAC inhibitors can rescue deficits in extinction-memory-impaired rodents indicates a potential clinical utility of this approach also for exposure therapy-resistant patients. Important future work includes investigation of the long-term safety aspects of HDAC inhibitor treatment, as well as design of isotype(s)-specific inhibitors. Taken together, HDAC inhibitors display promising potential as pharmacological adjuncts to augment the efficacy of exposure-based approaches in anxiety and trauma therapy.

  19. At the Nexus of Antibiotics and Metals: The Impact of Cu and Zn on Antibiotic Activity and Resistance.

    Science.gov (United States)

    Poole, Keith

    2017-10-01

    Environmental influences on antibiotic activity and resistance can wreak havoc with in vivo antibiotic efficacy and, ultimately, antimicrobial chemotherapy. In nature, bacteria encounter a variety of metal ions, particularly copper (Cu) and zinc (Zn), as contaminants in soil and water, as feed additives in agriculture, as clinically-used antimicrobials, and as components of human antibacterial responses. Importantly, there is a growing body of evidence for Cu/Zn driving antibiotic resistance development in metal-exposed bacteria, owing to metal selection of genetic elements harbouring both metal and antibiotic resistance genes, and metal recruitment of antibiotic resistance mechanisms. Many classes of antibiotics also form complexes with metal cations, including Cu and Zn, and this can hinder (or enhance) antibiotic activity. This review highlights the ways in which Cu/Zn influence antibiotic resistance development and antibiotic activity, and in so doing impact in vivo antibiotic efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. The use of antibiotics based on prescriptions dispenced in pharmacies

    OpenAIRE

    Vadapalaitė-Mašalienė, Vilma

    2017-01-01

    The Use of Antibiotics Based on Prescriptions Dispenced in Pharmacies SUMMARY Baronienė J., Vadapalaitė-Mašalienė V. The use of antibiotics based on prescriptions dispenced in pharmacies: pharmacy master's thesis. Vilnius University, faculty of medicine – Vilnius, 2017. – 43 p. Antibiotics are not a cure-all. There are many diseases that are insurmountable without antibiotics: these diseases are caused by bacteria. Antibacterial therapy prevents from complications and sometimes saves lives. H...

  1. The mthA mutation conferring low-level resistance to streptomycin enhances antibiotic production in Bacillus subtilis by increasing the S-adenosylmethionine pool size.

    Science.gov (United States)

    Tojo, Shigeo; Kim, Ji-Yun; Tanaka, Yukinori; Inaoka, Takashi; Hiraga, Yoshikazu; Ochi, Kozo

    2014-04-01

    Certain Str(r) mutations that confer low-level streptomycin resistance result in the overproduction of antibiotics by Bacillus subtilis. Using comparative genome-sequencing analysis, we successfully identified this novel mutation in B. subtilis as being located in the mthA gene, which encodes S-adenosylhomocysteine/methylthioadenosine nucleosidase, an enzyme involved in the S-adenosylmethionine (SAM)-recycling pathways. Transformation experiments showed that this mthA mutation was responsible for the acquisition of low-level streptomycin resistance and overproduction of bacilysin. The mthA mutant had an elevated level of intracellular SAM, apparently acquired by arresting SAM-recycling pathways. This increase in the SAM level was directly responsible for bacilysin overproduction, as confirmed by forced expression of the metK gene encoding SAM synthetase. The mthA mutation fully exerted its effect on antibiotic overproduction in the genetic background of rel(+) but not the rel mutant, as demonstrated using an mthA relA double mutant. Strikingly, the mthA mutation activated, at the transcription level, even the dormant ability to produce another antibiotic, neotrehalosadiamine, at concentrations of 150 to 200 μg/ml, an antibiotic not produced (antibiotic production, by introducing either the rsmG mutation to Streptomyces or the mthA mutation to eubacteria, since many eubacteria have mthA homologues.

  2. Nanoformulation and antibiotic releasing property of cefotaxime ...

    African Journals Online (AJOL)

    The objective of this study was to design nano-antibiotic to enhance their release from biomaterial agents. Cefotaxime was used as a model antibiotic substance in this carrier system. These nanoparticles were preformulated using different concentrations of polycaprolactone (PCL) and poly (vinyl alcohol) as coating material ...

  3. Antibiotic Resistance

    DEFF Research Database (Denmark)

    Hansen, Malene Plejdrup; Hoffmann, Tammy C; McCullough, Amanda R

    2015-01-01

    hygiene, and possibly vaccination and exercise, may be effective. Also, a large range of complementary and alternative medicines (e.g. zinc, vitamin C and probiotics) are proposed for preventing and treating ARIs, but evidence for efficacy is scarce. General practitioners' (GPs) attitudes towards...... wrong. Shared decision making might be a solution, as it enables clinician and patient to participate jointly in making a health decision, having discussed the options together with the evidence for their harms as well as benefits. Furthermore, GPs' diagnostic uncertainty - often leading...... will greatly improve the use of antibiotics for ARIs. However, used in concert, combinations are likely to enable clinicians and health care systems to implement the strategies that will reduce antimicrobial resistance in the future....

  4. Grievances in cases using antibiotics due to orodental problems and assessment of the need for antibiotics.

    Science.gov (United States)

    Kandemir, S; Ergül, N

    2000-04-01

    To assess the complaints of patients who were prescribed antibiotics following orodental problems and the need for antibiotics prescribed for this purpose. Examinations were carried out in the Department of Oral Diagnosis and Radiology, Ege University, Turkey. A total of 203 patients (129 females and 74 males) between 8-70 years of age (mean age 37.7 +/- 13.9). Examination and report. Frequency of unnecessary antibiotic use. Antibiotic therapy was not necessary for 151 (74.4 per cent) cases. Antibiotics were unnecessarily prescribed in 45 cases of acute irreversible pulpitis, 10 chronic apical abscess, 6 acute apical paradontitis, 7 gingivitis, 10 periodontitis, 4 epulis, 2 TMJ (temporomandibular junction) dysfunction, 2 sharp ridge of alveolar bone, 1 burning mouth syndrome and 1 recurrent aphthous stomatitis. In 108 (53.2 per cent) of the cases, the prescribed antibiotics were found to be penicillins, 102 of which were broad-spectrum. It was also determined that only 6 (7.7 per cent) of the 78 cases diagnosed as acute apical abscess were given drainage as local therapy. Principles for treating dental infections suggest that an antibiotic should only be used to supplement and not substitute for conventional surgical methods. Therefore, in cases with acute apical abscess, mechanical treatment (drainage) should be the first step. Inappropriate antibiotic use is quite widespread in dentistry. Dentists should avoid inappropriate use of antibiotics. To prevent inappropriate administration, necessary precautions need to be taken against dispensing antibiotics without prescription.

  5. Failure of oral antibiotic therapy, including azithromycin, in the treatment of a recurrent breast abscess caused by Salmonella enterica serotype Paratyphi A.

    Science.gov (United States)

    Fernando, Shelanah; Molland, Janice Gail; Gottlieb, Thomas

    2012-10-01

    We report a case of recurrent, multifocal Salmonella enterica serotype Paratyphi A breast abscesses, resistant to ciprofloxacin, which relapsed despite surgery, aspiration and multiple courses of antibiotics, including co-trimoxazole and azithromycin. The patient was cured after a prolonged course of intravenous ceftriaxone.

  6. Photon activation therapy with 127I-deoxyuridine: measurement of dose enhancement in cultured mammalian cells

    International Nuclear Information System (INIS)

    Fairchild, R.G.; Laster, B.H.; Commerford, S.L.; Furcinitti, P.S.; Sylvester, B.; Gabel, D.; Popenoe, E.; Foster, S.

    1985-01-01

    A technique for radiation enhancement of conventional photon radiotherapy is outlined which has been called photon activation therapy (PAT) (6). High linear energy transfer (LET) radiations in the form of Auger electron distributions are generated by photons of appropriate energies, through photon activation of stable iodine incorporated as an analog of thymidine (Tyd) in DNA. Of the several halogenated deoxyribonucleosides evaluated, iodinated deoxyuridine (IdUrd) has been chosen as the only Tyd analog providing effective photon activation. This mechanism is combined with radiation sensitization produced by IdUrd to produce an overall radiation enhancement. Calculations show that at 5% replacement (IdUrd for Tyd) therapeutic (TG) will vary from ∼2 (single acute dose) to ∼17 (low dose rates associated with permanent implant brachytherapy). Parameters used in the calculation of TG have been evaluated in cell culture; dose enhancements obtained with x-rays (including photon activation) were found to be significantly higher than values measured with γ-rays (no photon activation). Comparison is made between theoretical and measured values. Because of the evident lack of repair of damage produced by both sensitization and photon activation, significant gains are expected to be realized following protracted irradiations. Exchanges (IdUrd for Tyd) for 105 have been obtained in vivo (murine tumors). The authors believe that the application of PAT would be most advantageous in the treatment of brain tumors (grade IV astrocytomas) with implanted 145 Sm sources

  7. Contrast-enhanced harmonic ultrasound imaging in ablation therapy for primary hepatocellular carcinoma.

    Science.gov (United States)

    Minami, Yasunori; Kudo, Masatoshi

    2009-12-31

    The success rate of percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) depends on correct targeting via an imaging technique. However, RF electrode insertion is not completely accurate for residual HCC nodules because B-mode ultrasound (US), color Doppler, and power Doppler US findings cannot adequately differentiate between treated and viable residual tumor tissue. Electrode insertion is also difficult when we must identify the true HCC nodule among many large regenerated nodules in cirrhotic liver. Two breakthroughs in the field of US technology, harmonic imaging and the development of second-generation contrast agents, have recently been described and have demonstrated the potential to dramatically broaden the scope of US diagnosis of hepatic lesions. Contrast-enhanced harmonic US imaging with an intravenous contrast agent can evaluate small hypervascular HCC even when B-mode US cannot adequately characterize tumor. Therefore, contrast-enhanced harmonic US can facilitate RF ablation electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of contrast-enhanced harmonic US in ablation therapy for liver cancer is an efficient approach.

  8. Cost-effectiveness of focal psychodynamic therapy and enhanced cognitive-behavioural therapy in out-patients with anorexia nervosa.

    Science.gov (United States)

    Egger, N; Wild, B; Zipfel, S; Junne, F; Konnopka, A; Schmidt, U; de Zwaan, M; Herpertz, S; Zeeck, A; Löwe, B; von Wietersheim, J; Tagay, S; Burgmer, M; Dinkel, A; Herzog, W; König, H-H

    2016-12-01

    Anorexia nervosa (AN) is a serious illness leading to substantial morbidity and mortality. The treatment of AN very often is protracted; repeated hospitalizations and lost productivity generate substantial economic costs in the health care system. Therefore, this study aimed to determine the differential cost-effectiveness of out-patient focal psychodynamic psychotherapy (FPT), enhanced cognitive-behavioural therapy (CBT-E), and optimized treatment as usual (TAU-O) in the treatment of adult women with AN. The analysis was conducted alongside the randomized controlled Anorexia Nervosa Treatment of OutPatients (ANTOP) study. Cost-effectiveness was determined using direct costs per recovery at 22 months post-randomization (n = 156). Unadjusted incremental cost-effectiveness ratios (ICERs) were calculated. To derive cost-effectiveness acceptability curves (CEACs) adjusted net-benefit regressions were applied assuming different values for the maximum willingness to pay (WTP) per additional recovery. Cost-utility and assumptions underlying the base case were investigated in exploratory analyses. Costs of in-patient treatment and the percentage of patients who required in-patient treatment were considerably lower in both intervention groups. The unadjusted ICERs indicated FPT and CBT-E to be dominant compared with TAU-O. Moreover, FPT was dominant compared with CBT-E. CEACs showed that the probability for cost-effectiveness of FTP compared with TAU-O and CBT-E was ⩾95% if the WTP per recovery was ⩾€9825 and ⩾€24 550, respectively. Comparing CBT-E with TAU-O, the probability of being cost-effective remained <90% for all WTPs. The exploratory analyses showed similar but less pronounced trends. Depending on the WTP, FPT proved cost-effective in the treatment of adult AN.

  9. Motivation Enhancement Therapy with pregnant substance-abusing women: does baseline motivation moderate efficacy?

    Science.gov (United States)

    Ondersma, Steven J; Winhusen, Theresa; Erickson, Sarah J; Stine, Susan M; Wang, Yun

    2009-04-01

    Some evidence suggests that motivational approaches are less efficacious--or even counter-productive--with persons who are relatively motivated at baseline. The present study was conducted to examine whether disordinal moderation by baseline motivation could partially explain negative findings in a previous study [Winhusen, T., Kropp, F., Babcock, D., Hague, D., Erickson, S.J., Renz, C., Rau, L., Lewis, D., Leimberger, J., Somoza, E., 2008. Motivational enhancement therapy to improve treatment utilization and outcome in pregnant substance users. J. Subst. Abuse Treat. 35, 161-173]. Analyses also focused on the relative utility of the University of Rhode Island Change Assessment (URICA) scale, vs. a single goal question as potential moderators of Motivation Enhancement Therapy (MET). Participants were 200 pregnant women presenting for substance abuse treatment at one of four sites. Women were randomly assigned to either a three-session MET condition or treatment as usual (TAU). Generalized Estimating Equations (GEE) revealed no significant moderation effects on drug use at post-treatment. At follow-up, contrary to expectations, participants who had not set a clear quit goal at baseline were less likely to be drug-free if randomized to MET (OR=0.48); participants who did set a clear quit goal were more likely to be drug-free if randomized to MET (OR=2.53). No moderating effects were identified via the URICA. Disordinal moderation of MET efficacy by baseline motivation may have contributed somewhat to the negative results of the [Winhusen, T., Kropp, F., Babcock, D., Hague, D., Erickson, S.J., Renz, C., Rau, L., Lewis, D., Leimberger, J., Somoza, E., 2008. Motivational enhancement therapy to improve treatment utilization and outcome in pregnant substance users. J. Subst. Abuse Treat. 35, 161-173] study, but in the opposite direction expected. A simple question regarding intent to quit may be useful in identifying persons who may differentially respond to motivational

  10. Effects of antibiotic dry-cow therapy and internal teat sealant on milk somatic cell counts and clinical and subclinical mastitis in early lactation.

    Science.gov (United States)

    Golder, H M; Hodge, A; Lean, I J

    2016-09-01

    The objective of this study was to determine the efficacy of an internal teat sealant (TS; Teatseal; Zoetis Australia, Silverwater, NSW, Australia), when used in combination with antibiotic dry-cow therapy (ADCT) administered at dry-off, on milk individual somatic cell count (ISCC), milk production and components, and the incidence of clinical and subclinical mastitis in dairy cows up to 60 d after calving, when compared with ADCT only. Multiparous Holstein, Jersey, or Holstein cross cows (n=2,200) from 8 farms in southern and eastern Australia were randomly assigned to treatment of all 4 quarters with ADCT alone or with ADCT plus TS (ADCT + TS) at dry-off in this randomized, multisite clinical trial. Individual milk yield, fat and protein percentages, and ISCC were measured at intervals of 14±3 d after calving for the first 60 d of lactation. The first measurement occurred between 10 and 24 d after calving. Clinical mastitis and health events were recorded from dry-off to 60 d of lactation. Milk samples were collected from first cases of clinical mastitis and subjected to bacteriology. Treatment and the interaction of treatment by time did not affect milk yield, ISCC weighted by milk yield, or fat and protein percentages. Treatment with ADCT + TS decreased geometric mean ISCC compared with treatment with ADCT alone over the first 60 d of lactation. Geometric mean ISCC (×10(3) cells/mL) was 32.0 [95% confidence interval (CI): 26.8 to 38.3] and 43.5 (95% CI: 36.2 to 52.1) for ADCT + TS and ADCT alone, respectively. The odds of at least 1 case of subclinical mastitis (ISCC ≥250,000 cells/mL) were 1.9 times higher (95% CI: 1.4 to 2.6) with ADCT alone in the first 60 d of lactation compared with ADCT + TS. Use of ADCT + TS reduced the estimated incidence of at least 1 case of subclinical mastitis on all 8 farms, compared with use of ADCT alone. Only 4 cows that calved 40 to 100 d after dry-off had a first case of clinical mastitis in the dry period. Five percent of

  11. SU-F-T-666: Molecular-Targeted Gold Nanorods Enhances the RBE of Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Khoo, A; Sahoo, N; Krishnan, S; Diagaradjane, P [UT MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: In recent years, proton beam radiation therapy (PBRT) has gained significant attention in the treatment of tumors in anatomically complex locations. However, the therapeutic benefit of PBRT is limited by a relative biological effectiveness (RBE) of just 1.1. The purpose of this study is to evaluate whether this limitation can be overcome by artificially enhancing the RBE using molecular-targeted gold nanorods (GNRs). Methods: Molecular-targeting of GNRs was accomplished using Cetuximab (antibody specific to epidermal growth factor receptor that is over-expressed in tumors) conjugated GNRs (cGNRs) and their binding affinity to Head and Neck cancer cells was confirmed using dark field microscopy and Transmission Electron Microscopy (TEM). The radiosensitization potential of cGNRs when irradiated with photon (6MV) and proton (100 and 160 MeV) beams was determined using clonogenic assays. The RBE at 10% surviving fraction (RBE{sub 10}) for proton therapies at central and distal locations of SOBP was calculated with respect to 6 MV photons. IgGconjugated GNRs (iGNRs) were used as controls in all experiments. Results: cGNRs demonstrated significant radiosensitization when compared to iGNRs for 6MV photons (1.14 vs 1.04), 100 MeV protons (1.19 vs 1.04), and 160 MeV protons (1.17 vs 1.04). While RBE10 for proton beams at the center of SOBP revealed similar effects for both 100 and 160 MeV (RBE{sup 10}=1.39 vs 1.38; p>0.05), enhanced radiosensitization was observed at the distal SOBP with 100 MeV beams demonstrating greater effect than 160 MeV beams (RBE{sup 10}=1.79 vs 1.6; p<0.05). Conclusion: EGFR-targeting GNRs significantly enhance the RBE of protons well above the accepted 1.1 value. The enhanced RBE observed for lower energy protons (100 MeV) and at the distal SOBP suggests that low energy components may play a role in the observed radiosensitization effect. This strategy holds promise for clinical translation and could evolve as a paradigm-changing approach

  12. Variability in Antibiotic Use Across PICUs.

    Science.gov (United States)

    Brogan, Thomas V; Thurm, Cary; Hersh, Adam L; Gerber, Jeffrey S; Smith, Michael J; Shah, Samir S; Courter, Joshua D; Patel, Sameer J; Parker, Sarah K; Kronman, Matthew P; Lee, Brian R; Newland, Jason G

    2018-03-10

    To characterize and compare antibiotic prescribing across PICUs to evaluate the degree of variability. Retrospective analysis from 2010 through 2014 of the Pediatric Health Information System. Forty-one freestanding children's hospital. Children aged 30 days to 18 years admitted to a PICU in children's hospitals contributing data to Pediatric Health Information System. To normalize for potential differences in disease severity and case mix across centers, a subanalysis was performed of children admitted with one of the 20 All Patient Refined-Diagnosis Related Groups and the seven All Patient Refined-Diagnosis Related Groups shared by all PICUs with the highest antibiotic use. The study included 3,101,201 hospital discharges from 41 institutions with 386,914 PICU patients. All antibiotic use declined during the study period. The median-adjusted antibiotic use among PICU patients was 1,043 days of therapy/1,000 patient-days (interquartile range, 977-1,147 days of therapy/1,000 patient-days) compared with 893 among non-ICU children (interquartile range, 805-968 days of therapy/1,000 patient-days). For PICU patients, the median adjusted use of broad-spectrum antibiotics was 176 days of therapy/1,000 patient-days (interquartile range, 152-217 days of therapy/1,000 patient-days) and was 302 days of therapy/1,000 patient-days (interquartile range, 220-351 days of therapy/1,000 patient-days) for antimethicillin-resistant Staphylococcus aureus agents, compared with 153 days of therapy/1,000 patient-days (interquartile range, 130-182 days of therapy/1,000 patient-days) and 244 days of therapy/1,000 patient-days (interquartile range, 203-270 days of therapy/1,000 patient-days) for non-ICU children. After adjusting for potential confounders, significant institutional variability existed in antibiotic use in PICU patients, in the 20 All Patient Refined-Diagnosis Related Groups with the highest antibiotic usage and in the seven All Patient Refined-Diagnosis Related Groups shared

  13. Pharmacotherapy and group cognitive behavioral therapy enhance follow-up treatment duration in gambling disorder patients.

    Science.gov (United States)

    Choi, Sam-Wook; Shin, Young-Chul; Youn, HyunChul; Lim, Se-Won; Ha, Juwon

    2016-01-01

    Longer treatment duration is important for the successful treatment of gambling disorder (GD). This retrospective study investigated the factors and interventions that might enhance treatment duration in GD patients in South Korea. A total of 758 outpatients with a primary diagnosis of GD, who were treated in a clinical practice from 2002 to 2011, were assessed by retrospective chart review. We compared the treatment duration according to pharmacotherapy and group cognitive behavioral therapy (CBT). Pharmacotherapy contributed to a longer duration of treatment maintenance, despite the patients' gambling severity (p gambling severity. The treatment maintenance duration was the longest in those receiving combined antidepressant pharmacotherapy and group CBT (F = 35.79, p prevention and treatment strategies.

  14. Photon activation therapy: a Monte Carlo study on dose enhancement by various sources and activation media

    International Nuclear Information System (INIS)

    Bakhshabadi, Mahdi; Ghorbani, Mahdi; Meigooni, Ali Soleimani

    2013-01-01

    In the present study, a number of brachytherapy sources and activation media were simulated using MCNPX code and the results were analyzed based on the dose enhancement factor values. Furthermore, two new brachytherapy sources ( 131 Cs and a hypothetical 170 Tm) were evaluated for their application in photon activation therapy (PAT). 125 I, 103 Pd, 131 Cs and hypothetical 170 Tm brachytherapy sources were simulated in water and their dose rate constant and the radial dose functions were compared with previously published data. The sources were then simulated in a soft tissue phantom which was composed of Ag, I, Pt or Au as activation media uniformly distributed in the tumour volume. These simulations were performed using the MCNPX code, and dose enhancement factor (DEF) was obtained for 7, 18 and 30 mg/ml concentrations of the activation media. Each source, activation medium and concentration was evaluated separately in a separate simulation. The calculated dose rate constant and radial dose functions were in agreement with the published data for the aforementioned sources. The maximum DEF was found to be 5.58 for a combination of the 170 Tm source with 30 mg/ml concentration of I. The DEFs for 131 Cs and 170 Tm sources for all the four activation media were higher than those for other sources and activation media. From this point of view, these two sources can be more useful in photon activation therapy with photon emitter sources. Furthermore, 131 Cs and 170 Tm brachytherapy sources can be proposed as new options for use in the field of PAT.

  15. Attitudes Toward Combining Psychological, Mind-Body Therapies and Nutritional Approaches for the Enhancement of Mood.

    Science.gov (United States)

    Lores, Taryn Jade; Henke, Miriam; Chur-Hansen, Anna

    2016-01-01

    Context • Interest has been rising in the use of complementary and alternative medicine (CAM) for the promotion of health and treatment of disease. To date, the majority of CAM research has focused on exploring the demographic characteristics, attitudes, and motivations of CAM users and on the efficacy of different therapies and products. Less is known with respect to the psychological characteristics of people who use CAM. Previous research has not investigated the usefulness of integrating mind-body therapies with natural products in a combined mood intervention. Objective • The study intended to investigate attitudes toward a proposed new approach to the treatment of mood, one that integrates psychological mind-body therapies and natural nutritional products. Design • Participants completed an online survey covering demographics, personality traits, locus of control, use of CAM, attitudes toward the proposed psychonutritional approach, and mood. Setting • This study was conducted at the University of Adelaide School of Psychology (Adelaide, SA, Australia). Participants • Participants were 333 members of the Australian general public, who were recruited online via the social-media platform Facebook. The majority were women (83.2%), aged between 18 and 81 y. Outcome Measures • Measures included the Multidimensional Health Locus of Control Scale Form B, the Ten-Item Personality Inventory, and the Depression, Anxiety and Stress Scale. Results • Participants were positive about the proposed approach and were likely to try it to enhance their moods. The likeliness of use of the combined approach was significantly higher in the female participants and was associated with higher levels of the personality trait openness and an internal health locus of control, after controlling for all other variables. Conclusions • Interest exists for an intervention for mood that incorporates both psychological and nutritional approaches. Further research into the

  16. Synergistic Enhancement of Cancer Therapy Using a Combination of Ceramide and Docetaxel

    Directory of Open Access Journals (Sweden)

    Li-Xia Feng

    2014-03-01

    Full Text Available Ceramide (CE-based combination therapy (CE combination as a novel therapeutic strategy has attracted great attention in the field of anti-cancer therapy. The principal purposes of this study were to investigate the synergistic effect of CE in combination with docetaxel (DTX (CE + DTX and to explore the synergy mechanisms of CE + DTX. The 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and combination index (CI assay showed that simultaneous administration of CE and DTX with a molar ratio of 0.5:1 could generate the optimal synergistic effect on murine malignant melanoma cell (B16, CI = 0.31 and human breast carcinoma cell (MCF-7, CI = 0.48. The apoptosis, cell cycle, and cytoskeleton destruction study demonstrated that CE could target and destruct the microfilament actin, subsequently activate Caspase-3 and induce apoptosis. Meanwhile, DTX could target and disrupt the microtubules cytoskeleton, leading to a high proportion of cancer cells in G2/M-phase arrest. Moreover, CE plus DTX could cause a synergistic destruction of cytoskeleton, which resulted in a significantly higher apoptosis and a significantly higher arrest in G2/M arrest comparing with either agent alone (p < 0.01. The in vivo antitumor study evaluated in B16 tumor-bearing mice also validated the synergistic effects. All these results suggested that CE could enhance the antitumor activity of DTX in a synergistic manner, which suggest promising application prospects of CE + DTX combination treatment.

  17. Yoga-enhanced cognitive behavioural therapy (Y-CBT) for anxiety management: a pilot study.

    Science.gov (United States)

    Khalsa, Manjit K; Greiner-Ferris, Julie M; Hofmann, Stefan G; Khalsa, Sat Bir S

    2015-01-01

    Cognitive behavioural therapy (CBT) is an effective treatment for generalized anxiety disorder, but there is still room for improvement. The aim of the present study was to examine the potential benefit of enriching CBT with kundalini yoga (Y-CBT). Participants consisted of treatment resistant clients at a community mental health clinic. A total of 32 participants enrolled in the study and 22 completed the programme. After the Y-CBT intervention, pre-post comparisons showed statistically significant improvements in state and trait anxiety, depression, panic, sleep and quality of life. Results from this preliminary study suggest that Y-CBT may have potential as a promising treatment for those suffering from generalized anxiety disorder. Yoga-enhanced cognitive behavioural therapy (Y-CBT) may be a promising new treatment for those suffering from generalized anxiety disorder. Y-CBT may also reduce depression in those suffering from generalized anxiety. Y-CBT may reduce depression and anxiety in a clinic population where clients suffer from multiple diagnoses including generalized anxiety disorder. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Subinhibitory concentrations of antibiotics affect stress and virulence gene expression in Listeria monocytogenes and cause enhanced stress sensitivity but do not affect Caco‐2 cell invasion

    DEFF Research Database (Denmark)

    Knudsen, Gitte Maegaard; Holch, Anne; Gram, Lone

    2012-01-01

    with promoter fusions, 14 of 16 antibiotics induced or repressed expression of one or more stress and/or virulence genes. Despite ampicillin‐induced up‐regulation of PinlA‐lacZ expression, Caco‐2 cell invasion was not affected. Subinhibitory concentrations of ampicillin and tetracycline caused up‐ and down...

  19. Celecoxib Enhances the Efficacy of Low-Dose Antibiotic Treatment against Polymicrobial Sepsis in Mice and Clinical Isolates of ESKAPE Pathogens.

    Science.gov (United States)

    Annamanedi, Madhavi; Varma, Gajapati Y N; Anuradha, K; Kalle, Arunasree M

    2017-01-01

    Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter species). The in vivo results clearly demonstrated a significant reduction in the bacterial load in different organs and in the inflammatory markers such as COX-2 and NF-κB via activation of SIRT1 in mice treated with imipenem, a choice of antibiotic for polymicrobial sepsis treatment. Combinatorial treatment of ampicillin and celecoxib was effective on clinical isolates of ESKAPE pathogens, 45% of tested clinical isolates showed more than 50% reduction in the colony forming units when compared to ampicillin alone. In conclusion, this non-traditional treatment strategy might be effective in clinic to reduce the dose of antibiotic to treat drug-resistant bacterial infections.

  20. Effects of Improvisational Music Therapy vs Enhanced Standard Care on Symptom Severity Among Children With Autism Spectrum Disorder

    Science.gov (United States)

    Bieleninik, Łucja; Geretsegger, Monika; Mössler, Karin; Assmus, Jörg; Thompson, Grace; Gattino, Gustavo; Elefant, Cochavit; Gottfried, Tali; Igliozzi, Roberta; Muratori, Filippo; Suvini, Ferdinando; Kim, Jinah; Crawford, Mike J.; Odell-Miller, Helen; Oldfield, Amelia; Casey, Órla; Finnemann, Johanna; Carpente, John; Park, A-La; Grossi, Enzo

    2017-01-01

    Importance Music therapy may facilitate skills in areas affected by autism spectrum disorder (ASD), such as social interaction and communication. Objective To evaluate effects of improvisational music therapy on generalized social communication skills of children with ASD. Design, Setting, and Participants Assessor-blinded, randomized clinical trial, conducted in 9 countries and enrolling children aged 4 to 7 years with ASD. Children were recruited from November 2011 to November 2015, with follow-up between January 2012 and November 2016. Interventions Enhanced standard care (n = 182) vs enhanced standard care plus improvisational music therapy (n = 182), allocated in a 1:1 ratio. Enhanced standard care consisted of usual care as locally available plus parent counseling to discuss parents’ concerns and provide information about ASD. In improvisational music therapy, trained music therapists sang or played music with each child, attuned and adapted to the child’s focus of attention, to help children develop affect sharing and joint attention. Main Outcomes and Measures The primary outcome was symptom severity over 5 months, based on the Autism Diagnostic Observation Schedule (ADOS), social affect domain (range, 0-27; higher scores indicate greater severity; minimal clinically important difference, 1). Prespecified secondary outcomes included parent-rated social responsiveness. All outcomes were also assessed at 2 and 12 months. Results Among 364 participants randomized (mean age, 5.4 years; 83% boys), 314 (86%) completed the primary end point and 290 (80%) completed the last end point. Over 5 months, participants assigned to music therapy received a median of 19 music therapy, 3 parent counseling, and 36 other therapy sessions, compared with 3 parent counseling and 45 other therapy sessions for those assigned to enhanced standard care. From baseline to 5 months, mean ADOS social affect scores estimated by linear mixed-effects models decreased from 14

  1. Bactericidal antibiotics induce programmed metabolic toxicity

    Directory of Open Access Journals (Sweden)

    Aislinn D. Rowan

    2016-03-01

    Full Text Available The misuse of antibiotics has led to the development and spread of antibiotic resistance in clinically important pathogens. These resistant infections are having a significant impact on treatment outcomes and contribute to approximately 25,000 deaths in the U.S. annually. If additional therapeutic options are not identified, the number of annual deaths is predicted to rise to 317,000 in North America and 10,000,000 worldwide by 2050. Identifying therapeutic methodologies that utilize our antibiotic arsenal more effectively is one potential way to extend the useful lifespan of our current antibiotics. Recent studies have indicated that modulating metabolic activity is one possible strategy that can impact the efficacy of antibiotic therapy. In this review, we will address recent advances in our knowledge about the impacts of bacterial metabolism on antibiotic effectiveness and the impacts of antibiotics on bacterial metabolism. We will particularly focus on two studies, Lobritz, et al. (PNAS, 112(27: 8173-8180 and Belenky et al. (Cell Reports, 13(5: 968–980 that together demonstrate that bactericidal antibiotics induce metabolic perturbations that are linked to and required for bactericidal antibiotic toxicity.

  2. Effectiveness of anti-inflammatory treatment versus antibiotic therapy and placebo for patients with non-complicated acute bronchitis with purulent sputum. The BAAP Study protocol

    Directory of Open Access Journals (Sweden)

    Fernández Yvonne

    2011-06-01

    Full Text Available Abstract Background Acute bronchitis is one of the most prevalent respiratory infections in primary care, and in more than 90% of the cases antibiotics are prescribed, mainly when purulent expectoration is present. However, this process is usually viral in origin and the benefits of antibiotic treatment are marginal. On the other hand, in recent years bronchitis has been considered more as an inflammatory than an infectious process. Thus, the aim of this study is to evaluate the clinical effectiveness of a schedule of an oral anti-inflammatory compared with an antibiotic regimen and another group assigned to receive a placebo. Methods and design A total of 420 patients from 15 to 70 years of age with no associated comorbidity, presenting respiratory tract infection of at least one week of evolution, with cough as the predominant symptom, the presence of purulent expectoration and at least one other symptom of the respiratory tract (dyspnoea, wheezing, chest discomfort or pain, with no alternative explanation such as pneumonia, will be included in a prospective, randomised and controlled, clinical trial with placebo. The patients will be randomised to receive one of three treatments: ibuprofen, amoxycillin and clavulanic acid or placebo for 10 days. The main outcome measure is the number of days with frequent cough defined by the symptom diary with a score of 1 or more. Discussion This trial is designed to evaluate the number of days with frequent cough with anti-inflammatory treatment compared with antimicrobial treatment and placebo in previously healthy patients with a clinical picture of acute bronchitis and purulent expectoration. It is hypothesized that anti-inflammatory treatment is more effective than antibiotic treatment to reduce cough, which is the most disturbing symptom for patients with this infection. Trial registration ISRCTN07852892

  3. A manganese photosensitive tricarbonyl molecule [Mn(CO)3(tpa-κ3N)]Br enhances antibiotic efficacy in a multi-drug-resistant Escherichia coli.

    Science.gov (United States)

    Rana, Namrata; Jesse, Helen E; Tinajero-Trejo, Mariana; Butler, Jonathan A; Tarlit, John D; von Und Zur Muhlen, Milena L; Nagel, Christoph; Schatzschneider, Ulrich; Poole, Robert K

    2017-10-01

    Carbon monoxide-releasing molecules (CORMs) are a promising class of new antimicrobials, with multiple modes of action that are distinct from those of standard antibiotics. The relentless increase in antimicrobial resistance, exacerbated by a lack of new antibiotics, necessitates a better understanding of how such novel agents act and might be used synergistically with established antibiotics. This work aimed to understand the mechanism(s) underlying synergy between a manganese-based photoactivated carbon monoxide-releasing molecule (PhotoCORM), [Mn(CO)3(tpa-κ 3 N)]Br [tpa=tris(2-pyridylmethyl)amine], and various classes of antibiotics in their activities towards Escherichia coli EC958, a multi-drug-resistant uropathogen. The title compound acts synergistically with polymyxins [polymyxin B and colistin (polymyxin E)] by damaging the bacterial cytoplasmic membrane. [Mn(CO)3(tpa-κ 3 N)]Br also potentiates the action of doxycycline, resulting in reduced expression of tetA, which encodes a tetracycline efflux pump. We show that, like tetracyclines, the breakdown products of [Mn(CO)3(tpa-κ 3 N)]Br activation chelate iron and trigger an iron starvation response, which we propose to be a further basis for the synergies observed. Conversely, media supplemented with excess iron abrogated the inhibition of growth by doxycycline and the title compound. In conclusion, multiple factors contribute to the ability of this PhotoCORM to increase the efficacy of antibiotics in the polymyxin and tetracycline families. We propose that light-activated carbon monoxide release is not the sole basis of the antimicrobial activities of [Mn(CO)3(tpa-κ 3 N)]Br.

  4. Demographics of antibiotic persistence

    DEFF Research Database (Denmark)

    Kollerova, Silvia; Jouvet, Lionel; Steiner, Ulrich

    Persister cells, cells that can survive antibiotic exposure but lack heritable antibiotic resistance, are assumed to play a crucial role for the evolution of antibiotic resistance. Persistence is a stage associated with reduced metabolic activity. Most previous studies have been done on batch...... even play a more prominent role for the evolution of resistance and failures of medical treatment by antibiotics as currently assumed....

  5. "How do I say that?": Using communication principles to enhance medication therapy management instruction.

    Science.gov (United States)

    Denvir, Paul M; Cardone, Katie E; Parker, Wendy M; Cerulli, Jennifer

    2018-02-01

    Medication therapy management (MTM) is a comprehensive, patient-centered approach to improving medication use, reducing the risk of adverse events and improving medication adherence. Given the service delivery model and required outputs of MTM services, communication skills are of utmost importance. The objectives of this study were to identify and describe communication principles and instructional practices to enhance MTM training. Drawing on formative assessment data from interviews of both pharmacy educators and alumni, this article identifies and describes communication principles and instructional practices that pharmacy educators can use to enhance MTM training initiatives to develop student communication strategies. Analysis revealed five key communication challenges of MTM service delivery, two communication principles that pharmacy teachers and learners can use to address those challenges, and a range of specific strategies, derived from communication principles, that students can use when challenges emerge. Implications of the analysis for pharmacy educators and researchers are described. Proactive communication training provided during MTM advanced pharmacy practice experiences enabled students to apply the principles and instructional strategies to specific patient interactions during the advanced pharmacy practice experiences and in their post-graduation practice settings. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Resveratrol imparts photoprotection of normal cells and enhances the efficacy of radiation therapy in cancer cells.

    Science.gov (United States)

    Reagan-Shaw, Shannon; Mukhtar, Hasan; Ahmad, Nihal

    2008-01-01

    Solar radiation spans a whole range of electromagnetic spectrum including UV radiation, which are potentially harmful to normal cells as well as ionizing radiations which are therapeutically beneficial towards the killing of cancer cells. UV radiation is an established cause of a majority of skin cancers as well as precancerous conditions such as actinic keratosis. However, despite efforts to educate people about the use of sunscreens and protective clothing as preventive strategies, the incidence of skin cancer and other skin-related disorders are on the rise. This has generated an enormous interest towards finding alternative approaches for management of UV-mediated damages. Chemoprevention via nontoxic agents, especially botanical antioxidants, is one such approach that is being considered as a plausible strategy for prevention of photodamages including photocarcinogenesis. In this review, we have discussed the photoprotective effects of resveratrol, an antioxidant found in grapes and red wine, against UVB exposure-mediated damages in vitro and in vivo. In addition, we have also discussed studies showing that resveratrol can act as a sensitizer to enhance the therapeutic effects of ionizing radiation against cancer cells. Based on available literature, we suggest that resveratrol may be useful for (1) prevention of UVB-mediated damages including skin cancer and (2) enhancing the response of radiation therapies against hyperproliferative, precancerous and neoplastic conditions.

  7. Transferrin-Modified Nanoparticles for Photodynamic Therapy Enhance the Antitumor Efficacy of Hypocrellin A

    Directory of Open Access Journals (Sweden)

    Xi Lin

    2017-11-01

    Full Text Available Photodynamic therapy (PDT has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA and carboxymethyl chitosan (CMC nanoparticle loaded with a photosensitizer hypocrellin A (HA, named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.

  8. Development and validation of Monte Carlo dose computations for contrast-enhanced stereotactic synchrotron radiation therapy

    International Nuclear Information System (INIS)

    Vautrin, M.

    2011-01-01

    Contrast-enhanced stereotactic synchrotron radiation therapy (SSRT) is an innovative technique based on localized dose-enhancement effects obtained by reinforced photoelectric absorption in the tumor. Medium energy monochromatic X-rays (50 - 100 keV) are used for irradiating tumors previously loaded with a high-Z element. Clinical trials of SSRT are being prepared at the European Synchrotron Radiation Facility (ESRF), an iodinated contrast agent will be used. In order to compute the energy deposited in the patient (dose), a dedicated treatment planning system (TPS) has been developed for the clinical trials, based on the ISOgray TPS. This work focuses on the SSRT specific modifications of the TPS, especially to the PENELOPE-based Monte Carlo dose engine. The TPS uses a dedicated Monte Carlo simulation of medium energy polarized photons to compute the deposited energy in the patient. Simulations are performed considering the synchrotron source, the modeled beamline geometry and finally the patient. Specific materials were also implemented in the voxelized geometry of the patient, to consider iodine concentrations in the tumor. The computation process has been optimized and parallelized. Finally a specific computation of absolute doses and associated irradiation times (instead of monitor units) was implemented. The dedicated TPS was validated with depth dose curves, dose profiles and absolute dose measurements performed at the ESRF in a water tank and solid water phantoms with or without bone slabs. (author) [fr

  9. Antibiotics resistance of Stenotrophomonas maltophilia strains ...

    African Journals Online (AJOL)

    Background: A limited number of antibiotics are recommended for the therapy of Stenotrophomonas maltophilia infections due to therapy difficulties caused by its numerous mechanisms of resistance. Objectives: In this study conducted over a period of approximately 5 years we aimed to determine resistance rates of S.

  10. Transfer of antibiotic resistant bacteria from animals to man

    DEFF Research Database (Denmark)

    Wegener, Henrik Caspar; Aarestrup, Frank Møller; Gerner-Smidt, P.

    1999-01-01

    for animals either for therapy or for growth promotion. Antibiotic resistance in zoonotic bacteria constitute a public health hazard, primarily through the increased risk of treatment failures. This paper describes the zoonotic bacteria, salmonella, campylobacter, yersinia and enterohaemorrhagic E. coli (EHEC......Antibiotic resistance develops in zoonotic bacteria in response to antibiotics used in food animals. A close association exists between the amounts of antibiotics used and the levels of resistance observed. The classes of antibiotics routinely used for treatment of human infections are also used......). Infections with these agents do not generally require antibiotic therapy, but in some cases antibiotics are essential to obtain a successful cure. The levels and types of resistance observed in zoonotic bacteria in some countries, especially the increasing levels of fluoroquinolone resistance in salmonella...

  11. Antibiotic misuse in the community--a contributor to resistance?

    LENUS (Irish Health Repository)

    Carey, B

    2012-02-03

    The problem of antibiotic resistance is associated with the indiscriminate usage of antibiotics. Efforts have been directed at encouraging the rational use of these drugs to reduce the volume of antibiotic consumption and decrease resistance rates. There is evidence to suggest that the misuse of antibiotics by patients may also contribute to the problem. We describe a survey of a random selection of patients attending a General Practitioners\\' surgery over a six week period in an effort to estimate the level of non-compliance to antibiotic therapy in the community. The results suggest that there may be a significant level of antibiotic misuse prevalent in the local community. We discuss these results and present evidence in the literature suggesting how antibiotic misuse may affect resistance in the community. The factors affecting patient compliance to therapy are outlined along with suggested measures to improve compliance among patients.

  12. Risk of bleeding and antibiotic use in patients receiving continuous phenprocoumon therapy. A case-control study nested in a large insurance- and population-based German cohort.

    Science.gov (United States)

    Abbas, Sascha; Ihle, Peter; Harder, Sebastian; Schubert, Ingrid

    2014-05-05

    There is major concern about coumarins interacting with various drug classes and increasing the risk of overanticoagulation. The aim of the study was to assess bleeding risk in patients with concurrent use of antibiotics and phenprocoumon, the most widely prescribed coumarin in many European countries. We conducted a nested-case-control study within a cohort of 513,338 incident and continuous phenprocoumon users ≥ 18 years of age using claims data of the statutory health insurance company AOK, covering 30% of the German population. Bleeding risk associated with current use of antibiotics for systemic use (antibacterials/antimycotics) was calculated using conditional logistic regression in 13,785 cases with a bleeding event and 55,140 risk-set sampling-matched controls. Bleeding risk associated with any antibacterial use in phenprocoumon users was significantly increased [odds ratio (OR) 2.37, 95% confidence interval (CI) 2.20-2.56]. The association was stronger for gastrointestinal than for cerebral bleeding (OR 2.09, 95% CI 1.84-2.38 and OR 1.34, 95% CI 1.03-1.74, respectively) and highest for other/unspecified bleeding (OR 2.92, 95% CI 2.62-3.26). Specific antibiotic classes were strongly associated with bleeding risk, e.g. cotrimoxazole (OR 3.86, 95% CI 3.08-4.84) and fluorquinolones (OR 3.13, 95% CI 2.74-3.59), among those highest for ofloxacin (OR 5.00, 95% CI 3.01-8.32). Combined use of phenprocoumon and antimycotics was not significantly associated with bleeding risk. Risk was not significantly modified by age (pint=0.25) or sex (pint=0.96). The association was stronger the closer the antibiotic exposure was to the bleeding event. Among continuous phenprocoumon users, antibiotics - particularly quinolones and cotrimoxazole - should be prescribed after careful consideration due to an increased bleeding risk. Close monitoring of international normalised ratio levels after prescription is recommended.

  13. Ciprofloxacin prophylaxis delays initiation of broad-spectrum antibiotic therapy and reduces the overall use of antimicrobial agents during induction therapy for acute leukaemia: A single-centre study.

    Science.gov (United States)

    Hallböök, Helene; Lidström, Anna-Karin; Pauksens, Karlis

    2016-01-01

    Due to an outbreak of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate.

  14. Effects on combination of antibiotic-resistant bifidobacteria and corresponding antibiotics of survival of irradiated mice

    International Nuclear Information System (INIS)

    Korshunov, V.M.; Pinegin, B.V.; Ivanova, N.P.; Maltsev, V.N.

    1982-01-01

    Elimination of intestinal dysbacteriosis in irradiated animals by combining antibiotics and peparations of bifidobacteria resistant to these antibiotics prolonging the life of these animals was investigated. Broad spectrum antibiotics are used to treat intestinal dysbacteriosis. Bifidobacterial preparations are used to restore the microbial cenosis and their administration is started after antibiotics are discontinued. There are some flaws to deferred administration of bifidobacteria, since the process of colonization of the intestine with commercial bifidobacterial preparations is rather lengthy, and there is slow elevation of bifidobacterium level in the intestinal tract, whereas exogenous recontamination of the intestine by conditionally pathogenic bacteria is possible after antibiotic therapy is discontinued. Use of antibiotics alone could be the cause of intestinal dysbacteriosis

  15. Probiotics in antibiotic associated diarrhea in children

    Directory of Open Access Journals (Sweden)

    Matjaž Homan

    2013-10-01

    Full Text Available The use of antibiotics that disturb the gastrointestinal microbiota is associated with diarrhea, which occurs in up to half of treated children. Symptoms are usually mild and children do not need hospitalization. Probiotics are live microorganisms, which restore intestinal microbiota during antibiotic therapy through different mechanisms such as stimulation of immunity, secretion of anti-inflammatory factors, and production of antimicrobial substances. The use of different strains of probiotics in antibiotic-associated diarrhea was evaluated in several studies in adults but less frequently in pediatric population. They also confirmed the value of probiotics in the prevention of antibiotic-associated diarrhea in children, particularly Lactobacillus strain GG and Saccharomyces boulardii. The use of probiotics in childhood is safe. A proper strain must be introduced at the beginning of antibiotic treatment in a sufficient concentration.

  16. Qualitative evaluation of antibiotic usage in pediatric patients

    Directory of Open Access Journals (Sweden)

    Hindra Irawan Satari

    2011-12-01

    Methods We performed a descriptive, retrospective study of matient medical records of those admitted to the pediatric ward from January 1 – June 30, 2009. Records were screened for patient antibiotic use, followed by qualitative evaluation using Gyssens algorithm on data from patient who received antibiotic treatment. Results We found 49.2% of subject were prescribed antibiotics. The majority of patients given antibiotics were aged 1 month - 1 year (39.3%. Antibiotic use was categorized by therapy type : empirical, prophylactic, or definitive. We found empirical therapy in 73% of cases, prophylactic in 8%, and definitive in 15%. Cefotaxime was the most common antibiotic used (25.1%, followed by ceftazidime (14% and cotrimoxazole (1%. 39.6% of subjects were given antibiotics appropriately, while 48.3% were given inappropriately. In 3.3% of patients, antibiotics were given without indication and in 8.8% there was insufficient data. Conclusions Of hospitalized patients receiving antibiotic treatment at the Departement of Child Health, Cipto Mangunkusumo Hospital, 39.6% were given antibiotic appropriately, while 48.3% were given antibiotics inappropriately. Cefotaxime was the most commonly used, as well as most inappropriately given antibiotic.

  17. Priorities for antibiotic resistance surveillance in Europe

    DEFF Research Database (Denmark)

    Fluit, A. C.; van der Bruggen, J. T.; Aarestrup, Frank Møller

    2006-01-01

    Antibiotic resistance is an increasing global problem. Surveillance studies are needed to monitor resistance development, to guide local empirical therapy, and to implement timely and adequate countermeasures. To achieve this, surveillance studies must have standardised methodologies, be longitud......Antibiotic resistance is an increasing global problem. Surveillance studies are needed to monitor resistance development, to guide local empirical therapy, and to implement timely and adequate countermeasures. To achieve this, surveillance studies must have standardised methodologies...... to the various reservoirs of antibiotic-resistant bacteria, such as hospitalised patients, nursing homes, the community, animals and food. Two studies that could serve as examples of tailored programmes are the European Antimicrobial Resistance Surveillance System (EARSS), which collects resistance data during...... of antibiotic resistance....

  18. Enteropathogens and antibiotics.

    Science.gov (United States)

    González-Torralba, Ana; García-Esteban, Coral; Alós, Juan-Ignacio

    2018-01-01

    Infectious gastroenteritis remains a public health problem. The most severe cases are of bacterial origin. In Spain, Campylobacter and Salmonella are the most prevalent bacterial genus, while Yersinia and Shigella are much less frequent. Most cases are usually self-limiting and antibiotic therapy is not generally indicated, unless patients have risk factors for severe infection and shigellosis. Ciprofloxacin, third generation cephalosporins, azithromycin, ampicillin, cotrimoxazole and doxycycline are the most recommended drugs. The susceptibility pattern of the different bacteria determines the choice of the most appropriate treatment. The aim of this review is to analyse the current situation, developments, and evolution of resistance and multidrug resistance in these 4 enteric pathogens. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  19. Future directions for ICT in aphasia therapy for older adults: enhancing current practices through interdisciplinary perspectives

    OpenAIRE

    Kötteritzsch, Anna; Gerling, Kathrin

    2015-01-01

    Growing numbers of older adults requiring aphasia therapy create challenges for the health care system. Information and communication technology (ICT) has the potential to provide computer-mediated, self-administered aphasia therapy that complements conventional therapy. We explore overlaps in ICT for older adults and aphasia therapy applications with the goal of integrating innovative ICT in aphasia therapy. Based on a case study, we explain how results of different disciplines developing IC...

  20. Effectiveness of enhanced cognitive behavioral therapy (CBT-E) for eating disorders : Study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    de Jong, M.; Korrelboom, C.W.; van der Meer, I.; Deen, M.; Hoek, H.W.; Spinhoven, P.

    2016-01-01

    Background While eating disorder not otherwise specified (EDNOS) is the most common eating disorder (ED) diagnosis in routine clinical practice, no specific treatment methods for this diagnosis have yet been developed and studied. Enhanced cognitive behavioral therapy (CBT-E) has been described and

  1. Effectiveness of enhanced cognitive behavioral therapy (CBT-E) for eating disorders : study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    de Jong, Martie; Korrelboom, Kees; van der Meer, Iris; Deen, Mathijs; Hoek, Hans W.; Spinhoven, Philip

    2016-01-01

    Background: While eating disorder not otherwise specified (EDNOS) is the most common eating disorder (ED) diagnosis in routine clinical practice, no specific treatment methods for this diagnosis have yet been developed and studied. Enhanced cognitive behavioral therapy (CBT-E) has been described and

  2. Emotion Regulation Enhancement of Cognitive Behavior Therapy for College Student Problem Drinkers: A Pilot Randomized Controlled Trial

    Science.gov (United States)

    Ford, Julian D.; Grasso, Damion J.; Levine, Joan; Tennen, Howard

    2018-01-01

    This pilot randomized clinical trial tested an emotion regulation enhancement to cognitive behavior therapy (CBT) with 29 college student problem drinkers with histories of complex trauma and current clinically significant traumatic stress symptoms. Participants received eight face-to-face sessions of manualized Internet-supported CBT for problem…

  3. Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa.

    Science.gov (United States)

    Hakim, James; Musiime, Victor; Szubert, Alex J; Mallewa, Jane; Siika, Abraham; Agutu, Clara; Walker, Simon; Pett, Sarah L; Bwakura-Dangarembizi, Mutsa; Lugemwa, Abbas; Kaunda, Symon; Karoney, Mercy; Musoro, Godfrey; Kabahenda, Sheila; Nathoo, Kusum; Maitland, Kathryn; Griffiths, Anna; Thomason, Margaret J; Kityo, Cissy; Mugyenyi, Peter; Prendergast, Andrew J; Walker, A Sarah; Gibb, Diana M

    2017-07-20

    In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim-sulfamethoxazole plus at least 12 weeks of isoniazid-pyridoxine (coformulated with trimethoprim-sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim-sulfamethoxazole alone). The primary end point was 24-week mortality. A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan-Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had

  4. Spread of community-acquired meticillin-resistant Staphylococcus aureus skin and soft-tissue infection within a family: implications for antibiotic therapy and prevention.

    LENUS (Irish Health Repository)

    Amir, N H

    2010-04-01

    Outbreaks or clusters of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) within families have been reported. We describe a family cluster of CA-MRSA skin and soft-tissue infection where CA-MRSA was suspected because of recurrent infections which failed to respond to flucloxacillin. While the prevalence of CA-MRSA is low worldwide, CA-MRSA should be considered in certain circumstances depending on clinical presentation and risk assessment. Surveillance cultures of family contacts of patients with MRSA should be considered to help establish the prevalence of CA-MRSA and to inform the optimal choice of empiric antibiotic treatment.

  5. Impediments to Enhancement of CPT-11 Anticancer Activity by E. coli Directed Beta-Glucuronidase Therapy

    Science.gov (United States)

    Hsieh, Yuan-Ting; Chen, Kai-Chuan; Cheng, Chiu-Min; Cheng, Tian-Lu; Tao, Mi-Hua; Roffler, Steve R.

    2015-01-01

    CPT-11 is a camptothecin analog used for the clinical treatment of colorectal adenocarcinoma. CPT-11 is converted into the therapeutic anti-cancer agent SN-38 by liver enzymes and can be further metabolized to a non-toxic glucuronide SN-38G, resulting in low SN-38 but high SN-38G concentrations in the circulation. We previously demonstrated that adenoviral expression of membrane-anchored beta-glucuronidase could promote conversion of SN-38G to SN-38 in tumors and increase the anticancer activity of CPT-11. Here, we identified impediments to effective tumor therapy with E. coli that were engineered to constitutively express highly active E. coli beta-glucuronidase intracellularly to enhance the anticancer activity of CPT-11. The engineered bacteria, E. coli (lux/βG), could hydrolyze SN-38G to SN-38, increased the sensitivity of cultured tumor cells to SN-38G by about 100 fold and selectively accumulated in tumors. However, E. coli (lux/βG) did not more effectively increase CPT-11 anticancer activity in human tumor xenografts as compared to non-engineered E. coli. SN-38G conversion to SN-38 by E. coli (lux/βG) appeared to be limited by slow uptake into bacteria as well as by segregation of E. coli in necrotic regions of tumors that may be relatively inaccessible to systemically-administered drug molecules. Studies using a fluorescent glucuronide probe showed that significantly greater glucuronide hydrolysis could be achieved in mice pretreated with E. coli (lux/βG) by direct intratumoral injection of the glucuronide probe or by intratumoral lysis of bacteria to release intracellular beta-glucuronidase. Our study suggests that the distribution of beta-glucuronidase, and possibly other therapeutic proteins, in the tumor microenvironment might be an important barrier for effective bacterial-based tumor therapy. Expression of secreted therapeutic proteins or induction of therapeutic protein release from bacteria might therefore be a promising strategy to enhance anti

  6. Enhancing photodynamic therapy of a metastatic mouse breast cancer by immune stimulation

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    Castano, Ana P.; Hamblin, Michael R.

    2006-02-01

    One in 8 women in the United States will develop breast cancer during her lifetime and 40,000 die each year. Deaths are due to tumors that have metastasized despite local control. Photodynamic therapy (PDT) is a promising cancer treatment in which a photosensitizer (PS) accumulates in tumors and is subsequently activated by visible light of an appropriate wavelength. The energy of the light is transferred to molecular oxygen to produce reactive oxygen species that produce cell death and tumor ablation. Mechanisms include cytotoxicity to tumor cells, shutting down of the tumor vasculature, and the induction of a host immune response. The precise mechanisms involved in the PDT-mediated induction of anti-tumor immunity are not yet understood. Potential contributing factors are alterations in the tumor microenvironment via stimulation of proinflammatory cytokines and direct effects of PDT on the tumor that increase immunogenicity. We have studied PDT of 410.4 variant 4T1 tumors growing in the mammary fat pad (orthotopic) in Balb/c mice and which produce metastasis. We have shown that a PDT regimen that produces vascular shutdown and tumor necrosis leads to initial tumor ablation but the tumors recur at the periphery. We studied the combination of PDT with immunostimulating therapies. Low dose cyclophosphamide (CY) is a specific mechanism to deplete the regulatory T cells (CD4+CD25+), these cells play an important role in the immunosuppression activity of tumors. In combination with PDT that produces release of tumor specific antigens, this immunostimulation may lead to generation of cytotoxic CD8 T-lymphocytes that recognize and destroy the tumor. The second alternative therapy is the use of a novel combination of the immunostimulant CpG oligodeoxynucleotides (CpG-ODN) and PDT. CpG-ODN is recognized by Toll-like receptor 9 and directly or indirectly triggers B cells, NK cells, monocyte-macrophages and dendritic cells to proliferate, mature and secrete cytokines

  7. Concomitant nitrates enhance clopidogrel response during dual anti-platelet therapy.

    Science.gov (United States)

    Lee, Dong Hyun; Kim, Moo Hyun; Guo, Long Zhe; De Jin, Cai; Cho, Young Rak; Park, Kyungil; Park, Jong Sung; Park, Tae-Ho; Serebruany, Victor

    2016-01-15

    Despite advances in modern anti-platelet strategies, clopidogrel still remains the cornerstone of dual anti-platelet therapy (DAPT) in patients undergoing percutaneous coronary interventions (PCI). There is some inconclusive evidence that response after clopidogrel may be impacted by concomitant medications, potentially affecting clinical outcomes. Sustained released nitrates (SRN) are commonly used together with clopidogrel in post-PCI setting for mild vasodilatation and nitric oxide-induced platelet inhibition. We prospectively enrolled 458 patients (64.5 ± 9.6 years old, and 73.4% males) following PCI undergoing DAPT with clopidogrel and aspirin. Platelet reactivity was assessed by the VerifyNow™ P2Y12 assay at the maintenance outpatient setting. Concomitant SRN (n=266) significantly (p=0.008) enhanced platelet inhibition after DAPT (251.6 ± 80.9PRU) when compared (232.1 ± 73.5PRU) to the SRN-free (n=192) patients. Multivariate logistic regression analysis with the cut-off value of 253 PRU for defining heightened platelet reactivity confirmed independent correlation of more potent platelet inhibition during DAPT and use of SRN (Relative risk=1.675; Odds ratio [1.059-2.648]; p=0.027). In contrast, statins, calcium-channel blockers, beta blockers, angiotensin receptor blockers, ACE-inhibitors, diuretics, and anti-diabetic agents did not significantly impact platelet inhibition following DAPT. The synergic ability of SRN to enhance response during DAPT may have important clinical implications with regard to better cardiovascular protection, but extra bleeding risks, requiring further confirmation in a large randomized study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Vitamin D enhances the efficacy of photodynamic therapy in a murine model of breast cancer

    International Nuclear Information System (INIS)

    Rollakanti, Kishore R; Anand, Sanjay; Maytin, Edward V

    2015-01-01

    Cutaneous metastasis occurs more frequently in breast cancer than in any other malignancy in women, causing significant morbidity. Photodynamic therapy (PDT), which combines a porphyrin-based photosensitizer and activation by light, can be employed for breast cancer (especially cutaneous metastases) but tumor control after PDT has not surpassed traditional treatments methods such as surgery, radiation, and chemotherapy up to now. Here, we report that breast cancer nodules in mice can be effectively treated by preconditioning the tumors with 1α, 25-dihydroxyvitamin D 3 (calcitriol; Vit D) prior to administering 5-aminolevulinate (ALA)-based PDT. Breast carcinoma tumors (MDA-MB-231 cells implanted subcutaneously in nude mice) received systemic Vit D (1 μg/kg) for 3 days prior to receiving ALA. The addition of Vit D increased intratumoral accumulation of protoporphyrin IX (PpIX) by 3.3 ± 0.5-fold, relative to mice receiving ALA alone. Bioluminescence imaging in vivo and immunohistochemical staining confirmed that tumor-specific cell death after ALA-PDT was markedly enhanced (36.8 ± 7.4-fold increase in TUNEL-positive nuclei; radiance decreased to 14% of control) in Vit D pretreated tumors as compared to vehicle-pretreated tumors. Vit D stimulated proliferation (10.7 ± 2.8-fold) and differentiation (9.62 ± 1.7-fold) in tumor cells, underlying an augmented cellular sensitivity to ALA-PDT. The observed enhancement of tumor responses to ALA-PDT after low, nontoxic doses of Vit D supports a new combination approach that deserves consideration in the clinical setting, and offers potential for improved remission of cutaneous breast cancer metastases

  9. Outcomes of implementation of enhanced goal directed therapy in high-risk patients undergoing abdominal surgery

    Directory of Open Access Journals (Sweden)

    Lakshmi Kumar

    2015-01-01

    Full Text Available Background and Aims: Advanced monitoring targeting haemodynamic and oxygenation variables can improve outcomes of surgery in high-risk patients. We aimed to assess the impact of goal directed therapy (GDT targeting cardiac index (CI and oxygen extraction ratio (O 2 ER on outcomes of high-risk patients undergoing abdominal surgery. Methods: In a prospective randomised trial, forty patients (American Society of Anaesthesiologists II and III undergoing major abdominal surgeries were randomised into two groups. In-Group A mean arterial pressure ≥ 65 mmHg, central venous pressure ≥ 8-10 mmHg, urine output ≥ 0.5 mL/kg/h and central venous oxygen saturation ≥ 70% were targeted intra-operatively and 12 h postoperatively. In-Group-B (enhanced GDT, in addition to the monitoring in-Group-A, CI ≥ 2.5 L/min/m 2 and O 2 ER ≤ 27% were targeted. The end-points were lactate levels and base deficit during and after surgery. The secondary end points were length of Intensive Care Unit (ICU and hospital stay and postoperative complications. Wilcoxon Mann Whitney and Chi-square tests were used for statistical assessment. Results: Lactate levels postoperatively at 4 and 8 h were lower in-Group-B (P < 0.05. The mean base deficit at 3, 4, 5 and 6 h intra-operatively and postoperatively after 4, 8 and 12 h were lower in-Group-B (P < 0.05. There were no significant differences in ICU stay (2.10 ± 1.52 vs. 2.90 ± 2.51 days or hospital stay (10.85 + 4.39 vs. 13.35 + 6.77 days between Group A and B. Conclusions: Implementation of enhanced GDT targeting CI and OER was associated with improved tissue oxygenation.

  10. Analysis of antibiotic consumption in burn patients

    Directory of Open Access Journals (Sweden)

    Soleymanzadeh-Moghadam, Somayeh

    2015-06-01

    Full Text Available Infection control is very important in burn care units, because burn wound infection is one of the main causes of morbidity and mortality among burn patients. Thus, the appropriate prescription of antibiotics can be helpful, but unreasonable prescription can have detrimental consequences, including greater expenses to patients and community alike. The aim of this study was to determine the effect of antibiotic therapy on the emergence of antibiotic-resistant bacteria. 525 strains of and were isolated from 335 hospitalized burn patients. Antibiotic susceptibility tests were performed after identification the strains. The records of patients were audited to find the antibiotic used.The results indicated that is the most prevalent Gram-negative bacteria. Further, it showed a relation between abuse of antibiotics and emergence of antibiotic resistance. Control of resistance to antibiotics by appropriate prescription practices not only facilitates prevention of infection caused by multi-drug resistant (MDR microorganisms, but it can also decrease the cost of treatment.

  11. Protocol for a randomised crossover trial to evaluate patient and nurse satisfaction with electronic and elastomeric portable infusion pumps for the continuous administration of antibiotic therapy in the home: the Comparing Home Infusion Devices (CHID) study.

    Science.gov (United States)

    Hobbs, Jodie G; Ryan, Melissa K; Ritchie, Brett; Sluggett, Janet K; Sluggett, Andrew J; Ralton, Lucy; Reynolds, Karen J

    2017-07-31

    Previous studies comparing satisfaction with electronic and elastomeric infusion pumps are limited, and improvements in size and usability of electronic pumps have since occurred. The Comparing Home Infusion Devices (CHID) study plans to assess patient and nurse satisfaction with an elastomeric and electronic pump for delivering intravenous antibiotic treatment in the home. Secondary objectives are to determine pump-related complications and actual antibiotic dose administered, evaluate temperature variation and compare pump operating costs. The CHID study will be a randomised, crossover trial. A trained research nurse will recruit patients with infectious disease aged ≥18 years and prescribed ≥8 days of continuous intravenous antibiotic therapy from the Royal Adelaide Hospital (RAH) (Adelaide, Australia). Patients will be randomised to receive treatment at home via an elastomeric (Baxter Infusor) or an electronic (ambIT Continuous) infusion pump for 4-7 days, followed by the other for a further 4-7 days. Patient satisfaction will be assessed by a 10-item survey to be completed at the end of each arm. Nurse satisfaction will be assessed by a single 24-item survey. Patient logbooks and case notes from clinic visits will be screened to identify complications. Pumps/infusion bags will be weighed to estimate the volume of solution delivered. Temperature sensors will record skin and ambient temperatures during storage and use of the pumps throughout the infusion period. Costs relating to pumps, consumables, antibiotics and servicing will be determined. Descriptive statistics will summarise study data. This study has been approved by the RAH Human Research Ethics Committee (HREC/16/RAH/133 R20160420, version 6.0, 5 September 2016). Study results will be disseminated through peer-reviewed publications and conference presentations. The CHID study will provide key insights into patient and provider satisfaction with elastomeric and electronic infusion pumps and inform

  12. Technology-enhanced writing therapy for people with aphasia: results of a quasi-randomized waitlist controlled study.

    Science.gov (United States)

    Marshall, Jane; Caute, Anna; Chadd, Katie; Cruice, Madeline; Monnelly, Katie; Wilson, Stephanie; Woolf, Celia

    2018-05-10

    Acquired writing impairment, or dysgraphia, is common in aphasia. It affects both handwriting and typing, and may recover less well than other aphasic symptoms. Dysgraphia is an increasing priority for intervention, particularly for those wishing to participate in online written communication. Effective dysgraphia treatment studies have been reported, but many did not target, or did not achieve, improvements in functional writing. Functional outcomes might be promoted by therapies that exploit digital technologies, such as voice recognition and word prediction software. This study evaluated the benefits of technology-enhanced writing therapy for people with acquired dysgraphia. It aimed to explore the impact of therapy on a functional writing activity, and to examine whether treatment remediated or compensated for the writing impairment. The primary question was: Does therapy improve performance on a functional assessment of writing; and, if so, do gains occur only when writing is assisted by technology? Secondary measures examined whether therapy improved unassisted written nam