WorldWideScience

Sample records for title carbapenems 25-30d

  1. Sparing carbapenem usage.

    Science.gov (United States)

    Wilson, A Peter R

    2017-09-01

    Carbapenem resistance in Gram-negative bacteria is increasing in many countries and use of carbapenems and antibiotics to which resistance is linked should be reduced to slow its emergence. There are no directly equivalent antibiotics and the alternatives are less well supported by clinical trials. The few new agents are expensive. To provide guidance on strategies to reduce carbapenem usage. A literature review was performed as described in the BSAC/HIS/BIA/IPS Joint Working Party on Multiresistant Gram-negative Infection Report. Older agents remain active against some of the pathogens, although expectations of broad-spectrum cover for empirical treatment have risen. Education, expert advice on treatment and antimicrobial stewardship can produce significant reductions in use. More agents may need to be introduced onto the antibiotic formulary of the hospital, despite the poor quality of scientific studies in some cases. © 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.

  2. Recent updates of carbapenem antibiotics.

    Science.gov (United States)

    El-Gamal, Mohammed I; Brahim, Imen; Hisham, Noorhan; Aladdin, Rand; Mohammed, Haneen; Bahaaeldin, Amany

    2017-05-05

    Carbapenems are among the most commonly used and the most efficient antibiotics since they are relatively resistant to hydrolysis by most β-lactamases, they target penicillin-binding proteins, and generally have broad-spectrum antibacterial effect. In this review, we described the initial discovery and development of carbapenems, chemical characteristics, in vitro/in vivo activities, resistance studies, and clinical investigations for traditional carbapenem antibiotics in the market; imipenem-cilastatin, meropenem, ertapenem, doripenem, biapenem, panipenem/betamipron in addition to newer carbapenems such as razupenem, tebipenem, tomopenem, and sanfetrinem. We focused on the literature published from 2010 to 2016. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Options for treating carbapenem-resistant Enterobacteriaceae.

    Science.gov (United States)

    Rafailidis, Petros I; Falagas, Matthew E

    2014-12-01

    To address the therapeutic management of carbapenem-resistant Enterobacteriaceae on the basis of literature of the last 12 months. Retrospective and prospective (nonrandomized noncontrolled) studies provide data regarding the management of infections due to carbapenem-resistant Enterobacteriaceae. The combination of a carbapenem with colistin or high-dose tigecycline or aminoglycoside or even triple carbapenem-containing combinations if the minimum inhibitory concentration (MIC) range of carbapenem (meropenem and imipenem) resistance is 8 mg/l or less seems to have an advantage over monotherapy with either colistin or tigecycline or fosfomycin. For Enterobacteriaceae with MIC for carbapenems over 8 mg/l, combination regimens involve colistin, tigecycline usually administered in a double dose than that suggested by its manufacturer, fosfomycin and aminoglycosides in various combinations. Suggestions based on the limited literature cannot be made safely. Combination regimens involving carbapenems for Enterobacteriaceae with MICs 8 mg/l or less for carbapenems (in dual combination with colistin or high-dose tigecycline or aminoglycoside or even triple combinations) seem to confer some therapeutic advantage over monotherapy. For Enterobacteriaceae with higher than the above-mentioned MICs, a combination of two or even three antibiotics among colistin, high-dose tigecycline, aminoglycoside and fosfomycin seems to confer decreased mortality.

  4. Potency of carbapenems for the prevention of carbapenem-resistant mutants of Pseudomonas aeruginosa: the high potency of a new carbapenem doripenem.

    Science.gov (United States)

    Sakyo, Shihomi; Tomita, Haruyoshi; Tanimoto, Koichi; Fujimoto, Shuhei; Ike, Yasuyoshi

    2006-04-01

    The potencies of the carbapenems; doripenem (DRPM), meropenem (MEPM) and imipenem (IPM) in preventing the emergence of carbapenem-resistant mutants were examined in Pseudomonas aeruginosa strains. The carbapenems predominantly selected carbapenem-resistant mutants or carbapenem mutants with reduced susceptibilities that were specifically resistant to carbapenems and had arisen as a result of the reduced level of expression of the outer membrane protein with a molecular weight of about 48,000 (OprD). The potency of carbapenems in preventing the growth of the mutants differed for DRPM, MEPM and IPM. The isolation frequency of the mutant was examined on agar plates containing each of the carbapenems at a concentration of 1/2 or 1/4 MIC of each carbapenem for that mutant. Mutants were not selected on agar containing DRPM at a frequency of greater than 10(-9) per cell per generation, whereas mutants of each strain were selected on agar containing MEPM or IPM at frequencies of 10(-7) to 10(-9) per cell per generation. The drug concentrations and the drug concentration range for the selective increase of carbapenem resistant mutants in the broth culture containing each carbapenem differed for each carbapenem. DRPM exhibited both the lowest drug concentration and the narrowest range of drug concentration for selection of the carbapenem-resistant mutants. The results shown in this report indicated that DRPM exhibited the greatest ability to prevent the emergence of the mutant.

  5. Effect of carbapenem consumption patterns on the molecular epidemiology and carbapenem resistance of Acinetobacter baumannii.

    Science.gov (United States)

    Mózes, Julianna; Ebrahimi, Fatemeh; Gorácz, Orsolya; Miszti, Cecília; Kardos, Gábor

    2014-12-01

    This study investigated the molecular epidemiology of Acinetobacter baumannii in the University of Debrecen in relation to antibiotic consumption. Overall and ward-specific antibiotic consumption was measured by the number of defined daily doses (DDD) per 100 bed-days between 2002 and 2012. Consumption was analysed against the number of A. baumannii positive patients per 100 bed-days, number of isolates per positive sample, and proportion of carbapenem resistant A. baumannii, using time-series analysis. Altogether 160 A. baumannii isolates from different wards were collected and analysed. Carbapenemase genes bla(OXA-23-like), bla(OXA-24-like), bla(OXA-48-like), bla(OXA-51-like), bla(OXA-58-like) and integrons were sought by PCR. Relatedness of isolates was assessed by PFGE. Prevalence and carbapenem resistance of A. baumannii were statistically associated with carbapenem consumption. Prevalence data followed carbapenem usage with three quarterly lags (r = 0.51-0.53, Pcarbapenem consumption was associated with the carbapenem-susceptible cluster, as well as with the carbapenem-susceptible isolates in the cluster with variable susceptibility. Wards with high carbapenem usage almost exclusively harboured isolates from carbapenem-resistant clusters. All clusters were dominated by isolates of one or two wards, but most wards were represented in multiple clusters. Increases in prevalence and carbapenem resistance of A. baumannii were associated with usage of meropenem and ertapenem but not of imipenem, which led to the spread of multiple clones in the University. © 2014 The Authors.

  6. Carbapenems: Past, Present, and Future ▿

    Science.gov (United States)

    Papp-Wallace, Krisztina M.; Endimiani, Andrea; Taracila, Magdalena A.; Bonomo, Robert A.

    2011-01-01

    In this review, we summarize the current “state of the art” of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the β-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most β-lactamases, in some cases act as “slow substrates” or inhibitors of β-lactamases, and still target penicillin binding proteins. This “value-added feature” of inhibiting β-lactamases serves as a major rationale for expansion of this class of β-lactams. We describe the initial discovery and development of the carbapenem family of β-lactams. Of the early carbapenems evaluated, thienamycin demonstrated the greatest antimicrobial activity and became the parent compound for all subsequent carbapenems. To date, more than 80 compounds with mostly improved antimicrobial properties, compared to those of thienamycin, are described in the literature. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges and urge the medicinal chemist to continue development of these versatile and potent compounds, as they have served us well for more than 3 decades. PMID:21859938

  7. Carbapenem-resistant-only Pseudomonas aeruginosa infection in patients formerly infected by carbapenem-susceptible strains.

    Science.gov (United States)

    Tsai, Ming-Han; Wu, Tsu-Lan; Su, Lin-Hui; Lo, Wei-Lin; Chen, Chyi-Liang; Liang, Yi-Hua; Chiu, Cheng-Hsun

    2014-12-01

    Pseudomonas aeruginosa isolates that were initially carbapenem-susceptible and later became selective carbapenem-resistant following antimicrobial therapy were identified from individual cases during the same hospitalisation. Cross-resistance to other β-lactams was not found and their susceptibilities remained identical in consecutive isolates. Real-time quantitative reverse transcription PCR was performed to investigate the role of OprD, an outer membrane protein regulating the entry of carbapenems, in the appearance of carbapenem-resistant-only P. aeruginosa (CROPA). Fifteen paired isolates of carbapenem-susceptible P. aeruginosa (CS-PA) and CROPA were identified. All of the cases had carbapenem exposure history within 1 month before the appearance of CROPA (mean 10 days). Reduced OprD expression was found in 93% (14/15) of the isolates, suggesting that oprD inactivation was the major contributor to selective carbapenem resistance. Of the 14 cases with CROPA due to oprD mutation, 71% (10/14) were persistent infection, as genotype analysis revealed that their paired strains were isogenic; 29% (4/14) represented re-infections as they were heterogenic, suggesting that oprD-deficient CROPA existed in the hospital and that carbapenem selective pressure promoted its spread to patients. We conclude that CROPA may occur soon after the use of carbapenems to treat CS-PA infections and that oprD mutation is the major mechanism of resistance in CROPA. Restriction of empirical use of carbapenems by antibiotic stewardship is important to halt the occurrence of CROPA. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  8. Carbapenem stewardship: does ertapenem affect Pseudomonas susceptibility to other carbapenems? A review of the evidence.

    Science.gov (United States)

    Nicolau, David P; Carmeli, Yehuda; Crank, Christopher W; Goff, Debra A; Graber, Christopher J; Lima, Ana Lucia L; Goldstein, Ellie J C

    2012-01-01

    The group 2 carbapenems (imipenem, meropenem and, more recently, doripenem) have been a mainstay of treatment for patients with serious hospital infections caused by Pseudomonas aeruginosa, Enterobacteriaceae and other difficult-to-treat Gram-negative pathogens as well as mixed aerobic/anaerobic infections. When ertapenem, a group 1 carbapenem, was introduced, questions were raised about the potential for ertapenem to select for imipenem- and meropenem-resistant Pseudomonas. Results from ten clinical studies evaluating the effect of ertapenem use on the susceptibility of Pseudomonas to carbapenems have uniformly shown that ertapenem use does not result in decreased Pseudomonas susceptibility to these antipseudomonal carbapenems. Here we review these studies evaluating the evidence of how ertapenem use affects P. aeruginosa as well as provide considerations for ertapenem use in the context of institutional stewardship initiatives. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  9. Association of ertapenem and antipseudomonal carbapenem usage and carbapenem resistance in Pseudomonas aeruginosa among 12 hospitals in Queensland, Australia.

    Science.gov (United States)

    McDougall, David A J; Morton, Anthony P; Playford, E Geoffrey

    2013-02-01

    The objective of this study was to determine the association between ertapenem and antipseudomonal carbapenem use and carbapenem resistance in Pseudomonas aeruginosa in 12 hospitals in Queensland, Australia. Data on usage of ertapenem and other antipseudomonal carbapenems, measured in defined daily doses per 1000 occupied bed-days, were collated using statewide pharmacy dispensing and distribution software from January 2007 until June 2011. The prevalence of unique carbapenem-resistant P. aeruginosa isolates derived from statewide laboratory information systems was collected for the same time period. Mixed-effects models were used to determine any relationship between ertapenem and antipseudomonal carbapenem usage and carbapenem resistance among P. aeruginosa isolates in the 12 hospitals analysed. No relationship between ertapenem usage and P. aeruginosa carbapenem resistance was observed. The introduction of ertapenem did not replace antipseudomonal carbapenem prescribing to any significant extent. However, an association between greater usage of antipseudomonal carbapenems and greater P. aeruginosa carbapenem resistance was demonstrated. It is likely that the only mechanism by which ertapenem can improve P. aeruginosa resistance patterns is by being used as a substitute for, rather than in addition to, antipseudomonal carbapenems.

  10. The outcome of treating ESBL infections with carbapenems vs. non carbapenem antimicrobials.

    Science.gov (United States)

    Trivedi, Mayuri; Trivedi, Mayur; Patel, Vipul; Soman, Rajeev; Rodriguez, Camilla; Singhal, Tanu

    2012-08-01

    In India where the prevalence of extended spectrum beta lactamase (ESBL) producing organisms among gram negative organisms is 60-70% and Ertapenem was unavailable at the beginning of this study, exclusive use of Group 2 Carbapenems (Imipenem and Meropenem) for treatment raises issues of cost and development of resistance. Therefore the role of non-Carbapenem alternatives, chiefly Betalactam + Betalactamase inhibitors (BL-BLI) was explored in this prospective observational study at a private tertiary care teaching hospital. 522 consecutive in door patients from the period between June 2006 to March 2007and June 2008 to December 2008, who had true infections with ESBL producing organisms were enrolled in the study. Antimicrobials were prescribed or changed by the treating physicians on the basis of the nature and severity of infection, the susceptibility of the organism and the affordability of the patient. Patients who received a Carbapenem at any time during treatment were considered in the Carbapenem group. Those who never received a Carbapenem at any time during treatment were considered in the non-Carbapenem group. Of the 522 infections, 287 were urinary tract infections, 60 were skin structure infections, 60 were bacteremias, 55 were hospital acquired pneumonias, 31 were intra-abdominal infections and 29 were other infections. There were 351 E. coli, 119 K. pneumoniae, 23 K. oxytoca, 16 Enterobacter aerogenes, 5 Kozoanae, 4 Enterobacter agglomerans, 3 Citrobacter freundi, 1 E. cloacae, 1 Enterobacterspp. and 1 Morgenella morganii isolates. Clinical outcomes were available for 486 patients. 339 patients who were in the non-Carbapenem group and who might have had less serious infections had a clinical success rate of 79.6%. 147 patients who were in the Carbapenem group and who might have had more serious infections had a clinical success rate of 85.71%. It is possible to successfully treat at least the less serious infections due to ESBL producing gram negative

  11. CARBAPENEM-RESISTANT ACINETOBACTER BAUMANII POSTOPERATIVE MENINGITIS

    OpenAIRE

    Laura Ghibu; Egidia Miftode; Olivia Dorneanu; Carmen Dorobat

    2011-01-01

    Acinetobacter baumannii is an opportunistic pathogen of increasing relevance in hospital infections during the last 15 years.This organism causes a wide range of infection .Extensive use of antibiotics within hospitals has contribute to the emergence of multidrug-resistent A.baumannii strains that exhibit resistance to a wide range of antibiotics ,including carbapenems.We report the case of an 37 years old man diagnosed with Acinetobacter multidrug-resistant post-neurosurgical meningitis with...

  12. Effects of Group 1 versus Group 2 carbapenems on the susceptibility of Acinetobacter baumannii to carbapenems: a before and after intervention study of carbapenem-use stewardship.

    Directory of Open Access Journals (Sweden)

    Young Kyung Yoon

    Full Text Available OBJECTIVE: Antimicrobial stewardship programs have been proposed for reducing bacterial resistance in the hospital environment. The purpose of this study was to investigate the impact of a carbapenem-use stewardship program on the susceptibility of Acinetobacter baumannii to Group 2 carbapenems. METHODS: A before and after intervention study was conducted at a university hospital from September 2008 to February 2013. Three study periods were defined: Phase I, pre-intervention (months 1-18; Phase II, a postintervention period during which ertapenem use was mandated but carbapenem use was not restricted (months 19-36; and Phase III, a postintervention period during which Group 2 carbapenem use was restricted (months 37-54. RESULTS: During the study period, intervention resulted in diminished consumption of Group 2 carbapenems (antimicrobial use density (AUD: 21.3±6.0 in Phase I, 18.8±6.0 in Phase II, 16.1±4.4 in Phase III; P = 0.028 and increased consumption of ertapenem (AUD: 2.7±1.7 in Phase I, 7.2±4.5 in Phase II, 9.1±5.3 in Phase III; P<0.001. The use of autoregressive-error models showed that in contrast with ertapenem use, the use of Group 2 carbapenem during the previous one month was positively and significantly associated with a subsequent increase in the proportion of carbapenem-resistant A. baumannii (CRAB (P = 0.031. CONCLUSIONS: Implementing a carbapenem-use stewardship program featuring the preferential use of ertapenem for treating appropriate indications of infection resulted in reduced use of Group 2 carbapenems and had a positive impact on the susceptibility of A. baumannii to carbapenems. This approach could be integrated into CRAB-control strategies in hospitals.

  13. Effects of Group 1 versus Group 2 carbapenems on the susceptibility of Acinetobacter baumannii to carbapenems: a before and after intervention study of carbapenem-use stewardship.

    Science.gov (United States)

    Yoon, Young Kyung; Yang, Kyung Sook; Lee, Seung Eun; Kim, Hyun Jeong; Sohn, Jang Wook; Kim, Min Ja

    2014-01-01

    Antimicrobial stewardship programs have been proposed for reducing bacterial resistance in the hospital environment. The purpose of this study was to investigate the impact of a carbapenem-use stewardship program on the susceptibility of Acinetobacter baumannii to Group 2 carbapenems. A before and after intervention study was conducted at a university hospital from September 2008 to February 2013. Three study periods were defined: Phase I, pre-intervention (months 1-18); Phase II, a postintervention period during which ertapenem use was mandated but carbapenem use was not restricted (months 19-36); and Phase III, a postintervention period during which Group 2 carbapenem use was restricted (months 37-54). During the study period, intervention resulted in diminished consumption of Group 2 carbapenems (antimicrobial use density (AUD): 21.3±6.0 in Phase I, 18.8±6.0 in Phase II, 16.1±4.4 in Phase III; P = 0.028) and increased consumption of ertapenem (AUD: 2.7±1.7 in Phase I, 7.2±4.5 in Phase II, 9.1±5.3 in Phase III; Pcarbapenem during the previous one month was positively and significantly associated with a subsequent increase in the proportion of carbapenem-resistant A. baumannii (CRAB) (P = 0.031). Implementing a carbapenem-use stewardship program featuring the preferential use of ertapenem for treating appropriate indications of infection resulted in reduced use of Group 2 carbapenems and had a positive impact on the susceptibility of A. baumannii to carbapenems. This approach could be integrated into CRAB-control strategies in hospitals.

  14. Wastewater as a Source of Carbapenem Resistant Escherichia coli

    Science.gov (United States)

    Clinical studies have reported that the occurrence of carbapenem resistant E. coli is on the rise. This is of concern because carbapenem antibiotics are typically reserved for treating infections caused by bacteria resistant to other classes of antibiotics. Current literature st...

  15. Outbreak of carbapenem-resistant Providencia rettgeri in a tertiary ...

    African Journals Online (AJOL)

    Carbapenem resistance in Enterobacteriaceae is often plasmid mediated, necessitating stringent infection control practices. We describe an outbreak of carbapenem-resistant Providencia rettgeri involving 4 patients admitted to intensive care and high-care units at a tertiary hospital. Clinical and demographic characteristics ...

  16. Outbreak of carbapenem-resistant Providencia rettgeri in a tertiary ...

    African Journals Online (AJOL)

    2017-01-31

    Jan 31, 2017 ... discharged, transmission from inanimate objects and healthcare workers is a ... Isolation of carbapenem-resistant NDM-1-positive Providencia rettgeri in Mexico. ... Australian Commission on Safety and Quality in Health Care.

  17. NNDSS - Table II. Carbapenemase-producing carbapenem-resistant Enterobacteriaceae

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Carbapenemase-producing carbapenem-resistant Enterobacteriaceae - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000...

  18. Audit of carbapenem prescriptions comparing 2 assessment periods.

    Science.gov (United States)

    Lefébure, A; Papy, E; Rioux, C; Diamantis, S; Armand-Lefèvre, L; Longuet, P; Lescure, F X; Wolff, M; Arnaud, P; Lucet, J C

    2015-07-01

    The emergence of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae has resulted in the increase of carbapenem prescriptions. The objective of our study was to determine the appropriateness of carbapenem prescriptions from initiation to reassessment of treatment, between 2009 and 2011. A questionnaire drafted by infectious diseases specialists (IDS) and microbiologists was used to collect clinical and microbiological data concerning carbapenem prescriptions in 2009 and 2011. An IDS then compared the results to assess carbapenem prescription compliance with our hospital's local recommendations. Seventy-one prescriptions were included in 2009 and 32 in 2011. The carbapenem treatment had been most frequently probabilistic to treat nosocomial infections. The microbiological data revealed that the number of multidrug-resistant (MDR) infections had increased between 2009 and 2011, especially infections involving ESBL-producing Enterobacteriaceae. At treatment reassessment, in 2009 and 2011, 15 (21%) and 12 (38%) carbapenem prescriptions were appropriate and continued. Overall, when comparing the 2 periods, prescriptions complied with local guidelines from initiation to reassessment of treatment without any statistically significant difference (68% in 2009 and 75% in 2011). Our study results showed that MDR infections had increased and especially infections due to ESBL-producing Enterobacteriaceae; this was consistent with epidemiological data. We also proved that most carbapenem prescriptions were compliant with recommendations. The increased mobile IDS interventions in medical and surgical departments helped reach this rate of compliance. Carbapenem stewardship may be promoted even in a difficult epidemiological context, especially with IDS interventions for the duration of treatment or at treatment reassessment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. Compliance with carbapenem guidelines in a university hospital.

    Science.gov (United States)

    Van Hollebeke, M; Chapuis, C; Bernard, S; Foroni, L; Stahl, J P; Bedouch, P; Pavese, P

    2016-03-01

    We aimed to evaluate carbapenem prescription compliance with guidelines for nosocomial and community-acquired infections. We conducted a prospective study over a four-month period at our university hospital. We included all adult and pediatric hospitalized patients who had received at least one dose of carbapenem. Data was collected from patients' medical records (hard copy and computerized data; CristalLink software). Compliance with guidelines was assessed by two infectious disease specialists. Assessment criteria included indication, antibiotic choice, dosage, and treatment duration. We included 152 patients in the study (65.4% of men). Carbapenem prescription was appropriate for 76.3% of prescriptions. The use of carbapenems was considered appropriate for 73.9% of empirical prescriptions and for 77.8% of documented prescriptions. Non-compliance with guidelines was mainly due to prescriptions for community-acquired infections. Antibiotic de-escalation could not be initiated in 40.3% of patients and was only initiated in 51.7% of patients for whom it could be considered. Although the average treatment duration was 7.5 days, 23.7% of patients received carbapenems for more than 10 days. These results highlight the need for a strong carbapenem stewardship program in our hospital. Copyright © 2016. Published by Elsevier SAS.

  20. Global prevalence of carbapenem resistance in neutropenic patients and association with mortality and carbapenem use: systematic review and meta-analysis.

    Science.gov (United States)

    Righi, Elda; Peri, Anna Maria; Harris, Patrick N A; Wailan, Alexander M; Liborio, Mariana; Lane, Steven W; Paterson, David L

    2017-03-01

    Carbapenem-resistant Gram-negative bacteria are recognized as a cause of difficult-to-treat infections associated with high mortality. To perform a systematic review of currently available data on distribution, characteristics and outcome associated with carbapenem-resistant bloodstream infections in adult neutropenic patients. Included studies were identified through Medline, Embase and Cochrane databases between January 1995 and April 2016. Random effect meta-analysis was used to quantify the association between carbapenem resistance and mortality and between carbapenem exposure and resistance. A total of 30 studies from 21 countries were included. Overall carbapenem resistance varied from 2% to 53% (median 9%) among studies. Infections due to carbapenem-resistant Pseudomonas spp . were reported in 18 (60%) studies showing high median resistance rates (44% of all carbapenem-resistant Gram-negatives and 19% of Pseudomonas isolates). Resistance of Enterobacteriaceae was less commonly reported and bloodstream infections due to carbapenem-resistant Klebsiella spp. were mainly documented from endemic areas (Greece, Italy, Israel). Carbapenem resistance in Acinetobacter spp. was reported in 9 (30%) studies (median resistance 58% of Acinetobacter isolates). Mortality rates ranged from 33% to 71% (median 50%) in patients with carbapenem-resistant infections. Carbapenem resistance appeared to correlate with mortality (OR 4.89, 95% CI 3.30-7.26) and previous exposure to carbapenems (OR 4.63, 95% CI 3.08-6.96). Carbapenem resistance represents a threat to neutropenic patients. In this group, resistance is likely promoted by previous carbapenem use and leads to high mortality rates. The knowledge of resistance patterns is crucial and can direct clinicians in the use of alternatives to carbapenem-based regimens. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please

  1. In vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin against carbapenem-resistant Acinetobacter baumannii clinical isolates.

    Science.gov (United States)

    Singkham-In, Uthaibhorn; Chatsuwan, Tanittha

    2018-01-31

    Carbapenem-resistant Acinetobacter baumannii clinical isolates (n=23) were investigated for carbapenem resistance mechanisms and in vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin. Major carbapenem resistance mechanism was OXA-23 production. The vast majority of these isolates were OXA-23-producing A. baumannii ST195 and ST542, followed by novel STs, ST1417, and ST1423. The interuption of carO by a novel insertion sequence, ISAba40, was found in two isolates. The combinations of imipenem and fosfomycin, meropenem and amikacin, imipenem and amikacin, and imipenem and colistin were synergistic against carbapenem-resistant A. baumannii by 65.2%, 46.2%, 30.8%, and 17.4%, respectively. Surprisingly, the combination of imipenem and fosfomycin was the most effective in this study against A. baumannii, which is intrinsically resistant to fosfomycin. Imipenem and fosfomycin inhibit cell wall synthesis; therefore, fosfomycin may be an adjuvant and enhance the inhibition of cell wall synthesis of carbapenem-resistant A. baumannii when combined with imipenem. Copyright © 2018. Published by Elsevier Inc.

  2. Carbapenem-Nonsusceptible Enterobacteriaceae in Taiwan

    Science.gov (United States)

    Wang, Jann-Tay; Wu, Un-In; Lauderdale, Tsai-Ling Yang; Chen, Mei-Chen; Li, Shu-Ying; Hsu, Le-Yin; Chang, Shan-Chwen

    2015-01-01

    A total of 1135 carbapenem-resistant (nonsusceptible) Enterobacteriaceae (CRE) isolates were recovered between November 2010 and July 2012 (517 from 2010-2011 and 618 from 2012) from 4 hospitals in Taiwan. Carbapenemase-producing Enterobacteriaceae (CPE) comprised 5.0% (57 isolates), including 17 KPC-2 (16 Klebsiella pneumoniae and 1 Escherichia coli), 1 NDM-1 (K. oxytoca), 37 IMP-8 (26 Enterobacter cloacae, 4 Citrobacter freundii, 4 Raoultella planticola, 1 K. pneumoniae, 1 E. coli and 1 K. oxytoca), and 2 VIM-1 (1 E. cloacae, 1 E. coli). The KPC-2-positive K. pneumoniae were highly clonal even in isolates from different hospitals, and all were ST11. IMP-8 positive E. cloacae from the same hospitals showed higher similarity in PFGE pattern than those from different hospitals. A total of 518 CRE isolates (45.6%) were positive for bla ESBL, while 704 (62.0%) isolates were bla AmpC-positive, 382 (33.6% overall) of which carried both bla ESBL and bla AmpC. CTX-M (414, 80.0%) was the most common bla ESBL, while DHA (497, 70.6%) and CMY (157, 22.3%) were the most common bla AmpC. Co-carriage of bla ESBL and bla AmpC was detected in 31 (54.4%) and 15 (26.3%) of the 57 CPE, respectively. KPC-2 was the most common carbapenemase detected in K. pneumoniae (2.8%), while IMP-8 was the most common in E. cloacae (9.7%). All KPC-2-positive CRE were resistant to all three tested carbapenems. However, fourteen of the 37 IMP-8-positive CRE were susceptible to both imipenem and meropenem in vitro. Intra- and inter-hospital spread of KPC-2-producing K. pneumoniae and IMP-8-producing E. cloacae likely occurred. Although the prevalence of CPE is still low, careful monitoring is urgently needed. Non-susceptibility to ertapenem might need to be considered as one criterion of definition for CRE in areas where IMP type carbapenemase is prevalent. PMID:25794144

  3. Recent advances in the chemistry and biology of carbapenem antibiotics.

    Science.gov (United States)

    Coulton, S; Hunt, E

    1996-01-01

    The discovery of the olivanic acids and thienamycin aroused considerable interest amongst medicinal chemists and microbiologists around the world. The susceptibility of these agents to metabolic degradation has, however, been a major obstacle in their development. For many years the only notable success from such intensive research was the combination of imipenem with cilastatin, an inhibitor of the renal dipeptidase enzyme DHP-1. The enormous success of Primaxin for the treatment of a range of life-threatening bacterial infections provided the impetus for the discovery of totally synthetic, non-natural carbapenem derivatives that combine the broad spectrum of antimicrobial activity with stability to enzymatic degradation. This has indeed been realised in the development of meropenem; it possesses the broad spectrum of activity and resistance to beta-lactamases that are embodied in imipenem as well as displaying increased stability to human dehydropeptidases. Most recent research has focused upon the development of carbapenem antibiotics which combine broad spectrum antimicrobial activity and metabolic stability with oral absorption, for the treatment of community-acquired infections. Indeed, the pro-drug esters of the tricyclic carbapenems represent the first significant advance in this respect. However, the increased use of carbapenem antibiotics would undoubtedly accelerate the emergence of carbapenem-hydrolysing enzymes. The ultimate challenge could therefore be the design and synthesis of carbapenem derivatives that are resistant to these metallo-beta-lactamases. Due to the enormous problems encountered in the development of the carbapenem antibiotics, this area of research has, in the past, been described as a battlefield that did not bode well for the future [181]. Primaxin and meropenem proved however that these problems were not insurmountable, and are therefore a testimony to the persistence and dedication of those scientists in their war against

  4. Comparative pharmacodynamics of four different carbapenems in combination with polymyxin B against carbapenem-resistant Acinetobacter baumannii.

    Science.gov (United States)

    Lenhard, Justin R; Gall, Jonathan S; Bulitta, Jurgen B; Thamlikitkul, Visanu; Landersdorfer, Cornelia B; Forrest, Alan; Nation, Roger L; Li, Jian; Tsuji, Brian T

    2016-12-01

    The objective of this study was to determine the comparative pharmacodynamics of four different carbapenems in combination with polymyxin B (PMB) against carbapenem-resistant Acinetobacter baumannii isolates using time-kill experiments at two different inocula. Two A. baumannii strains (03-149-1 and N16870) with carbapenem minimum inhibitory concentrations (MICs) ranging from 8 to 64 mg/L were investigated in 48-h time-kill experiments using starting inocula of 10 6  CFU/mL and 10 8  CFU/mL. Concentration arrays of ertapenem, doripenem, meropenem and imipenem at 0.25×, 0.5×, 1×, 1.5× and 2× published maximum serum concentration (C max ) values (C max concentrations of 12, 21, 48 and 60 mg/L, respectively) were investigated in the presence of 1.5 mg/L PMB. Use of carbapenems without PMB resulted in drastic re-growth. All carbapenem combinations were able to achieve a ≥3 log 10 CFU/mL reduction by 4 h against both strains at 10 6  CFU/mL, whereas maximum reductions against strain 03-149-1 at 10 8  CFU/mL were 1.0, 3.2, 2.2 and 3.3 log 10 CFU/mL for ertapenem, doripenem, meropenem and imipenem, respectively. None of the combinations were capable of reducing 10 8  CFU/mL of N16870 by ≥2 log 10 CFU/mL. Ertapenem combinations consistently displayed the least activity, whereas doripenem, meropenem and imipenem combinations had similar activities that were poorly predicted by carbapenem MICs. As doripenem, meropenem, or imipenem displayed similar pharmacodyanmics in combination, the decision of which carbapenem to use in combination with PMB may be based on toxicodynamic profiles if drastic discordance in MICs is not present. Copyright © 2016. Published by Elsevier B.V.

  5. The rapid spread of carbapenem-resistant Enterobacteriaceae.

    Science.gov (United States)

    Potter, Robert F; D'Souza, Alaric W; Dantas, Gautam

    2016-11-01

    Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids. Improved characterization helps detail the co-occurrence of other antibiotic resistance genes in CRE isolates and helps identify pan-drug resistance mechanisms. The novel β-lactamase inhibitor, avibactam, combined with ceftazidime or aztreonam, is a promising CRE treatment compared to current colistin or tigecycline regimens. To halt increasing CRE-associated morbidity and mortality, we must continue quality, cooperative monitoring and urgently investigate novel treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The rapid spread of carbapenem-resistant Enterobacteriaceae

    Science.gov (United States)

    Potter, Robert F.; D’Souza, Alaric W.; Dantas, Gautam

    2016-01-01

    Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids. Improved characterization helps detail the co-occurrence of other antibiotic resistance genes in CRE isolates and helps identify pan-drug resistance mechanisms. The novel β-lactamase inhibitor, avibactam, combined with ceftazidime or aztreonam, is a promising CRE treatment compared to current colistin or tigecycline regimens. To halt increasing CRE-associated morbidity and mortality, we must continue quality, cooperative monitoring and urgently investigate novel treatments. PMID:27912842

  7. [Risk factors for Pseudomonas aeruginosa infections, resistant to carbapenem].

    Science.gov (United States)

    Ghibu, Laura; Miftode, Egidia; Teodor, Andra; Bejan, Codrina; Dorobăţ, Carmen Mihaela

    2010-01-01

    Since their introduction in clinical practice,carbapenems have been among the most powerful antibiotics for treating serious infections cased by Gram-negative nosocomial pathogens, including Pseudomonas aeruginosa. The emergence of betalactamases with carbapenem-hydrolyzing activity is of major clinical concern. Pseudomonas aeruginosa is a leading cause of nosocomial infection. Risk factors for colonization with carbapenems-resistant Pseudomonas in hospital are: history of P. aeruginosa infection or colonization within the previous year, (length of hospital stay, being bedridden or in the ICU, mechanical ventilation, malignant disease, and history of chronic obstructive pulmonary disease have all been identified as independent risk factors for MDR P. aeruginosa infection. Long-term-care facilities are also reservoirs of resistant bacteria. Risk factors for colonization of LTCF residents with resistant bacteria included age > 86 years, antibiotic treatment in the previous 3 months, indwelling devices, chronic obstructive pulmonary disease, physical disability, and the particular LTCF unit.

  8. Characterization of carbapenem-nonsusceptible Klebsiella pneumoniae bloodstream isolates at a Taiwanese hospital: clinical impacts of lowered breakpoints for carbapenems.

    Science.gov (United States)

    Lee, N Y; Wu, J J; Lin, S H; Ko, W C; Tsai, L H; Yan, J J

    2012-08-01

    This study was conducted in order to characterize carbapenem-nonsusceptible Klebsiella pneumoniae isolates and to evaluate the impacts of recently lowered interpretative breakpoints for carbapenems for Enterobacteriaceae. Among 152 K. pneumoniae bloodstream isolates suspected as AmpC or extended-spectrum β-lactamase (ESBL) producers, 58 (38.2%) isolates were currently interpreted as nonsusceptible to ertapenem, imipenem, or meropenem, and 42 (72.4%) of them were categorized as carbapenem-susceptible by the previous criteria. The high revision rate was associated with the predominance (79.3%) of DHA-1 among the carbapenem-nonsusceptible isolates due to both polyclonal and clonal spread. ESBLs were common (~57%) in both ertapenem-susceptible and -nonsusceptible isolates; however, 84.8% of the carbapenem-nonsusceptible isolates were also AmpC producers. The IMP-8 metallo-β-lactamase was detected in three isolates. Polyacrylamide gel electrophoresis suggested decreased OmpK35 expression in all but one ertapenem-nonsusceptible isolate, and genetic disruptions of ompK35 and ompK36 were detected in 30 and six ertapenem-nonsusceptible isolates, respectively. A comparison between patients infected by AmpC- or ESBL-producing ertapenem-susceptible (n=62) isolates and those with isolates revised as ertapenem-nonsusceptible (n=41) revealed more cases of malignancies (36.6% versus 14.5%; p=0.01) and higher Charlson score (p=0.033) among the patients with ertapenem-nonsusceptible isolates; however, the acquisition of an isolate revised as carbapenem-nonsusceptible was not identified as an independent mortality risk factor.

  9. Investigating of four main carbapenem-resistance mechanisms in high-level carbapenem resistant Pseudomonas aeruginosa isolated from burn patients

    Directory of Open Access Journals (Sweden)

    Soodabeh Rostami

    2018-02-01

    Conclusion: Emerging antimicrobial resistance in burn wound bacterial pathogens is a serious therapeutic challenge for clinicians. In the present study, most of the isolates were MDR. This finding indicated an alarming spread of resistant isolates and suggested that infection control strategies should be considered. Resistance to carbapenems is influenced by several factors, not all of which were evaluated in our study; however, the results showed that production of MBLs and overexpression of the mexB gene were the most frequent mechanisms in carbapenem-resistant isolates.

  10. Widespread increase of empirical carbapenem use in acute care hospitals in Catalonia, Spain.

    Science.gov (United States)

    Grau, Santiago; Fondevilla, Esther; Echeverría-Esnal, Daniel; Alcorta, Amaia; Limon, Enric; Gudiol, Francesc

    2018-04-24

    The overall increase in the use of carbapenems could lead to the selection of carbapenem-resistant bacteria. The objectives of this study were to analyze carbapenem use from 2008 to 2015 and their prescription profile in 58 hospitals affiliated to the VINCat Programme (nosocomial infection vigilance system). Retrospective, longitudinal and descriptive study of carbapenem use. Consecutive case-series study, looking for carbapenem prescription characteristics, conducted in January 2016. Use was calculated in defined daily doses (DDD)/100 patient-days (PD); prescription profiles were assessed using a standardized survey. Carbapenem use increased 88.43%, from 3.37 DDD/100-PD to 6.35 DDD/100-PD (pCatalonia. Stewardship interventions are required to prevent carbapenem overuse. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  11. Factors associated with acquisition of carbapenem-resistant Enterobacteriaceae

    Directory of Open Access Journals (Sweden)

    Lilian Silva Lavagnoli

    2017-10-01

    Full Text Available ABSTRACT Objective: to identify possible risk factors for acquisition of Enterobacterial strains with a marker for resistance to carbapenems. Methods: exploratory case-control study performed in hospital settings. The study sample consisted of patients with biological specimens that tested positive for carbapenem-resistant Enterobacteriaceae (cases, with the disk diffusion test and Etest, and controls with biological samples testing negative for carbapenem-resistant Enterobacteriaceae. In all, 65 patients were included: 13 (20% cases and 52 (80% controls. Results: the microorganisms isolated were Serratia marcescens (6, Klebsiella pneumoniae (4, and Enterobacter cloacae (3. Univariate analysis revealed that length of hospitalization prior to sample collection (p=0.002 and having a surgical procedure (p=0.006 were statistically significant. In the multivariable logistic regression model, both were still significant, with odds ratios of 0.93 (p = 0.009; 95% CI: 0.89 to 0.98 for length of hospitalization prior to sample collection, and 9.28 (p = 0.05; 95% CI: 1.01 to 85.14 for having a surgical procedure. Conclusion: shorter hospitalization times and increased surveillance of patients undergoing surgery could play a decisive role in reducing the spread of carbapenem-resistant microorganisms in hospital settings.

  12. Deaths Attributable to Carbapenem-Resistant Enterobacteriaceae Infections

    Centers for Disease Control (CDC) Podcasts

    2014-08-06

    Dr. Mike Miller reads an abridged version of the article, Deaths Attributable to Carbapenem-Resistant Enterobacteriaceae Infections.  Created: 8/6/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/13/2014.

  13. Invasive carbapenem-resistant Enterobacteriaceae infection at a ...

    African Journals Online (AJOL)

    Background. There are no paediatric reports of invasive infection caused by carbapenem-resistant Enterobacteriaceae (CRE) from Africa. Objectives. To document a series of cases of CRE infections at a tertiary children's hospital in Cape Town, South Africa, describing the clinical and microbiological findings in these ...

  14. The outcome of non-carbapenem-based empirical antibacterial ...

    African Journals Online (AJOL)

    Background: Febrile neutropenia (FN) is generally a complication of cancer chemotherapy. Objective: ... Furthermore, non-carbapenem-based empirical therapy provides benefit in regard to cost-effectiveness and antimicrobial stewardship when local antibiotic resistance patterns of gram-negative bacteria are considered.

  15. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 721 ... Vol 21, No 1 (2015), Antimicrobial susceptibility of urinary Klebsiella pneumoniae and the emergence of carbapenem-resistant strains: A retrospective study from a university hospital in Morocco, North Africa, Abstract PDF. MC El Bouamri, L Arsalane, Y El Kamouni, S Zouhair. Vol 23, No 2 (2017) ...

  16. ST37 Klebsiella pneumoniae: development of carbapenem resistance in vivo during antimicrobial therapy in neonates.

    Science.gov (United States)

    Li, Pengling; Wang, Min; Li, Xianping; Hu, Feihu; Yang, Min; Xie, Yixin; Cao, Wei; Xia, Xiaomeng; Zheng, Rong; Tian, Jingjing; Zhang, Kan; Chen, Fang; Tang, Aiguo

    2017-08-01

    To investigate the mechanism leading to in vivo carbapenem resistance development in Klebsiella pneumoniae. Carbapenemase was detected using the modified carbapenem inactivation method. β-lactamases resistant genes were identified by PCR and sequencing. Clonal relatedness was evaluated by random amplified polymorphic DNA and multiple locus sequence typing. The relationship between sequence typing and resistant genes was analyzed by using the chi-squared test. All ST37 carbapenem-resistant isolates were bla OXA-1 positive and all ST37 carbapenem-sensitive isolates were bla OXA-1 negative at Stage I. A significant relationship between carbapenem resistance and bla OXA-1 was observed. The bla OXA-1 -positive rate was significantly higher in ST37 K. pneumoniae than others. This is the first study about the development of carbapenem resistance in vivo potentially mediated by bla OXA-1 in ST37 K. pneumoniae among neonates.

  17. Clinical and Epidemiological Significance of Carbapenem Resistance in Acinetobacter baumannii Infections.

    Science.gov (United States)

    Tal-Jasper, Ruthy; Katz, David E; Amrami, Nadav; Ravid, Dor; Avivi, Dori; Zaidenstein, Ronit; Lazarovitch, Tsilia; Dadon, Mor; Kaye, Keith S; Marchaim, Dror

    2016-05-01

    Carbapenems are considered the treatment of choice for Acinetobacter baumannii infections. Many facilities implement preventive measures toward only carbapenem-resistant A. baumannii (CRAB). However, the independent role of the carbapenem resistance determinant on patient outcomes remains controversial. In a 6-year analysis of adults with A. baumannii bloodstream infection (BSI), the outcomes of 149 CRAB isolates were compared to those of 91 patients with carbapenem-susceptible A. baumannii In bivariable analyses, CRAB BSIs were significantly associated with worse outcomes and with a delay in the initiation of appropriate antimicrobial therapy (DAAT). However, in multivariable analyses, carbapenem resistance status was no longer associated with poor outcomes, while DAAT remained an independent predictor. The epidemiological significance of A. baumannii should not be determined by its resistance to carbapenems. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  18. EFFECT OF TOBRACEF IN CARBAPENEM RESISTANT PNEUMONIA INFECTION

    OpenAIRE

    A. Ahmad, V.K. Dwivedi * , and M. Chaudhary

    2010-01-01

    To determine ef ect of Tobracef and imipenem drug on antioxidant enzyme actvity and lipid peroxidation leveland some biochemical parametrs in carbapenem resistant pneumonia infection rat model. Total 40 rats wereselected and diveded into 4 groups of 10 rats each. Group I was control group; group II was infected via A.baumanni bacterial strain. Group III and IV were infected plus treated group with tobracef and imipenemdrugs.Our results showed that a significant (p

  19. The risk of seizures among the carbapenems: a meta-analysis.

    Science.gov (United States)

    Cannon, Joan P; Lee, Todd A; Clark, Nina M; Setlak, Paul; Grim, Shellee A

    2014-08-01

    A consensus exists among clinicians that imipenem/cilastatin is the most epileptogenic carbapenem, despite inconsistencies in the literature. We conducted a meta-analysis of all randomized controlled trials comparing carbapenems with each other or with non-carbapenem antibiotics to assess the risk of seizures for imipenem, meropenem, ertapenem and doripenem. In the risk difference (RD) analysis, there were increased patients with seizure (2 per 1000 persons, 95% CI 0.001, 0.004) among recipients of carbapenems versus non-carbapenem antibiotics. This difference was largely attributed to imipenem as its use was associated with an additional 4 patients per 1000 with seizure (95% CI 0.002, 0.007) compared with non-carbapenem antibiotics, whereas none of the other carbapenems was associated with increased seizure. Similarly, in the pooled OR analysis, carbapenems were associated with a significant increase in the risk of seizures relative to non-carbapenem comparator antibiotics (OR 1.87, 95% CI 1.35, 2.59). The ORs for risk of seizures from imipenem, meropenem, ertapenem and doripenem compared with other antibiotics were 3.50 (95% CI 2.23, 5.49), 1.04 (95% CI 0.61, 1.77), 1.32 (95% CI 0.22, 7.74) and 0.44 (95% CI 0.13, 1.53), respectively. In studies directly comparing imipenem and meropenem, there was no difference in epileptogenicity in either RD or pooled OR analyses. The absolute risk of seizures with carbapenems was low, albeit higher than with non-carbapenem antibiotics. Although imipenem was more epileptogenic than non-carbapenem antibiotics, there was no statistically significant difference in the imipenem versus meropenem head-to-head comparison. © 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.

  20. Biofilm Production in Carbapenem Resistant Isolates from Chronic Wound Infections

    Directory of Open Access Journals (Sweden)

    Swarna SR

    2017-02-01

    Full Text Available Biofilms are communities of microorganisms covered with extracellular polymeric substances. Such biofilm phenotype makes the microorganism resistant to antibiotics and plays a role in wound chronicity. This results in prolonged hospital stays in ICU, greater cost, and increased mortality. Methods: Pus swabs (59 were collected from a tertiary care hospital near Chennai were processed and identified using standard procedure followed by antibiotic susceptibility testing and identification of carbapenem resistance by Modified Hodge test as per CLSI guidelines. The biofilm formation was tested using plastic microtiter plate method. Results: Out of 59 pus swabs, 51 yielded growth with 69 isolates and 8 yielded no growth. Among the 69 isolates, 51 were GNB and 18 were GPC. Biofilm detection was noted in 84.31% (43/51 GNB isolates with 0.1% crystal violet whereas 100% (51/51 showed biofilm positive with 0.1% safranin. About 74.50% (38/51 isolates of GNB were carbapenem resistant by screening with disk diffusion method. Only 24% (6/25 of GNB isolates among Enterobacteriaceae were positive by Modified Hodge test method. Conclusion: The result shows the association of biofilm production among carbapenem resistant isolates obtained from chronic wound infections.

  1. Emergence and nosocomial spread of carbapenem-resistant OXA-232-producing Klebsiella pneumoniae in Brunei Darussalam

    NARCIS (Netherlands)

    Abdul Momin, Muhd Haziq Fikry; Liakopoulos, Apostolos; Phee, Lynette M.; Wareham, David W.

    2017-01-01

    Objectives Carbapenem-resistant Enterobacteriaceae (CRE) are identified as a major global health concern. The success of CRE is facilitated by the emergence, acquisition and spread of successful clones carrying plasmid-encoded resistance genes. In this study, an outbreak of carbapenem-resistant

  2. Wastewater as a Source of Carbapenem-Resistant E. coli (Webinar)

    Science.gov (United States)

    Clinical studies have reported that the occurrence of carbapenem-resistant E. coli is on the rise. This is of concern because carbapenem antibiotics are typically reserved for treating infections caused by bacteria resistant to other classes of antibiotics. Current literature st...

  3. Acquisition of carbapenem resistance by plasmid-encoded-AmpC-expressing Escherichia coli

    NARCIS (Netherlands)

    Tommassen - van Boxtel, Ria; Wattel, Agnes A.; Arenas Busto, Jesus; Goessens, Wil H.F.; Tommassen, J

    2017-01-01

    Although AmpC β-lactamases can barely degrade carbapenems, if at all, they can sequester them and prevent them from reaching their targets. Thus, carbapenem resistance in Escherichia coli and other Enterobacteriaceae can result from AmpC production and simultaneous reduction of antibiotic influx

  4. Clinical laboratory detection of carbapenem-resistant and carbapenemase-producing Enterobacteriaceae.

    Science.gov (United States)

    Miller, Shelley; Humphries, Romney M

    2016-08-01

    Carbapenemases, enzymes that hydrolyze carbapenem-class antimicrobials, pose serious clinical and diagnostic challenges, including their recent rapid spread among members of the Enterobacteriaceae, a family with no inherent carbapenem resistance. Currently there is no one-size-fits-all method for detecting carbapenem-resistant Enterobacteriaceae (CRE) in the laboratory, nor how to differentiate carbapenemase-producers (CP) from isolates that are carbapenem-resistant via other or combined mechanisms. This article reviews definitions for CRE and CP-CRE, and discusses current phenotypic and molecular methods available to the clinical laboratory for the detection of both CP and non-CP CRE. Expert commentary: Routine evaluation of carbapenem resistance mechanism by the routine clinical laboratory are not necessary for patient care, as clinical breakpoints best predict response. However, evaluation for carbapenemase is integral to infection control efforts, and laboratories should have the capacity to do such testing, either in house or by submitting isolates to a reference laboratory.

  5. Carbapenem-resistant Klebsiella pneumoniae colonization in pediatric and neonatal intensive care units: risk factors for progression to infection.

    Science.gov (United States)

    Akturk, Hacer; Sutcu, Murat; Somer, Ayper; Aydın, Derya; Cihan, Rukiye; Ozdemir, Aslı; Coban, Asuman; Ince, Zeynep; Citak, Agop; Salman, Nuran

    2016-01-01

    Little is known about factors associated with carbapenem-resistant Klebsiella pneumoniae infections in pediatric patients, who are initally colonized with carbapenem-resistant Klebsiella pneumoniae. A retrospective case-control study was conducted involving pediatric and neonatal intensive care units throughout a five-year period (January 2010-December 2014). Clinical and microbiological data were extracted from Hospital Infection Control Committee reports and patients' medical records. Risk factors were assessed in carbapenem-resistant Klebsiella pneumoniae colonized patients who developed subsequent systemic infection (cases) and compared to carbapenem-resistant Klebsiella pneumoniae colonized patients who did not develop infection (controls). Throughout the study period, 2.6% of patients admitted to neonatal intensive care units and 3.6% of patients admitted to pediatric intensive care units had become colonized with carbapenem-resistant Klebsiella pneumoniae. After a mean of 10.6±1.9 days (median: 7 days, range: 2-38 days) following detection of colonization, 39.0% of the carbapenem-resistant Klebsiella pneumoniae colonized patients in pediatric intensive care units and 18.1% of carbapenem-resistant Klebsiella pneumoniae colonized patients in neonatal intensive care units developed systemic carbapenem-resistant Klebsiella pneumoniae infection. Types of systemic carbapenem-resistant Klebsiella pneumoniae infections included bacteremia (n=15, 62.5%), ventilator-associated pneumonia (n=4, 16.6%), ventriculitis (n=2, 8.3%), intraabdominal infections (n=2, 8.3%), and urinary tract infection (n=1, 4.1%). A logistic regression model including parameters found significant in univariate analysis of carbapenem resistant Klebsiella pneumoniae colonization and carbapenem resistant Klebsiella pneumoniae infection groups revealed underlying metabolic disease (OR: 10.1; 95% CI: 2.7-37.2), previous carbapenem use (OR: 10.1; 95% CI: 2.2-40.1), neutropenia (OR: 13.8; 95% CI: 3

  6. OXA beta-lactamase-mediated carbapenem resistance in Acinetobacter baumannii

    Directory of Open Access Journals (Sweden)

    S M Amudhan

    2011-01-01

    Full Text Available Objectives: Acinetobacter baumannii is a significant pathogen in health care settings. In recent years, an increase in carbapenem resistance among A. baumannii due to Ambler class B metallo-beta-lactamases or class D OXA carbapenamases has been reported. In this study we detected the presence of OXA carbapenamases and coproduction of metallo-beta-lactamases (blaVIM and blaIMP by phenotypic and genotypic methods in carbapenem resistant clinical isolates of Acinetobacter baumannii. Materials and Methods: A total of 116 consecutive, non-duplicate carbapenem resistant A. baumannii isolated from various clinical specimens were included in the study. The modified Hodge test and inhibitor potentiated disk diffusion tests were done for the screening of carbapenamase and metallo-beta-lactamase production, respectively. Polymerase chain reaction (PCR was performed for the detection of OXA (blaOXA 23 like, blaOXA 24 like, blaOXA-51 like and blaOXA-58 like genes and metallo-beta-lactamases (blaVIM and blaIMP genes. Gene sequencing was performed for representative isolates. Results: Among 116 A. baumannii, OXA genes were detected in 106 isolates. BlaOXA 51 like (n = 99 and blaOXA -23 like (n = 95 were the most common and they coexisted in 89 isolates. blaOXA-24 like gene was detected in two isolates of which one also carried blaOXA-51 like and blaOXA-58 like genes. The modified Hodge test was positive in 113 isolates. The metallo-beta-lactamase screening test was positive in 92 isolates. blavim was detected in 54 isolates of which 1 also carried the blaIMP gene. Conclusions: blaOXA-23 like and bla OXA 51 like genes are the most common types of OXA carbapenamases while the blaVIM type is the most common type of metallo-beta-lactamase contributing to carbapenem resistance in clinical isolates of A. baumannii. The coproduction of OXA and metallo-beta-lactamases is not an uncommon phenomenon in A. baumannii.

  7. Correlation between carbapenem consumption and resistance to carbapenems among Enterobacteriaceae isolates collected from patients with intra-abdominal infections at five medical centers in Taiwan, 2006-2010.

    Science.gov (United States)

    Ho, Cheng-Mao; Ho, Mao-Wang; Liu, Yung-Ching; Toh, Han-Siong; Lee, Yu-Lin; Liu, Yuag-Meng; Huang, Chi-Chang; Lu, Po-Liang; Liu, Chun-Eng; Chen, Yen-Hsu; Ko, Wen-Chien; Tang, Hung-Jen; Yu, Kwok-Woon; Chen, Yao-Shen; Chuang, Yin-Ching; Wang, Jen-Hsien; Hsueh, Po-Ren

    2012-06-01

    We investigated the trend in resistance to carbapenems among isolates of Enterobacteriaceae that had been collected from patients with intra-abdominal infections at five medical centers in Taiwan from 2006 to 2010 and evaluated the correlation between resistance to carbapenems and consumption of said agents as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). During the study period, the usage of ertapenem and that of total carbapenems (ertapenem, imipenem, and meropenem) increased significantly from 6.13 to 13.38 defined daily doses per 1000 patient-days for ertapenem and from 20.43 to 34.25 defined daily doses per 1000 patient-days for total carbapenems. The most common species were Escherichia coli (n = 1095), Klebsiella spp. (n = 663), and Enterobacter spp. (n = 202). The susceptibility of all isolates to ertapenem and to imipenem varied during the study period. For ertapenem, the rates of nonsusceptibility ranged from 3.5% to 10.3% and those for imipenem ranged from 3.5% to 10.7%. Although the use of carbapenems increased during the study period, there was no marked increase in resistance to carbapenems. Continuous monitoring of resistance trends is necessary so that antimicrobial prescription policies can be adjusted and infection control intervention programs can be implemented. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Browse Title Index

    African Journals Online (AJOL)

    2004): Special Issue 2004, Differential production of immune parameters by mouse strains ... agglutination and complement fixation tests in the field diagnosis ... List All Titles · Free To Read Titles This Journal is Open Access.

  9. Title IX Resource Guide

    Science.gov (United States)

    Office for Civil Rights, US Department of Education, 2015

    2015-01-01

    Title IX of the Education Amendments of 1972 (Title IX) prohibits discrimination based on sex in education programs and activities in federally funded schools at all levels. If any part of a school district or college receives any Federal funds for any purpose, all of the operations of the district or college are covered by Title IX. The essence…

  10. Carbapenem Breakpoints for Acinetobacter baumannii Group: Supporting Clinical Outcome Data from Patients with Bacteremia.

    Science.gov (United States)

    Lee, Yi-Tzu; Chiang, Mei-Chun; Kuo, Shu-Chen; Wang, Yung-Chih; Lee, I-Hsin; Chen, Te-Li; Yang, Ya-Sung

    2016-01-01

    The carbapenem breakpoints set by different organizations for Acinetobacter are discordant, but supporting clinical data are lacking. This study aimed to provide the first clinical outcome data to support the carbapenem breakpoints for Acinetobacter baumannii (Ab) group in patients with bacteremia. This study included 117 adults who received carbapenems for treatment of Ab group bacteremia in Taipei Veterans General Hospital over an 8-year period. We analyzed 30-day mortality rates among patient groups acquiring isolates with different carbapenem minimal inhibitory concentrations (MICs). The carbapenem MIC breakpoint derived from classification and regression tree (CART) analysis to delineate the risk of 30-day mortality was between MICs of ≤ 4 mg/L and ≥ 8 mg/L. Mortality rate was higher in patients acquiring isolates with carbapenem MIC ≥ 8 mg/L than ≤ 4 mg/L, by bivariate (54.9% [28/51] vs 25.8% [17/66]; P = 0.003) and survival analysis (P = 0.001 by log-rank test). Multivariate analysis using logistic regression and Cox regression models including severity of illness indices demonstrated that treating patients with Ab group bacteremia caused by isolates with a carbapenem MIC ≥ 8 mg/L with carbapenem was an independent predictor of 30-day mortality (odds ratio, 5.125; 95% confidence interval [CI], 1.946-13.498; P = 0.001, and hazard ratio, 2.630; 95% CI, 1.431-4.834; P = 0.002, respectively). The clinical outcome data confirmed that isolates with MIC ≤ 4 mg/L were susceptible to carbapenem, and those with MIC ≥ 8 mg/L were resistant in patients with Ab group bacteremia.

  11. Phenotypic characterization and colistin susceptibilities of carbapenem-resistant of Pseudomonas aeruginosa and Acinetobacter spp.

    Science.gov (United States)

    Mohanty, Srujana; Maurya, Vijeta; Gaind, Rajni; Deb, Monorama

    2013-11-15

    Pseudomonas aeruginosa and Acinetobcter spp. are important nosocomial pathogens and carbapenem resistance is an emerging threat. Therapeutic options for infections with these isolates include colistin. This study was conducted to determine the prevalence of carbapenem resistance in P. aeruginosa and Acinetobacter spp. bloodstream isolates, phenotypically characterize the resistance mechanisms and evaluate the in vitro activity of colistin. Consecutive 145 (95 P.aeruginosa and 50 Acinetobacter spp.) non-repeat isolates were included. Antibiotic susceptibility testing was performed per CLSI guidelines. MIC for carbapenems and colistin was performed using Etest. Isolates showing reduced susceptibility or resistance to the carbapenems were tested for metallo-β-lactamase (MBL) production using imipenem-EDTA combined disk and MBL Etest. Carbapenem resistance was observed in 40% P. aeruginosa and 66.0% Acinetobacter spp. Carbapenem-resistant (CA-R) isolates were significantly (p carbapenem-susceptible isolates. Approximately half of the CA-R strains were multidrug-resistant, and 3.1-5.5% were resistant to all antibiotics tested. MBL was found in 76.3% and 69.7% of the P. aeruginosa and Acinetobacter spp., respectively. Colistin resistance was observed in three (6.0%) Acinetobacter isolates and eight (8.4%) P. aeruginosa. MIC50 for carbapenems were two to four times higher for MBL-positive compared to MBL-negative isolates, but no difference was seen in MIC for colistin. Carbapenem resistance was observed to be mediated by MBL in a considerable number of isolates. Colistin is an alternative for infections caused by CA-R isolates; however, MIC testing should be performed whenever clinical use of colistin is considered.

  12. Comparative activity of carbapenem testing (the COMPACT study in Turkey

    Directory of Open Access Journals (Sweden)

    Leblebicioglu Hakan

    2012-02-01

    Full Text Available Abstract Background Recent evidence indicates that Gram-negative bacterial pathogens, the most common of which are Pseudomonas spp., Enterobacteriaceae, and Acinetobacter baumannii, are frequent causes of hospital-acquired infections. This study aims to evaluate the in vitro activity of doripenem and comparator carbapenem antibiotics against Gram-negative clinical isolates collected from COMParative Activity of Carbapenem Testing (COMPACT study centres in Turkey. Methods Ten centres in Turkey were invited to submit Pseudomonas aeruginosa, Enterobacteriaceae, and other Gram-negative isolates from intensive care unit (ICU/non-ICU patients with complicated intra-abdominal infections, bloodstream infections, or nosocomial pneumonia, including ventilator-associated pneumonia, between May and October 2008. Susceptibility was determined by each centre using E-test. A central laboratory performed species confirmation as well as limited susceptibility and quality-control testing. Results Five hundred and ninety six isolates were collected. MIC90 values for doripenem, meropenem, and imipenem, respectively, were 32, ≥ 64, and ≥ 64 mg/L against Pseudomonas spp.; 0.12, 0.12, and 0.5 mg/L against Enterobacteriaceae; and ≥ 64 mg/L for each against other Gram-negative isolates. In determining the susceptibility of hospital isolates of selected Gram-negative pathogens to doripenem, imipenem, and meropenem, we found that against all pathogens combined, the MIC90 for ICU compared with non-ICU isolates was higher. Conclusions Doripenem showed similar or slightly better activity than meropenem and better activity than imipenem against the Gram-negative pathogens collected in Turkey.

  13. Outbreak of carbapenem-resistant Providencia rettgeri in a tertiary hospital

    Directory of Open Access Journals (Sweden)

    V S Tshisevhe

    2017-01-01

    Full Text Available The emergence of resistance to multiple antimicrobial agents in pathogenic bacteria is a significant public health threat, as there are limited effective antimicrobial agents for infections caused by multidrug-resistant (MDR bacteria. Several MDR bacteria are now frequently detected. Carbapenem resistance in Enterobacteriaceae is often plasmid mediated, necessitating stringent infection control practices. We describe an outbreak of carbapenem-resistant Providencia rettgeri involving 4 patients admitted to intensive care and high-care units at a tertiary hospital. Clinical and demographic characteristics of 4 patients with carbapenem-resistant P. rettgeri were documented. All P. rettgeri isolated in these cases had a carbapenem-resistant antibiogram, with resistance to imipenem, ertapenem and meropenem. These cases could be epidemiologically linked. A multiprong approach, simultaneously targeting antibiotic stewardship, universal precautions and appropriate transmission-based precaution practices, is integral to prevention and control of nosocomial infections.

  14. Effects of Carbapenem consumption on the prevalence of Acinetobacter infection in intensive care unit patients.

    Science.gov (United States)

    Ogutlu, Aziz; Guclu, Ertugrul; Karabay, Oguz; Utku, Aylin Calica; Tuna, Nazan; Yahyaoglu, Mehmet

    2014-01-09

    The consumption of carbapenems has increased worldwide, together with the increase in resistant gram negative bacilli. Subsequently, the prevalence of carbapenem-resistant Acinetobacter infections has increased rapidly and become a significant problem particularly in intensive care unit patients. The aim of the present study was to evaluate the changes in the prevalence of Acinetobacter infection by restricting the consumption of carbapenems in intensive care unit patients. This study was conducted between May 1, 2011 and February 28, 2013. The amount of carbapenem consumption and the number of patients with multi-drug resistant Acinetobacter baumannii (MDRAB) isolates during the study period were retrospectively obtained from the records of the patients, who were hospitalized in the intensive care unit. The study period was divided into two periods named as: Carbapenem non-restricted period (CNRP) and carbapenem-restricted period (CRP). During CNRP, no restrictions were made on the use of carbapenems. During CRP, the use of carbapenems was not allowed if there was an alternative to carbapenems. Primary Endpoint: MDRAB infection after ICU admission. The definition of nosocomial infections related to Acinetobacter spp. was based on the criteria of the Center for Disease Control (CDC). The correlation between the amount of carbapenem consumption and the number of infections with MDRAB strains between the two periods were evaluated. During the study period, a total of 1822 patients' (1053 patients in CNRP and 769 patients in CRP) records were evaluated retrospectively. A total of 10.82 defined daily dose (DDD/100 ICU days) of anti-pseudomonal carbapenem were used in CNRP, and this figure decreased to 6.95 DDD/100 ICU days in CRP. In the 8-month CNRP, 42 (3.98%) MDRAB-related nosocomial infections were detected, and 14 (1.82%) infections were detected in CRP (p = 0.012). The prevalence of MDRAB strains isolated in the CNRP was 2.24-fold higher than the prevalence in

  15. Transrectal ultrasound-guided biopsy sepsis and the rise in carbapenem antibiotic use.

    Science.gov (United States)

    Leahy, Olivia R; O'Reilly, Mary; Dyer, David R; Phillips, David; Grummet, Jeremy P

    2015-12-01

    This study sought to determine the number of hospital admissions for sepsis following transrectal ultrasound-guided (TRUS) biopsy, and the rate of both prophylactic and therapeutic use of carbapenem antibiotics for TRUS biopsy, at a single institution. A retrospective review of prospectively collected data from the medical records electronic database of Cabrini Health, a private metropolitan hospital, was queried for coding of admissions under any admitting urologist for sepsis and prostate-related infections from 2009 to 2012. Records were examined for whether a TRUS biopsy had been performed within 14 days prior and if a therapeutic carbapenem was required. The database also queried the use of carbapenems as prophylaxis in patients undergoing TRUS biopsy. Of the 63 admissions for TRUS biopsy sepsis, multi-drug-resistant organisms were isolated from 26 (41%). Twenty-three admissions were from the 1937 patients who underwent a TRUS biopsy at Cabrini (a sepsis rate of 1.2%) and 40 were following TRUS biopsies at other centres. Thirty-seven (58.7%) patients received therapeutic carbapenems either empirically, or after culture results. Of the 1937 Cabrini TRUS biopsy patients, 154 (8%) were given a carbapenem as prophylaxis, with a rapid increase in prophylactic use over the 4 years studied from 0.25% to 13%. This study did not show evidence of an increasing rate of hospital admissions for TRUS biopsy sepsis at this institution. However, there was a dramatic uptake in prophylactic administration of carbapenems. Increasing carbapenem use may contribute to development of carbapenem-resistant bacteria. Alternative methods of prostate biopsy that avoid sepsis should be considered. © 2014 Royal Australasian College of Surgeons.

  16. Molecular epidemiology of carbapenem non-susceptible Acinetobacter nosocomialis in a medical center in Taiwan.

    Science.gov (United States)

    Yang, Ya-Sung; Lee, Yi-Tzu; Wang, Yung-Chih; Chiu, Chun-Hsiang; Kuo, Shu-Chen; Sun, Jun-Ren; Yin, Ti; Chen, Te-Li; Lin, Jung-Chung; Fung, Chang-Phone; Chang, Feng-Yee

    2015-04-01

    The mechanism by which carbapenem non-susceptible Acinetobacter nosocomialis (CNSAN) is disseminated is rarely described in the literature. In this study, we delineated the molecular epidemiology of CNSAN isolated from patients in a medical center in Taiwan. Fifty-four non-duplicate bloodstream isolates of CNSAN were collected at the Taipei Veterans General Hospital between 2001 and 2007. Pulsed-field gel electrophoresis (PFGE) was performed to determine their clonal relationship. Carbapenem-resistance genes and associated genetic structures were detected by polymerase chain reaction (PCR) mapping. Southern hybridization was performed to determine the plasmid location of carbapenem-resistance genes. Transmissibility of these genes to Acinetobacterbaumannii was demonstrated by conjugation tests. The overall carbapenem non-susceptibility rate among A. nosocomialis isolates during the study period was 21.6% (54/250). PFGE revealed three major pulsotypes: H (n=23), I (n=10), and K (n=8). The most common carbapenem-resistance gene was blaOXA-58 (43/54, 79.6%), containing an upstream insertion sequence IS1006 and a truncated ISAba3 (IS1006-ΔISAba3-like-blaOXA-58). All isolates belonging to the pulsotypes H, I, and K carried plasmid located IS1006-ΔISAba3-like-blaOXA-58. A common plasmid carrying ISAba1-blaOXA-82 was found in six isolates, which belonged to five pulsotypes. A type 1 integron that carried blaIMP-1 was detected in different plasmids of seven isolates, which belonged to five pulsotypes. Plasmids carrying these carbapenem-resistant determinants were transmissible from A. nosocomialis to A. baumannii via conjugation. In this medical center, CNSAN mainly emerged through clonal dissemination; propagation of plasmids and integrons carrying carbapenem-resistant determinants played a minor role. This study showed that plasmids carrying carbapenem-resistant determinants are transmissible from A. nosocomialis to A. baumannii. Copyright © 2015 Elsevier B.V. All

  17. A general reaction mechanism for carbapenem hydrolysis by mononuclear and binuclear metallo-β-lactamases.

    Science.gov (United States)

    Lisa, María-Natalia; Palacios, Antonela R; Aitha, Mahesh; González, Mariano M; Moreno, Diego M; Crowder, Michael W; Bonomo, Robert A; Spencer, James; Tierney, David L; Llarrull, Leticia I; Vila, Alejandro J

    2017-09-14

    Carbapenem-resistant Enterobacteriaceae threaten human health, since carbapenems are last resort drugs for infections by such organisms. Metallo-β-lactamases (MβLs) are the main mechanism of resistance against carbapenems. Clinically approved inhibitors of MBLs are currently unavailable as design has been limited by the incomplete knowledge of their mechanism. Here, we report a biochemical and biophysical study of carbapenem hydrolysis by the B1 enzymes NDM-1 and BcII in the bi-Zn(II) form, the mono-Zn(II) B2 Sfh-I and the mono-Zn(II) B3 GOB-18. These MβLs hydrolyse carbapenems via a similar mechanism, with accumulation of the same anionic intermediates. We characterize the Michaelis complex formed by mono-Zn(II) enzymes, and we identify all intermediate species, enabling us to propose a chemical mechanism for mono and binuclear MβLs. This common mechanism open avenues for rationally designed inhibitors of all MβLs, notwithstanding the profound differences between these enzymes' active site structure, β-lactam specificity and metal content.Carbapenem-resistant bacteria pose a major health threat by expressing metallo-β-lactamases (MβLs), enzymes able to hydrolyse these life-saving drugs. Here the authors use biophysical and computational methods and show that different MβLs share the same reaction mechanism, suggesting new strategies for drug design.

  18. [Carbapenem antibiotics in hospitalised paediatric patients. Adherence to a therapeutic protocol].

    Science.gov (United States)

    Montesinos-Sanchis, Elena; Moraga-Llop, Fernando A; Soler-Palacín, Pere; Oliveras-Arenas, María; Larrosa Escartín, M Nieves; Martínez Gómez, Xavier; Figueras-Nadal, Concepción

    2014-12-01

    To describe the use of carbapenems in children hospitalised outside intensive care and onco-haematology units, and assess adherence to a therapeutic protocol. A retrospective observational study was conducted on the use of carbapenems between January 2009 and December 2010. The study included children with a community-acquired infectious disease or a health care-associated infectious disease, and who were admitted to paediatric areas of the Vall d'Hebron University Hospital (Barcelona, Spain), other than intensive care, neonatology and onco-haematology units. Clinical data were collected and antibiotic consumption data were provided by the Pharmacy Department. A total of 51 episodes fulfilled the inclusion criteria. Carbapenem as initial empirical treatment was indicated in 31.4%, and applied as rescue therapy in the remainder. The instructions of the protocol were adhered to in 70.6% of the empirical and 87.5% of the targeted prescriptions (77.6% overall). A better match was found for empirical carbapenem in patients with a previous admission or underlying condition. Factors such as diagnosis, age or antibiotic use prior to admission did not affect the empirical indication of carbapenem. The establishment of a treatment protocol with carbapenem indications in our centre since 2007 has yielded significantly better results on the appropriateness of the prescription than those obtained in other studies. Copyright © 2012 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  19. A retrospective study of risk factors for carbapenem-resistant Klebsiella pneumoniae acquisition among ICU patients.

    Science.gov (United States)

    Hu, Yangmin; Ping, Yanting; Li, Leiqing; Xu, Huimin; Yan, Xiaofeng; Dai, Haibin

    2016-03-31

    Carbapenem-resistant Klebsiella pneumoniae (CRKP) is rapidly emerging as a life-threatening nosocomial infection. In this study, we aim to identify risk factors, especially antibiotic use, for CRKP infection among intensive care unit (ICU) patients. This was a matched case-control study of a 67-bed ICU in a tertiary care teaching hospital from 1 January 2011 through 30 June 2013. The control cases were selected among the patients with carbapenem-susceptible Klebsiella pneumoniae (CSKP) and were matched with CRKP cases for year of ICU admission and site of infection. The clinical outcomes and antibiotic treatments were analyzed. One hundred and thirty patients were included in the study (65 cases and 65 controls). Bivariable analysis showed that age of patients (p = 0.044), number of antibiotic groups (p = 0.001), and exposure to carbapenems (p carbapenems, previous carbapenem exposure (p carbapenems is an independent risk factor for CRKP infection. Patients with this clinical factor should be targeted for interventions to reduce the subsequent risk of infection.

  20. PHARMACOEPIDEMIOLOGY OF CARBAPENEMS APPLICATION AMONG THE PREMATURE NEWBORNS IN SAINT PETERSBURG. WORLD EXPERIENCE IN NEONATOLOGY

    Directory of Open Access Journals (Sweden)

    A.S. Kolbin

    2008-01-01

    Full Text Available Premature newborns are a high risk group in terms of the infection complications growth. therefore, it is highly urgent to choose the efficient and safe antibacterial medications for the given category of patients. The authors carried out a pharma coepidemiological study of the carbapenems application among 353 newborns with very low body weight at birth, as well as the literature analysis on the use of this medications group in compliance with the evidence based medicine. As a result, they showed that for the last 8 years the frequency of the carbapenems application in Saint-Petersburg among the newborns has grown from 10 to 52%. It is statistically accurate that imipenem/cilastatin was more often used to the amount of 25 mg/kg twice a day. In 71% of cases, carbapenems were applied in the form of the empiric therapy against the general bacterial infection in combination with vancomycin and/or metronidazole. Antibiotics proved to be safe. The literature analysis showed that there is no data, which would allow one to compare the efficiency of carbapenems with other antibiotics among the newborns based on the results of the meta analyses and randomized clinical studies. Nowadays, carbapenems demonstrated high efficiency and safety in the small clinical observations.Key words: carbapenems, imipenem, meropenem, newborns with very low body weight at birth.

  1. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 229 ... Browse Title Index ... Issue, Title. Vol 14, No 2 ... Vol 15, No 1 (2017), Qualitative and quantitative methods of suicide research in old age, Abstract PDF ... Vol 11, No 2 (2013), Simple Algorithm in the Management of Fetal ...

  2. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 488 ... African Journal of Paediatric Surgery. ... Ileocecal valve atresia: Introduction of a new surgical approach ... Vol 4, No 1 (2007), Isolated Bilateral Macrostomia: Case Series and ... Vol 9, No 2 (2012), Laparoscopic inguinal hernia repair in ... List All Titles · Free To Read Titles This Journal is Open Access.

  3. Browse Title Index

    African Journals Online (AJOL)

    Items 601 - 650 of 788 ... Browse Title Index ... Issue, Title ... Vol 14, No 1 (2006), Social science research: a critique of quantitative and qualitative methods ... Vol 18, No 1 (2010), Stress among part-time business students: a study in a Ghanaian ...

  4. Title to mining properties

    International Nuclear Information System (INIS)

    Crouch, K.M.

    1976-01-01

    The requirements of the law which must be met in order to create title to an unpatented mining claim and the procedures which should be followed when an attempt is made to determine the title to the claim is acceptable are reviewed

  5. Cefmetazole for bacteremia caused by ESBL-producing enterobacteriaceae comparing with carbapenems.

    Science.gov (United States)

    Fukuchi, Takahiko; Iwata, Kentaro; Kobayashi, Saori; Nakamura, Tatsuya; Ohji, Goh

    2016-08-18

    ESBL (Extended spectrum beta-lactamase) producing enterobacteriaceae are challenging organisms with little treatment options. Carbapenems are frequently used, but the emergence of carbapenem resistant enterobacteriaceae is a concerning issue, which may hinder the use of carbapenems. Although cephamycins such as cefoxitin, cefmetazole or cefotetan are effective against ESBL-producers in vitro, there are few clinical data demonstrating effects against bacteremia caused by these organisms. We performed a retrospective observational study on cases of bacteremia caused by ESBL-producers to investigate the efficacy of cefmetazole compared with carbapenems. We also evaluated whether the trend of antibiotic choice changed over years. Sixty-nine patients (male 34, age 69.2 ± 14.4), including two relapse cases, were reviewed for this analysis. The most common causative organisms were Escherichia coli (64, 93 %), followed by Klebsiella pneumoniae and K. oxytoca (2 each, 4 %). The group that received carbapenem therapy (43, 62 %) had increased severity in the Pittsburgh Bacteremic score than the group that received cefmetazole therapy, (1.5 ± 1.5 vs 2.5 ± 2.1, p = 0.048), while analysis of other factors didn't reveal any statistical differences. Five patients in the carbapenem group and one patient in the cefmetazole group died during the observation period (p = 0.24). CTX-M-9 were predominant in this series (59 %). Infectious disease physicians initially recommended carbapenems at the beginning of the current research period, which gradually changed over time favoring the use of cefmetazole instead (p = 0.002). Cefmetazole may be safely given to patients with bacteremia caused by ESBL-producers as a definitive therapy, if one can select out relatively stable patients.

  6. Impact of carbapenem heteroresistance among clinical isolates of invasive Escherichia coli in Chongqing, southwestern China.

    Science.gov (United States)

    Sun, J D; Huang, S F; Yang, S S; Pu, S L; Zhang, C M; Zhang, L P

    2015-05-01

    Although heteroresistance is common in a wide range of microorganisms, carbapenem heteroresistance among invasive Escherichia coli infections has not been reported. The objective of this study was to evaluate the clinical significance of carbapenem heteroresistance and to identify risk factors for its acquisition. A case-control study was conducted at a 3200-bed teaching hospital in Chongqing, southwestern China. Successive and non-duplicate nosocomial E. coli isolates (n = 332) were obtained from July 2011 to June 2013. Bloodstream isolates made up 50.6% of the strains collected. The rates of heteroresistance were 25.0% to imipenem, 17.2% to ertapenem, and 3.9% to meropenem. The population analysis profile revealed the presence of subpopulations with higher carbapenem resistance, showing MICs ranging from 2.0-128.0mg/L. Male gender, invasive intervention, antibiotic use and bacterial extended-spectrum β-lactamase (ESBL) production contributed to invasive infections by carbapenem-heteroresistant E. coli (CHEC). The production of ESBL was identified as the common independent risk factor for heteroresistance to both ertapenem and imipenem. Pulsed-field gel electrophoresis revealed clonal diversity among the CHEC isolates. Most importantly, characterization of two successive E. coli strains isolated from the same patient indicated that carbapenem resistance evolved from heteroresistance. In conclusion, the high prevalence of heteroresistance to carbapenem among invasive E. coli merits great attention. Routine detection of ESBLs and the prudent use of imipenem and ertapenem are advocated. The early targeted intervention should be formulated to reduce CHEC infection and carbapenem resistance of E. coli. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. A systematic review and meta-Analyses show that carbapenem use and medical devices are the leading risk factors for carbapenem- resistant pseudomonas aeruginosa

    NARCIS (Netherlands)

    A.F. Voor (Anne); J.A. Severin (Juliëtte); E.M.E.H. Lesaffre (Emmanuel); M.C. Vos (Margreet)

    2014-01-01

    textabstractA systematic review and meta-Analyses were performed to identify the risk factors associated with carbapenem-resistant Pseudomonas aeruginosa and to identify sources and reservoirs for the pathogen. A systematic search of PubMed and Embase databases from 1 January 1987 until 27 January

  8. Bulgecin A as a β-lactam enhancer for carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii clinical isolates containing various resistance mechanisms.

    Science.gov (United States)

    Skalweit, Marion J; Li, Mei

    2016-01-01

    Genetic screening of Pseudomonas aeruginosa (PSDA) and Acinetobacter baumannii (ACB) reveals genes that confer increased susceptibility to β-lactams when disrupted, suggesting novel drug targets. One such target is lytic transglycosylase. Bulgecin A (BlgA) is a natural product of Pseudomonas mesoacidophila and a lytic transglycosolase inhibitor that works synergistically with β-lactams targeting PBP3 for Enterobacteriaceae. BlgA also weakly inhibits di-Zn 2+ metallo-β-lactamases like L1 of Stenotrophomonas maltophilia . We hypothesized that because of its unique mechanism of action, BlgA could restore susceptibility to carbapenems in carbapenem-resistant PSDA (CR-PSDA) and carbapenem-resistant ACB, as well as ACB resistant to sulbactam. A BlgA-containing extract was prepared using a previously published protocol. CR-PSDA clinical isolates demonstrating a variety of carbapenem resistance mechanisms (VIM-2 carbapenemases, efflux mechanisms, and AmpC producer expression) were characterized with agar dilution minimum inhibitory concentration (MIC) testing and polymerase chain reaction. Growth curves using these strains were prepared using meropenem, BlgA extract, and meropenem plus BlgA extract. A concentrated Blg A extract combined with low concentrations of meropenem, was able to inhibit the growth of clinical strains of CR-PSDA for strains that had meropenem MICs ≥8 mg/L by agar dilution, and a clinical strain of an OXA-24 producing ACB that had a meropenem MIC >32 mg/L and intermediate ampicillin/sulbactam susceptibility. Similar experiments were conducted on a TEM-1 producing ACB strain resistant to sulbactam. BlgA with ampicillin/sulbactam inhibited the growth of this organism. As in Enterobacteriaceae, BlgA appears to restore the efficacy of meropenem in suppressing the growth of CR-PSDA and carbapenem-resistant ACB strains with a variety of common carbapenem resistance mechanisms. BlgA extract also inhibits VIM-2 β-lactamase in vitro. BlgA may prove to be

  9. In vitro activity of SecA inhibitors in combination with carbapenems against carbapenem-hydrolysing class D β-lactamase-producing Acinetobacter baumannii.

    Science.gov (United States)

    Chiu, Chun-Hsiang; Liu, Yu-Han; Wang, Yung-Chih; Lee, Yi-Tzu; Kuo, Shu-Chen; Chen, Te-Li; Lin, Jung-Chung; Wang, Fu-Der

    2016-12-01

    According to our previous study, OXA-58 translocates to the periplasm via the Sec pathway in carbapenem-resistant Acinetobacter baumannii (CRAb). In the present study, carbapenem-hydrolysing class D β-lactamases (CHDLs) belonging to the OXA-23, OXA-40 and OXA-51 families were examined to determine whether they are also Sec-dependent. Additionally, the effects of SecA inhibitors combined with carbapenems against CHDL-producing CRAb were examined. Cell fractionation and western blot analyses were performed to detect periplasmic His-tagged CHDLs. A chequerboard analysis with pairwise combinations of carbapenems (imipenem or meropenem) and SecA inhibitors (rose bengal, sodium azide or erythrosin B) was performed using six clinical CRAb isolates harbouring different CHDL genes. The fractional inhibitory concentration (FIC) index was determined. The combination with the lowest FIC index was subjected to a time-kill analysis to examine synergistic effects. In an in silico analysis, the CHDLs OXA-23, OXA-40 and OXA-51 were preferentially translocated via the Sec system. The SecA inhibitor rose bengal decreased periplasmic translocation of His-tagged OXA-23 and OXA-83 (belonging to the OXA-51 family), but not OXA-72 (belonging to the OXA-40 family) from ATCC 15151 transformants. Imipenem or meropenem with rose bengal showed synergistic effects (FIC index, ≤0.5) for six and four clinical isolates, respectively. Imipenem or meropenem with sodium azide showed no interactions (FIC index, 0.5-4) against all clinical isolates. Imipenem and rose bengal had the lowest FIC index and showed synergy at 24 h in the time-kill assay. Combinations of SecA inhibitors and carbapenems have synergistic effects against CHDL-producing CRAb. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. The basis for carbapenem hydrolysis by class A β-lactamases: a combined investigation using crystallography and simulations.

    Science.gov (United States)

    Fonseca, Fátima; Chudyk, Ewa I; van der Kamp, Marc W; Correia, António; Mulholland, Adrian J; Spencer, James

    2012-11-07

    Carbapenems are the most potent β-lactam antibiotics and key drugs for treating infections by Gram-negative bacteria. In such organisms, β-lactam resistance arises principally from β-lactamase production. Although carbapenems escape the activity of most β-lactamases, due in the class A enzymes to slow deacylation of the covalent acylenzyme intermediate, carbapenem-hydrolyzing class A β-lactamases are now disseminating in clinically relevant bacteria. The reasons why carbapenems are substrates for these enzymes, but inhibit other class A β-lactamases, remain to be fully established. Here, we present crystal structures of the class A carbapenemase SFC-1 from Serratia fonticola and of complexes of its Ser70 Ala (Michaelis) and Glu166 Ala (acylenzyme) mutants with the carbapenem meropenem. These are the first crystal structures of carbapenem complexes of a class A carbapenemase. Our data reveal that, in the SFC-1 acylenzyme complex, the meropenem 6α-1R-hydroxyethyl group interacts with Asn132, but not with the deacylating water molecule. Molecular dynamics simulations indicate that this mode of binding occurs in both the Michaelis and acylenzyme complexes of wild-type SFC-1. In carbapenem-inhibited class A β-lactamases, it is proposed that the deacylating water molecule is deactivated by interaction with the carbapenem 6α-1R-hydroxyethyl substituent. Structural comparisons with such enzymes suggest that in SFC-1 subtle repositioning of key residues (Ser70, Ser130, Asn132 and Asn170) enlarges the active site, permitting rotation of the carbapenem 6α-1R-hydroxyethyl group and abolishing this contact. Our data show that SFC-1, and by implication other such carbapenem-hydrolyzing enzymes, uses Asn132 to orient bound carbapenems for efficient deacylation and prevent their interaction with the deacylating water molecule.

  11. Duodenoscope-Related Outbreak of a Carbapenem-Resistant Klebsiella pneumoniae Identified Using Advanced Molecular Diagnostics.

    Science.gov (United States)

    Humphries, Romney M; Yang, Shuan; Kim, Stephen; Muthusamy, Venkatara Raman; Russell, Dana; Trout, Alisa M; Zaroda, Teresa; Cheng, Quen J; Aldrovandi, Grace; Uslan, Daniel Zachary; Hemarajata, Peera; Rubin, Zachary Aaron

    2017-10-01

    Carbapenem-resistant Klebsiella pneumoniae infections are increasingly prevalent in North American hospitals. We describe an outbreak of carbapenem-resistant K. pneumoniae containing the blaOXA-232 gene transmitted by contaminated duodenoscopes during endoscopic retrograde cholangiopancreatography (ERCP) procedures. An outbreak investigation was performed when 9 patients with blaOXA-232 carbapenem-resistant K. pneumoniae infections were identified at a tertiary care hospital. The investigation included 2 case-control studies, review of duodenoscope reprocessing procedures, and culture of devices. Carbapenem-resistant Enterobacteriacieae (CRE) isolates were evaluated with polymerase chain reaction analysis for carbapenemase genes, and isolates with the blaOXA-232 gene were subjected to whole-genome sequencing and chromosome single-nucleotide polymorphism analysis. On recognition of ERCP as a key risk factor for infection, targeted patient notification and CRE screening cultures were performed. Molecular testing ultimately identified 17 patients with blaOxa-232 carbapenem-resistant K. pneumoniae isolates, including 9 with infections, 7 asymptomatic carriers who had undergone ERCP, and 1 additional patient who had been hospitalized in India and was probably the initial carrier. Two case-control studies established a point-source outbreak associated with 2 specific duodenoscopes. A field investigation of the use, reprocessing, and storage of deuodenoscopes did not identify deviations from US Food and Drug Administration or manufacturer recommendations for reprocessing. This outbreak demonstrated the previously underappreciated potential for duodenoscopes to transmit disease, even after undergoing high-level disinfection according to manufacturers' guidelines.

  12. Clinical review: Balancing the therapeutic, safety, and economic issues underlying effective antipseudomonal carbapenem use

    Science.gov (United States)

    Slama, Thomas G

    2008-01-01

    Antipseudomonal carbapenems have played a useful role in our antimicrobial armamentarium for 20 years. However, a review of their use during that period creates concern that their clinical effectiveness is critically dependent on attainment of an appropriate dosing range. Unfortunately, adequate carbapenem dosing is missed for many reasons, including benefit/risk misconceptions, a narrow therapeutic window for imipenem and meropenem (due to an increased rate of seizures at higher doses), increasingly resistant pathogens requiring higher doses than are typically given, and cost containment issues that may limit their use. To improve the use of carbapenems, several initiatives should be considered: increase awareness about appropriate treatment with carbapenems across hospital departments; determine optimal dosing regimens for settings where multidrug resistant organisms are more likely encountered; use of, or combination with, an alternative antimicrobial agent having more favorable pharmacokinetic, pharmacodynamic, or adverse event profile; and administer a newer carbapenem with lower propensity for resistance development (for example, reduced expression of efflux pumps or greater stability against carbapenemases). PMID:18983709

  13. The purpose and appropriateness of carbapenem use in a single university hospital, 2009-2013.

    Science.gov (United States)

    Yoon, Doran; Koo, Hei Lim; Choe, Pyeong Gyun; Song, Kyoung-Ho; Park, Wan Beom; Bang, Ji Hwan; Kim, Eu Suk; Park, Sang Won; Kim, Hong Bin; Oh, Myoung-Don; Kim, Nam Joong

    2016-06-01

    This is a retrospective review study to investigate changes in carbapenem consumption and to evaluate the proportion of inappropriate empirical use of carbapenem in the months of September and October of 2009, 2011, and 2013 in a single university-affiliated hospital. Total carbapenem use was classified into 3 categories: prophylactic, directed, and empirical. If an empirical prescription was continued without documentation of any eligible etiologic microorganism, we defined this as 'inappropriate' use. We also considered it 'inappropriate' when a patient's culture revealed no pathogen and the patient was initially not in severe sepsis or septic shock and did not have a history of admission to a health-care facility or of colonization with a pathogen eligible for carbapenem within 3 months. The total amount was 48.1, 51.1, and 91.0 defined daily doses/1000 patient-days in 2009, 2011, and 2013, respectively. Empirical use accounted for 78.4% of all prescriptions. The proportion of inappropriate empirical use ranged from 15.0 to 38.9% of the empirical carbapenem prescriptions.

  14. Treatment Options for Carbapenem-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections

    Science.gov (United States)

    Viehman, J. Alexander; Nguyen, Minh-Hong; Doi, Yohei

    2014-01-01

    Acinetobacter baumannii is a leading cause of healthcare-associated infections worldwide. Due to various intrinsic and acquired mechanisms of resistance, most β-lactam agents are not effective against many strains, and carbapenems have played an important role in therapy. Recent trends show many infections are caused by carbapenem-resistant, or even extensively drug-resistant (XDR) strains, for which effective therapy is not well established. Evidence to date suggests that colistin constitutes the backbone of therapy, but the unique pharmacokinetic properties of colistin have led many to suggest the use of combination antimicrobial therapy. However, the combination of agents and dosing regimens that delivers the best clinical efficacy while minimizing toxicity is yet to be defined. Carbapenems, sulbactam, rifampin and tigecycline have been the most studied in the context of combination therapy. Most data regarding therapy for invasive, resistant A. baumannii infections come from uncontrolled case series and retrospective analyses, though some clinical trials have been completed and others are underway. Early institution of appropriate antimicrobial therapy is shown to consistently improve survival of patients with carbapenem-resistant and XDR A. baumannii infection, but the choice of empiric therapy in these infections remains an open question. This review summarizes the most current knowledge regarding the epidemiology, mechanisms of resistance, and treatment considerations of carbapenem-resistant and XDR A. baumannii. PMID:25091170

  15. Browse Title Index

    African Journals Online (AJOL)

    1986), University Engineering Education and Training in Nigeria: Development, ... Vol 29, No 1 (2010), Use of Energy Method to Simulate the ... of Optimal Rational Composition of Titles Producible from Nigerian Clays ...

  16. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 194 ... Journal Home > Advanced Search > Browse Title Index ... Vol 14, No 1 (2000), A functional categoriality of adjectives in ... Vol 1, No 1 (1987), Alienation and affirmation: The humanistic vision of Bessie Head, Abstract PDF.

  17. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 879 ... South African Journal of Higher Education. ... Browse Title Index ... in a USA school setting: Merging transition theory with a narrative approach, Abstract ... Citation analysis of theses and dissertations submitted at the ...

  18. Browse Title Index

    African Journals Online (AJOL)

    Items 601 - 650 of 879 ... South African Journal of Higher Education. ... Browse Title Index .... The challenge of thesis supervision in an art university, Abstract ... No 2 (2004), Robert Sternberg's mental self-government theory and its contribution to ...

  19. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 533 ... Southern African Linguistics and Applied Language Studies. ... Issue, Title ... Vol 34, No 1 (2016), Book Review: Qualitative-Quantitative Analyses of .... The complex consonants of simple CV-syllables in Zezuru, Abstract.

  20. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 346 ... Journal Home > Advanced Search > Browse Title Index ... and hygiene promotion services in Rungwe district, Tanzania, Abstract .... as seen in NIgerian teaching hospital: pattern and a simple classification, Abstract.

  1. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 437 ... Journal Home > Advanced Search > Browse Title Index ... prospects and realistic strategies to its implementation in Nigeria\\'s Institute of ... and Communication Technology (ICT) in information dissemination, Abstract.

  2. Browse Title Index

    African Journals Online (AJOL)

    Items 901 - 950 of 1355 ... Journal of Applied Sciences and Environmental Management. ... Journal Home > Advanced Search > Browse Title Index .... Vol 22, No 2 (2018), Performance evaluation of a locally fabricated sawdust fired oven for ...

  3. Browse Title Index

    African Journals Online (AJOL)

    Items 301 - 350 of 788 ... Journal Home > Advanced Search > Browse Title Index ... Vol 26, No 1 (2018), Gender differentials in the perception of .... Vol 25, No 1 (2017), Impact of total quality management on students' academic performance in ...

  4. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 465 ... Journal Home > Advanced Search > Browse Title Index ... and twinning data of an igbo kindred during the Nigerian Civil War, Abstract ... on laboratory estimations with special reference to clinical chemistry, Abstract.

  5. Browse Title Index

    African Journals Online (AJOL)

    Items 251 - 300 of 1260 ... Journal Home > Advanced Search > Browse Title Index ... Consumption of ammonia-nitrogen by aob in immobilized batch culture, Abstract PDF .... Vol 9, No 3S (2017): Special Issue, Design an automatic temperature ...

  6. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 294 ... Journal Home > Advanced Search > Browse Title Index. Log in or .... S Edwards, M Hlongwane, J Thwala, N Robinson ... Vol 16, No 1 (2017), Infancy of internet cafe: The substitute of ubuntu-padare pedagogy, Abstract.

  7. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 130 ... Journal Home > Advanced Search > Browse Title Index. Log in or ... using the technological pedagogical content knowledge(TPACK) framework, Abstract PDF ... Tamara N. Hrin, Dušica D. Milenković, Mirjana D. Segedinac.

  8. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 278 ... Journal Home > Advanced Search > Browse Title Index ... drie paradigmas beskou: 'n eenheid, of 'n veelheid van perspektiewe? ... Vol 45, No 1 (2011), Genre pedagogy in the mediation of socially-situated literacies ...

  9. Browse Title Index

    African Journals Online (AJOL)

    Items 551 - 600 of 879 ... Journal Home > Advanced Search > Browse Title Index ... A James, E Ralfe, L van Laren, N Ngcobo ... 1 (2011), Recognition of prior learning in promoting lifelong learning: A pedagogy of hope or a shattering of dreams?

  10. Browse Title Index

    African Journals Online (AJOL)

    Items 451 - 500 of 533 ... Journal Home > Advanced Search > Browse Title Index .... for past tense forms in Northern Sotho: verb stems with final 'm' and 'n', Abstract ... in an academic writing class: Implications for a dialogic pedagogy, Abstract.

  11. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 183 ... Journal Home > Advanced Search > Browse Title Index ... Vol 61 (2017), New interventions and sustainable solutions: .... Vol 35 (2011), Resurgence of tribal levies: Double taxation for the rural poor, Abstract PDF.

  12. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 736 ... Journal Home > Advanced Search > Browse Title Index ... Vol 5 (2008), A Contagious Malady: The Human Quest for Truth through Religion, Abstract ... A Study of Politeness Strategies Used by the National University of ...

  13. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 414 ... Journal Home > Advanced Search > Browse Title Index. Log in or ... of an algebraic function for the permutation of truth table columns, Abstract ... appraisal and productivity levels in selected Nigerian universities, Abstract.

  14. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 879 ... Journal Home > Advanced Search > Browse Title Index ... Vol 20, No 4 (2006), Assessing academic potential for university admission: ... Vol 16, No 2 (2002), Book Review: Rethinking truth by Higgs, P & Smith, J, Details.

  15. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 165 ... Journal Home > Advanced Search > Browse Title Index ... Vol 43 (2011), Assessment of the Learning Commons takeoff at the University of ... the archive of South Africa's Truth and Reconciliation Commission, Abstract.

  16. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 644 ... Journal Home > Advanced Search > Browse Title Index. Log in or ... Ethics review n international health research: quality assurance or bureaucratic nightmare? Details ... Audit of Management of Open Fractures, Details PDF.

  17. Browse Title Index

    African Journals Online (AJOL)

    Items 651 - 700 of 1199 ... Issue, Title ... Vol 5, No 1 (2011), Motivation, an Essential Ingredient for Optimal Performance in Emerging Markets, Abstract PDF ... Vol 3, No 5 (2009), Multinational transfer pricing and international taxation: what, why, ...

  18. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 153 ... Issue, Title. Vol 9, No 2 (2006):, Effects of efficient water utilisation on water resources development in Swaziland under climate change, Abstract .... Ethical, Indigenous and Socio-Economic Perspectives, Abstract.

  19. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 98 ... Journal Home > Advanced Search > Browse Title Index ... model for the continued professionalisation of student affairs in Africa, Abstract PDF ... Vol 2, No 2 (2014), Book Review: How College Affects Students, A Third decade ...

  20. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 76 ... Journal Home > Advanced Search > Browse Title Index ... Vol 4, No 1 (2011), Automation of AutoCAD for Detailing of Reinforced .... Vol 10, No 1 (2017), Housing data base for sustainable housing provision, Abstract PDF.

  1. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 147 ... Journal Home > Advanced Search > Browse Title Index .... Library (TEEAL) Database among faculty members in Federal University, ... Vol 5, No 2 (2014), Effects of corporate culture on the implementation of automation in ...

  2. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 41 of 41 ... Issue, Title ... Vol 1, No 3 (2004): Special Edition, Assessment of the quality and reserves of Bat ... Vol 1, No 1 (1997), Bovine dermatophilosis in Zambia: epidemiology, socio-economic impacts and future perspectives, Abstract.

  3. Browse Title Index

    African Journals Online (AJOL)

    Items 701 - 750 of 808 ... Issue, Title ... Vol 58, No 2 (2010), Short Communicaton: The socio-economic impact of helminth infections and the ... Vol 62 (2014): Special Edition, Special edition summarizing the scientific discourse which took place ...

  4. Browse Title Index

    African Journals Online (AJOL)

    Items 351 - 391 of 391 ... Issue, Title ... Vol 2, No 3 (1999): Special Edition, The efficacy of low volume application of roundup ... Vol 1, No 1 (1998), The relationships among National Socio-Economic Indicators and Child Health Statistics, Abstract.

  5. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 531 ... Journal Home > Advanced Search > Browse Title Index ... thermal conductivity and viscosity in a flat plate solar collector, Abstract PDF .... similarity method in unsteady two-dimensional MHD boundary layer on the body ...

  6. Evaluating the Impact of Antibiotic Exposures as Time-Dependent Variables on the Acquisition of Carbapenem-Resistant Acinetobacter baumannii.

    Science.gov (United States)

    Munoz-Price, L Silvia; Rosa, Rossana; Castro, Jose G; Laowansiri, Panthipa; Latibeaudiere, Rachel; Namias, Nicholas; Tarima, Sergey

    2016-10-01

    To determine the time-dependent effect of antibiotics on the initial acquisition of carbapenem-resistant Acinetobacter baumannii. Retrospective cohort study. Forty-bed trauma ICU in Miami, FL. All consecutive patients admitted to the unit from November 1, 2010, to November 30, 2011. None. Patients underwent surveillance cultures at admission to the unit and weekly thereafter. The primary outcome was the acquisition of carbapenem-resistant A. baumannii on surveillance cultures. Daily antibiotic exposures during the time of observation were used to construct time-dependent variables, including cumulative exposures (in grams and daily observed doses [defined daily doses]). Among 360 patients, 45 (12.5%) became colonized with carbapenem-resistant A. baumannii. Adjusted Cox models showed that each additional point in the Acute Physiologic and Chronic Health Evaluation score increased the hazard by 4.8% (hazard ratio, 1.048; 95% CI, 1.010-1.087; p = 0.0124) and time-dependent exposure to carbapenems quadrupled the hazard (hazard ratio, 4.087; 95% CI, 1.873-8.920; p = 0.0004) of acquiring carbapenem-resistant A. baumannii. Additionally, adjusted Cox models determined that every additional carbapenem defined daily dose increased the hazard of acquiring carbapenem-resistant A. baumannii by 5.1% (hazard ratio, 1.051; 95% CI, 1.007-1.093; p = 0.0243). Carbapenem exposure quadrupled the hazards of acquiring A. baumannii even after controlling for severity of illness.

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

    Directory of Open Access Journals (Sweden)

    Deepjyoti Paul

    2017-02-01

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

  8. Molecular mechanisms associated with nosocomial carbapenem-resistant Acinetobacter baumannii in Mexico.

    Science.gov (United States)

    Alcántar-Curiel, María Dolores; García-Torres, Luis Francisco; González-Chávez, María Inés; Morfín-Otero, Rayo; Gayosso-Vázquez, Catalina; Jarillo-Quijada, Ma Dolores; Fernández-Vázquez, José Luis; Giono-Cerezo, Silvia; Rodríguez-Noriega, Eduardo; Santos-Preciado, José Ignacio

    2014-10-01

    Acinetobacter baumannii is an emerging pathogen worldwide that is most commonly associated with nosocomial infections and multi-drug resistance. In the present study we determined the mechanisms of carbapenem resistance and clonal diversity of A. baumannii nosocomial isolates in Hospital Civil de Guadalajara, Mexico. A total of 303 clinical isolates of A. baumannii identified during a period expanding from 2004-2011 were analyzed for carbapenem resistance using several microbiological and molecular methods. Clonal relatedness of these isolates was determined using pulsed-field gel electrophoresis. Of the 303 isolates, 84% were resistant to meropenem, 71.3% to imipenem and 78.3% the resistant isolates were positive for metallo-β-lactamases as determined by the phenotypic assay. In addition, 49.6% of carbapenem-intermediate or -resistant isolates carried the blaOXA-72 gene and 1.2% carried the blaVIM-1 gene. Efflux pump phenotype was responsible for reduced susceptibility to meropenem in 14.5% and to imipenem in 31.6% of the resistant isolates, respectively in the presence of the efflux pump inhibitor, carbonyl cyanide 3-chlorophenylhydrazone. Strains representing different carbapenem-resistant patterns exhibited reduced expression of 22, 29, 33, and 43 kDa OMPs. Among the bacterial collection studied, 48 different clones were identified, two of which were predominant and persistently transmitted. Carbapenemase production in combination with efflux pump expression, reduction in OMPs expression and the cross-transmission of clones appear to be major contributors to the high frequency of carbapenem-resistance observed in A. baumannii. To our knowledge, this is the first study to define the molecular mechanisms associated with carbapenem-resistance in A. baumannii in Mexico. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

  9. Sublethal Concentrations of Carbapenems Alter Cell Morphology and Genomic Expression of Klebsiella pneumoniae Biofilms

    Science.gov (United States)

    Van Laar, Tricia A.; Chen, Tsute; You, Tao

    2015-01-01

    Klebsiella pneumoniae, a Gram-negative bacterium, is normally associated with pneumonia in patients with weakened immune systems. However, it is also a prevalent nosocomial infectious agent that can be found in infected surgical sites and combat wounds. Many of these clinical strains display multidrug resistance. We have worked with a clinical strain of K. pneumoniae that was initially isolated from a wound of an injured soldier. This strain demonstrated resistance to many commonly used antibiotics but sensitivity to carbapenems. This isolate was capable of forming biofilms in vitro, contributing to its increased antibiotic resistance and impaired clearance. We were interested in determining how sublethal concentrations of carbapenem treatment specifically affect K. pneumoniae biofilms both in morphology and in genomic expression. Scanning electron microscopy showed striking morphological differences between untreated and treated biofilms, including rounding, blebbing, and dimpling of treated cells. Comparative transcriptome analysis using RNA sequencing (RNA-Seq) technology identified a large number of open reading frames (ORFs) differentially regulated in response to carbapenem treatment at 2 and 24 h. ORFs upregulated with carbapenem treatment included genes involved in resistance, as well as those coding for antiporters and autoinducers. ORFs downregulated included those coding for metal transporters, membrane biosynthesis proteins, and motility proteins. Quantitative real-time PCR validated the general trend of some of these differentially regulated ORFs. Treatment of K. pneumoniae biofilms with sublethal concentrations of carbapenems induced a wide range of phenotypic and gene expression changes. This study reveals some of the mechanisms underlying how sublethal amounts of carbapenems could affect the overall fitness and pathogenic potential of K. pneumoniae biofilm cells. PMID:25583711

  10. Genetic Characterization of Carbapenem-Resistant Enterobacteriaceae and the Spread of Carbapenem-Resistant Klebsiella pneumonia ST340 at a University Hospital in Thailand

    Science.gov (United States)

    Netikul, Thidarat; Kiratisin, Pattarachai

    2015-01-01

    Carbapenem-resistant Enterobacteriaceae (CRE) has increasingly spread worldwide in the past decade. The prevalence and characteristics of CRE in Thailand are unknown. In this study, we conducted a 2-year surveillance of CRE among 12,741 clinical isolates of Enterobacteriaceae at the largest university hospital in Thailand with molecular characterization of beta-lactamase (bla) genes, including carbapenemase genes. The CRE prevalence was 1.4%. blaKPC-13 and blaIMP-14a were the only carbapenemase genes detected among these CRE isolates. blaKPC-13 gene was found in a single isolate of Escherichia coli, Enterobacter cloacae and Citrobacter freundii, and blaIMP-14a was found in four isolates of Klebsiella pneumoniae. Carbapenem-resistant K. pneumoniae (CRKP) isolates were resistant to multiple carbapenems at a higher ratio than other CRE species, and thus were further characterized for resistance phenotypes, bla genotypes and molecular epidemiology. Most CRKP isolates harboured multiple bla genes, especially those related to extended-spectrum beta-lactamases. Seven CRKP isolates were resistant to all tested carbapenems, and showed decreased ompK35 and/or ompK36 porin gene expression. Molecular typing of CRKP based on pulsed-field gel electrophoresis (PFGE) demonstrated several unrelated clones. Multilocus sequence typing (MLST) was partially concordant with PFGE results and revealed that ST340, a member of drug-resistant K. pneumoniae clonal complex 258, was the most predominant clone, followed by ST48, ST11 and ST273. The novel ST1645 was identified from this study. ST340 has neither been shown to be predominated among CRKP from other studies, nor been reported in Thailand. Therefore, it emphases a critical concern to monitor and control the spread of CRKP. PMID:26407326

  11. Sustained pediatric antimicrobial stewardship program with consultation to infectious diseases reduced carbapenem resistance and infection-related mortality.

    Science.gov (United States)

    Horikoshi, Yuho; Suwa, Junichi; Higuchi, Hiroshi; Kaneko, Tetsuji; Furuichi, Mihoko; Aizawa, Yuta; Fukuoka, Kahoru; Okazaki, Kaoru; Ito, Kenta; Shoji, Takayo

    2017-11-01

    The impact of pediatric antimicrobial stewardship programs (ASP) on antimicrobial resistance (AMR) remains largely unknown. This study aimed to evaluate the AMR for carbapenem of Gram-negative bacilli (GNB) and carbapenem use with infectious diseases consultation after the implementation of an ASP. This quasi-experimental study was conducted at Tokyo Metropolitan Children's Medical Center in Japan. The pre- and post-intervention periods were April 2010 to September 2011 and October 2011 to March 2017, respectively. The pre-intervention phase consisted of consultations with the infectious diseases service alone. The ASP was implemented during the post-intervention phase. The carbapenem resistance rates of GNB were calculated. The correlation between carbapenem resistance rates and carbapenem day of therapy (DOT) was examined. The outcome metrics were compared by average length of hospitalization, all-cause mortality, and infection-related mortality. A positive correlation was observed between the carbapenem resistance rate in Pseudomonas aeruginosa and DOT (0.76, p=0.04). The carbapenem resistance rate in P. aeruginosa (pcarbapenem use and resistance in P. aeruginosa, leading to favorable outcomes in terms of length of hospitalization and infection-related mortality. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. Susceptibilities to carbapenems and presence of cphA gene on food-borne Aeromonas

    Directory of Open Access Journals (Sweden)

    Bibiana María Martín Talavera

    2006-07-01

    Full Text Available The purpose of this study was to determine the susceptibilities of food-borne Aeromonas to carbapenems, as well as to investigate the presence of a metallo carbapenemase-encoding gene, named cphA. Minimum Inhibitory Concentration (MIC was determined following NCCLS standards. All the tested microorganisms were susceptible to imipenem, meropenem and biapenem. However, a strong inoculum size effect on carbapenem MICs was observed for most of the strains. Six strains, out of seven, showed the presence of metallo--beta-lactamases but cphA gene was detected in only two strains of A. veronii bv. sobria.O objetivo deste estudo foi determinar a suscetibilidade de aeromonas de origem alimentar a carbapenems bem como investigar a presença de um gene codificante de metalocarbapenemase, denominado "cph A". A suscetibilidade in vitro foi determinada pelo metodo de diluição em agar. Todas as cepas foram suscetíveis a Imipenem, Meropenem e Biapenem. Porém foi observado um forte efeito de tamanho do inóculo sobre as CIM das carbapenems na maioria das cepas. A detecção de metalo-beta-lactamase foi realizada pelo metodo lodometrico. Seis cepas das sete testadas demostraron a presença da enzima. A presença do gene cphA foi determinada por PCR e foi detectada em duas cepas de A veronii bv. sobria.

  13. Outcomes of an Enhanced Surveillance Program for Carbapenem-Resistant Enterobacteriaceae

    OpenAIRE

    Fitzpatrick, Margaret; Zembower, Teresa; Malczynski, Michael; Qi, Chao; Bolon, Maureen K.

    2014-01-01

    Optimal surveillance strategies for identifying patients colonized with and at risk for transmitting carbapenem-resistant Enterobacteriaceae (CRE) are urgently needed. We instituted an enhanced surveillance program for CRE that identified unrecognized CRE-colonized patients but failed to identify possible CRE transmissions. We also identified risk factors associated with transmitting CRE.

  14. Definition of the Common and Divergent Steps in Carbapenem β-Lactam Antibiotic Biosynthesis

    Science.gov (United States)

    Bodner, Micah J.; Li, Rongfeng; Phelan, Ryan M.; Freeman, Michael F.; Moshos, Kristos A.; Lloyd, Evan P.

    2012-01-01

    Approximately 50 naturally occurring carbapenem β-lactam antibiotics are known. All but one of these have been isolated from Streptomyces species and are disubstituted structural variants of a simple core that is synthesized by Pectobacterium carotovorum (Erwinia carotovora), a phylogenetically distant plant pathogen. While the biosynthesis of the simple carbapenem, (5R)-carbapen-2-em-3-carboxylic acid, is impressively efficient requiring only three enzymes, CarA, CarB and CarC, the formation of thienamycin, one of the former group of metabolites from Streptomyces, is markedly more complex. Despite their phylogenetic separation, bioinformatic analysis of the encoding gene clusters suggests that the two pathways could be related. Here we demonstrate with gene swapping, stereochemical and kinetics experiments that CarB and CarA and their S. cattleya orthologues, ThnE and ThnM, respectively, are functionally and stereochemically equivalent, although their catalytic efficiencies differ. The biosynthetic pathways, therefore, to thienamycin, and likely to the other disubstituted carbapenems, and to the simplest carbapenem, (5R)-carbapen-2-em-3-carboxylic acid, are initiated in the same manner, but share only two common steps before diverging. PMID:21913298

  15. Acquisition of Carbapenem Resistance by Plasmid-Encoded-AmpC-Expressing Escherichia coli.

    Science.gov (United States)

    van Boxtel, Ria; Wattel, Agnes A; Arenas, Jesús; Goessens, Wil H F; Tommassen, Jan

    2017-01-01

    Although AmpC β-lactamases can barely degrade carbapenems, if at all, they can sequester them and prevent them from reaching their targets. Thus, carbapenem resistance in Escherichia coli and other Enterobacteriaceae can result from AmpC production and simultaneous reduction of antibiotic influx into the periplasm by mutations in the porin genes. Here we investigated the route and genetic mechanisms of acquisition of carbapenem resistance in a clinical E. coli isolate carrying bla CMY-2 on a plasmid by selecting for mutants that are resistant to increasing concentrations of meropenem. In the first step, the expression of OmpC, the only porin produced in the strain under laboratory conditions, was lost, leading to reduced susceptibility to meropenem. In the second step, the expression of the CMY-2 β-lactamase was upregulated, leading to resistance to meropenem. The loss of OmpC was due to the insertion of an IS1 element into the ompC gene or to frameshift mutations and premature stop codons in this gene. The bla CMY-2 gene was found to be located on an IncIγ plasmid, and overproduction of the CMY-2 enzyme resulted from an increased plasmid copy number due to a nucleotide substitution in the inc gene. The clinical relevance of these genetic mechanisms became evident from the analysis of previously isolated carbapenem-resistant clinical isolates, which appeared to carry similar mutations. Copyright © 2016 American Society for Microbiology.

  16. Carbapenems to Treat Multidrug and Extensively Drug-Resistant Tuberculosis: A Systematic Review.

    Science.gov (United States)

    Sotgiu, Giovanni; D'Ambrosio, Lia; Centis, Rosella; Tiberi, Simon; Esposito, Susanna; Dore, Simone; Spanevello, Antonio; Migliori, Giovanni Battista

    2016-03-12

    Carbapenems (ertapenem, imipenem, meropenem) are used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), even if the published evidence is limited, particularly when it is otherwise difficult to identify the recommended four active drugs to be included in the regimen. No systematic review to date has ever evaluated the efficacy, safety, and tolerability of carbapenems. A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of carbapenem-containing regimens in individuals with pulmonary/extra-pulmonary disease which was bacteriologically confirmed as M/XDR-TB. We used PubMed to identify relevant full-text, English manuscripts up to the 20 December 2015, excluding editorials and reviews. Seven out of 160 studies satisfied the inclusion criteria: two on ertapenem, one on imipenem, and four on meropenem, all published between 2005 and 2016. Of seven studies, six were retrospective, four were performed in a single center, two enrolled children, two had a control group, and six reported a proportion of XDR-TB cases higher than 20%. Treatment success was higher than 57% in five studies with culture conversion rates between 60% and 94.8%. The safety and tolerability is very good, with the proportion of adverse events attributable to carbapenems below 15%.

  17. Low overlap between carbapenem resistant Pseudomonas aeruginosa genotypes isolated from hospitalized patients and wastewater treatment plants.

    Directory of Open Access Journals (Sweden)

    Andrej Golle

    Full Text Available The variability of carbapenem-resistant Pseudomonas aeruginosa strains (CRPA isolated from urine and respiratory samples in a large microbiological laboratory, serving several health care settings, and from effluents of two wastewater treatment plants (WWTP from the same region was assessed by PFGE typing and by resistance to 10 antibiotics. During the 12-month period altogether 213 carbapenem-resistant P. aeruginosa isolates were cultured and distributed into 65 pulsotypes and ten resistance profiles. For representatives of all 65 pulsotypes 49 different MLSTs were determined. Variability of clinical and environmental strains was comparable, 130 carbapenem-resistant P. aeruginosa obtained from 109 patients were distributed into 38 pulsotypes, while 83 isolates from WWTPs were classified into 31 pulsotypes. Only 9 pulsotypes were shared between two or more settings (hospital or WWTP. Ten MLST were determined for those prevalent pulsotypes, two of them (ST111 and ST235 are among most successful CRPA types worldwide. Clinical and environmental carbapenem-resistant P. aeruginosa strains differed in antibiotic resistance. The highest proportion of clinical isolates was resistant to piperacillin/tazobactam (52.3% and ceftazidime (42.3%. The highest proportion of environmental isolates was resistant to ceftazidime (37.1% and ciprofloxacin (35.5%. The majority of isolates was resistant only to imipenem and/or meropenem. Strains with additional resistances were distributed into nine different patterns. All of them included clinically relevant strains, while environmental strains showed only four additional different patterns.

  18. Emergence and mechanism of carbapenem-resistant Escherichia coli in Henan, China, 2014

    Directory of Open Access Journals (Sweden)

    Wen-juan Liang

    2018-05-01

    Full Text Available The emergence and dissemination of carbapenem-resistant Escherichia coli (E. coli strains is a main risk for global public health, but little is known of carbapenemase producing E. coli in Henan, China. The study was undertaken to investigate the prevalence and mechanism of carbapenem-resistant E. coli strains in a hospital in Xinxiang, Henan, China, 2014. A total of 5 carbapenemase-producing E. coli strains were screened from 1014 isolates. We found that they were all resistant to meropenem and imipenem. Amikacin showed the best sensitivity, with gentamicin coming up next. The positive rate of blaNDM was 80% (4/5. The sequencing results showed that two isolates belonged to blaNDM-1 whereas other 2 isolates carried the blaNDM-5. Other carbapenemase genes including blaIMP, blaVIM, blaKPC and blaOXA-48 were not detected. The blaCTX-M-15, blaTEM-1, sul2, aad, and aac(6”–Ib–cr were also detected. MLST analysis showed that NDM-producing E. coli were sporadic. Conjugation test indicated blaNDM could be transferred. In conclusion, the blaNDM was the principal resistance mechanism of carbapenem-resistant E. coli in the hospital, Henan, China. Keywords: blaNDM, Carbapenem-resistant, Escherichia coli

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

    Directory of Open Access Journals (Sweden)

    Yo Sugawara

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

  20. Tolerance of Norway spruce (Picea abies [L.] Karst.) embryogenic tissue to penicillin, carbapenem and aminoglycoside antibiotics

    Czech Academy of Sciences Publication Activity Database

    Malá, J.; Pavingerová, Daniela; Cvrčková, H.; Bříza, Jindřich; Dostál, J.; Šíma, P.

    2009-01-01

    Roč. 55, č. 4 (2009), s. 156-161 ISSN 1212-4834 R&D Projects: GA MZe QH71290 Institutional research plan: CEZ:AV0Z50510513 Keywords : somatic embryogenesis * Norway spruce * penicillin antibiotics * Agrobacterium tumefaciens * carbapenem antibiotics Subject RIV: EB - Genetics ; Molecular Biology

  1. The influence of carbapenem resistance on mortality in solid organ transplant recipients with Acinetobacter baumannii infection

    Directory of Open Access Journals (Sweden)

    de Gouvêa Erika

    2012-12-01

    Full Text Available Abstract Background Infection with carbapenem-resistant Acinetobacter baumannii has been associated with high morbidity and mortality in solid organ transplant recipients. The main objective of this study was to assess the influence of carbapenem resistance and other potential risk factors on the outcome of A. baumannii infection after kidney and liver transplantation. Methods Retrospective study of a case series of A. baumannii infection among liver and renal transplant recipients. The primary outcome was death associated with A. baumannii infection. Multivariate logistic regression was used to assess the influence of carbapenem resistance and other covariates on the outcome. Results Forty-nine cases of A. baumannii infection affecting 24 kidney and 25 liver transplant recipients were studied. Eighteen cases (37% were caused by carbapenem-resistant isolates. There were 17 (35% deaths associated with A. baumannii infection. In unadjusted analysis, liver transplantation (p = 0.003, acquisition in intensive care unit (p = 0.001, extra-urinary site of infection (p A. baumannii infection. The number of deaths associated with A. baumannii infection was higher among patients infected with carbapenem-resistant isolates, but the difference was not significant (p = 0.28. In multivariate analysis, the risk of A. baumannii-associated mortality was higher in patients with infection acquired in the intensive care unit (odds ratio [OR] = 34.8, p = 0.01 and on mechanical ventilation (OR = 15.2, p = 0.04. Appropriate empiric antimicrobial therapy was associated with significantly lower mortality (OR = 0.04, p = 0.03, but carbapenem resistance had no impact on it (OR = 0.73, p = 0.70. Conclusion These findings suggest that A. baumannii-associated mortality among liver and kidney transplant recipients is influenced by baseline clinical severity and by the early start of appropriate therapy, but not by carbapenem

  2. Characterization of carbapenem-resistant Gram-negative bacteria from Tamil Nadu.

    Science.gov (United States)

    Nachimuthu, Ramesh; Subramani, Ramkumar; Maray, Suresh; Gothandam, K M; Sivamangala, Karthikeyan; Manohar, Prasanth; Bozdogan, Bülent

    2016-10-01

    Carbapenem resistance is disseminating worldwide among Gram-negative bacteria. The aim of this study was to identify carbapenem-resistance level and to determine the mechanism of carbapenem resistance among clinical isolates from two centres in Tamil Nadu. In the present study, a total of 93 Gram-negative isolates, which is found to be resistant to carbapenem by disk diffusion test in two centres, were included. All isolates are identified at species level by 16S rRNA sequencing. Minimal inhibitory concentrations (MICs) of isolates for Meropenem were tested by agar dilution method. Presence of blaOXA, blaNDM, blaVIM, blaIMP and blaKPC genes was tested by PCR in all isolates. Amplicons were sequenced for confirmation of the genes. Among 93 isolates, 48 (%52) were Escherichia coli, 10 (%11) Klebsiella pneumoniae, nine (%10) Pseudomonas aeruginosa. Minimal inhibitory concentration results showed that of 93 suspected carbapenem-resistant isolates, 27 had meropenem MICs ≥ 2 μg/ml. The MIC range, MIC50 and MIC90 were 128 μg/ml, 0.12 and 16 μg/ml, respectively. Fig. 1 . Among meropenem-resistant isolates, E. coli were the most common (9/48, 22%), followed by K. pneumoniae (7/9, 77%), P. aeruginosa (6/10, 60%), Acinetobacter baumannii (2/2, 100%), Enterobacter hormaechei (2/3, 67%) and one Providencia rettgeri (1/1, 100%). PCR results showed that 16 of 93 carried blaNDM, three oxa181, and one imp4. Among blaNDM carriers, nine were E. coli, four Klebsiella pneumoniae, two E. hormaechei and one P. rettgeri. Three K. pneumoniae were OXA-181 carriers. The only imp4 carrier was P. aeruginosa. A total of seven carbapenem-resistant isolates were negatives by PCR for the genes studied. All carbapenem-resistance gene-positive isolates had meropenem MICs >2 μg/ml. Our results confirm the dissemination of NDM and emergence of OXA-181 beta-lactamase among Gram-negative bacteria in South India. This study showed the emergence of NDM producer in clinical isolates of E

  3. Browse Title Index

    African Journals Online (AJOL)

    Issue, Title. Vol 25, No 2 (2005), Yam-based farm practices and nematode problems in stored yams (Dioscorea spp.) in Ghana, Abstract PDF. CK Kwoseh, RA Plowright, J Bridge, R Asiedu. Vol 27, No 2 (2007), Yield, irrigation production efficiency and economic returns of broccoli under variable drip irrigation and lateral ...

  4. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 68 of 68 ... Issue, Title. Vol 12, No 1-2 (2009), Sécurité et ordre politique au Cameroun : entre dynamiques internes et connexions internationales, Abstract PDF. BEP Chantal. Vol 6, No 1-2 (2003), Self-Determination, Nationalism, Development and Pan-Africanism Stuck on the Runway: Are Intellectuals to be Blamed ...

  5. Browse Title Index

    African Journals Online (AJOL)

    Items 551 - 600 of 1463 ... Issue, Title. Vol 15, No 2 (2015), Evaluation of the diagnostic performance and operational characteristics of four rapid immunochromatographic syphilis tests in Burkina Faso, Abstract PDF. FY Bocoum, H Ouedraogo, G Tarnagda, A Kiba, S Tiendrebeogo, F Bationo, B Liestman, S Diagbouga, ...

  6. Browse Title Index

    African Journals Online (AJOL)

    Items 351 - 400 of 400 ... Issue, Title. Vol 9, No 1 (2010), Soft tissue sarcoma of the thigh: Need for angiography in the developing, Abstract PDF. IA Adigun, GA Rahman, KO Ogundipe. Vol 3, No 1 (2004), Spectrum of rheumatic heart disease in Zaria, Northern Nigeria, Abstract. SS Danbauchi, MA Alhassan, SO David, ...

  7. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 183 ... Issue, Title. Vol 62 (2017), #SchoolsOnFire: Criminal justice responses to protests that impede the right to basic education, Abstract PDF. Ann Skelton, Martin Nsibirwa. Vol 45 (2013), 'Pale Face'/'Pointy Face: SA Criminology in Denial, Abstract PDF. S Henkeman. Vol 59 (2017), Aluta continua: Police ...

  8. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 14 of 14 ... Issue, Title. Vol 2, No 1 (2009), Auditory and Respiratory Health Disorders Among Workers in an Iron and Steel Factory, Abstract. GM Abdel – Rasoul, OAE Mahrous, ME Abou Salem, MA Al-Batanony, HK Allam. Vol 2, No 1 (2009), Effect of An Educational Program About Medical Waste Management on ...

  9. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 391 ... Journal Home > Advanced Search > Browse Title Index ... Efficacy of four Rodenticides on the Ghanaian Market, Abstract ... Vol 2, No 1 (2000):, Determination of some wear elements in used car engine oil and oil filter ...

  10. Browse Title Index

    African Journals Online (AJOL)

    Items 251 - 300 of 490 ... Issue, Title. Vol 6, No 2 (2010), Knowledge and patterns of use of highly active antiretroviral therapies in HIV management at Abuja, Nigeria, Abstract. Jill I Okpalugo, US Inyang, K Ibrahim, F Anita, Chinwe V Ukwe, NC Aguwa. Vol 5, No 4 (2009), Knowledge and utilization of the acts in two major ...

  11. Browse Title Index

    African Journals Online (AJOL)

    Items 9951 - 10000 of 11090 ... Issue, Title. Vol 10, No 36 (2011), Study of heavy metals bioaccumulation in the process of vermicomposting, Abstract PDF. MM Aleagha, G Ebadi. Vol 10, No 45 (2011), Study of malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in ...

  12. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 412 ... Issue, Title. Vol 32, No 2 (2013), Seinsverständnis and meaning in Heidegger, Abstract. Rafael Winkler. Vol 21, No 3 (2002), A defense of peace as a human right, Abstract. Patrick Hayden. Vol 26, No 2 (2007), A Kantian stance on teleology in biology, Abstract. AA Cohen. Vol 30, No 1 (2011), A Likely ...

  13. Browse Title Index

    African Journals Online (AJOL)

    Items 251 - 300 of 328 ... Issue, Title. Vol 7, No 1 (2003), Sexual Harassment in Academia in Nigeria: How Real? Details PDF. Olugbenga Jelil Ladebo. Vol 8, No 2 (2004), Shaping the internet for match-making/dating: a challenge for the contemporary Nigerian family institution, Abstract PDF. Wale Adesina. Vol 6, No 1 (2002) ...

  14. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 73 of 73 ... Journal Home > Advanced Search > Browse Title Index ... Vol 13 (2006), The ageing eye” functional changes from cradle to gray: A ... Vol 12 (2005), The evaluation of vision in children using monocular vision acuity and ...

  15. Browse Title Index

    African Journals Online (AJOL)

    Issue, Title. Vol 22, No 2 (2008), Voltammetric determination of heparin based on its interaction with malachite green, Abstract PDF. Xueliang Niu, Weili Zhang, Na Zhao, Wei Sun. Vol 22, No 2 (2008), Voltammetric determination of l-cysteic acid on a 1-[4-(ferrocenyl-ethynyl)phenyl]-1-ethanone modified carbon paste ...

  16. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 577 ... Issue, Title. Vol 20, No 2 (2003), Emergency Contraception: A Global Overview of Knowledge, Attitudes and Practices Among Providers, Abstract PDF. Deborah Haggai. Vol 23 (2006):, Emergency laparotomy for peripartum haemorrhage in Bida North Central Nigeria, Abstract PDF. Sunny Abiodun O ...

  17. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 11090 ... Issue, Title. Vol 12, No 49 (2013), In vitro regeneration of selected Kenyan papaya (Carica papaya L.) lines through shoot tip culture, Abstract PDF. Naomi Nzilani Mumo, Fredah Karambu Rimberia, George Edward Mamati, Agnes Wanjiru Kihurani. Vol 7, No 12 (2008), In vitro regeneration of Turkish ...

  18. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 221 ... Issue, Title ... Vol 38 (2010), Soft drink consumption of Grade 4 and Grade 7 learners in the Wynberg area, City of Cape Town, South .... Vol 42 (2014), The meaning of food for obese men: a qualitative study, Abstract PDF.

  19. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 1215 ... Journal Home > Advanced Search > Browse Title Index. Log in or ... Vol 12, No 1 (2018), Analysis of the effects of frequent strikes on academic performance of students in universities in Nigeria: Edo State as a focal point, Abstract PDF ... Vol 6, No 1 (2012), Appraisal as a Determinant for Adequate ...

  20. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 20 of 20 ... Issue, Title. Vol 9, No 2 (2000), Age dependent changes in the hypothalamic amino acid neurotransmitters in response to nicotine, Abstract. NM Radwan, NA Ahmed, YAM Aly. Vol 9, No 2 (2000), Autoantibodies, ocular and auditory changes in patients with vitiligo, Abstract. AE Fathia, EA Nagwa, ...

  1. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 76 of 76 ... Issue, Title. Vol 6, No 1 (2013), Integrating Sustainability into the Real Estate Valuation Process: A Nigerian Perspective, Abstract PDF. G K Babawale, B A Oyalowo. Vol 5, No 1 (2012), Internalising internationa valuation standards: Relevance and applicability issues in the Nigerian context, Abstract PDF.

  2. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 201 ... Issue, Title. Vol 12, No 1 (2006), Conservative management of cervical ectopic pregnancy: case report, Abstract PDF. TD Naidoo, MR Ramogale, J Moodley. Vol 18, No 2 (2012), Contraceptive use and associated factors among South African youth (18 - 24 years): A population-based survey, Abstract ...

  3. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 183 of 183 ... Issue, Title. Vol 9, No 1 (2004), Socio-economic constraints affecting youths involvement in national economic development, Abstract. Josephine U Nwagwu. Vol 12, No 2 (2007), Stabilizing Potential Of Cement-Fly Ash Mixture On Expansive Clay Soil, Abstract. OO Amu, AB Fajobi, SO Afekhuai. Vol 11 ...

  4. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 76 ... Issue, Title. Vol 16, No 2 (2006), A profile of the theatre procedures in paediatrict ophthalmic practice, Abstract. E O Onwasigwe. Vol 15, No 2 (2005), Abdominal cocoon, Abstract. Abdulrasheed K Adesunkanmi, Tajudeen A Badmus, Olukayode Ogundoyin, Akinwumi B Ogunrombi. Vol 18, No 1 (2008) ...

  5. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 647 ... Issue, Title. Vol 13, No 2 (2010), 'N toekomstige perspektief op grondwetlike stabiliteit, Abstract PDF. F.W de Klerk. Vol 18, No 5 (2015), Cloete murray and Another v Firstrand bank ltd t/a Wesbank [2015] ZASCA 39A, Abstract PDF. M Laubscher. Vol 15, No 5 (2012), Cave Pecuniam: Lawyers as ...

  6. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 15 of 15 ... Issue, Title. Vol 1, No 1 (2008), Assessment Of Ophthalmic Patients' Satisfaction In Owo, Abstract. CO Omolase, CO Fadamiro, BO Omolase, AS Aina, EO Omolade. Vol 3, No 1 (2010), Case Report: Strongyloides stercoralis coinfection in a Nigerian with HIV. Abstract. A.A Oyekunle, R.A.A Bolarinwa, O.A ...

  7. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 15 of 15 ... Issue, Title. Vol 1, No 1 (2007), An Action Five Strategy For Bridging The Gender Gap In Academic Research Activities In African Universities. The Case of Nigeria, Abstract PDF. DN Okorie, OG Agabi, CM Uche. Vol 1, No 1 (2007), Book Review: Confronting sexual harassment in Ghanaian Universities ...

  8. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 93 ... Issue, Title. Vol 5 (2013), A cost-effective Geographic Information Systems for Transportation (GIS-T) application for traffic congestion analyses in the Developing World, Abstract PDF. E Agyemang. Vol 3 (2011), A Historical and Gendered Perspective on HIV / AIDS in Botswana, Abstract PDF. J Hesselberg ...

  9. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 327 ... Issue, Title. Vol 10, No 4 (2016), Omphalocoeles: A decade in review, Abstract PDF. S Singh, A Madaree. Vol 2, No 4 (2008), Ortner syndrome, Abstract PDF. E Meyer, NE Jones, LJ Zühlke. Vol 10, No 3 (2016), Outcome of children admitted to a general highcare unit in a regional hospital in the ...

  10. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 814 ... Issue, Title. Vol 21, No 2 (2016), A 10 years trend of peptic ulcer disease and other gastrointestinal disorders in northern Uganda, Abstract PDF. T.R. Okello, D.M. Ogwang, I Pecorella. Vol 21, No 2 (2016), A 2-years description of traumatic brain injury admissions in Tikur Anbessa Specialized Hospital ...

  11. Browse Title Index

    African Journals Online (AJOL)

    Items 301 - 350 of 577 ... Issue, Title. Vol 32, No 2 (2015), Late arrival in hospital during labour: any correlation with materno-foetal outcome? The state specialist hospital, Asubiaro, Osogbo Experience. Abstract PDF. OO Awolola. Vol 30, No 2 (2013), Late Reproductive Effects of Cancer Treatment in Young People, Abstract ...

  12. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 319 ... Issue, Title. Vol 23, No 2 (2016), Carica papaya juice enhanced in-vitro cell proliferation better than freeze-dried PBS extract using scratch assay, Abstract. A.B. Nafiu, E Abdulaziz, M.T. Rahman. Vol 23, No 2 (2016), A comparative study of the ownership and utilization of insecticide treated nets in ...

  13. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 52 ... Issue, Title. Vol 15 (2000), Ammi analysis of maize yield trials in South-Western Nigeria, Abstract. SR Ajibade, BA Ogunbodede. Vol 20 (2006), Association of yield with some agronomic characters in potatoes in a cool mid-altitude location, Abstract. CO Amadi, EE Ene Obong. Vol 20 (2006), Casein (CSN3) ...

  14. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 240 of 240 ... Issue, Title. Vol 8, No 4 (2005), Status equipment in primary health centres of Tafa Lga, North Central Nigeria, Abstract. MN Sambo, I Lewis, K Sabitu. Vol 10, No 1 (2007), Stroke at a tertiary medical institution in Northern Nigeria: Patients\\' profile and predictors of outcome, Abstract. KW Wahab, MU ...

  15. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 249 ... Issue, Title. Vol 10, No 1 (2010), Ye Shakoch Chilot (the court of the sheikhs): A traditional institution of conflict resolution in Oromiya zone of Amhara regional state, Ethiopia, Abstract PDF. M Zeleke. Vol 15, No 3 (2015), A comparative analysis of the Post- Arab Spring National Dialogues in Tunisia and ...

  16. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 670 ... Issue, Title. Vol 9, No 2 (2012), Business Planning and the Economic Growth of Small and Medium Scale Enterprises in Nigeria, Abstract. Egbe Aneozeng A, Ejoh Ndifon Ojong, Obo Ekpenyong Bassey. Vol 11, No 2 (2014), Calabar Humaphors: An Analysis of Selected Jokes in Nigerian Stand Up ...

  17. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 107 of 107 ... Issue, Title. Vol 6, No 1 (2017), The Ophthalmic status manifestations of nutritional and lifestyle disorders of men in a peri urban community in Ghana, Abstract PDF. F. Vuvor, M. Steiner-Asiedu, F.K. Saalia. Vol 2, No 1 (2013), Thyroid Disorders in Accra, Ghana: A Retrospective Histopathological Study ...

  18. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 165 ... Issue, Title. Vol 30 (2005), Digitisation projects at the University of Cape Town Libraries, Abstract. Janine Dunlop, Lesley Hart. Vol 24 (2002), DISA: an African Perspective on Digital Technology, Abstract. Michele Pickover, Dale Peters. Vol 30 (2005), Doing it right – or are we? Basic principles in the ...

  19. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 251 ... Issue, Title. Vol 55 (2014), 20 Years of democracy: Transforming the public service, Abstract. A Ruiters. Vol 63 (2016), Zemk' iinkomo magwala ndini! Wake up! The cows are being stolen! Abstract. Sipho Pityana. Vol 56 (2014), A layperson's guide to Nene's budget statement, Abstract. B Turok.

  20. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 1007 ... Issue, Title. Vol 11, No 1 (1997), (+)-Floribundone 3 from the pods of Senna septemtrionalis, Details PDF. Gizachew Alemayehu, Bekuretsion Woldeyesus, Berhanu M Abegaz. Vol 14, No 1 (2000), 11α-Hydroxy muzigadiolide, a novel drimane sesquiterpene from the stem bark of warburgia ugandensis ...

  1. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 356 ... Issue, Title. Vol 27, No 3 (2014), A desire for weight loss in season increases disordered eating behaviour risk and energy deficiency in athletes, Abstract PDF. HH Wright, R Ford, CR Botha. Vol 29, No 3 (2016), A review of infant and young child feeding practice in hospital and the home in KwaZulu-Natal ...

  2. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 66 ... Issue, Title. Vol 48, No 1-2 (2015), A hierarchical modeling of information seeking behavior of school teachers in rural areas of Nigeria, Abstract. Manir Abdullahi Kamba. Vol 49, No 1-2 (2016), Access to electronic information resources by students of federal college of education in south east Nigeria ...

  3. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 683 ... Issue, Title. Vol 54, No 1 (2006), Bovine tuberculosis survey in urban and peri urban dairy farms in coastal humid region of Tanga, Tanzania, Abstract. ES Swai, G Shirima, S Bwanga, W Moshy. Vol 60, No 3 (2012), Browsing capacity and nutritive value of indigenous browses in a tropical Coastal ...

  4. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 387 ... Issue, Title. Vol 15, No 2 (2015), Introduction to Christian philosophy, Abstract. Charles Ogundu Nnaji. Vol 8, No 2 (2006), Is Quantum Mechanics a Complete Theory?: A Philosophical Defense of Einstein's Position, Abstract. U O Egbai. Vol 10, No 1 (2007), Jesus in Africa, Abstract. FF Edet. Vol 10, No ...

  5. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 98 of 98 ... Issue, Title. Vol 4, No 1 (2016), First-year seminar intervention: Enhancing firstyear mathematics performance at the University of Johannesburg, Abstract PDF. Melanie Jacobs, Estherna Pretorius. Vol 5, No 2 (2017), From Inky Pinky Ponky to Improving Student Understanding in Assessment: Exploring the ...

  6. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 167 of 167 ... Issue, Title ... Vol 2, No 2 (2013), Women and the Leadership Paradigm: Bridging the Workplace Gender-Gap in Nigeria, Abstract PDF ... Vol 5, No 2 (2016), Women's participation and gender issues in local governance ...

  7. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 110 ... Issue, Title. Vol 10, No 1 (2003), Incidence and Determinants of Child Labour in Nigeria: Implications for Poverty Alleviation, Abstract. Benjamin Chiedozie Okpukpara, Ngozi Odurukwu. Vol 20, No 1 (2013), Inflation and capacity utilisation in Nigeria's manufacturing sector, Abstract. OA Ishola. Vol 19, No ...

  8. Browse Title Index

    African Journals Online (AJOL)

    Items 251 - 300 of 367 ... Issue, Title. Vol 43 (2014), Some interlingual communicative challenges for foreign African interpreters in South African courtrooms, Abstract PDF. SE Usadolo, E Kotze. Vol 29 (1996), South Africa's new language policy in the context of the organisation for African unity's language plan of action for ...

  9. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 89 ... Issue, Title ... of two-phased approaches to load balancing in cloud computing, Abstract ... Vol 19, No 1 (2012), Assessing Network Services and Security in ... Vol 23, No 1 (2016), Cloud model construct for transaction-based ...

  10. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 198 ... Issue, Title ... Vol 13, No 1 (2015), Biometric Enhancement of Home and Office Security to Reduce Assassinations in Nigeria, Abstract PDF ... Vol 9, No 1 (2013), Cloud Computing: Key to IT Development in West Africa ...

  11. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 198 of 198 ... Issue, Title ... scheme for QoS and energy conservation in cloud computing, Abstract PDF ... Vol 9, No 1 (2013), Performance and Security Evaluation of ... Vol 18, No 1 (2017), Reducing capital flight through local cloud ...

  12. Browse Title Index

    African Journals Online (AJOL)

    Items 251 - 300 of 652 ... Journal Home > Advanced Search > Browse Title Index ... Vol 18, No 7 (2015), Introduction to virtual property: Lex virtualis ipsa ... Vol 17, No 1 (2014), Legal challenges relating to the commercial use of outer space, with ...

  13. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 170 of 170 ... Issue, Title. Vol 20, No 2 (2004), The Impact of Mine Closures on Rural Population Dynamics: The Case of Zhombe in Kwekwe District, Midlands Province, Zimbabwe, Abstract. Crescentia Madebwe. Vol 29, No 1 (2013), The Influence of Organisational Culture and Job Satisfaction on Intentions to ...

  14. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 263 ... Issue, Title. Vol 1, No 2 (2002), Effect of Light and Darkness on Packed Cell Volume in the Rat, Abstract. A. A. OSINUBI, F. I. DURU, C. C. NORONHA, A. O. OKANLAWON. Vol 4, No 1 (2005), Effect of Marijuana Smoking on Blood Chemistry and Serum Biogenic Amines Concentrations in Humans ...

  15. Browse Title Index

    African Journals Online (AJOL)

    Items 751 - 800 of 846 ... Journal Home > Advanced Search > Browse Title Index ... Vol 9, No 3S (2017): Special Issue, The effect of torrefaction on oil palm ... core competency skills of IRBM tax auditors towards their performance, Abstract PDF ... of exchange rates behavior in Malaysia by using NATREX model, Abstract PDF.

  16. Browse Title Index

    African Journals Online (AJOL)

    Issue, Title. Vol 38, No 1 (2004), Book Review: Unexpected Voices – Theory, Practice and Identity in the Writing Classroom. Abstract. Charly Dyers. Vol 38, No 1 (2004), Book Review: Shelley Angelil-Carter: Stolen Language? Plagiarism in Writing. Abstract. Elizabeth de Kadt. Vol 37, No 1 (2003), Book Review: The Green ...

  17. Browse Title Index - AJOL

    African Journals Online (AJOL)

    Items 501 - 508 of 508 ... Issue, Title. Vol 33, No 2 (2011), Visuele stereotipering van sportvroue in die sportmedia, Abstract. M Brandt, A Carstens. Vol 30, No 1 (2008), Volunteers\\' perceptions of benefits derived from volunteering: an empirical study, Abstract. J Surujlal, M Dhurup. Vol 33, No 1 (2011), Was the Conconi test ...

  18. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 108 of 108 ... Issue, Title. Vol 8, No 2 (2016), The status and challenges of clinical informatics development in South Africa, Abstract PDF. Abayomi Kehinde Owolabi, Thokozani Patrick Mhlongo, Neil Evans. Vol 4, No 1 (2012), The stuttering implementation of language policies in the South African education system ...

  19. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 100 ... Issue, Title. Vol 28 (2013): Special Issue, Occurrence of Cryptosporidium and Giardia in domestic animals in peri-urban communities of Kafue district, Zambia, Abstract. J Siwila, IGK Phiri, HI Enemark, M Nchito, A Olsen. Vol 26, No 1 (2009), Occurrence of foot and mouth disease serotypes in Tanzania: A ...

  20. Browse Title Index

    African Journals Online (AJOL)

    Items 801 - 850 of 11090 ... Issue, Title. Vol 10, No 61 (2011), Analysis of chemical constituents in medicinal plants of selected districts of Pakhtoonkhwa, Pakistan, Abstract PDF. I Hussain, R Ullah, J Khan, N Khan, M Zahoor, N Ullah, MuR Khattak, FA Khan, A Baseer, M Khurram. Vol 10, No 77 (2011), Analysis of chloroplast ...

  1. Browse Title Index

    African Journals Online (AJOL)

    Items 501 - 550 of 670 ... Issue, Title. Vol 11, No 4 (2014), Strategies for Fostering Creativity Among Business Education Graduates in Nigeria, Abstract. BO Nwosu, KE Ojo. Vol 13, No 1 (2015) ... Vol 10, No 1 (2013), The Challenges Facing Accounting Education: The Nigerian Experience, Abstract. OR Okolie. Vol 5 (2008), The ...

  2. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 198 ... Issue, Title ... Vol 7, No 1 (2013), Enterprise Cloud Adoption: Leveraging on the Business ... Load Balancing And Job Scheduling In Cloud Computing ... Vol 13, No 1 (2015), ICT-Based Framework for Improved Food Security in Nigeria ... Vol 5, No 1 (2012), IT-Based Solutions to the Electoral System in ...

  3. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 1117 ... Journal Home > Advanced Search > Browse Title Index ... Vol 13, No 3 (2007):, an edu-ethical perspecitve on the nature of truth: case studies in elite ... 2009: September: Supplement, An empirical study of university ...

  4. Browse Title Index

    African Journals Online (AJOL)

    Issue, Title. Vol 20, No 1 (2015), Assessment of iron status among preschool children (6 to 59 months) with and without malaria in Western Province, Kenya, Abstract. I Kisiangani, C Mbakaya, A Makokha, D Magu. Vol 20, No 1 (2015), Assessment of iron status among preschool children (6 to 59 months) with and without ...

  5. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 232 ... Issue, Title. Vol 5 (2003), Pre-School Education for a Democratic Society: Identifying Views of Stakeholders in Tanzania, Abstract. Willy LM Komba, Satoki T Mahenge, Gadi Koda. Vol 13, No 2 (2012), Process of Assuring Quality in Counselling at the National Open University of Nigeria: A Critique ...

  6. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 1732 ... Journal Home > Advanced Search > Browse Title Index ... Vol 10, No 3 (2007), An Audit Of Perioperative Cardiac Arrest At ... Vol 11, No 4 (2008), An Audit Of Rejected Repeated X-ray Films As A Quality Assurance ...

  7. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 1038 ... Issue, Title. Vol 31, No 2 (2009), Assessing the utility of a continuous, underway fish egg sampler (CUFES) for sampling zooplankton, Abstract. S Sono, CL Moloney, CD van der Lingen. Vol 38, No 4 (2016), Assessing trophic adaptability is critical for understanding the response of predatory fishes to ...

  8. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 101 ... Issue, Title. Vol 3, No 4 (2014), Chlamydia trachomatis IgG antibodies seroprevalence among students in two tertiary institutions in Anambra state, Nigeria: a comparative study, Abstract PDF. CB Duru, FE Emele, ED Adinma, CO Ifeadike, KA Uwakwe, AO Oluboyo, BO Oluboyo, C Abejegah. Vol 2, No 1 ...

  9. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 367 ... Issue, Title. Vol 42 (2013), Nursing the Cure: A Phonetic Analysis of /ʊə/ in South African English, Abstract PDF. I Bekker. Vol 1 (1980), Nuwe ontwikkelings binne chomsky se teorle van kerngrammatika, Abstract PDF. J Maartens. Vol 42 (2013), Obligatory Reflexivity in a Minimalist Grammar of ...

  10. Browse Title Index

    African Journals Online (AJOL)

    Items 651 - 700 of 1007 ... Issue, Title. Vol 4, No 1 (1990), Kinetics of oxidation of β-diimihe macrocyclic complexes and accessibility of six-coordinate copper(III) complexes generated by electrochemical oxidation of copper(II) complexes, Abstract PDF. Mohamed A. Khalifa. Vol 14, No 2 (2000), Kinetics of periodate oxidation of ...

  11. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 1020 ... Issue, Title ... Vol 48, No 2 (2006), Barriers to HIV Care and Treatment by Doctors: A review of the literature. ... Vol 48, No 5 (2006), Breast cancer – early detection and screening in South African women from the ...

  12. Browse Title Index

    African Journals Online (AJOL)

    Issue, Title. Vol 23, No 2 (2011), Dynamique foliaire et croissance du maïs: Application du modèle «STICS» en conditions tropicales en RD-Congo, Abstract PDF. MM Lufuluabo, RV Kizungu, KK Nkongolo. Vol 18, No 1 (2006), Dynamique spatio-temporelle des populations d\\'Altises Podagrica spp. (Coleoptera ...

  13. Browse Title Index

    African Journals Online (AJOL)

    Items 251 - 300 of 2005 ... Issue, Title. Vol 92, No 4 (2015), Blood Pressure and Obesity Index Assessment in a Typical Urban Slum in Enugu, Nigeria, Abstract. GI Ahaneku, CU Osuji, OC Oguejiofor, BC Anisiuba, VO Ikeh, JE Ahaneku. Vol 80, No 10 (2003):, Blood pressure control in a population where antihypertensives are ...

  14. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 661 ... Journal Home > Advanced Search > Browse Title Index. Log in or Register to get access to full text downloads. .... A El-Mahdy, B Bolduc, J Upadhyay, R Shoukr, A Khoury. Vol 19, No 1 (2013), Factors affecting lower calyceal stone clearance after Extracorporeal shock wave lithotripsy, Abstract PDF.

  15. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 985 ... Journal Home > Advanced Search > Browse Title Index ... Vol 17 (2010), Alternating Direction Implicit Finite Difference Time Domain Acoustic Wave Algorithm, Abstract. E Ikata .... Vol 17 (2010), Analytic derivation of the wave profile and phase speed of sixth order Stokes waves in deep water, Abstract.

  16. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 286 ... Issue, Title. Vol 2, No 3-4 (2008), Impact of fire wood collection on trees species diversity in Bauchi state, Nigeria, Abstract. A Nura, A Ibrahim, I Mohammed, U Haruna. Vol 5, No 3 (2011), Impact of national special program for food security in Abia State, nigeria, Abstract. CO Emerole. Vol 5, No 1 (2011) ...

  17. Browse Title Index

    African Journals Online (AJOL)

    Items 351 - 400 of 979 ... Issue, Title. Vol 45, No 9 (2003), Erectile dysfunction: A GP's guide to clinical assessment, Abstract PDF. PJ Harden. Vol 47, No 4 (2005), Ethical Issues in Family Practice: My Culture – Right or Wrong? Abstract PDF. GA Ogunbanjo, D Knapp van Bogaert. Vol 59, No 3 (2017), Ethical issues with ...

  18. Browse Title Index

    African Journals Online (AJOL)

    Items 301 - 350 of 745 ... Issue, Title. Vol 9, No 3 (1999), Frequency And Outcome In AIDS Patients In A University Teaching Hospital – A Five Year Review, Abstract. SA Ogun, OO Adelowo, AEA ... Vol 18, No 2 (2008), Good cllinical practice in clinical drug trials - What you need to know, Abstract. K Soyebi, Y Abosede, HAB ...

  19. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 217 ... Browse Title Index. Journal Home > Advanced ... Vol 13, No 1 (2016), Access to specialized surgical care, Abstract PDF. H Saidi ... Vol 9, No 2 (2012), Clinical Assessment of the Palmaris Longus – Accuracy of common tests, Abstract PDF ... Vol 11, No 2 (2014), Clinical trials in Surgery, Abstract PDF.

  20. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 633 ... Issue, Title. Vol 19, No 1 (2009), Delays in Tuberculosis Treatment and Associated Factors in Jimma Zone, Southwest Ethiopia, Abstract PDF. Ayalew Tegegn, Meseret Yazachew. Vol 26, No 1 (2016), Delivery Site Preferences and Associated Factors among Married Women of Child Bearing Age in ...

  1. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 4119 ... Issue, Title. Vol 86, No 2 (1996), A re-evaluation of isotope screening for skeletal metastases in nodenegative breast cancer, Abstract PDF. C.A. Gudgeon, I.D. Werner, D.M. Dent. Vol 104, No 6 (2014), A reflection on the South African Medical Association – past, present and future, Abstract PDF.

  2. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 1006 ... Issue, Title. Vol 49, No 8 (2007), Clinical approach to a patient with abnormal uterine bleeding, Abstract PDF. B G Lindeque. Vol 57, No 5 (2015), Clinical evidence in the management of swimmer's ear, Abstract PDF. Andre Marais. Vol 50, No 1 (2008), Clinical features of Systemic Lupus ...

  3. Browse Title Index

    African Journals Online (AJOL)

    Items 701 - 750 of 1010 ... Issue, Title. Vol 6, No 2 (1998), Performance et stabilité de rendement des génotypes de patate douce dans divers environnements à l'est du Congo, Abstract. P Phemba, T Mutombo, N B Lutaladio, E E Carey. Vol 22 (2014): Supplement, Performance of Artemia shell-free embryos, Moina micrura and ...

  4. Browse Title Index

    African Journals Online (AJOL)

    Issue, Title. Vol 17 (2005), A. C. conduction behaviour in amorphous WO3/CEO2 thin film, Abstract. B Yagoubi, C A Hogarth, A Boukorrt. Vol 16 (2003), A lossless image compression algorithm using variable block size segmentation, Abstract. Z Brahimi, K A Saadi, N Baraka. Vol 15 (2003), Analysis method of wavelet ...

  5. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 97 of 97 ... Journal Home > Advanced Search > Browse Title Index ... Vol 20, No 2 (2008), Research Note: Anthropometric data of the foot of ... Vol 26, No 1 (2014), Validation of the Automation Attitude Questionnaire for Airline Pilots ...

  6. Titles of Midas

    Directory of Open Access Journals (Sweden)

    G. L. Huxley

    2001-09-01

    Full Text Available The Phrygian inscription on the tomb at Yazılıkaya (8th century gives Midas the titles wanax and lawagtas, paralled in Mycenaean, and there were strong connections between his dynasty and Greek Aeolis.

  7. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 333 ... Issue, Title. Vol 15, No 1 (2016), Irrigation potential of Inuakpa in Odukpani local government of Cross river using Kostiakov model, Abstract PDF. B.O. Unuigbe, K.I. Ofem, N.R.B. Antigha. Vol 2, No 2 (2003), LABOUR USE IN SMALL-SCALE YAM PRODUCTION IN QUA'AN PAN LOCAL GOVERNMENT ...

  8. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 644 ... Issue, Title. Vol 19, No 2 (2007), A qualitative study of medical student socialization in Malawi\\'s College of Medicine: Clincal crisis and beyond, Abstract PDF. C Wendland, C Bandawe. Vol 19, No 2 (2007), A qualitative study of medical student socialization in Malawi\\'s College of Medicine: Preclinical ...

  9. Browse Title Index

    African Journals Online (AJOL)

    Issue, Title. Vol 13, No 2 (2013), Using Mindfulness as a Teaching Aid for Phenomenology, Abstract PDF. IR Owen. Vol 8, No 1 (2008), Were Nietzsche's Cardinal Ideas – Delusions? Abstract PDF. Eva M Cybulska. Vol 12, No 1 (2012), What did you learn in school today? Abstract PDF. Carina Henriksson. Vol 5, No 1 (2005) ...

  10. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 265 ... Issue, Title. Vol 35, No 2 (2008), Choice of place for childbirth: prevalence and correlates of utilization of health facilities in Chongwe district, Zambia, Abstract PDF. AN Hazemba, S Siziya. Vol 43, No 1 (2016), Clinical and Radiological Features of Multiple Myeloma Patients at the University Teaching ...

  11. Browse Title Index

    African Journals Online (AJOL)

    Issue, Title. Vol 88, No 8 (1998), New birth and death registration forms - a foundation for the future, a challenge for health workers? Abstract PDF. Debbie Bradshaw, Danuta Kielkowski, Freddy Sitas. Vol 83, No 3 (1993), New estimates of infant and child mortality for blacks in South Africa, 1968-1979, Abstract PDF.

  12. Browse Title Index

    African Journals Online (AJOL)

    Items 151 - 200 of 643 ... Issue, Title. Vol 18, No 2 (2015), Contraceptive Knowledge and Compliance with Guidelines for Providing Contraceptive Services by Patent Medicine Vendors In Ibadan North Local Government Area, Nigeria, Abstract PDF. OO Ajayi, AJ Ajuwon. Vol 16, No 2 (2013), Coping Strategy for Food Security ...

  13. Browse Title Index

    African Journals Online (AJOL)

    Items 851 - 900 of 1006 ... Issue, Title. Vol 54, No 2 (2012), The effect of the introduction of a standard monitoring protocol on the investigations performed on the metabolic control of type 2 diabetes at Addington Hospital Medical Outpatients Department, Durban, South Africa, Abstract PDF. JM Gill, A Ross, F Pirie, ...

  14. Browse Title Index

    African Journals Online (AJOL)

    Issue, Title. Vol 8, No 2 (2016): Supplement, Using operative models (ICF and CBR) within an interprofessional context to address community needs, Abstract PDF. A Rhoda, F Waggie, G.C. Filies, J.M. Frantz. Vol 2, No 1 (2010), Using portfolios to assess professional competence and development in medical laboratory ...

  15. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 412 ... Issue, Title. Vol 30, No 3 (2011) ... Transferring the principle of double effect from war to business, Abstract. G. J. Rossouw ... Vol 22, No 2 (2003), Can more business ethics teaching halt corruption in companies? Abstract.

  16. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 155 ... Issue, Title. Vol 12 (2012), Political Dissent and Autonomy in Wum Local Government, Southern (West) Cameroons, 1957 – 1968, Abstract. TP Mbeum. Vol 9 (2009), Post-Emancipation Slave Commerce: Increasing Child Slave Trafficking and Women's Agency in Late Nineteenth-century Ghana ...

  17. Browse Title Index

    African Journals Online (AJOL)

    Items 451 - 500 of 581 ... Issue, Title. Vol 30, No 1 (2016), Risky sexual behaviour and associated factors among students of Debre Tabor University, Northwest Ethiopia: a cross-sectional study, Abstract PDF. Awoke Derbie, Mekonnen Assefa, Daniel Mekonnen, Fantahun Biadglegne. Vol 28, No 1 (2014), Road traffic accident: ...

  18. Browse Title Index

    African Journals Online (AJOL)

    Items 451 - 500 of 1346 ... Issue, Title. Vol 32, No 1 (2015), Fire and the dynamics of two unpalatable grass species (Cymbopogon pospischilii and Elionurus muticus) in a semi-arid climate, Abstract. Hennie A Snyman. Vol 8, No 1 (1973), Fire as a method of controlling macchia (Fynos) vegetation on the Amathole Mountains of ...

  19. Browse Title Index

    African Journals Online (AJOL)

    Issue, Title. Vol 43, No 2 (2006), Review: "'n Wonderlike geweld. Jeugherinneringe", By Elsa Joubert (2005), Abstract PDF. Henriette Roos. Vol 53, No 1 (2016), Review: Breyten Breytenbach, A Monologue in Two Voices, Abstract PDF. Andy Carolin. Vol 53, No 1 (2016), Review: The Shadow of the Hummingbird, Abstract ...

  20. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 103 ... Issue, Title ... SE Edusah, E Osei-Tutu ... Vol 6, No 2 (2016), Interrelationships among unemployment, inflation and economic growth in Nigeria, Abstract .... Vol 4, No 3 (2014): Special Edition, Socio-cultural Issues for ...

  1. Browse Title Index

    African Journals Online (AJOL)

    Items 4351 - 4386 of 4386 ... Issue, Title. Vol 107, No 6 (2017), When students become patients: TB disease among medical undergraduates in Cape Town, South Africa, Abstract PDF. H van der Westhuizen, A Dramowski. Vol 106, No 4 (2016), Where do children die and what are the causes? Under-5 deaths in the Metro West ...

  2. Browse Title Index

    African Journals Online (AJOL)

    Issue, Title. Vol 10, No 2 (2014), Sorindeia warneckei Engl. (Anacardiaceae), une espèce multi-usagère de la dépression de la Lama au Togo, Abstract PDF. A Akodewou, S Akpavi, M Dourma, K Batawila, KB Amegnaglo, W Atakpama, K Akpagama. Vol 10, No 1 (2014), Sterculia setigera Del.: influence de quelques ...

  3. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 126 ... Issue, Title. Vol 8, No 2 (2016), 2010 FIFA World Cup stadium investment: Does the post-event usage justify the expenditure? Abstract PDF. Luke Humphrey, Gavin Fraser. Vol 6, No 1 (2014), 7Implication of mergers and acquisitions on stock returns before and during the 2007–2009 credit crunch: An ...

  4. Association between hypoalbuminemia and mortality among subjects treated with ertapenem versus other carbapenems: prospective cohort study.

    Science.gov (United States)

    Zusman, O; Farbman, L; Tredler, Z; Daitch, V; Lador, A; Leibovici, L; Paul, M

    2015-01-01

    The aim of this study was to determine whether ertapenem, being highly protein bound, is less effective than other carbapenems in the presence of hypoalbuminemia. In a prospective cohort study, we included adults with clinically and microbiologically documented infections caused by carbapenem-susceptible Enterobacteriaceae who were hospitalized in a tertiary medical center from March 2010 to September 2012. We tested whether hypoalbuminemia (serum albumin carbapenem drug and the interaction between albumin and the carbapenem. Of 279 individual subjects included, 173 were treated with ertapenem and 106 with I/M. The odds ratio (OR) for 30-day mortality with hypoalbuminemia was 4.6 (95% confidence interval (CI) 2.1-10.1) among subjects with ertapenem versus 1.2 (95% CI 0.5-2.70) with I/M (p = 0.02 for difference between groups). In the regression model, the interaction between carbapenem type and albumin levels was significant (p = 0.03); for ertapenem lower albumin levels were associated with increased 30-day mortality (OR 2.45, 95% CI 1.19-5.05), while for I/M the change was not significant (OR 0.67, 95% CI 0.31-1.41). The model suggests that the risk of death for ertapenem-treated subjects quintupled when albumin was 2 g/dL compared to 4 g/dL. Hypoalbuminemia was associated with mortality significantly more among subjects treated with ertapenem compared to subjects treated with I/M. The effectiveness of current dosing schemes of ertapenem in subjects with significant hypoalbuminemia should be revisited. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  5. Carbapenem use in French hospitals: A nationwide survey at the patient level.

    Science.gov (United States)

    Gauzit, Rémy; Pean, Yves; Alfandari, Serge; Bru, Jean-Pierre; Bedos, Jean-Pierre; Rabaud, Christian; Robert, Jérôme

    2015-12-01

    The objective of this study was to evaluate the characteristics of carbapenem use in French healthcare settings in order to guide future actions. Healthcare facilities voluntarily participated in a nationwide cross-sectional survey in 2011. Medical data and reasons for carbapenem treatment (CPR) and discontinuation were recorded for all patients treated with carbapenems. A total of 2338 patients were recorded by 207 facilities. The median duration of CPR was 8 days, and 31.4% of patients received CPR for >10 days. An antibiotic consultant was involved in the initial choice of CPR in 36.8% of cases. CPR was chosen on an empirical (EP) basis for 1229 patients (52.6%), mainly because of severe sepsis (48.6%) or a perceived risk of bacterial resistance (33.7%). Among EP patients, de-escalation was more frequent in the case of intervention of an antibiotic consultant (35.1%) than without intervention (22.9%) (Pcarbapenems or to fluoroquinolones. Among the latter, de-escalation was performed in 59 cases (14.9%). The intervention of an antibiotic consultant did not favour de-escalation in this group. In conclusion, carbapenems are frequently used for treating suspected or confirmed multidrug-resistant bacteria, and overall CPR duration is long. De-escalation is frequently not implemented despite isolates being susceptible to other drugs. More frequent antibiotic consultant intervention may help to decrease carbapenem use in the case of EP treatment. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  6. Phenotypic and genotypic characterization of Klebsiella pneumoniae strains with reduced susceptibiliy to carbapenems

    Directory of Open Access Journals (Sweden)

    Simone Ambretti

    2009-12-01

    Full Text Available Reduced susceptibility to carbapenems in Gram-negative pathogens is an emerging feature of the antibiotic-resistance phenomenom Reports about strains resistant to this class of antibiotics among Enterobacteriaceae, particularly in Klebsiella pneumoniae, are increasing.The aims of this study were to assess the incidence of Klebsiella pneumoniae with reduced susceptibility to carbapenems in Bologna area and to carry out the characterization of these strains.The study included isolates of K. pneumoniae that showed reduced susceptibility to carbapenems, as detected by an automated system (Vitek2, bioMérieux. Between January and May 2009, 26 strains were collected (mainly isolated from urinary samples.These isolates were tested for susceptibility to carbapenems by E-test, to define MIC values for meropenem and ertapenem. Moreover, to detect the production of metallo-beta lactamases (MBL and carbapenemases (KPC were respectively performed the Etest with imipenem and imipenem/EDTA (IPM-IPM/EDTA and the modified Hodge test. Susceptibility assays performed by E-test showed that 25/26 strains were susceptible to meropenem, while for ertapenem 20/26 strains resulted resistant.The modified Hodge test was positive for 1 strain, while all the isolates were negative to the IPM-IPM/EDTA E-test.These results show that, as recently reported, the majority of strains of K. pneumoniae exhibiting reduced susceptibility to carbapenems, especially to ertapenem, are characterized by the production of ESBLs, which likely is associated with the loss of porins. On the other side, one strain was found to produce KPC and this finding confirms that the diffusion of carbapenemases producing K. pneumoniae has also to be considered in this geographic area.

  7. Risk factors and outcomes of carbapenem-resistant Klebsiella pneumoniae infections

    Directory of Open Access Journals (Sweden)

    Eleonora Pistella

    2016-12-01

    Full Text Available In the nosocomial setting, antimicrobial-resistant Enterobacteriaceae are a growing challenge, and alarming trends in resistance are currently reported all over the world. Isolates of Enterobacteriaceae producing ampC β-lactamases and extended spectrum β-lactamases are endemic in many hospitals, and are frequently resistant also to other classes of antibiotics, such as fluoroquinolones and aminoglycosides. The risk of infections due to multi-drug resistant strains should be considered also for outpatients who have had recent contact with the health system. Both nosocomial and health-care associated infections should be treated with a combination of antibiotics active against multi-drug resistant Gram negative and methicillin-resistant Staphylococcus aureus. In the absence of effective antimicrobial stewardship programs, this aggressive therapeutic approach might lead to abuse of broad-spectrum antibiotics, with consequent increase in resistances. To contain the possible antibiotic overuse, several decisional strategies, often based on risk-score systems supporting the clinical decisions, have been proposed. In this context of high antibiotic selection pressure, carbapenem-resistant pathogens recently began to spread in many hospitals. Carbapenem-resistant Klebsiella pneumoniae, as well as carbapenem-resistant Acinetobacter baumannii and P. aeruginosa, represent the new major challenges to patient safety. Against these organisms the initial empiric treatment is generally ineffective. The poor clinical outcome associated with carbapenem- resistant K. pneumoniae infections is probably due to the delete in the beginning of an appropriate antibiotic treatment, rather than to the increased virulence of pathogens. Only few therapeutic options are available, including colistin, tigecycline, aminoglycosides and carbapenems in selected cases. Several combinations of these antibiotics have been used, but no ideal regimen has been currently established.

  8. Minocycline and Tigecycline: What Is Their Role in the Treatment of Carbapenem-Resistant Gram-Negative Organisms?

    Science.gov (United States)

    Shankar, Chaitra; Nabarro, Laura E B; Anandan, Shalini; Veeraraghavan, Balaji

    2017-06-01

    Carbapenem-resistant organisms are increasingly common worldwide, particularly in India and are associated with high mortality rates especially in patients with severe infection such as bacteremia. Existing drugs such as carbapenems and polymyxins have a number of disadvantages, but remain the mainstay of treatment. The tetracycline class of antibiotics was first produced in the 1940s. Minocycline, tetracycline derivative, although licensed for treatment of wide range of infections, has not been considered for treatment of multidrug-resistant organisms until recently and needs further in vivo studies. Tigecycline, a derivative of minocycline, although with certain disadvantages, has been frequently used in the treatment of carbapenem-resistant organisms. In this article, we review the properties of minocycline and tigecycline, the common mechanisms of resistance, and assess their role in the management of carbapenem-resistant organisms.

  9. Actividad comparativa in vitro de doripenem y de otros carbapenemes frente a Pseudomonas aeruginosa In vitro activity of doripenem and other carbapenems against Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    F. Nicola

    2010-09-01

    Full Text Available Según estudios previos, el nuevo carbapeneme doripenem sería más activo frente a Pseudomonas aeruginosa en comparación con otros carbapenemes. En este estudio evaluamos la actividad in vitro del doripenem, el meropenem y el imipenem frente a 93 aislamientos de P. aeruginosa mediante los métodos de dilución en agar y de difusión con discos. Las CIM50 y CIM90 de los carbapenemes fueron (μg/ml: imipenem, 4 y 8; meropenem, 2 y 8; doripenem, 2 y 4, respectivamente. El doripenem fue 1 a 3 diluciones más activo que el imipenem para un 82% de los aislamientos. Comparado con el meropenem, el doripenem fue, 1-3 diluciones más activo frente a un 50% de los aislamientos, mientras que en el 49% la CIM fue la misma. Los porcentajes de resistencia según los métodos de dilución y de difusión fueron: imipenem = 7,5%/49,5% y meropenem = 3,2%/9,7%. Para el doripenem, estos valores variaron según los puntos de corte (PC que se consideraron: 1,1%/2,2% usando el PC del CLSI para el imipenem y el meropenem, o 1,1%/17,2% según los PC sugeridos por Brown et al. El método de difusión presentó un elevado porcentaje de errores menores en la categorización de los aislamientos respecto de la dilución en agar, lo que sobrestimó la resistencia. El doripenem mostró muy buena actividad frente a P. aeruginosa, superior a la del imipenem y al menos equiparable a la del meropenem, por lo que puede considerarse una interesante opción para el tratamiento de infecciones por esta bacteria.Doripenem, a new carbapenem, has shown to be more active against Pseudomonas aeruginosa than other carbapenems. The activity of doripenem, imipenem and meropenem was evaluated against 93 P. aeruginosa isolates, by agar dilution and disk diffusion methods. MIC50 and MIC90 were as follows (μg/ml: doripenem, 2 and 4; meropenem, 2 and 8; and imipenem, 4 and 8, respectively. Doripenem MICs were 1 to 3 dilutions lower (i.e. more active than those for imipenem in 82% of the isolates

  10. Overexpression of an Outer Membrane Protein Associated with Decreased Susceptibility to Carbapenems in Proteus mirabilis

    Science.gov (United States)

    Tsai, Yi-Lin; Wang, Min-Cheng; Hsueh, Po-Ren; Liu, Ming-Che; Hu, Rouh-Mei; Wu, Yue-Jin; Liaw, Shwu-Jen

    2015-01-01

    Proteus mirabilis isolates commonly have decreased susceptibility to imipenem. Previously, we found P. mirabilis hfq mutant was more resistant to imipenem and an outer membrane protein (OMP) could be involved. Therefore, we investigated the role of this OMP in carbapenem susceptibility. By SDS-PAGE we found this OMP (named ImpR) was increased in hfq mutant and LC-MS/MS revealed it to be the homologue of Salmonella YbfM, which is a porin for chitobiose and subject to MicM (a small RNA) regulation. We demonstrated that ImpR overexpression resulted in increased carbapenem MICs in the laboratory strain and clinical isolates. Chitobiose induced expression of chb (a chitobiose utilization operon). Real-time RT-PCR and SDS-PAGE were performed to elucidate the relationship of hfq, impR, chb and MicM in P. mirabilis. We found MicM RNA was decreased in hfq mutant and chbBC-intergenic region (chbBC-IGR) overexpression strain (chbIGRov), while impR mRNA was increased in hfq mutant, micM mutant and chbIGRov strain. In addition, mutation of hfq or micM and overexpression of chbBC-IGR increased ImpR protein level. Accordingly, chitobiose made wild-type have higher levels of ImpR protein and are more resistant to carbapenems. Hfq- and MicM-complemented strains restored wild-type MICs. Mutation of both impR and hfq eliminated the increase in carbapenem MICs observed in hfq mutant and ImpR-complementation of hfq/impR double mutant resulted in MICs as hfq mutant, indicating that the ImpR-dependent decreased carbapenem susceptibility of hfq mutant. These indicate MicM was antisense to impR mRNA and was negatively-regulated by chbBC-IGR. Together, overexpression of ImpR contributed to the decreased carbapenem susceptibility in P. mirabilis. PMID:25756370

  11. Incidence of carbapenem-resistant gram negatives in Italian transplant recipients: a nationwide surveillance study.

    Science.gov (United States)

    Lanini, Simone; Costa, Alessandro Nanni; Puro, Vincenzo; Procaccio, Francesco; Grossi, Paolo Antonio; Vespasiano, Francesca; Ricci, Andrea; Vesconi, Sergio; Ison, Michael G; Carmeli, Yehuda; Ippolito, Giuseppe

    2015-01-01

    Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients. Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not. The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant and in those

  12. Incidence of carbapenem-resistant gram negatives in Italian transplant recipients: a nationwide surveillance study.

    Directory of Open Access Journals (Sweden)

    Simone Lanini

    Full Text Available Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients.Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively. Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days. Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%. Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not.The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant

  13. Treatment and Outcome of Carbapenem-Resistant Gram-Negative Bacilli Blood-Stream Infections in a Tertiary Care Hospital.

    Science.gov (United States)

    Shah, Pooja G; Shah, Sweta R

    2015-07-01

    Infections caused by carbapenem-resistant bacteria constitute a major challenge for current medical practice. To describe treatment and outcome of carbapenem-resistant Gram-negative bacilli (GNB) blood-stream infection (BSI) caused by these organisms at a tertiary care hospital in Mumbai. Carbapenem-resistant isolates from blood cultures were collected from January 2013 to April 2013. Identification and antimicrobial susceptibility testing were performed using Vitek 2 analyzer (Biomerieux Ltd.). Carbapenemase production was detected by modified Hodge's test (MHT). Patient's medical history, treatment and co-morbid conditions were noted. Outcomes of BSIs were evaluated. Forty-two isolates of carbapenem-resistant GNB isolated from BSIs were Enterobacteriaceae spp. (19), Acinetobacter baumannii (15), and Pseudomonas aeruginosa (8). Colistin had maximum in vitro activity with 97% against Enterobacteriaceae, 100% against Acinetobacter, and 100% activity against Pseudomonas aeruginosa isolates. Positivity of MHT was 92.9%. Outcome of colistin mono and combination therapy was comparable with 83% and 79%, respectively. Outcome of colistin and carbapenem combination therapy was found to be 100 percent. High incidences of bacteremia by carbapenem-resistant GNB including Enterobacteriaceae is a worrisome trend. Treatment options are compromised and only available option is colistin which has its own limitation. Colistin monotherapy may be non-inferior compared to combination therapy for treating BSIs caused by isolates with minimum inhibitory concentration (MIC) for colistin as ≤0.5 mg/l. Combined use of the colistin and carbapenem may provide good therapeutic options for BSI caused by carbapenem-resistant GNB and warrants further investigations.

  14. Carbapenem-Resistant Bacteria Recovered from Faeces of Dairy Cattle in the High Plains Region of the USA.

    Science.gov (United States)

    Webb, Hattie E; Bugarel, Marie; den Bakker, Henk C; Nightingale, Kendra K; Granier, Sophie A; Scott, H Morgan; Loneragan, Guy H

    2016-01-01

    A study was conducted to recover carbapenem-resistant bacteria from the faeces of dairy cattle and identify the underlying genetic mechanisms associated with reduced phenotypic susceptibility to carbapenems. One hundred and fifty-nine faecal samples from dairy cattle were screened for carbapenem-resistant bacteria. Phenotypic screening was conducted on two media containing ertapenem. The isolates from the screening step were characterised via disk diffusion, Modified Hodge, and Carba NP assays. Carbapenem-resistant bacteria and carbapenemase-producing isolates were subjected to Gram staining and biochemical testing to include Gram-negative bacilli. Whole genome sequencing was performed on bacteria that exhibited either a carbapenemase-producing phenotype or were not susceptible to ertapenem and were presumptively Enterobacteriaceae. Of 323 isolates collected from the screening media, 28 were selected for WGS; 21 of which were based on a carbapenemase-producing phenotype and 7 were presumptively Enterobacteriaceae and not susceptible to ertapenem. Based on analysis of WGS data, isolates included: 3 Escherichia coli harbouring blaCMY-2 and truncated ompF genes; 8 Aeromonas harbouring blacphA-like genes; 1 Acinetobacter baumannii harbouring a novel blaOXA gene (blaOXA-497); and 6 Pseudomonas with conserved domains of various carbapenemase-producing genes. Carbapenem resistant bacteria appear to be rare in cattle. Nonetheless, carbapenem-resistant bacteria were detected across various genera and were found to harbour a variety of mechanisms conferring reduced susceptibility. The development and dissemination of carbapenem-resistant bacteria in livestock would have grave implications for therapeutic treatment options in human medicine; thus, continued monitoring of carbapenem susceptibility among enteric bacteria of livestock is warranted.

  15. Novel carbapenem antibiotics for parenteral and oral applications: in vitro and in vivo activities of 2-aryl carbapenems and their pharmacokinetics in laboratory animals.

    Science.gov (United States)

    Fujimoto, Koichi; Takemoto, Koji; Hatano, Kazuo; Nakai, Toru; Terashita, Shigeyuki; Matsumoto, Masahiro; Eriguchi, Yoshiro; Eguchi, Ken; Shimizudani, Takeshi; Sato, Kimihiko; Kanazawa, Katsunori; Sunagawa, Makoto; Ueda, Yutaka

    2013-02-01

    SM-295291 and SM-369926 are new parenteral 2-aryl carbapenems with strong activity against major causative pathogens of community-acquired infections such as methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus pyogenes, Enterococcus faecalis, Klebsiella pneumoniae, Moraxella catarrhalis, Haemophilus influenzae (including β-lactamase-negative ampicillin-resistant strains), and Neisseria gonorrhoeae (including ciprofloxacin-resistant strains), with MIC(90)s of ≤ 1 μg/ml. Unlike tebipenem (MIC(50), 8 μg/ml), SM-295291 and SM-369926 had no activity against hospital pathogens such as Pseudomonas aeruginosa (MIC(50), ≥ 128 μg/ml). The bactericidal activities of SM-295291 and SM-369926 against penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae were equal or superior to that of tebipenem and greater than that of cefditoren. The therapeutic efficacies of intravenous administrations of SM-295291 and SM-369926 against experimentally induced infections in mice caused by penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae were equal or superior to that of tebipenem and greater than that of cefditoren, respectively, reflecting their in vitro activities. SM-295291 and SM-369926 showed intravenous pharmacokinetics similar to those of meropenem in terms of half-life in monkeys (0.4 h) and were stable against human dehydropeptidase I. SM-368589 and SM-375769, which are medoxomil esters of SM-295291 and SM-369926, respectively, showed good oral bioavailability in rats, dogs, and monkeys (4.2 to 62.3%). Thus, 2-aryl carbapenems are promising candidates that show an ideal broad spectrum for the treatment of community-acquired infections, including infections caused by penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae, have low selective pressure on antipseudomonal

  16. Single or in Combination Antimicrobial Resistance Mechanisms of Klebsiella pneumoniae Contribute to Varied Susceptibility to Different Carbapenems

    Science.gov (United States)

    Tsai, Yu-Kuo; Liou, Ci-Hong; Fung, Chang-Phone; Lin, Jung-Chung; Siu, L. Kristopher

    2013-01-01

    Resistance to carbapenems has been documented by the production of carbapenemase or the loss of porins combined with extended-spectrum β-lactamases or AmpC β-lactamases. However, no complete comparisons have been made regarding the contributions of each resistance mechanism towards carbapenem resistance. In this study, we genetically engineered mutants of Klebsiella pneumoniae with individual and combined resistance mechanisms, and then compared each resistance mechanism in response to ertapenem, imipenem, meropenem, doripenem and other antibiotics. Among the four studied carbapenems, ertapenem was the least active against the loss of porins, cephalosporinases and carbapenemases. In addition to the production of KPC-2 or NDM-1 alone, resistance to all four carbapenems could also be conferred by the loss of two major porins, OmpK35 and OmpK36, combined with CTX-M-15 or DHA-1 with its regulator AmpR. Because the loss of OmpK35/36 alone or the loss of a single porin combined with bla CTX-M-15 or bla DHA-1-ampR expression was only sufficient for ertapenem resistance, our results suggest that carbapenems other than ertapenem should still be effective against these strains and laboratory testing for non-susceptibility to other carbapenems should improve the accurate identification of these isolates. PMID:24265784

  17. The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace

    Science.gov (United States)

    Weinstein, Robert A.

    2017-01-01

    Abstract Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Mechanisms of drug resistance in gram-negative bacteria (GNB) are numerous; β-lactamase genes carried on mobile genetic elements are a key mechanism for the rapid spread of antibiotic-resistant GNB worldwide. Transmissible carbapenem-resistance in Enterobacteriaceae has been recognized for the last 2 decades, but global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a more recent problem that, once initiated, has been occurring at an alarming pace. In this article, we discuss the evolution of CRE, with a focus on the epidemiology of the CPE pandemic; review risk factors for colonization and infection with the most common transmissible CPE worldwide, Klebsiella pneumoniae carbapenemase–producing K. pneumoniae; and present strategies used to halt the striking spread of these deadly pathogens. PMID:28375512

  18. Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant Enterobacteriaceae (CRE).

    Science.gov (United States)

    Goodman, K E; Simner, P J; Tamma, P D; Milstone, A M

    2016-01-01

    The Centers for Disease Control and Prevention (CDC) defines carbapenem-resistant Enterobacteriaceae (CRE) based upon a phenotypic demonstration of carbapenem resistance. However, considerable heterogeneity exists within this definitional umbrella. CRE may mechanistically differ by whether they do or do not produce carbapenemases. Moreover, patients can acquire CRE through multiple pathways: endogenously through antibiotic selective pressure on intestinal microbiota, exogenously through horizontal transmission or through a combination of these factors. Some evidence suggests that non-carbapenemase-producing CRE may be more frequently acquired by antibiotic exposure and carbapenemase-producing CRE via horizontal transmission, but definitive data are lacking. This review examines types of CRE resistance mechanisms, antibiotic exposure and horizontal transmission pathways of CRE acquisition, and the implications of these heterogeneities to the development of evidence-based CRE healthcare epidemiology policies. In our Expert Commentary & Five-Year View, we outline specific nosocomial CRE knowledge gaps and potential methodological approaches for their resolution.

  19. Emergence of Serratia marcescens isolates possessing carbapenem-hydrolysing β-lactamase KPC-2 from China.

    Science.gov (United States)

    Lin, X; Hu, Q; Zhang, R; Hu, Y; Xu, X; Lv, H

    2016-09-01

    Eighty-three carbapenem-resistant Serratia marcescens isolates were recovered from Zhejiang Provincial People's Hospital, China. The minimum inhibitory concentrations of imipenem, meropenem, and ertapenem for all isolates were 2 to >128 μg/mL. Polymerase chain reaction indicated that 63 S. marcescens isolates produced Klebsiella pneumoniae carbapenemase (KPC)-2. Clone A (15 isolates) and clone B (41 isolates) were the two dominant clones and clone A strains were gradually replaced by clone B strains between 2011 and 2014. The results indicate that blaKPC-2-positive S. marcescens emerged in our hospital as the major mechanism of carbapenem resistance. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  20. Modified Carbapenem Inactivation Method for Phenotypic Detection of Carbapenemase Production among Enterobacteriaceae.

    Science.gov (United States)

    Pierce, Virginia M; Simner, Patricia J; Lonsway, David R; Roe-Carpenter, Darcie E; Johnson, J Kristie; Brasso, William B; Bobenchik, April M; Lockett, Zabrina C; Charnot-Katsikas, Angella; Ferraro, Mary Jane; Thomson, Richard B; Jenkins, Stephen G; Limbago, Brandi M; Das, Sanchita

    2017-08-01

    The ability of clinical microbiology laboratories to reliably detect carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) is an important element of the effort to prevent and contain the spread of these pathogens and an integral part of antimicrobial stewardship. All existing methods have limitations. A new, straightforward, inexpensive, and specific phenotypic method for the detection of carbapenemase production, the carbapenem inactivation method (CIM), was recently described. Here we describe a two-stage evaluation of a modified carbapenem inactivation method (mCIM), in which tryptic soy broth was substituted for water during the inactivation step and the length of this incubation was extended. A validation study was performed in a single clinical laboratory to determine the accuracy of the mCIM, followed by a nine-laboratory study to verify the reproducibility of these results and define the zone size cutoff that best discriminated between CP-CRE and members of the family Enterobacteriaceae that do not produce carbapenemases. Bacterial isolates previously characterized through whole-genome sequencing or targeted PCR as to the presence or absence of carbapenemase genes were tested for carbapenemase production using the mCIM; isolates with Ambler class A, B, and D carbapenemases, non-CP-CRE isolates, and carbapenem-susceptible isolates were included. The sensitivity of the mCIM observed in the validation study was 99% (95% confidence interval [95% CI], 93% to 100%), and the specificity was 100% (95% CI, 82% to 100%). In the second stage of the study, the range of sensitivities observed across nine laboratories was 93% to 100%, with a mean of 97%; the range of specificities was 97% to 100%, with a mean of 99%. The mCIM was easy to perform and interpret for Enterobacteriaceae , with results in less than 24 h and excellent reproducibility across laboratories. Copyright © 2017 American Society for Microbiology.

  1. Systematic Review and Meta-Analysis of In Vitro Synergy of Polymyxins and Carbapenems

    Science.gov (United States)

    Avni, Tomer; Leibovici, Leonard; Adler, Amos; Friberg, Lena; Stergiopoulou, Theodouli; Carmeli, Yehuda; Paul, Mical

    2013-01-01

    Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gram-negative bacteria (GNB). A systematic review and meta-analysis were performed. All studies examining in vitro interactions of antibiotic combinations consisting of any carbapenem with colistin or polymyxin B against any GNB were used. A broad search was conducted with no language, date, or publication status restrictions. Synergy rates, defined as a fractional inhibitory concentration index of ≤0.5 or a >2-log reduction in CFU, were pooled separately for time-kill, checkerboard, and Etest methods in a mixed-effect meta-analysis of rates. We examined whether the synergy rate depended on the testing method, type of antibiotic, bacteria, and resistance to carbapenems. Pooled rates with 95% confidence intervals (CI) are shown. Thirty-nine published studies and 15 conference proceeding were included, reporting on 246 different tests on 1,054 bacterial isolates. In time-kill studies, combination therapy showed synergy rates of 77% (95% CI, 64 to 87%) for Acinetobacter baumannii, 44% (95% CI, 30 to 59%) for Klebsiella pneumoniae, and 50% (95% CI, 30 to 69%) for Pseudomonas aeruginosa, with low antagonism rates for all. Doripenem showed high synergy rates for all three bacteria. For A. baumannii, meropenem was more synergistic than imipenem, whereas for P. aeruginosa the opposite was true. Checkerboard and Etest studies generally reported lower synergy rates than time-kill studies. The use of combination therapy led to less resistance development in vitro. The combination of a carbapenem with a polymyxin against GNB, especially A. baumannii, is supported in vitro by high synergy rates, with low antagonism and less resistance development. These findings should be examined in clinical studies. PMID:23917322

  2. Inactivation of Mycobacterium tuberculosis l,d-Transpeptidase LdtMt1 by Carbapenems and Cephalosporins

    Science.gov (United States)

    Dubée, Vincent; Triboulet, Sébastien; Mainardi, Jean-Luc; Ethève-Quelquejeu, Mélanie; Gutmann, Laurent; Marie, Arul; Dubost, Lionel

    2012-01-01

    The structure of Mycobacterium tuberculosis peptidoglycan is atypical since it contains a majority of 3→3 cross-links synthesized by l,d-transpeptidases that replace 4→3 cross-links formed by the d,d-transpeptidase activity of classical penicillin-binding proteins. Carbapenems inactivate these l,d-transpeptidases, and meropenem combined with clavulanic acid is bactericidal against extensively drug-resistant M. tuberculosis. Here, we used mass spectrometry and stopped-flow fluorimetry to investigate the kinetics and mechanisms of inactivation of the prototypic M. tuberculosis l,d-transpeptidase LdtMt1 by carbapenems (meropenem, doripenem, imipenem, and ertapenem) and cephalosporins (cefotaxime, cephalothin, and ceftriaxone). Inactivation proceeded through noncovalent drug binding and acylation of the catalytic Cys of LdtMt1, which was eventually followed by hydrolysis of the resulting acylenzyme. Meropenem rapidly inhibited LdtMt1, with a binding rate constant of 0.08 μM−1 min−1. The enzyme was unable to recover from this initial binding step since the dissociation rate constant of the noncovalent complex was low (carbapenem side chains affected both the binding and acylation steps, ertapenem being the most efficient LdtMt1 inactivator. Cephalosporins also formed covalent adducts with LdtMt1, although the acylation reaction was 7- to 1,000-fold slower and led to elimination of one of the drug side chains. Comparison of kinetic constants for drug binding, acylation, and acylenzyme hydrolysis indicates that carbapenems and cephems can both be tailored to optimize peptidoglycan synthesis inhibition in M. tuberculosis. PMID:22615283

  3. Systematic review and meta-analysis of in vitro synergy of polymyxins and carbapenems.

    Science.gov (United States)

    Zusman, Oren; Avni, Tomer; Leibovici, Leonard; Adler, Amos; Friberg, Lena; Stergiopoulou, Theodouli; Carmeli, Yehuda; Paul, Mical

    2013-10-01

    Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gram-negative bacteria (GNB). A systematic review and meta-analysis were performed. All studies examining in vitro interactions of antibiotic combinations consisting of any carbapenem with colistin or polymyxin B against any GNB were used. A broad search was conducted with no language, date, or publication status restrictions. Synergy rates, defined as a fractional inhibitory concentration index of ≤0.5 or a >2-log reduction in CFU, were pooled separately for time-kill, checkerboard, and Etest methods in a mixed-effect meta-analysis of rates. We examined whether the synergy rate depended on the testing method, type of antibiotic, bacteria, and resistance to carbapenems. Pooled rates with 95% confidence intervals (CI) are shown. Thirty-nine published studies and 15 conference proceeding were included, reporting on 246 different tests on 1,054 bacterial isolates. In time-kill studies, combination therapy showed synergy rates of 77% (95% CI, 64 to 87%) for Acinetobacter baumannii, 44% (95% CI, 30 to 59%) for Klebsiella pneumoniae, and 50% (95% CI, 30 to 69%) for Pseudomonas aeruginosa, with low antagonism rates for all. Doripenem showed high synergy rates for all three bacteria. For A. baumannii, meropenem was more synergistic than imipenem, whereas for P. aeruginosa the opposite was true. Checkerboard and Etest studies generally reported lower synergy rates than time-kill studies. The use of combination therapy led to less resistance development in vitro. The combination of a carbapenem with a polymyxin against GNB, especially A. baumannii, is supported in vitro by high synergy rates, with low antagonism and less resistance development. These findings should be examined in clinical studies.

  4. Comparison of Molecular and Phenotypic Methods for the Detection and Characterization of Carbapenem Resistant Enterobacteriaceae.

    Science.gov (United States)

    Somily, Ali M; Garaween, Ghada A; Abukhalid, Norah; Absar, Muhammad M; Senok, Abiola C

    2016-03-01

    In recent years, there has been a rapid dissemination of carbapenem resistant Enterobacteriaceae (CRE). This study aimed to compare phenotypic and molecular methods for detection and characterization of CRE isolates at a large tertiary care hospital in Saudi Arabia. This study was carried out between January 2011 and November 2013 at the King Khalid University Hospital (KKUH) in Saudi Arabia. Determination of presence of extended-spectrum beta-lactamases (ESBL) and carbapenem resistance was in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines. Phenotypic classification was done by the MASTDISCS(TM) ID inhibitor combination disk method. Genotypic characterization of ESBL and carbapenemase genes was performed by the Check-MDR CT102. Diversilab rep-PCR was used for the determination of clonal relationship. Of the 883 ESBL-positive Enterobacteriaceae detected during the study period, 14 (1.6%) isolates were carbapenem resistant. Both the molecular genotypic characterization and phenotypic testing were in agreement in the detection of all 8 metalo-beta-lactamases (MBL) producing isolates. Of these 8 MBL-producers, 5 were positive for blaNDM gene and 3 were positive for blaVIM gene. Molecular method identified additional blaOXA gene isolates while MASTDISCS(TM) ID detected one AmpC producer isolate. Both methods agreed in identifying 2 carbapenem resistant isolates which were negative for carbapenemase genes. Diversilab rep-PCR analysis of the 9 Klebsiella pneumoniae isolates revealed polyclonal distribution into eight clusters. MASTDISCS(TM) ID is a reliable simple cheap phenotypic method for detection of majority of carbapenemase genes with the exception of the blaOXA gene. We recommend to use such method in the clinical laboratory.

  5. Resistance to Carbapenems in Non-Typhoidal Salmonella enterica Serovars from Humans, Animals and Food.

    Science.gov (United States)

    Fernández, Javier; Guerra, Beatriz; Rodicio, M Rosario

    2018-04-08

    Non-typhoidal serovars of Salmonella enterica (NTS) are a leading cause of food-borne disease in animals and humans worldwide. Like other zoonotic bacteria, NTS have the potential to act as reservoirs and vehicles for the transmission of antimicrobial drug resistance in different settings. Of particular concern is the resistance to critical "last resort" antimicrobials, such as carbapenems. In contrast to other Enterobacteriaceae (e.g., Klebsiella pneumoniae , Escherichia coli , and Enterobacter , which are major nosocomial pathogens affecting debilitated and immunocompromised patients), carbapenem resistance is still very rare in NTS. Nevertheless, it has already been detected in isolates recovered from humans, companion animals, livestock, wild animals, and food. Five carbapenemases with major clinical importance-namely KPC ( Klebsiella pneumoniae carbapenemase) (class A), IMP (imipenemase), NDM (New Delhi metallo-β-lactamase), VIM (Verona integron-encoded metallo-β-lactamase) (class B), and OXA-48 (oxacillinase, class D)-have been reported in NTS. Carbapenem resistance due to the production of extended spectrum- or AmpC β-lactamases combined with porin loss has also been detected in NTS. Horizontal gene transfer of carbapenemase-encoding genes (which are frequently located on self-transferable plasmids), together with co- and cross-selective adaptations, could have been involved in the development of carbapenem resistance by NTS. Once acquired by a zoonotic bacterium, resistance can be transmitted from humans to animals and from animals to humans through the food chain. Continuous surveillance of resistance to these "last resort" antibiotics is required to establish possible links between reservoirs and to limit the bidirectional transfer of the encoding genes between S. enterica and other commensal or pathogenic bacteria.

  6. Resistance to Carbapenems in Non-Typhoidal Salmonella enterica Serovars from Humans, Animals and Food

    Directory of Open Access Journals (Sweden)

    Javier Fernández

    2018-04-01

    Full Text Available Non-typhoidal serovars of Salmonella enterica (NTS are a leading cause of food-borne disease in animals and humans worldwide. Like other zoonotic bacteria, NTS have the potential to act as reservoirs and vehicles for the transmission of antimicrobial drug resistance in different settings. Of particular concern is the resistance to critical “last resort” antimicrobials, such as carbapenems. In contrast to other Enterobacteriaceae (e.g., Klebsiella pneumoniae, Escherichia coli, and Enterobacter, which are major nosocomial pathogens affecting debilitated and immunocompromised patients, carbapenem resistance is still very rare in NTS. Nevertheless, it has already been detected in isolates recovered from humans, companion animals, livestock, wild animals, and food. Five carbapenemases with major clinical importance—namely KPC (Klebsiella pneumoniae carbapenemase (class A, IMP (imipenemase, NDM (New Delhi metallo-β-lactamase, VIM (Verona integron-encoded metallo-β-lactamase (class B, and OXA-48 (oxacillinase, class D—have been reported in NTS. Carbapenem resistance due to the production of extended spectrum- or AmpC β-lactamases combined with porin loss has also been detected in NTS. Horizontal gene transfer of carbapenemase-encoding genes (which are frequently located on self-transferable plasmids, together with co- and cross-selective adaptations, could have been involved in the development of carbapenem resistance by NTS. Once acquired by a zoonotic bacterium, resistance can be transmitted from humans to animals and from animals to humans through the food chain. Continuous surveillance of resistance to these “last resort” antibiotics is required to establish possible links between reservoirs and to limit the bidirectional transfer of the encoding genes between S. enterica and other commensal or pathogenic bacteria.

  7. Spatial molecular epidemiology of carbapenem-resistant and New Delhi metallo beta-lactamase (blaNDM)-producing Escherichia coli in the piglets of organized farms in India.

    Science.gov (United States)

    Pruthvishree, B S; Vinodh Kumar, O R; Sinha, D K; Malik, Y P S; Dubal, Z B; Desingu, P A; Shivakumar, M; Krishnaswamy, N; Singh, B R

    2017-06-01

    A cross-sectional study was conducted in 10 government-organized pig farms between 2014 and 2016 representing seven states of India to understand the epidemiology of carbapenem resistance in the Escherichia coli. In this study, fecal sample (n = 673) from non-diarrheic (n = 501) and diarrheic (n = 172) piglets were processed for isolation of carbapenem resistant E. coli. Of 673, E. coli isolate (n = 112) was genotyped for confirming the carbapenem resistance and associated virulence factors. Of the 112 isolates, 23 were phenotypically resistant to carbapenem and 8 were carrying the New Delhi metallo beta-lactamase (blaNDM) gene. The carbapenem-resistant isolates also produced extended spectrum beta-lactamases and were multidrug resistant. The PCR-based pathotyping revealed the presence of stx1, stx2, eae and hlyA genes. The enterobacterial repetitive intergenic consensus PCR dendrogram analysis of the isolates yielded three distinct clusters. The statistical analysis revealed no association between carriages of carbapenem-resistant E. coli in different breed of piglets however, location, sex, health status of piglets and age showed significant difference. The spatial analysis with SaTScan helped in identification of carbapenem-resistant clusters. The presence of carbapenem resistant E. coli isolates with virulence genes in the piglet poses a potential public health risk through possible access and spread via the food chain and environment. Efflux pump may also play an important role in carbapenem resistance in piglet E. coli isolates. Furthermore, identification of risk factors in relation to spatial clusters will help in designing preventive strategies for reducing the risk of spread of carbapenem resistant bacteria. 1. Piglets harbor carbapenem resistant E. coli and have great public health significance. 2. Apart from carbapenemase, efflux pump is also important for carbapenem resistance. 3. This is the first report of blaNDM in the piglets from India. © 2017

  8. The Implementation of a Hospital-wide Practice for the Selective Use of Carbapenems Based on the Monitoring of Susceptibility of Pseudomonas aeruginosa Isolates.

    Science.gov (United States)

    Ohshima, Toshio; Asai, Satomi; Miyazawa, Miki; Yamamoto, Yukari; Hisada, Akifumi; Kumazawa, Chie; Hashimoto, Masayoshi; Fukawa, Katsuji; Iwashita, Hideo; Umezawa, Kazuo; Yamada, Sanetoshi; Yamamoto, Yoshiro; Miyachi, Hayato

    2017-12-20

    To control carbapenem-resistant Pseudomonas aeruginosa, we implemented a hospital-wide policy concerning the selective use of carbapenems based on the monitoring of P. aeruginosa isolates for susceptibility to five carbapenems using a customized dry plate method. In this study, we retrospectively investigated the outcome of our measures to control carbapenem-resistant P. aeruginosa. To select effective carbapenems, 100 clinical isolates were collected, and the minimum inhibitory concentration (MIC) to 5 carbapenems (IPM/CS, MEPM, DRPM, BIPM and PAPM/BP) was monitored using a customized dry plate method from 2006 to 2013. Carbapenems, which were associated with a high rate of drug resistance in P. aeruginosa, were restricted from use during our intervention study. The antimicrobial use density per 100 bed-days (AUD 100 ) of carbapenems and the detection rates of carbapenem (IPM/CS and MEPM)-resistant P. aeruginosa were determined during the period of the intervention. The isolates consistently showed higher rates of drug-resistant P. aeruginosa in IPM/CS and PAPM/BP. Thus, DRPM, MEPM and BIPM were adopted for hospital-wide use. The detection rates of all IPM/Cs and MEPM-resistant P. aeruginosa significantly decreased. Meanwhile, the consumption of carbapenems showed an increasing trend. The outcome of the hospital-wide implementation of the selective use of carbapenems based on periodic monitoring of the susceptibility of P. aeruginosa isolates was retrospectively studied. Implementation of this measure might have contributed in part to the control of carbapenem-resistant P. aeruginosa in our hospital.

  9. Carbapenem-Resistant Acinetobacter baumannii and Enterobacteriaceae in South and Southeast Asia

    Science.gov (United States)

    Apisarnthanarak, Anucha; Khan, Erum; Ghafur, Abdul

    2016-01-01

    SUMMARY Carbapenem-resistant Gram-negative bacteria, in particular the Acinetobacter baumannii-calcoaceticus complex and Enterobacteriaceae, are escalating global public health threats. We review the epidemiology and prevalence of these carbapenem-resistant Gram-negative bacteria among countries in South and Southeast Asia, where the rates of resistance are some of the highest in the world. These countries house more than a third of the world's population, and several are also major medical tourism destinations. There are significant data gaps, and the almost universal lack of comprehensive surveillance programs that include molecular epidemiologic testing has made it difficult to understand the origins and extent of the problem in depth. A complex combination of factors such as inappropriate prescription of antibiotics, overstretched health systems, and international travel (including the phenomenon of medical tourism) probably led to the rapid rise and spread of these bacteria in hospitals in South and Southeast Asia. In India, Pakistan, and Vietnam, carbapenem-resistant Enterobacteriaceae have also been found in the environment and community, likely as a consequence of poor environmental hygiene and sanitation. Considerable political will and effort, including from countries outside these regions, are vital in order to reduce the prevalence of such bacteria in South and Southeast Asia and prevent their global spread. PMID:27795305

  10. Carbapenem-resistant Pseudomonas aeruginosa: association with virulence genes and biofilm formation

    Directory of Open Access Journals (Sweden)

    Iara Rossi Gonçalves

    Full Text Available Abstract Pseudomonas aeruginosa is an opportunistic pathogen that causes frequently nosocomial infections, currently becoming more difficult to treat due to the various resistance mechanisms and different virulence factors. The purpose of this study was to determine the risk factors independently associated with the development of bacteremia by carbapenem-resistant P. aeruginosa, the frequency of virulence genes in metallo-β-lactamases producers and to evaluate their ability to produce biofilm. We conducted a case–control study in the Uberlândia Federal University – Hospital Clinic, Brazil. Polymerase Chain Reaction was performed for metallo-β-lactamases and virulence genes. Adhesion and biofilm assays were done by quantitative tests. Among the 157 strains analyzed, 73.9% were multidrug-resistant, 43.9% were resistant to carbapenems, 16.1% were phenotypically positive for metallo-β-lactamases, and of these, 10.7% were positive for blaSPM gene and 5.3% positive for blaVIM. The multivariable analysis showed that mechanical ventilation, enteral/nasogastric tubes, primary bacteremia with unknown focus, and inappropriate therapy were independent risk factors associated with bacteremia. All tested strains were characterized as strongly biofilm producers. A higher mortality was found among patients with bacteremia by carbapenem-resistant P. aeruginosa strains, associated independently with extrinsic risk factors, however it was not evident the association with the presence of virulence and metallo-β-lactamases genes.

  11. Carbapenem-Resistant Acinetobacter baumannii and Enterobacteriaceae in South and Southeast Asia.

    Science.gov (United States)

    Hsu, Li-Yang; Apisarnthanarak, Anucha; Khan, Erum; Suwantarat, Nuntra; Ghafur, Abdul; Tambyah, Paul Anantharajah

    2017-01-01

    Carbapenem-resistant Gram-negative bacteria, in particular the Acinetobacter baumannii-calcoaceticus complex and Enterobacteriaceae, are escalating global public health threats. We review the epidemiology and prevalence of these carbapenem-resistant Gram-negative bacteria among countries in South and Southeast Asia, where the rates of resistance are some of the highest in the world. These countries house more than a third of the world's population, and several are also major medical tourism destinations. There are significant data gaps, and the almost universal lack of comprehensive surveillance programs that include molecular epidemiologic testing has made it difficult to understand the origins and extent of the problem in depth. A complex combination of factors such as inappropriate prescription of antibiotics, overstretched health systems, and international travel (including the phenomenon of medical tourism) probably led to the rapid rise and spread of these bacteria in hospitals in South and Southeast Asia. In India, Pakistan, and Vietnam, carbapenem-resistant Enterobacteriaceae have also been found in the environment and community, likely as a consequence of poor environmental hygiene and sanitation. Considerable political will and effort, including from countries outside these regions, are vital in order to reduce the prevalence of such bacteria in South and Southeast Asia and prevent their global spread. Copyright © 2016 American Society for Microbiology.

  12. Could Frequent Carbapenem Use Be a Risk Factor for Colistin Resistance?

    Science.gov (United States)

    Gundogdu, Aycan; Ulu-Kilic, Aysegul; Kilic, Huseyin; Ozhan, Esra; Altun, Dilek; Cakir, Ozlem; Alp, Emine

    2017-10-13

    The antibiotic colistin, which had been previously abandoned, is being brought back as a last line of defense against bacterial infection. However, colistin resistance was reported shortly after its reintroduction. This study evaluated the risk factors for colonization/infections due to colistin-resistant Acinetobacter baumannii (ColR-Ab) and Klebsiella pneumoniae (ColR-Kp) strains and characterized the molecular epidemiology of these two strains. Age, previous hospitalization duration, and previous use of carbapenem and colistin were risk factors for ColR-Kp, whereas previous use of carbapenem and colistin was a risk factor for ColR-Ab. According to pulsed-field gel electrophoresis analysis, most ColR-Kp strains could be grouped into two major pulsotypes. This appears to be an indicator of cross contamination of ColR-Kp strain, since different isolates appeared to be belonging to the same clones. The existence of colistin-susceptible (ColS) and colistin-resistant (ColR) strains in the same pulsotypes might also be an indicator of the recent emergence of resistance mechanisms. The results highlight the emergence of ColR pathogens in Turkey, which is considered to be developing country, and that carbapenem use coupled with insufficient infection control measures might increase the risk of ColR outbreaks.

  13. Higher third-generation cephalosporin prescription proportion is associated with lower probability of reducing carbapenem use: a nationwide retrospective study

    Directory of Open Access Journals (Sweden)

    Allison Muller

    2018-01-01

    Full Text Available Abstract Background The ongoing extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE pandemic has led to an increasing carbapenem use, requiring release of guidelines for carbapenem usage in France in late 2010. We sought to determine factors associated with changes in carbapenem use in intensive care units (ICUs, medical and surgical wards between 2009 and 2013. Methods This ward-level multicentre retrospective study was based on data from French antibiotic and multidrug-resistant bacteria surveillance networks in healthcare facilities. Antibiotic use was expressed in defined daily doses per 1000 patient-days. Factors associated with the reduction in carbapenem use (yes/no over the study period were determined from random-effects logistic regression model (493 wards nested within 259 healthcare facilities: ward characteristics (type, size…, ward antibiotic use (initial antibiotic use [i.e., consumption of a given antibiotic in 2009], initial antibiotic prescribing profile [i.e., proportion of a given antibiotic in the overall antibiotic consumption in 2009] and reduction in the use of a given antibiotic between 2009 and 2013 and regional ESBL-PE incidence rate in acute care settings in 2011. Results Over the study period, carbapenem consumption in ICUs (n = 85, medical (n = 227 and surgical wards (n = 181 was equal to 73.4, 6.2 and 5.4 defined daily doses per 1000 patient-days, respectively. Release of guidelines was followed by a significant decrease in carbapenem use within ICUs and medical wards, and a slowdown in use within surgical wards. The following factors were independently associated with a higher probability of reducing carbapenem use: location in Eastern France, higher initial carbapenem prescribing profile and reductions in consumption of fluoroquinolones, glycopeptides and piperacillin/tazobactam. In parallel, factors independently associated with a lower probability of reducing carbapenem use were

  14. Plasmid borne Carbapenem-Hydrolyzing Class D β-Lactamases (CHDLs) and AdeABC efflux pump conferring carbapenem-tigecycline resistance among Acinetobacter baumannii isolates harboring TnAbaRs.

    Science.gov (United States)

    Savari, Mohammad; Ekrami, Alireza; Shoja, Saeed; Bahador, Abbas

    2017-03-01

    Here we studied the prevalence and mechanisms of simultaneous resistance to carbapenem and tigecycline and accumulation of resistance determinants reservoirs in genome of Acinetobacter baumannii (A. baumannii) clinical isolates. Susceptibility of the isolates were measured to 18 antimicrobial agents. Genetic diversity of the microbial population was determined using the International Clonal lineage typing (IC typing), multiple locus VNTR analysis (MLVA) and plasmid profiling methods. To detect the AbaRs, Carbapenem-Hydrolyzing Class D β-Lactamases (CHDLs) genes, AdeABC efflux pump genes and resistance determinants, PCR was used. Filter mating experiments were used to prove that if carbapenem resistance genes are located on conjugative plasmids or not. Among the A. baumannii clinical isolates, 40.8% were carbapenem-tigecycline resistant and in this population, 46.9% were belonging to IC I, IC II or IC III and 53.1% were IC variants. These isolates had fallen in 40 MLVA types and were harboring plasmids in multiple numbers and sizes. In this study, bla OXA-23-like was the most prevalent CHDL and conjugation analysis proved that the carbapenem resistance genes are located on conjugative plasmids. All efflux pump genes, except for adeC, were detected in all carbapenem-tigecycline resistant A. baumannii (CTRAb) isolates. Resistance determinants were distributed in both TnAbaRs and R plasmids with a shift toward the R plasmids. Emerging of carbapenem resistant A. baumannii (CRAB) with simultaneous resistance to the last line therapy including tigecycline represent emerging of extensively drug resistance (XDR) and pandrug resistance (PDR) phenotypes that would be a great threat to our public health system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Isolation of Klebsiella pneumoniae strains with altered susceptibility to carbapenems not carbapenemase mediated

    Directory of Open Access Journals (Sweden)

    Franca Cian

    2009-12-01

    Full Text Available The spread of enterobacteria producing extended-spectrum ß-lactamases (ESBLs is sharply increasing in Italy, while the detection of isolates resistant to carbapenems is still sporadic. Isolates of Klebsiella pneumoniae resistant to all cephalosporins, aminoglycosides and fluoroquinolones have been isolated in Trieste since 2008. Because of the altered profile of resistance to carbapenems, these strains were reported as ESBL-negative and possible carbapenemases producer by the expert system, leaving tigecycline as the only therapeutic choice.The purpose of this study is the characterization of the mechanisms involved in resistance to carbapenems in these strains and the evaluation of a reliable and simple test for phenotypic confirmation of ESBL and/or carbapenemase production. 25 isolates of MDR K. pneumoniae were collected between October 2008 and May 2009, mainly from urinary samples of elderly patients hospitalized in medicine wards. Identification and susceptibility testing were performed using the Vitek 2 system.The double-disc (DD test was used to check the production of ESBLs, while imipenem and imipenem-EDTA synergy test was used to detect the production of metallo-ßlactamase (MBL. Carbapenemase activity was tested by an hydrolysis assay and the production of MBLs was also investigated by PCR. The DD synergy test highlighted the possible production of ESBLs in 18 out of 22 strains, considered as negative by Vitek. All ESBLs producers tested positive for the blaCTX-M-15 allele. Only one isolate was resistant to carbapenems and resulted positive for production of MBL by the phenotypic test.The crude extract showed carbapenemase activity inhibited by EDTA; PCR test gave positive result for a blaVIM-type allele. PCR analysis performed on representative isolates, followed by sequencing, showed that coding sequence of ompk35 was not functional. Results of this study confirmed the emergence of ESBL-positive strains of K. pneumoniae that

  16. Dissemination of carbapenem-resistant Acinetobacter baumannii in patients with burn injuries.

    Science.gov (United States)

    Shoja, Saeed; Moosavian, Mojtaba; Rostami, Soodabeh; Farahani, Abbas; Peymani, Amir; Ahmadi, Khadijeh; Ebrahimifard, Nasim

    2017-04-01

    Carbapenem-resistant Acinetobacter baumannii has emerged as an important cause of infection in burn patients. This study aimed to characterize the antimicrobial susceptibility pattern, determine the prevalence of oxacillinase and metallo-beta-lactamase (MBL) genes, and type the A. baumannii isolates obtained from burn patients. During a 1-year period, a total of 40 nonduplicated isolates of A. baumannii were obtained from burn patients who were hospitalized in the Taleghani Burn Hospital in Ahvaz, in the southwest of Iran. Testing for antimicrobial susceptibility was carried out by disk diffusion and E-test. To screen MBL production, a double disk synergy and MBL E-test were performed. The presence of bla OXA-23-like , bla OXA-24-like , bla OXA-51-like and bla OXA-58-like , bla VIM , bla IMP and bla SPM , and bla NDM was sought by polymerase chain reaction (PCR). Repetitive extragenic palindromic sequence-based PCR was carried out for determination of isolates clonality. Overall, 92.5% of isolates were carbapenem-resistant. Polymyxin B, colistin, and ampicillin-sulbactam were the most effective agents in vitro, with a susceptibility rate of 100%, 97.5%, and 72.5%, respectively. According to the double disk synergy and E-test, 55.6% and 97.3% of isolates were MBL producers, respectively. Furthermore, 70% of isolates harbored bla OXA-23-like and 20% were positive for bla OXA-24-like. However, no encoding genes were detected for bla VIM , bla IMP and bla SPM , bla NDM , and bla OXA-58-like . Repetitive extragenic palindromic sequence-based PCR revealed that carbapenem-resistant isolates belonged to four clones, including A, B, C, and D; the predominant clones were B and C. The rate of carbapenem resistance was high, and it appeared that bla OXA-23-like and bla OXA-24-like contributed to the carbapenem resistance of A. baumannii isolates. This result suggests that the two predominant clones of A. baumannii were spread among burn patients. In order to prevent future

  17. Low Prevalence of Carbapenem-Resistant Bacteria in River Water: Resistance Is Mostly Related to Intrinsic Mechanisms.

    Science.gov (United States)

    Tacão, Marta; Correia, António; Henriques, Isabel S

    2015-10-01

    Carbapenems are last-resort antibiotics to handle serious infections caused by multiresistant bacteria. The incidence of resistance to these antibiotics has been increasing and new resistance mechanisms have emerged. The dissemination of carbapenem resistance in the environment has been overlooked. The main goal of this research was to assess the prevalence and diversity of carbapenem-resistant bacteria in riverine ecosystems. The presence of frequently reported carbapenemase-encoding genes was inspected. The proportion of imipenem-resistant bacteria was on average 2.24 CFU/ml. Imipenem-resistant strains (n=110) were identified as Pseudomonas spp., Stenotrophomonas maltophilia, Aeromonas spp., Chromobacterium haemolyticum, Shewanella xiamenensis, and members of Enterobacteriaceae. Carbapenem-resistant bacteria were highly resistant to other beta-lactams such as quinolones, aminoglycosides, chloramphenicol, tetracyclines, and sulfamethoxazole/trimethoprim. Carbapenem resistance was mostly associated with intrinsically resistant bacteria. As intrinsic resistance mechanisms, we have identified the blaCphA gene in 77.3% of Aeromonas spp., blaL1 in all S. maltophilia, and blaOXA-48-like in all S. xiamenensis. As acquired resistance mechanisms, we have detected the blaVIM-2 gene in six Pseudomonas spp. (5.45%). Integrons with gene cassettes encoding resistance to aminoglycosides (aacA and aacC genes), trimethoprim (dfrB1b), and carbapenems (blaVIM-2) were found in Pseudomonas spp. Results suggest that carbapenem resistance dissemination in riverine ecosystems is still at an early stage. Nevertheless, monitoring these aquatic compartments for the presence of resistance genes and its host organisms is essential to outline strategies to minimize resistance dissemination.

  18. Impact of Combination Antimicrobial Therapy on Mortality Risk for Critically Ill Patients with Carbapenem-Resistant Bacteremia

    Science.gov (United States)

    Bauer, Seth R.; Neuner, Elizabeth A.; Lam, Simon W.

    2015-01-01

    There are limited treatment options for carbapenem-resistant Gram-negative infections. Currently, there are suggestions in the literature that combination therapy should be used, which frequently includes antibiotics to which the causative pathogen demonstrates in vitro resistance. This case-control study evaluated risk factors associated with all-cause mortality rates for critically ill patients with carbapenem-resistant Gram-negative bacteremia. Adult patients who were admitted to an intensive care unit with sepsis and a blood culture positive for Gram-negative bacteria resistant to a carbapenem were included. Patients with polymicrobial, recurrent, or breakthrough infections were excluded. Included patients were classified as survivors (controls) or nonsurvivors (cases) at 30 days after the positive blood culture. Of 302 patients screened, 168 patients were included, of whom 90 patients died (53.6% [cases]) and 78 survived (46.4% [controls]) at 30 days. More survivors received appropriate antibiotics (antibiotics with in vitro activity) than did nonsurvivors (93.6% versus 53.3%; P carbapenems) (87.2% versus 80%; P = 0.21). After adjustment for baseline factors with multivariable logistic regression, combination therapy was independently associated with decreased risk of death (odds ratio, 0.19 [95% confidence interval, 0.06 to 0.56]; P carbapenem-resistant Gram-negative bacteremia. However, that association is lost if in vitro activity is not considered. PMID:25845872

  19. Increasing Resistance to Extended-Spectrum Cephalosporins, Fluoroquinolone, and Carbapenem in Gram-Negative Bacilli and the Emergence of Carbapenem Non-Susceptibility in Klebsiella pneumoniae: Analysis of Korean Antimicrobial Resistance Monitoring System (KARMS) Data From 2013 to 2015.

    Science.gov (United States)

    Kim, Dokyun; Ahn, Ji Young; Lee, Chae Hoon; Jang, Sook Jin; Lee, Hyukmin; Yong, Dongeun; Jeong, Seok Hoon; Lee, Kyungwon

    2017-05-01

    National surveillance of antimicrobial resistance becomes more important for the control of antimicrobial resistance and determination of treatment guidelines. We analyzed Korean Antimicrobial Resistance Monitoring System (KARMS) data collected from 2013 to 2015. Of the KARMS participants, 16 secondary or tertiary hospitals consecutively reported antimicrobial resistance rates from 2013 to 2015. Data from duplicate isolates and institutions with fewer than 20 isolates were excluded. To determine the long-term trends, previous KARMS data from 2004 to 2012 were also considered. The prevalence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium from 2013 to 2015 was 66-72% and 29-31%, respectively. The resistance rates of Escherichia coli to cefotaxime and cefepime gradually increased to 35% and 31%, respectively, and fluoroquinolone resistance reached 48% in 2015. The resistance rates of Klebsiella pneumoniae to cefotaxime, cefepime, and carbapenem were 38-41%, 33-41%, and carbapenem susceptibility rates of E. coli and K. pneumoniae decreased from 100% and 99.3% in 2011 to 99.0% and 97.0% in 2015, respectively. The resistance rate of Pseudomonas aeruginosa to carbapenem increased to 35% and the prevalence of carbapenem-resistant Acinetobacter baumannii increased from 77% in 2013 to 85% in 2015. Between 2013 and 2015, the resistance rates of E. coli to third- and fourth-generation cephalosporins increased continuously, while carbapenem-susceptibility gradually decreased, particularly in K. pneumoniae. The prevalence of carbapenem-resistant P. aeruginosa and A. baumannii increased significantly; therefore, few treatment options remain for these resistant strains. © The Korean Society for Laboratory Medicine

  20. Clinical study of carbapenem sensitive and resistant Gram-negative bacteremia in neutropenic and nonneutropenic patients: The first series from India.

    Science.gov (United States)

    Ghafur, A K; Vidyalakshmi, P R; Kannaian, P; Balasubramaniam, R

    2014-01-01

    Carbapenem resistance is a growing global concern. There is a lack of published clinical studies on the topic from Indian subcontinent. Aim of this study was to analyze clinical profile of patients with carbapenem sensitive and resistant bacteremia among neutropenic and nonneutropenic patients. Retrospective analysis of 141 patients who had carbapenem resistant or sensitive Gram-negative bacteremia, identified over a period of 1-year was done by medical records review, in Apollo Specialty Hospital, a 300-bedded tertiary care Oncology, neurosurgical and orthopedic center in South India. Of the total 141 patients with Gram-negative bacteremia, 44 had carbapenem resistant ones. Of these 44 patients, 17 were neutropenics (resistant neutropenic group) and 27 nonneutropenic patients (resistant nonneutropenic group). Of the 97 patients with carbapenem sensitive bacteremia, 43 were neutropenic (sensitive neutropenic group) and 54 nonneutropenics (sensitive nonneutropenic group). The 28 days mortality was significantly higher in carbapenem resistant bacteremic group compared to the sensitive one (P = 0.008). This is the first study from India comparing clinical features of patients with carbapenem sensitive and resistant blood stream infections. Patients with carbapenem resistant bacteremia had higher mortality compared to patients with sensitive bacteremia.

  1. Antibiotic Trapping by Plasmid-Encoded CMY-2 beta-Lactamase Combined with Reduced Outer Membrane Permeability as a Mechanism of Carbapenem Resistance in Escherichia coli

    NARCIS (Netherlands)

    Goessens, W.H.F.; van der Bij, A.K.; van Boxtel, R.; Pitout, J.D.D.; van Ulsen, J.P.; Melles, D.C.; Tommassen, J.

    2013-01-01

    A liver transplant patient was admitted with cholangitis, for which meropenem therapy was started. Initial cultures showed a carbapenem-susceptible (CS) Escherichia coli strain, but during admission, a carbapenem-resistant (CR) E. coli strain was isolated. Analysis of the outer membrane protein

  2. Antibiotic trapping by plasmid-encoded cmy-2-lactamase combined with reduced outer membrane permeability as a mechanism of carbapenem resistance in escherichia coli

    NARCIS (Netherlands)

    W.H.F. Goessens (Wil); A.K. van der Bij (Akke); R. van Boxtel (Ria); J.D.D. Pitout (J. D D); P. van Ulsen (Peter); D.C. Melles (Damian); J. Tommassen (Jan)

    2013-01-01

    textabstractA liver transplant patient was admitted with cholangitis, for which meropenem therapy was started. Initial cultures showed a carbapenem-susceptible (CS) Escherichia coli strain, but during admission, a carbapenem-resistant (CR) E. coli strain was isolated. Analysis of the outer membrane

  3. The Complex Epidemiology of Carbapenem-Resistant Enterobacter Infections: A Multicenter Descriptive Analysis.

    Science.gov (United States)

    Lazarovitch, Tsilia; Amity, Keren; Coyle, Joseph R; Ackerman, Benjamin; Tal-Jasper, Ruthy; Ofer-Friedman, Hadas; Hayakawa, Kayoko; Bogan, Christopher; Lephart, Paul R; Kaplansky, Tamir; Maskit, Moran; Azouri, Tal; Zaidenstein, Ronit; Perez, Federico; Bonomo, Robert A; Kaye, Keith S; Marchaim, Dror

    2015-11-01

    The pandemic of carbapenem-resistant Enterobacteriaceae (CRE) was primarily due to clonal spread of bla KPC producing Klebsiella pneumoniae. Thus, thoroughly studied CRE cohorts have consisted mostly of K. pneumoniae. To conduct an extensive epidemiologic analysis of carbapenem-resistant Enterobacter spp. (CREn) from 2 endemic and geographically distinct centers. CREn were investigated at an Israeli center (Assaf Harofeh Medical Center, January 2007 to July 2012) and at a US center (Detroit Medical Center, September 2008 to September 2009). bla KPC genes were queried by polymerase chain reaction. Repetitive extragenic palindromic polymerase chain reaction and pulsed-field gel electrophoresis were used to determine genetic relatedness. In this analysis, 68 unique patients with CREn were enrolled. Sixteen isolates (24%) were from wounds, and 33 (48%) represented colonization only. All isolates exhibited a positive Modified Hodge Test, but only 93% (27 of 29) contained bla KPC. Forty-three isolates (63%) were from elderly adults, and 5 (7.4%) were from neonates. Twenty-seven patients died in hospital (40.3% of infected patients). Enterobacter strains consisted of 4 separate clones from Assaf Harofeh Medical Center and of 4 distinct clones from Detroit Medical Center. In this study conducted at 2 distinct CRE endemic regions, there were unique epidemiologic features to CREn: (i) polyclonality, (ii) neonates accounting for more than 7% of cohort, and (iii) high rate of colonization (almost one-half of all cases represented colonization). Since false-positive Modified Hodge Tests in Enterobacter spp. are common, close monitoring of carbapenem resistance mechanisms (particularly carbapenemase production) among Enterobacter spp. is important.

  4. Outbreak of Imipenemase-1-Producing Carbapenem-Resistant in an Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Jin Young Lee

    2017-02-01

    Full Text Available Background Carbapenem-resistant Enterobacteriaceae (CRE with acquired metallo β-lactamase (MBL resistance have been increasingly reported worldwide and associated with significant mortality and morbidity. Here, an outbreak of genetically related strains of Klebsiella pneumoniae producing the imipenemase (IMP-1 MBL in a medical intensive care unit (MICU in Korea is reported. Methods Since isolating carbapenem-resistant K. pneumoniae (CRKP at the MICU of the hospital on August 10, 2011, surveillance cultures for CRE in 31 hospitalized patients were performed from August to September 2011. Carbapenem resistance was determined based on the disk diffusion method outlined in the Clinical and Laboratory Standards Institute guidelines. Polymerase chain reaction (PCR was performed for genes coding for β-lactamase. Associations among isolates were assessed via pulsed-field gel electrophoresis (PFGE. In addition, a surveillance study of environmental cultures and health-care workers (HCWs was conducted in the MICU during the same time frame. Results During the study period, non-duplicated CRKP specimens were discovered in four patients in the MICU, suggestive of an outbreak. On August 10, 2011, CRKP was isolated from the sputum of a 79-year-old male patient who was admitted to the MICU. A surveillance study to detect additional CRE carriers by rectal swab revealed an additional three CRKP isolates. PCR and sequencing of the four isolates identified the presence of the IMP-1 gene. In addition, PFGE showed that the four isolated strains were genetically related. CRE was not identified in specimens taken from the hands of HCWs or other environmental sources during surveillance following the outbreak. Transmission of the carbapenemase-producing Enterobacteriaceae strain was controlled by isolation of the patients and strict contact precautions. Conclusions This study shows that rapid and systemic detection of CRE and strict infection controls are important

  5. Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms

    Science.gov (United States)

    Temkin, Elizabeth; Torre-Cisneros, Julian; Beovic, Bojana; Benito, Natividad; Giannella, Maddalena; Gilarranz, Raúl; Jeremiah, Cameron; Loeches, Belén; Machuca, Isabel; Jiménez-Martín, María José; Martínez, José Antonio; Mora-Rillo, Marta; Navas, Enrique; Osthoff, Michael; Pozo, Juan Carlos; Ramos Ramos, Juan Carlos; Rodriguez, Marina; Sánchez-García, Miguel; Viale, Pierluigi; Wolff, Michel

    2016-01-01

    ABSTRACT Ceftazidime-avibactam (CAZ-AVI) is a recently approved β-lactam–β-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro. Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited. PMID:27895014

  6. Anti-Restriction Protein, KlcAHS, Promotes Dissemination of Carbapenem Resistance

    Directory of Open Access Journals (Sweden)

    Xiaofei Jiang

    2017-05-01

    Full Text Available Carbapenemase-producing Klebsiella pneumoniae (KPC has emerged and spread throughout the world. A retrospective analysis was performed on carbapenem-resistant K. pneumoniae isolated at our teaching hospital during the period 2009–2010, when the initial outbreak occurred. To determine the mechanism(s that underlies the increased infectivity exhibited by KPC, Multilocus Sequence Typing (MLST was conducted. A series of plasmids was also extracted, sequenced and analyzed. Concurrently, the complete sequences of blaKPC−2-harboring plasmids deposited in GenBank were summarized and aligned. The blaKPC−2 and KlcAHS genes in the carbapenem-resistant K. pneumoniae isolates were examined. E. coli strains, carrying different Type I Restriction and Modification (RM systems, were selected to study the interaction between RM systems, anti-RM systems and horizontal gene transfer (HGT. The ST11 clone predominated among 102 carbapenem-resistant K. pneumoniae isolates, all harbored the blaKPC−2 gene; 98% contained the KlcAHS gene. KlcAHS was one of the core genes in the backbone region of most blaKPC−2 carrying plasmids. Type I RM systems in the host bacteria reduced the rate of pHS10842 plasmid transformation by 30- to 40-fold. Presence of the anti-restriction protein, KlcAHS, on the other hand, increased transformation efficiency by 3- to 6-fold. These results indicate that RM systems can significantly restrict HGT. In contrast, KlcAHS can disrupt the RM systems and promote HGT by transformation. These findings suggest that the anti-restriction protein, KlcAHS, represents a novel mechanism that facilitates the increased transfer of blaKPC-2 and KlcAHS-carrying plasmids among K. pneumoniae strains.

  7. Carbapenem inactivation: a very affordable and highly specific method for phenotypic detection of carbapenemase-producing Pseudomonas aeruginosa isolates compared with other methods.

    Science.gov (United States)

    Akhi, Mohammad Taghi; Khalili, Younes; Ghotaslou, Reza; Kafil, Hossein Samadi; Yousefi, Saber; Nagili, Behroz; Goli, Hamid Reza

    2017-06-01

    This investigation was undertaken to compare phenotypic and molecular methods for detection of carbapenemase-producing Pseudomonas aeruginosa. A total of 245 non-duplicated isolates of P. aeruginosa were collected from hospitalized patients. Disc diffusion method was used to identify carbapenem-resistant bacteria. Three phenotypic methods, including Modified Hodge Test (MHT), Modified Carba NP (MCNP) test and Carbapenem Inactivation Method (CIM) were used for investigation of carbapenemase production. In addition, polymerase chain reaction (PCR) was used to detect carbapenemase encoding genes. Of 245 P. aeruginosa isolates investigated, 121 isolates were carbapenem-resistant. Among carbapenem-resistant isolates, 40, 39 and 35 isolates exhibited positive results using MHT, MCNP test and CIM, respectively. PCR indicated the presence of carbapenemase genes in 35 of carbapenem-resistant isolates. MHT showed low sensitivity and specificity for carbapenemase detection among P. aeruginosa isolates in comparison to PCR. CIM was most affordable and highly specific than MCNP test compared with the molecular method.

  8. Clinical evaluation of the need for carbapenems to treat community-acquired and healthcare-associated pneumonia.

    Science.gov (United States)

    Kamata, Kazuhiro; Suzuki, Hiromichi; Kanemoto, Koji; Tokuda, Yasuharu; Shiotani, Seiji; Hirose, Yumi; Suzuki, Masatsune; Ishikawa, Hiroichi

    2015-08-01

    Carbapenems have an overall broad antibacterial spectrum and should be protected against from the acquisition of drug resistance. The clinical advantages of carbapenem in cases of pneumonia have not been certified and the need for antipseudomonal antimicrobial agents to treat healthcare-associated pneumonia (HCAP) remains controversial. We introduced an antimicrobial stewardship program for carbapenem and tazobactam/piperacillin use and investigated the effects of this program on the clinical outcomes of 591 pneumonia cases that did not require intensive care unit management, mechanical ventilation or treatment with vasopressor agents [221 patients with community-acquired pneumonia (CAP) and 370 patients with HCAP]. Compared with the pre-intervention period, age, comorbidities and the severity and etiology of pneumonia did not differ during the intervention period. Carbapenems were rarely used during the intervention period in cases of pneumonia (CAP: 12% vs. 1%, HCAP: 13% vs. 1%), while antipseudomonal beta-lactam use was reduced from 33% to 8% among cases with HCAP. This reduction in the rate of carbapenem administration did not have an impact on the prognosis in the cases of CAP, and the in-hospital mortality was lower among the patients with HCAP during the intervention period (15% vs. 5%, p = 0.013). The causes of death in the cases of HCAP were not directly related to pneumonia during the intervention period. The current study shows that carbapenem use can be avoided in cases of CAP or HCAP that are not in a critical condition. The frequent use of antipseudomonal beta-lactams does not improve the clinical outcomes of HCAP. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Impact of antibiotic exposure on occurrence of nosocomial carbapenem-resistant Acinetobacter baumannii infection: a case control study.

    Science.gov (United States)

    Chusri, Sarunyou; Silpapojakul, Kachornsakdi; McNeil, Edward; Singkhamanan, Kamonnut; Chongsuvivatwong, Virasakdi

    2015-02-01

    Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is one of the most important healthcare associated diseases worldwide. Although antibiotic use is recognized as a risk factor for CRAB infection, the impact of antibiotic class and length of use on CRAB infection is still unclear. A case-control study was conducted in adult intensive care units and general wards of Songklanagarind Hospital, a tertiary-care hospital in southern Thailand, to investigate the effect of different antibiotic exposure and the duration of use on the risk of developing CRAB infection. Cases were defined as patients with carbapenem-susceptible A. baumannii (CSAB) or CRAB infection. Controls were randomly selected from patients and matched 1:1 with cases using ward and date of admission. Multinomial logistic regression was used to compute relative risk ratios (RRR) and 95% confidence intervals (CI) for CRAB infection. Of 197 cases with A. baumannii infection, there were 139 with CRAB infection and 58 with CSAB infection. Compared to the control group, use of fluoroquinolones, broad-spectrum cephalosporins and carbapenems for more than three days increased the risk of CRAB infection with RRR (95% CI) of 81.2 (38.1-862.7), 31.3 (9.9-98.7) and 112.1 (7.1-1770.6), respectively. The RRR (95% CI) for one to three day treatment of fluoroquinolones, broad-spectrum cephalosporins and carbapenems were 5.4 (0.8-38.7), 6.2 (0.1-353.2) and 63.3 (15.6-256.9), respectively. Long-term use of certain antibiotics and even short term use of carbapenems increased the risk of CRAB infection. In this setting, use of these antibiotics, especially carbapenems, should be limited to reduce CRAB infection. Copyright © 2014. Published by Elsevier Ltd.

  10. Risk factors for hospital-acquired bacteremia due to carbapenem-resistant Pseudomonas aeruginosa in a Colombian hospital.

    Science.gov (United States)

    Valderrama, Sandra Liliana; González, Pedro Felipe; Caro, María Alejandra; Ardila, Natalia; Ariza, Beatriz; Gil, Fabián; Álvarez, Carlos

    2016-02-23

    Bacteremia due to Pseudomonas aeruginosa resistant to carbapenems is a public health problem due to the limitations it places on therapeutic options, as well as the increased time patients must spend in hospital, costs and the risk of mortality.  To evaluate the risk factors for presentation of bacteremia due to carbapenem-resistant P. aeruginosa acquired in the Hospital Universitario San Ignacio between January 2008 and June 2014.  This was a case control study in which the case patients presented bacteremia due to P. aeruginosa resistant to carbapenems and the control group included patients with P. aeruginosa susceptible to this group of antibiotics. Variables such as the previous use of meropenem and ertapenem, immunosuppression and neoplasia were measured. Mortality and duration of hospital were also described.  In all, 168 patients were evaluated, of which 42 were cases and 126 controls. Using a multivariate model, the risk factors related to bacteremia due to carbapenem-resistant P. aeruginosa acquired in hospital were the following: use of parenteral nutrition (OR=8.28; 95% CI: 2.56-26.79; p=0); use of meropenem (OR=1.15; 95% CI: 1.03-1.28; p=0.01); and use of ciprofloxacin (OR=81.99; 95% CI: 1.14-5884; p=0.043).  In order to prevent the emergence of carbapenem-resistant P. aeruginosa, antimicrobial control programs should be strengthened by promoting the prudent administration of carbapenems and quinolones. The correct use of parenteral nutrition should also be monitored.

  11. Impact of carbapenem resistance on the outcome of patients' hospital-acquired bacteraemia caused by Klebsiella pneumoniae.

    Science.gov (United States)

    Hussein, K; Raz-Pasteur, A; Finkelstein, R; Neuberger, A; Shachor-Meyouhas, Y; Oren, I; Kassis, I

    2013-04-01

    Carbapenem-resistant Enterobacteriaceae, especially Klebsiella spp., have become a major health problem recently worldwide. Since 2006 the incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections has increased substantially in Israel. Bloodstream infections (BSIs) caused by these strains have been associated with high rates of treatment failure and mortality. This study was designed to identify risk factors for carbapenem resistance among patients with healthcare-related (HCR) K. pneumoniae bacteraemia and predictors of mortality associated with HCR-CRKP bacteraemia compared with carbapenem-susceptible K. pneumoniae (CSKP). In this retrospective case-control study, all cases of K. pneumoniae bacteraemia during 2006-2008 were identified. Resistance patterns, underlying morbidities, risk factors for drug resistance and mortality rates were compared for patients with CRKP and CSKP bacteraemia. Two hundred and fourteen patients with CSKP bacteraemia were compared with 103 patients with CRKP bacteraemia. Severe, chronic comorbidities and prior antibiotic use were more frequent among patients with CRKP bacteraemia. On multivariate analysis prior use of macrolides and antibiotic exposure for ≥14 days remained the only independent factors associated with CRKP bacteraemia. Mortality rates of CRKP patients were significantly higher than those of CSKP patients. On multivariate analyses: bedridden status, chronic liver disease, Charlson comorbidity index ≥5, mechanical ventilation, and haemodialysis remained independently associated with mortality among patients with K. pneumoniae bacteraemia. Carbapenem resistance was not a risk factor for mortality. Previous antibiotic exposure is a risk factor for CRKP-BSI. Mortality among patients with K. pneumoniae bacteraemia is associated with serious comorbidities, but not with carbapenem resistance. Copyright © 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  12. Carbapenem-resistance and pathogenicity of bovine Acinetobacter indicus-like isolates.

    Directory of Open Access Journals (Sweden)

    Peter Klotz

    Full Text Available The objective of this study was to characterize blaOXA-23 harbouring Acinetobacter indicus-like strains from cattle including genomic and phylogenetic analyses, antimicrobial susceptibility testing and evaluation of pathogenicity in vitro and in vivo. Nasal and rectal swabs (n = 45 from cattle in Germany were screened for carbapenem-non-susceptible Acinetobacter spp. Thereby, two carbapenem resistant Acinetobacter spp. from the nasal cavities of two calves could be isolated. MALDI-TOF mass spectrometry and 16S rDNA sequencing identified these isolates as A. indicus-like. A phylogenetic tree based on partial rpoB sequences indicated closest relation of the two bovine isolates to the A. indicus type strain A648T and human clinical A. indicus isolates, while whole genome comparison revealed considerable intraspecies diversity. High mimimum inhibitory concentrations were observed for carbapenems and other antibiotics including fluoroquinolones and gentamicin. Whole genome sequencing and PCR mapping revealed that both isolates harboured blaOXA-23 localized on the chromosome and surrounded by interrupted Tn2008 transposon structures. Since the pathogenic potential of A. indicus is unknown, pathogenicity was assessed employing the Galleria (G. mellonella infection model and an in vitro cytotoxicity assay using A549 human lung epithelial cells. Pathogenicity in vivo (G. mellonella killing assay and in vitro (cytotoxicity assay of the two A. indicus-like isolates was lower compared to A. baumannii ATCC 17978 and similar to A. lwoffii ATCC 15309. The reduced pathogenicity of A. indicus compared to A. baumannii correlated with the absence of important virulence genes encoding like phospholipase C1+C2, acinetobactin outer membrane protein BauA, RND-type efflux system proteins AdeRS and AdeAB or the trimeric autotransporter adhesin Ata. The emergence of carbapenem-resistant A. indicus-like strains from cattle carrying blaOXA-23 on transposable elements and

  13. Mutant prevention concentrations of four carbapenems against gram-negative rods.

    Science.gov (United States)

    Credito, Kim; Kosowska-Shick, Klaudia; Appelbaum, Peter C

    2010-06-01

    We tested the propensities of four carbapenems to select for resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii mutants by determining the mutant prevention concentrations (MPCs) for 100 clinical strains with various ss-lactam phenotypes. Among the members of the Enterobacteriaceae family and A. baumannii strains, the MPC/MIC ratios were mostly 2 to 4. In contrast, for P. aeruginosa the MPC/MIC ratios were 4 to > or =16. The MPC/MIC ratios for beta-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 microg/ml) than those for ss-lactamase-negative strains.

  14. Mutant Prevention Concentrations of Four Carbapenems against Gram-Negative Rods▿ †

    Science.gov (United States)

    Credito, Kim; Kosowska-Shick, Klaudia; Appelbaum, Peter C.

    2010-01-01

    We tested the propensities of four carbapenems to select for resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii mutants by determining the mutant prevention concentrations (MPCs) for 100 clinical strains with various ß-lactam phenotypes. Among the members of the Enterobacteriaceae family and A. baumannii strains, the MPC/MIC ratios were mostly 2 to 4. In contrast, for P. aeruginosa the MPC/MIC ratios were 4 to ≥16. The MPC/MIC ratios for β-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 μg/ml) than those for ß-lactamase-negative strains. PMID:20308376

  15. Incidence of carbapenem resistant nonfermenting gram negative bacilli from patients with respiratory infections in the intensive care units

    Directory of Open Access Journals (Sweden)

    Gladstone P

    2005-01-01

    Full Text Available Resistance to carbapenems is commonly seen in nonfermenting gram negative bacilli (NFGNB. We document herein the prevalence of carbapenem resistance in NFGNB isolated from patients with respiratory tract infections in the intensive care units (ICUs. A total of 460 NFGNB were isolated from 606 endotracheal aspirate specimens during January through December 2003, of which 56 (12.2% were found to be resistant to imipenem and meropenem. Of these, 24 (42.8% were Pseudomonas aeruginosa , 8 (14.2% were Acinetobacter spp. and 24 (42.8% were other NFGNB. Stringent protocols such as antibiotic policies and resistance surveillance programs are mandatory to curb these bacteria in ICU settings.

  16. 32 CFR 644.62 - Title evidence.

    Science.gov (United States)

    2010-07-01

    ... HANDBOOK Acquisition Procurement of Title Evidence, Title Clearance, and Closings § 644.62 Title evidence... and their charter to issue the same. They must also be financially sound and be willing and able to...

  17. Region 7 Title V facilities

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web map shows the Region 7 Title V facilities (Clean Air Act major sources), any Class I areas within 300 km of R7 States, and any Tribal areas within 50 miles...

  18. Title V Permitting Statistics Inventory

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Title V Permitting Statistics Inventory contains measured and estimated nationwide statistical data, consisting of counts of permitted sources, types of permits...

  19. Molecular Epidemiology of Carbapenem Non-Susceptible Acinetobacter baumannii in France

    Science.gov (United States)

    Jeannot, Katy; Diancourt, Laure; Vaux, Sophie; Thouverez, Michelle; Ribeiro, Amandina; Coignard, Bruno; Courvalin, Patrice; Brisse, Sylvain

    2014-01-01

    Carbapenem-resistant Acinetobacter baumannii have emerged globally. The objective of this study was to investigate the epidemiology, clonal diversity and resistance mechanisms of imipenem non-susceptible A. baumannii isolates in France. Between December 2010 and August 2011, 132 notifications were collected, including 37 outbreaks corresponding to 242 cases (2 to 55 per cluster). Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on 110 non-repetitive isolates. Gene bla OXA-23 was the most frequently detected (82%), followed by bla OXA-24 (11%) and bla OXA-58 (7%). Eleven sequence types (ST) were distinguished, among which sequence types ST1, ST2 (64%), ST20, ST25, ST85 and ST107. Isolates from epidemiological clusters had the same ST and resistance genes, indicating probable transmission within centres. In contrast, PFGE types of isolates differed among centres, arguing against transmission among centers. This study provides the first epidemiological snapshot of the population of A. baumannii with reduced susceptibility to carbapenems from France, and further underlines the predominance of international clones. PMID:25517732

  20. Prevalence of carbapenem resistant Enterobacteriaceae from a tertiary care hospital in Mumbai, India

    Directory of Open Access Journals (Sweden)

    Pravin K. Nair

    2013-12-01

    Full Text Available Objective: The emergence of Carbapenem Resistant Enterobacteriaceae (CRE in recent times has become a serious threat to public health due to the high mortality, potential dissemination rates and limited treatment options associated with these organisms. Thus, the present study was conducted in our tertiary care hospital in Mumbai, to retrospectively analyze the prevalence of CRE in the hospital. Methods: The study was carried out in the microbiology department of the tertiary care hospital over a period of 12 months. The samples tested were clinical samples from hospitalized and Out-Patient Department (OPD patients sent to the department for microbiological testing. CRE isolates were identified using the Vitek 2- Compact system (BioMérieux, France. Results: A CRE prevalence rate of 12.26% was obtained from the study, from which the majority of the isolates were detected in urine samples (46%. Although most of the CRE isolates were detected in patient samples from the wards (42% and the ICU (26%, a significant number of isolates was also detected from the OPD patients (19%. Conclusion:Thus, the study shows a significant rate of carbapenem resistance among Enterobacteriaceae isolated from hospitalized and OPD patients. This emphasizes the urgent need for CRE control at the hospital and community level, and to rationalize the use of antibiotics. J Microbiol Infect Dis 2013;3(4: 207-210

  1. Study of Klebsiella pneumoniae strains resistant to carbapenems isolated from blood in eastern Liguria

    Directory of Open Access Journals (Sweden)

    Giulia Carnesecchi

    2012-12-01

    Full Text Available Objectives. Study of multi-resistant Klebsiella pneumoniae strains isolated from blood cultures collected from in-patients of hospitals located in eastern Liguria, and evaluation of the susceptibility to carbapenems and other antibiotics by E-test and automated methods. Methods. At the Laboratory of Clinical Microbiology, of Lavagna Hospital in eastern Liguria, 397 Klebsiella pneumoniae strains were collected from in-patients from different wards of hospitals sites, during the year 2011. They included 115 isolates from blood cultures (aerobic and anaerobic and various biological materials. All strains were tested in the laboratory for their susceptibility to antibiotics. Results. Of the 115 strains of Klebsiella pneumoniae collected from blood cultures 59.1% showed resistance to imipenem, ertapenem, meropenem. Conclusions. The data show a high incidence of resistance to carbapenems in Klebsiella pneumoniae isolated from blood cultures.This is important to implement surveillance programs for control and prevention, but also reduce the intake of antibiotics when they are not strictly necessary.

  2. The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace.

    Science.gov (United States)

    Logan, Latania K; Weinstein, Robert A

    2017-02-15

    Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Mechanisms of drug resistance in gram-negative bacteria (GNB) are numerous; β-lactamase genes carried on mobile genetic elements are a key mechanism for the rapid spread of antibiotic-resistant GNB worldwide. Transmissible carbapenem-resistance in Enterobacteriaceae has been recognized for the last 2 decades, but global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a more recent problem that, once initiated, has been occurring at an alarming pace. In this article, we discuss the evolution of CRE, with a focus on the epidemiology of the CPE pandemic; review risk factors for colonization and infection with the most common transmissible CPE worldwide, Klebsiella pneumoniae carbapenemase-producing K. pneumoniae; and present strategies used to halt the striking spread of these deadly pathogens. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  3. Emergence and clonal dissemination of carbapenem-hydrolysing OXA-58-producing Acinetobacter baumannii isolates in Bolivia.

    Science.gov (United States)

    Sevillano, Elena; Fernández, Elena; Bustamante, Zulema; Zabalaga, Silvia; Rosales, Ikerne; Umaran, Adelaida; Gallego, Lucía

    2012-01-01

    Acinetobacter baumannii is an emerging multidrug-resistant pathogen and very little information is available regarding its imipenem resistance in Latin American countries such as Bolivia. This study investigated the antimicrobial resistance profile of 46 clinical strains from different hospitals in Cochabamba, Bolivia, from March 2008 to July 2009, and the presence of carbapenemases as a mechanism of resistance to imipenem. Isolates were obtained from 46 patients (one isolate per patient; 30 males,16 females) with an age range of 1 day to 84 years, and were collected from different sample types, the majority from respiratory tract infections (17) and wounds (13). Resistance to imipenem was detected in 15 isolates collected from different hospitals of the city. These isolates grouped into the same genotype, named A, and were resistant to all antibiotics tested including imipenem, with susceptibility only to colistin. Experiments to detect carbapenemases revealed the presence of the OXA-58 carbapenemase. Further analysis revealed the location of the bla(OXA-58) gene on a 40 kb plasmid. To our knowledge, this is the first report of carbapenem resistance in A. baumannii isolates from Bolivia that is conferred by the OXA-58 carbapenemase. The presence of this gene in a multidrug-resistant clone and its location within a plasmid is of great concern with regard to the spread of carbapenem-resistant A. baumannii in the hospital environment in Bolivia.

  4. Rapid Increase in Prevalence of Carbapenem-Resistant Enterobacteriaceae (CRE) and Emergence of Colistin Resistance Gene mcr-1 in CRE in a Hospital in Henan, China.

    Science.gov (United States)

    Li, Yi; Sun, Qiao-Ling; Shen, Yingbo; Zhang, Yangjunna; Yang, Jun-Wen; Shu, Ling-Bin; Zhou, Hong-Wei; Wang, Yang; Wang, Bing; Zhang, Rong; Wang, Shaolin; Shen, Zhangqi

    2018-04-01

    The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is one of the most severe threats to human health in a clinical setting. The recent emergence of plasmid-mediated colistin resistance gene mcr-1 among CRE strains greatly compromises the use of colistin as a last resort for the treatment of infections caused by CRE. This study aimed to understand the current epidemiological trends and characteristics of CRE from a large hospital in Henan, the most populous province in China. From 2014 to 2016, a total of 7,249 Enterobacteriaceae isolates were collected from clinical samples, among which 18.1% (1,311/7,249) were carbapenem resistant. Carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli were the two most common CRE species, with Klebsiella pneumoniae carbapenemases (KPC) and New Delhi metallo-β-lactamases (NDM), respectively, responsible for the carbapenem resistance of the two species. Notably, >57.0% ( n = 589) of the K. pneumoniae isolates from the intensive care unit were carbapenem resistant. Furthermore, bla NDM-5 and mcr-1 were found to coexist in one E. coli isolate, which exhibited resistance to almost all tested antibiotics. Overall, we observed a significant increase in the prevalence of CRE isolates during the study period and suggest that carbapenems may no longer be considered to be an effective treatment for infections caused by K. pneumoniae in the studied hospital. Copyright © 2018 American Society for Microbiology.

  5. Empiric Piperacillin-Tazobactam versus Carbapenems in the Treatment of Bacteraemia Due to Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae.

    Science.gov (United States)

    Ng, Tat Ming; Khong, Wendy X; Harris, Patrick N A; De, Partha P; Chow, Angela; Tambyah, Paul A; Lye, David C

    2016-01-01

    Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are a common cause of bacteraemia in endemic countries and may be associated with high mortality; carbapenems are considered the drug of choice. Limited data suggest piperacillin-tazobactam could be equally effective. We aimed to compare 30-day mortality of patients treated empirically with piperacillin-tazobactam versus a carbapenem in a multi-centre retrospective cohort study in Singapore. Only patients with active empiric monotherapy with piperacillin-tazobactam or a carbapenem were included. A propensity score for empiric carbapenem therapy was derived and an adjusted multivariate analysis of mortality was conducted. A total of 394 patients had ESBL-Escherichia.coli and ESBL-Klebsiella pneumoniae bacteraemia of which 23.1% were community acquired cases. One hundred and fifty-one received initial active monotherapy comprising piperacillin-tazobactam (n = 94) or a carbapenem (n = 57). Patients who received carbapenems were less likely to have health-care associated risk factors and have an unknown source of bacteraemia, but were more likely to have a urinary source. Thirty-day mortality was comparable between those who received empiric piperacillin-tazobactam and a carbapenem (29 [30.9%] vs. 17 [29.8%]), P = 0.89). Those who received empiric piperacillin-tazobactam had a lower 30-day acquisition of multi-drug resistant and fungal infections (7 [7.4%] vs. 14 [24.6%]), Pcarbapenem.

  6. Treatment of ESBL-producing Klebsiella pneumoniae bacteraemia with carbapenems or flomoxef: a retrospective study and laboratory analysis of the isolates.

    Science.gov (United States)

    Lee, Chen-Hsiang; Su, Lin-Hui; Tang, Ya-Fen; Liu, Jien-Wei

    2006-11-01

    To better understand the clinical outcomes of patients with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) bacteraemia treated with either flomoxef or a carbapenem, and to evaluate the in vitro activities of these antibiotics against ESBL-KP. Retrospective analyses to identify risk factors for mortality in patients with flomoxef-susceptible ESBL-KP, especially addressing the therapeutic roles of flomoxef and carbapenem. In vitro activities of flomoxef and carbapenem against flomoxef-susceptible ESBL-KP isolates were evaluated by susceptibility testing and time-kill study. Twenty-seven patients (flomoxef group, n=7; carbapenem group, n=20) were included. Clinical severity reflected by high Pitt bacteraemia score (>or=6) was an independent risk factor for mortality (OR 13.43; 95% CI, 1.08-166.73; P=0.043), while use of flomoxef or a carbapenem was not. The MICs of flomoxef and carbapenem indicated that the tested ESBL-KP were susceptible to these antibiotics regardless of the inoculum size of 10(5) or 10(7) cfu/mL. Time-kill study showed that these antibiotics (flomoxef 8 mg/L and meropenem 4 mg/L) each acted actively against and inhibited the regrowth of the tested ESBL-KP for at least 24 h. Flomoxef might be as clinically effective as a carbapenem in treating flomoxef-susceptible ESBL-KP bacteraemia.

  7. Presence of the KPC carbapenemase gene in Enterobacteriaceae causing bacteremia, and the correlation with in vitro carbapenem susceptibility

    Science.gov (United States)

    During six months, we obtained Enterobacteriaceae isolates from patients with Gram-negative bacteremia at a 1250-bed teaching hospital in St. Louis, Missouri, and compared carbapenem susceptibility with the presence of blaKPC, a transferable carbapenemase gene. Three (1.2%) out of 243 isolates were ...

  8. Carbapenem MICs in Escherichia coli and Klebsiella Species Producing Extended-Spectrum β-Lactamases in Critical Care Patients from 2001 to 2009.

    Science.gov (United States)

    Johnson, J Kristie; Robinson, Gwen L; Pineles, Lisa L; Ajao, Adebola O; Zhao, LiCheng; Albrecht, Jennifer S; Harris, Anthony D; Thom, Kerri A; Furuno, Jon P

    2017-04-01

    Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae strains are increasing in prevalence worldwide. Carbapenem antibiotics are used as a first line of therapy against ESBL-producing Enterobacteriaceae We examined a cohort of critical care patients for gastrointestinal colonization with carbapenem-resistant ESBL-producing strains (CR-ESBL strains). We cultured samples from this cohort of patients for ESBL-producing Klebsiella spp. and Escherichia coli and then tested the first isolate from each patient for susceptibility to imipenem, doripenem, meropenem, and ertapenem. Multilocus sequence typing was performed on isolates that produced an ESBL and that were carbapenem resistant. Among all patients admitted to an intensive care unit (ICU), 4% were positive for an ESBL-producing isolate and 0.64% were positive for a CR-ESBL strain on surveillance culture. Among the first ESBL-producing E. coli and Klebsiella isolates from the patients' surveillance cultures, 11.2% were carbapenem resistant. Sequence type 14 (ST14), ST15, ST42, and ST258 were the dominant sequence types detected in this cohort of patients, with ST15 and ST258 steadily increasing in prevalence from 2006 to 2009. Patients colonized by a CR-ESBL strain were significantly more likely to receive antipseudomonal and anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) therapy prior to ICU admission than patients colonized by carbapenem-susceptible ESBL-producing strains. They were also significantly more likely to have received a cephalosporin or a carbapenem antibiotic than patients colonized by carbapenem-susceptible ESBL-producing strains. In conclusion, in a cohort of patients residing in intensive care units within the United States, we found that 10% of the isolates were resistant to at least one carbapenem antibiotic. The continued emergence of carbapenem-resistant ESBL-producing strains is of significant concern, as infections due to these organisms are notoriously difficult to

  9. Carbapenem-resistant and cephalosporin-susceptible: a worrisome phenotype among Pseudomonas aeruginosa clinical isolates in Brazil.

    Science.gov (United States)

    Campana, Eloiza Helena; Xavier, Danilo Elias; Petrolini, Fernanda Villas-Boas; Cordeiro-Moura, Jhonatha Rodrigo; Araujo, Maria Rita Elmor de; Gales, Ana Cristina

    The mechanisms involved in the uncommon resistance phenotype, carbapenem resistance and broad-spectrum cephalosporin susceptibility, were investigated in 25 Pseudomonas aeruginosa clinical isolates that exhibited this phenotype, which were recovered from three different hospitals located in São Paulo, Brazil. The antimicrobial susceptibility profile was determined by CLSI broth microdilution. β-lactamase-encoding genes were investigated by PCR followed by DNA sequencing. Carbapenem hydrolysis activity was investigated by spectrophotometer and MALDI-TOF assays. The mRNA transcription level of oprD was assessed by qRT-PCR and the outer membrane proteins profile was evaluated by SDS-PAGE. Genetic relationship among P. aeruginosa isolates was assessed by PFGE. Carbapenems hydrolysis was not detected by carbapenemase assay in the carbapenem-resistant and cephalosporin-susceptible P. aueruginosa clinical isolates. OprD decreased expression was observed in all P. aeruginosa isolates by qRT-PCR. The outer membrane protein profile by SDS-PAGE suggested a change in the expression of the 46kDa porin that could correspond to OprD porin. The isolates were clustered into 17 genotypes without predominance of a specific PFGE pattern. These results emphasize the involvement of multiple chromosomal mechanisms in carbapenem-resistance among clinical isolates of P. aeruginosa, alert for adaptation of P. aeruginosa clinical isolates under antimicrobial selective pressure and make aware of the emergence of an uncommon phenotype among P. aeruginosa clinical isolates. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  10. SME-type carbapenem-hydrolyzing class A beta-lactamases from geographically diverse Serratia marcescens strains.

    Science.gov (United States)

    Queenan, A M; Torres-Viera, C; Gold, H S; Carmeli, Y; Eliopoulos, G M; Moellering, R C; Quinn, J P; Hindler, J; Medeiros, A A; Bush, K

    2000-11-01

    Three sets of carbapenem-resistant Serratia marcescens isolates have been identified in the United States: 1 isolate in Minnesota in 1985 (before approval of carbapenems for clinical use), 5 isolates in Los Angeles (University of California at Los Angeles [UCLA]) in 1992, and 19 isolates in Boston from 1994 to 1999. All isolates tested produced two beta-lactamases, an AmpC-type enzyme with pI values of 8.6 to 9.0 and one with a pI value of approximately 9.5. The enzyme with the higher pI in each strain hydrolyzed carbapenems and was not inhibited by EDTA, similar to the chromosomal class A SME-1 beta-lactamase isolated from the 1982 London strain S. marcescens S6. The genes encoding the carbapenem-hydrolyzing enzymes were cloned in Escherichia coli and sequenced. The enzyme from the Minnesota isolate had an amino acid sequence identical to that of SME-1. The isolates from Boston and UCLA produced SME-2, an enzyme with a single amino acid change relative to SME-1, a substitution from valine to glutamine at position 207. Purified SME enzymes from the U. S. isolates had beta-lactam hydrolysis profiles similar to that of the London SME-1 enzyme. Pulsed-field gel electrophoresis analysis revealed that the isolates showed some similarity but differed by at least three genetic events. In conclusion, a family of rare class A carbapenem-hydrolyzing beta-lactamases first described in London has now been identified in S. marcescens isolates across the United States.

  11. SME-Type Carbapenem-Hydrolyzing Class A β-Lactamases from Geographically Diverse Serratia marcescens Strains

    Science.gov (United States)

    Queenan, Anne Marie; Torres-Viera, Carlos; Gold, Howard S.; Carmeli, Yehuda; Eliopoulos, George M.; Moellering, Robert C.; Quinn, John P.; Hindler, Janet; Medeiros, Antone A.; Bush, Karen

    2000-01-01

    Three sets of carbapenem-resistant Serratia marcescens isolates have been identified in the United States: 1 isolate in Minnesota in 1985 (before approval of carbapenems for clinical use), 5 isolates in Los Angeles (University of California at Los Angeles [UCLA]) in 1992, and 19 isolates in Boston from 1994 to 1999. All isolates tested produced two β-lactamases, an AmpC-type enzyme with pI values of 8.6 to 9.0 and one with a pI value of approximately 9.5. The enzyme with the higher pI in each strain hydrolyzed carbapenems and was not inhibited by EDTA, similar to the chromosomal class A SME-1 β-lactamase isolated from the 1982 London strain S. marcescens S6. The genes encoding the carbapenem-hydrolyzing enzymes were cloned in Escherichia coli and sequenced. The enzyme from the Minnesota isolate had an amino acid sequence identical to that of SME-1. The isolates from Boston and UCLA produced SME-2, an enzyme with a single amino acid change relative to SME-1, a substitution from valine to glutamine at position 207. Purified SME enzymes from the U.S. isolates had β-lactam hydrolysis profiles similar to that of the London SME-1 enzyme. Pulsed-field gel electrophoresis analysis revealed that the isolates showed some similarity but differed by at least three genetic events. In conclusion, a family of rare class A carbapenem-hydrolyzing β-lactamases first described in London has now been identified in S. marcescens isolates across the United States. PMID:11036019

  12. National Ignition Facility Title II Design Plan

    International Nuclear Information System (INIS)

    Kumpan, S

    1997-01-01

    This National Ignition Facility (NIF) Title II Design Plan defines the work to be performed by the NIF Project Team between November 1996, when the U.S. Department of Energy (DOE) reviewed Title I design and authorized the initiation of Title H design and specific long-lead procurements, and September 1998, when Title 11 design will be completed

  13. ISAba1 Regulated OXA-23 Carbapenem Resistance in Acinetobacter baumannii Strains in Durban, South Africa.

    Science.gov (United States)

    Agoba, Esther Eyram; Govinden, Usha; Peer, Abdool Kader Cassim; Osei Sekyere, John; Essack, Sabiha Yusuf

    2018-03-20

    This study investigated the molecular mechanisms of resistance to carbapenems and cephalosporins in 24 consecutive, multidrug-resistant Acinetobacter baumannii (MDRAB) isolates collected between January and April 2015 by a private sector laboratory in Durban, South Africa. All isolates were resistant to all carbapenems tested. bla OXA-23 and bla OXA-51 genes were found in 23 isolates, while bla OXA-24 , bla OXA-48 , and bla OXA-58 were absent in all isolates. The most prevalent extended-spectrum β-lactamase was TEM-116 (92%). bla ADC was present in 83.3% of isolates, of which two were new variants with three and five amino acid differences compared to Acinetobacter-derived cephalosporinase (ADC)-1, the first at positions 64E → K, 341N → T, and 342R → G and the second at positions 24G → D, 167S → P, 283R → F, 341N → T, and 342R → G, respectively. All isolates were negative for bla PER , bla CMY , bla GES , bla KPC , bla CTX-M , and bla SHV . Metallo-β-lactamase IMP and VIM were absent in all isolates, and NDM-1 was present in 1 isolate. ISAba1 was located upstream bla OXA-23 in all isolates and upstream bla ADC (30, 78, 79, 87 and the ADC variants) in 54.2% of the ADC-carrying isolates. None of the isolates had ISAba1 inserted upstream bla OXA-51 gene. Four isolates were clonally related and showed two clusters (A and B), while 20 isolates remained unclustered. There was no direct relationship between the clusters and the hospitals they were isolated from. This study reports the first NDM-1-producing carbapenem resistant Acinetobacter baumannii isolate in South Africa and highlights the presence of OXA-23, the known ADCs (ADC-30, ADC-78, ADC-79, and ADC-87), and two new ADC variants associated with ISAba1 from the private health sector in Durban, South Africa. The complexity and diversity of MDRAB severely limit treatment options.

  14. Genomically Informed Surveillance for Carbapenem-Resistant Enterobacteriaceae in a Health Care System.

    Science.gov (United States)

    Pecora, Nicole D; Li, Ning; Allard, Marc; Li, Cong; Albano, Esperanza; Delaney, Mary; Dubois, Andrea; Onderdonk, Andrew B; Bry, Lynn

    2015-07-28

    Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent public health concern. Rapid identification of the resistance genes, their mobilization capacity, and strains carrying them is essential to direct hospital resources to prevent spread and improve patient outcomes. Whole-genome sequencing allows refined tracking of both chromosomal traits and associated mobile genetic elements that harbor resistance genes. To enhance surveillance of CREs, clinical isolates with phenotypic resistance to carbapenem antibiotics underwent whole-genome sequencing. Analysis of 41 isolates of Klebsiella pneumoniae and Enterobacter cloacae, collected over a 3-year period, identified K. pneumoniae carbapenemase (KPC) genes encoding KPC-2, -3, and -4 and OXA-48 carbapenemases. All occurred within transposons, including multiple Tn4401 transposon isoforms, embedded within more than 10 distinct plasmids representing incompatibility (Inc) groups IncR, -N, -A/C, -H, and -X. Using short-read sequencing, draft maps were generated of new KPC-carrying vectors, several of which were derivatives of the IncN plasmid pBK31551. Two strains also had Tn4401 chromosomal insertions. Integrated analyses of plasmid profiles and chromosomal single-nucleotide polymorphism (SNP) profiles refined the strain patterns and provided a baseline hospital mobilome to facilitate analysis of new isolates. When incorporated with patient epidemiological data, the findings identified limited outbreaks against a broader 3-year period of sporadic external entry of many different strains and resistance vectors into the hospital. These findings highlight the utility of genomic analyses in internal and external surveillance efforts to stem the transmission of drug-resistant strains within and across health care institutions. We demonstrate how detection of resistance genes within mobile elements and resistance-carrying strains furthers active surveillance efforts for drug resistance. Whole-genome sequencing is increasingly

  15. New Delhi Metallo-Β-Lactamase-Producing Carbapenem-Resistant Enterobacteriacae Isolated From Bronchial Washings.

    LENUS (Irish Health Repository)

    Cullivan, S

    2017-11-01

    The prevalence of Carbapenem resistance among Enterobacteriacae species is increasing and poses a potential major public health risk. In recent years, several new carbapenemases have been identified, including New Delhi metallo-β-lactamase (NDM). A 78-year-old non-smoking female with prior medical history of type 2 diabetes mellitus, gastroesophageal reflux disease (GERD) and prior coronary artery bypass grafting was referred to our respiratory outpatient service for evaluation of a chronic cough and dyspnoea in 2013. Clinical examination revealed bibasal pulmonary crepitations but was otherwise unremarkable. Computed tomography of the chest demonstrated atelectasis of the lingula and right middle lobe. She underwent bronchoscopy, which demonstrated laryngeal mucosa inflammation, consistent with her GERD. There was no growth on bacterial, fungal or mycobacterial bronchial washings cultures.

  16. Carbapenem-resistant Acinetobacter baumannii from Serbia: revision of CarO classification.

    Directory of Open Access Journals (Sweden)

    Katarina Novovic

    Full Text Available Carbapenem-resistant A. baumannii present a significant therapeutic challenge for the treatment of nosocomial infections in many European countries. Although it is known that the gradient of A. baumannii prevalence increases from northern to southern Europe, this study provides the first data from Serbia. Twenty-eight carbapenem-resistant A. baumannii clinical isolates were collected at a Serbian pediatric hospital during a 2-year period. The majority of isolates (67.68% belonged to the sequence type Group 1, European clonal complex II. All isolates harbored intrinsic OXA-51 and AmpC cephalosporinase. OXA-23 was detected in 16 isolates (57.14%, OXA-24 in 23 isolates (82.14% and OXA-58 in 11 isolates (39.29%. Six of the isolates (21.43% harbored all of the analyzed oxacillinases, except OXA-143 and OXA-235 that were not detected in this study. Production of oxacillinases was detected in different pulsotypes indicating the presence of horizontal gene transfer. NDM-1, VIM and IMP were not detected in analyzed clinical A. baumannii isolates. ISAba1 insertion sequence was present upstream of OXA-51 in one isolate, upstream of AmpC in 13 isolates and upstream of OXA-23 in 10 isolates. In silico analysis of carO sequences from analyzed A. baumannii isolates revealed the existence of two out of six highly polymorphic CarO variants. The phylogenetic analysis of CarO protein among Acinetobacter species revised the previous classification CarO variants into three groups based on strong bootstraps scores in the tree analysis. Group I comprises four variants (I-IV while Groups II and III contain only one variant each. One half of the Serbian clinical isolates belong to Group I variant I, while the other half belongs to Group I variant III.

  17. Aminoglycoside Concentrations Required for Synergy with Carbapenems against Pseudomonas aeruginosa Determined via Mechanistic Studies and Modeling.

    Science.gov (United States)

    Yadav, Rajbharan; Bulitta, Jürgen B; Schneider, Elena K; Shin, Beom Soo; Velkov, Tony; Nation, Roger L; Landersdorfer, Cornelia B

    2017-12-01

    This study aimed to systematically identify the aminoglycoside concentrations required for synergy with a carbapenem and characterize the permeabilizing effect of aminoglycosides on the outer membrane of Pseudomonas aeruginosa Monotherapies and combinations of four aminoglycosides and three carbapenems were studied for activity against P. aeruginosa strain AH298-GFP in 48-h static-concentration time-kill studies (SCTK) (inoculum: 10 7.6 CFU/ml). The outer membrane-permeabilizing effect of tobramycin alone and in combination with imipenem was characterized via electron microscopy, confocal imaging, and the nitrocefin assay. A mechanism-based model (MBM) was developed to simultaneously describe the time course of bacterial killing and prevention of regrowth by imipenem combined with each of the four aminoglycosides. Notably, 0.25 mg/liter of tobramycin, which was inactive in monotherapy, achieved synergy (i.e., ≥2-log 10 more killing than the most active monotherapy at 24 h) combined with imipenem. Electron micrographs, confocal image analyses, and the nitrocefin uptake data showed distinct outer membrane damage by tobramycin, which was more extensive for the combination with imipenem. The MBM indicated that aminoglycosides enhanced the imipenem target site concentration up to 4.27-fold. Tobramycin was the most potent aminoglycoside to permeabilize the outer membrane; tobramycin (0.216 mg/liter), gentamicin (0.739 mg/liter), amikacin (1.70 mg/liter), or streptomycin (5.19 mg/liter) was required for half-maximal permeabilization. In summary, our SCTK, mechanistic studies and MBM indicated that tobramycin was highly synergistic and displayed the maximum outer membrane disruption potential among the tested aminoglycosides. These findings support the optimization of highly promising antibiotic combination dosage regimens for critically ill patients. Copyright © 2017 American Society for Microbiology.

  18. Bacteremia due to carbapenem-resistant Enterobacteriaceae in neutropenic patients with hematologic malignancies.

    Science.gov (United States)

    Satlin, Michael J; Cohen, Nina; Ma, Kevin C; Gedrimaite, Zivile; Soave, Rosemary; Askin, Gülce; Chen, Liang; Kreiswirth, Barry N; Walsh, Thomas J; Seo, Susan K

    2016-10-01

    To determine the prevalence, risk factors, treatments, and outcomes of bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) in adult neutropenic patients with hematologic malignancies. We reviewed all BSIs between 2008 and 2012 in this population at two New York City oncology centers. A case-control study was conducted to identify CRE BSI risk factors, using three controls of non-CRE BSIs per case. CRE caused 43 (2.2%) of 1992 BSIs overall and 4.7% of Gram-negative bacteremias. Independent risk factors for CRE BSI were prior β-lactam/β-lactamase inhibitor (adjusted odds ratio [aOR] 3.2; P = 0.03) or carbapenem (aOR 3.0; P = 0.05) use, current trimethoprim-sulfamethoxazole (aOR 24; P = 0.001) or glucocorticoid (aOR 5.4, P = 0.004) use, and having a prior CRE culture (aOR 12; P = 0.03). Patients with CRE bacteremia had a median of 52 h from culture collection until receipt of active therapy. They had a 51% BSI-related mortality rate, with a median of 4 days from bacteremia onset until death. CRE-active empirical therapy was associated with a lower 30-day mortality rate (17% vs. 59%; P = 0.08). CRE are lethal emerging causes of bacteremia in neutropenic patients. New strategies are needed to shorten the delay in administration of CRE-active agents and improve outcomes in this vulnerable population. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  19. Resistencia a carbapenemes en aislamientos de Pseudomonas aeruginosa: un ejemplo de interacción entre distintos mecanismos Carbapenem resistance in Pseudomonas aeruginosa isolates: an example of interaction between different mechanisms

    Directory of Open Access Journals (Sweden)

    Gisela Santella

    2011-12-01

    Full Text Available OBJETIVO: Identificar la proteína de membrana externa ausente en los aislamientos resistentes y determinar tanto las causas de su ausencia en la membrana, como la presencia de otros mecanismos de resistencia a carbapenemes en aislamientos clínicos de Pseudomonas aeruginosa. MÉTODOS: Se estudió un brote de 20 aislamientos de P. aeruginosa previamente caracterizados como productores de la metalobetalactamasa IMP-13. Estos aislamientos presentaron igual expresión de la enzima IMP-13, pero solo cinco de ellos fueron resistentes a carbapenemes. En esos cinco aislamientos resistentes se confirmó la ausencia de una proteína de membrana externa. Se secuenciaron oprD y ampC; se identificaron las proteínas de membrana externa por desorción/ionización láser asistida por matriz/espectometría de masa tiempo de vuelo (MALDI-TOF; se determinó el nivel de expresión de oprD, de AmpC y de los sistemas de eflujo tipo Mex, por reacción en cadena de polimerasa en tiempo real, y por último, se determinó la contribución del déficit de oprD a la resistencia a carbapenemes. RESULTADOS: La proteína de la membrana externa ausente en el grupo R (resistentes a ambos carbapenemes fue identificada como OprD-TS, pero no se observaron variaciones en su expresión. El gen oprD presentó mutaciones en los cinco aislamientos resistentes. Se observó la misma producción de la enzima tipo AmpC PDC-5 y del sistema de eflujo Mex AB-OprM entre los aislamientos sensibles y resistentes a carbapenemes. Se analizó cómo la presencia conjunta de IMP-13 y el déficit de oprD contribuyen al aumento de la resistencia. CONCLUSIONES: Distintos mecanismos contribuyen a la resistencia de aislamientos productores de IMP-13 a carbapenemes. La posibilidad de no detectar estos aislamientos productores de IMP-13 representa un riesgo latente de selección de mutantes con mecanismos de resistencia que se suman para aumentar la resistencia a carbapenemes.OBJECTIVE: To identify the

  20. A systematic review: can one prescribe carbapenems to patients with IgE-mediated allergy to penicillins or cephalosporins?

    Science.gov (United States)

    Kula, Brittany; Djordjevic, Gordana; Robinson, Joan L

    2014-10-15

    Cross-reactivity between penicillins or cephalosporins and carbapenems is anticipated as all have a beta lactam ring. However, the true incidence of immunoglobulin (Ig)E-mediated cross-reactivity is not known. A systematic review was conducted to collect and combine all published data on children and adults reported to have a clinical history of IgE-mediated hypersensitivity to a penicillin and/or cephalosporin who were subsequently given a carbapenem. Reactions were classified as proven, suspected, or possible IgE-mediated and non-IgE-mediated. Ten studies and 12 case reports describing 854 participants fit the study criteria. For patients with previous proven, suspected, or possible IgE-mediated penicillin reactions (N = 838), the incidence of any type of suspected hypersensitivity reaction to a carbapenem was 36/838 (4.3%; 95% confidence interval [CI], 3.1%-5.9%) and the incidence of proven (1/838), suspected (0/838), or possible (19/838) IgE-mediated reactions was 20/838 (2.4%; 95% CI, 1.6%-3.7%). Of the subset of patients with positive penicillin skin tests (n = 295), only 1 had a hypersensitivity reaction (0.3%; 95% CI, .06%-1.9%), and this was a possible IgE-mediated reaction. For patients with previous proven, suspected, or possible IgE-mediated cephalosporin reactions (N = 12), the incidence of any type of hypersensitivity reaction to a carbapenem was 3/12 (25%); this included 2 non-IgE-mediated reactions and 1 possible IgE-mediated reaction. The cross-reactivity between penicillins and carbapenems for IgE-mediated reactions is very low, but caution is still advised. Cross-reactivity rates may be higher between cephalosporins and carbapenems; however, minimal data are available. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species: a systematic review with meta-analysis.

    Science.gov (United States)

    Harris, Patrick N A; Wei, Jane Y; Shen, Andrew W; Abdile, Ahmed A; Paynter, Stuart; Huxley, Rachel R; Pandeya, Nirmala; Doi, Yohei; Huh, Kyungmin; O'Neal, Catherine S; Talbot, Thomas R; Paterson, David L

    2016-02-01

    This systematic review and meta-analysis compared effects of different antibiotics on mortality in patients with bloodstream infections caused by Enterobacteriaceae with chromosomal AmpC β-lactamase. Databases were systematically searched for studies reporting mortality in patients with bloodstream infections caused by AmpC producers treated with carbapenems, broad-spectrum β-lactam/β-lactamase inhibitors (BLBLIs), quinolones or cefepime. Pooled ORs for mortality were calculated for cases that received monotherapy with these agents versus carbapenems. PROSPERO international prospective register of systematic reviews (CRD42014014992; 18 November 2014). Eleven observational studies were included. Random-effects meta-analysis was performed on studies reporting empirical and definitive monotherapy. In unadjusted analyses, no significant difference in mortality was found between BLBLIs versus carbapenems used for definitive therapy (OR 0.87, 95% CI 0.32-2.36) or empirical therapy (OR 0.48; 95% CI 0.14-1.60) or cefepime versus carbapenems as definitive therapy (OR 0.61; 95% CI 0.27-1.38) or empirical therapy (0.60; 95% CI 0.17-2.20). Use of a fluoroquinolone as definitive therapy was associated with a lower risk of mortality compared with carbapenems (OR 0.39; 95% CI 0.19-0.78). Three studies with patient-level data were used to adjust for potential confounders. The non-significant trends favouring non-carbapenem options in these studies were diminished after adjustment for age, sex and illness severity scores, suggestive of residual confounding. Despite limitations of available data, there was no strong evidence to suggest that BLBLIs, quinolones or cefepime were inferior to carbapenems. The reduced risk of mortality observed with quinolone use may reflect less serious illness in patients, rather than superiority over carbapenems. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights

  2. Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum β-lactamase bacteremia.

    Science.gov (United States)

    Tamma, Pranita D; Han, Jennifer H; Rock, Clare; Harris, Anthony D; Lautenbach, Ebbing; Hsu, Alice J; Avdic, Edina; Cosgrove, Sara E

    2015-05-01

    The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem. Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort. A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45). PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of

  3. INIS: Authority List for Journal Titles

    International Nuclear Information System (INIS)

    1992-01-01

    This is the nineteenth revision of the INIS: Authority List for Journal Titles (IAEA-INIS-11). It lists 10,797 journal titles which have contained articles within the scope of INIS. The purpose of this Authority List is to provide descriptive cataloguers with a standard abbreviation for journal titles and to assist users of INIS products with a tool for verifying the full title of a journal. A journal, or periodical, is generally published within a defined, fixed interval between issues, which usually has more than one issue a year, and which usually includes a mixture of articles, letters, summaries, etc. Within this definition, annuals such as Annual Review of Nuclear Science are included. Series titles as, for example the McGraw-Hill Series in Nuclear Engineering, are not included in this Authority. Entries: Each entry consists of: - the full journal title (highlighted); - the abbreviated title; - ISSN, if available; - CODEN, if available; - additional information related to the journal title. Arrangement: In Part I, the full journal titles are grouped by country or international organization name and ordered alphabetically, followed by the ISSN, the CODEN in square brackets if available, and then the abbreviated title. The abbreviated title is based on the rules of ISO 4: Documentation - International Code for the Abbreviation of Titles of Periodicals. The abbreviations of the words are taken from the ISDS List of Periodical Title Word Abbreviation. In Part II, the order of the citations is reversed: the abbreviated journal titles are arranged alphabetically, followed by country code. Then the full journal titles are followed by the country of publication, and if available, ISSN and CODEN. Additional Information: There is important information related to the journal titles which are fundamental for tracing the history of the title and the present status. They are listed below and are entered whenever applicable: - Ceased publication; - Superseded by

  4. Risk factors for the acquisition of carbapenem-resistant Escherichia coli at a tertiary care center in South Korea: a matched case-control study.

    Science.gov (United States)

    Ahn, Jin Young; Song, Je Eun; Kim, Min Hyung; Choi, Heun; Kim, Jae Kyung; Ann, Hea Won; Kim, Jung Ho; Jeon, Yongduk; Jeong, Su Jin; Kim, Sun Bean; Ku, Nam Su; Han, Sang Hoon; Song, Young Goo; Yong, Dongeun; Lee, Kyungwon; Kim, June Myung; Choi, Jun Yong

    2014-06-01

    Carbapenem resistance among gram-negative bacilli is an emerging threat worldwide. The objective of this study was to identify risk factors for the acquisition of carbapenem-resistant Escherichia coli (CRE). We conducted a matched case-control study comprising 57 cases of acquisition of CRE and 114 controls (1:2 matched) selected from patients with a culture of carbapenem-susceptible E coli between January 2006 and December 2010 at a 2000-bed tertiary care center in South Korea. On univariate analysis, previous use of carbapenem (P carbapenem (odds ratio [OR], 4.56; 95% confidence interval [CI] 1.44-14.46; P = .01) and previous use of fluoroquinolone (OR, 2.81; 95% CI, 1.14-6.99; P = .03) were independent risk factors. At this institute, the antibiotic selective pressure of carbapenems and fluoroquinolones was shown to be an important risk factor for the acquisition of CRE. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  5. Associated factors and outcomes for OXA-232 Carbapenem-resistant Enterobacteriaceae infections in a tertiary care centre in Mexico City: A case-control-control study.

    Science.gov (United States)

    Torres-González, Pedro; Ortiz-Brizuela, Edgar; Cervera-Hernandez, Miguel Enrique; Bobadilla-Del Valle, Miriam; Martínez-Gamboa, Areli; Sifuentes-Osornio, José; Ponce-de-Leon, Alfredo

    2016-10-01

    We describe the outcomes and factors associated with OXA-232 producing carbapenem-resistant Enterobacteriaceae infections. A case-control-control study was performed; each case of infection by a carbapenem-resistant/OXA-232 (OXA-232-cases, n=27) was matched by isolation site, species, and date, with 2 cases of infection by carbapenem-susceptible/third-generation cephalosporin-susceptible (TGCS-controls, n=54) and 2 cases by carbapenem-susceptible/ESBL producing Enterobacteriaceae (ESBL-controls, n=54); 66% were urinary tract and 18.5% intra-abdominal infections. In the multivariable analysis with ESBL-controls, previous use β-lactam/β-lactamase antibiotics (OR 6.2; 95% CI 1.6-23.8) and, third-generation cephalosporins (OR 0.2; 95% CI 0.05-0.8) were associated with OXA-232 infection; with TGSC-controls previous use of β-lactam/β-lactamase antibiotics (OR 3.7; 95% 1.1-12.0) was associated. Among the OXA-232-cases, 29% received imipenem/cilastatin or meropenem, 11.1% ceftriaxone, 22.2% a carbapenem-based combination and 33.3% other antimicrobials as treatment. Previous β-lactam/β-lactamase antibiotics are associated with OXA-232 infections, and some may be treated with other active carbapenems or, in the absence of ESBL, third-generation cephalosporins. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards), 2013. Scientific Opinion on Carbapenem resistance in food animal ecosystems

    DEFF Research Database (Denmark)

    Hald, Tine; Baggesen, Dorte Lau

    -1-encoding genes were located on IncHI2 plasmids. A methodology including selective culture is proposed for the detection of CP strains of Enterobacteriaceae and Acinetobacter spp. The choice of selective media for the surveillance of carbapenem resistance for testing animal and food samples needs...... and effective option. As genes encoding carbapenemase production are mostly plasmid-mediated, and co-resistance may be an important issue in the spread of such resistance mechanisms, decreasing the frequency of use of antimicrobials in animal production in the EU in accordance with prudent use guidelines......Carbapenems are broad-spectrum β-lactam antimicrobials used for the treatment of serious infections in humans. To date only sporadic studies have reported the occurrence of carbapenemase-producing (CP) bacteria in food-producing animals and their environment. The bacteria and enzymes isolated...

  7. Carbapenem-Resistant Non-Glucose-Fermenting Gram-Negative Bacilli: the Missing Piece to the Puzzle

    Science.gov (United States)

    Gniadek, Thomas J.; Carroll, Karen C.

    2016-01-01

    The non-glucose-fermenting Gram-negative bacilli Pseudomonas aeruginosa and Acinetobacter baumannii are increasingly acquiring carbapenem resistance. Given their intrinsic antibiotic resistance, this can cause extremely difficult-to-treat infections. Additionally, resistance gene transfer can occur between Gram-negative species, regardless of their ability to ferment glucose. Thus, the acquisition of carbapenemase genes by these organisms increases the risk of carbapenemase spread in general. Ultimately, infection control practitioners and clinical microbiologists need to work together to determine the risk carried by carbapenem-resistant non-glucose-fermenting Gram-negative bacilli (CR-NF) in their institution and what methods should be considered for surveillance and detection of CR-NF. PMID:26912753

  8. [Investigation of OXA type beta-lactamases and PFGE patterns in Acinetobacter baumannii strains resistant to carbapenems].

    Science.gov (United States)

    Keyik, Serafettin; Arslan, Uğur; Türk Dağı, Hatice; Seyhan, Tuba; Fındık, Duygu

    2014-10-01

    Acinetobacter baumannii is an important opportunistic and multidrug-resistant pathogen leading to nosocomial infections. Over the last 10 years, a significant and threatening increase in resistance to carbapenems, mainly due to the dissemination of class D beta-lactamases, has been reported in A.baumannii worldwide. The most common types of beta-lactamases causing carbapenem resistance in A.baumannii are the OXA-23, OXA-24, OXA-40, OXA-58 and OXA-143 type serine beta-lactamases. The aim of this study was to investigate the presence of OXA type beta-lactamases in carbapenem-resistant A.baumannii strains and the clonal relationship between the strains. A total of 105 non-duplicate carbapenem-resistant A.baumannii strains isolated from various clinical samples (68 blood, 18 bronchoalveolar lavage, 13 drainage, 3 urine, 2 cerebrospinal fluid and 1 catheter samples) in the Microbiology Laboratories of Selcuk University, Meram (2009-2012) and Selcuklu (2007-2008) Medical School Hospitals, were included in the study. The isolates were identified by conventional methods and Phoenix 100 BD (BD Diagnostic, USA) and Vitek II (bioMerieux, France) automated systems. Carbapenem susceptibility test was performed by Kirby-Bauer disk diffusion method according to the CLSI standards. bla(OXA 23-like), bla(OXA 24-like), bla(OXA 58-like) and bla(OXA 51-like) genes were amplified by multiplex PCR assay and clonal relatedness was investigated by pulsed-field gel electrophoresis (PFGE) using ApaI enzyme. The bla(OXA 51-like) gene was determined in all carbapenem-resistant A.baumannii isolates, while the bla(OXA 23-like) and bla(OXA 58-like) genes were detected in 46.6% and 53.3% of isolates, respectively. However bla(OXA 24-like) gene was not demonstrated in any isolates. bla(OXA 23-like) gene was determined in both Meram and Selcuklu Medical School hospitals, but bla(OXA 58-like) gene was detected only in Meram Medical School hospital. PFGE analysis of the isolates revealed 32 different

  9. Prevalence of Invasive Infections Due to Carbapenem-Resistant Enterobacteriaceae among Adult Patients in U.S. Hospitals.

    Science.gov (United States)

    Lodise, Thomas; Ye, Michael J; Zhao, Qi

    2017-08-01

    This large-scale retrospective analysis ( n = 60,551) of the Premier inpatient database (1 January 2011 to 31 December 2014) found an overall prevalence of carbapenem-resistant Enterobacteriaceae strains of 2.3% (range, 0.9% to 5.8% by geographic region) among patients with infections due to Enterobacteriaceae Ongoing monitoring and development of decision support tools/algorithms are needed for identification of high-risk patients. Copyright © 2017 American Society for Microbiology.

  10. Factors associated with carriage of carbapenem-non-susceptible Enterobacteriaceaein North-Eastern France and outcomes of infected patients.

    Science.gov (United States)

    Muggeo, Anaëlle; Guillard, Thomas; Barbe, Coralie; Thierry, Aurore; Bajolet, Odile; Vernet-Garnier, Véronique; Limelette, Anne; Brasme, Lucien; De Champs, Christophe

    2017-05-01

    Carbapenems are frequently used as a last resort to treat infections caused by multidrug-resistant Gram-negative organisms, thus carbapenem-non-susceptible Enterobacteriaceae (CNSE) is an emerging health threat. To assess risk factors and outcomes of CNSE carriage. We conducted a matched case-control study in six hospitals in North-Eastern France. The controls were patients harbouring carbapenem-susceptible Enterobacteriaceae. Fifty-five cases and 110 controls were included. Most of the CNSE isolates were Enterobacter cloacae and Klebsiella pneumoniae . Carbapenemase production was observed in 40% of isolates and they produced OXA-48 only. CNSE carriage was significantly associated with recent antibiotic use ( P =  0.014), particularly carbapenems ( P =  0.03) and fluoroquinolones ( P =  0.016). A multivariate analysis using conditional logistic regression showed that the presence of concomitant infection(s) (OR: 9.83; 95% CI 3.04-21.39, P =  0.0031), nosocomial infections (OR: 7.84; 95% CI 2.00-12.54, P  =   0.0063) and a high age (OR: 1.07; 95% CI 1.01-1.06, P =  0.038) were independently associated with CNSE carriage. Moreover, patients infected with CNSE had worse outcomes: fewer resolved infections at 1 month ( P =  0.02), and they had a higher mortality rate ( P =  0.0004) and longer hospital stays ( P =  0.02). We identified three independent risk factors for CNSE carriage as well as worse outcomes in infected patients in North-Eastern France. This highlights the importance of early detection of CNSE and the need for antimicrobial therapy re-evaluation after bacteriological analysis has been performed. © 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.

  11. Risk factors for carbapenem resistant bacteraemia and mortality due to gram negative bacteraemia in a developing country

    International Nuclear Information System (INIS)

    Kalam, K.; Kumar, S.; Ali, S.; Baqi, S.; Qamar, F.

    2014-01-01

    Objective: To identify the risk factors for carbapenem resistant bacteraemia and mortality due to gram negative bacteraemia in a developing country. Methods: A prospective cohort study was conducted at the Sindh Institute of Urology and Transplantation (SIUT) from June to October 2012. Hospitalized patients > 15 years of age with gram negative bacteraemia were included and followed for a period of 2 weeks for in hospital mortality. Data was collected and analyzed for 243 subjects. Multivariate analysis was used to determine the risk factors for carbapenem resistant bacteraemia and mortality due to gram negative bacteraemia. Crude and adjusted odds ratio and 95% CI are reported. Results: A total of 729 out of 1535 (47.5%) cultures were positive for gram negative isolates. Out of 243 subjects, 117 (48%) had an MDR isolate. Having an MDR isolate on culture (AOR, 2.33; 95% CI, 1.35 -4.0), having multiple positive cultures (AOR, 1.8; 95% CI, 0.94 -3.4) and stay in ICU >48 hours (AOR, 2.0 ; 95% CI, 1.12 -3.78) were identified as significant risk factors for mortality due to gram negative organisms. Risk factors for carbapenem resistant bacteraemia were age >50 years (AOR, 1.83; 95% CI, 1.0-3.5), septic shock on presentation (AOR 2.53; 95% CI, 1.03 -6.2) , ICU stay of >72 hours (AOR 2.40; 95% CI, 1.14-5.0) and receiving immunosuppressant medications (AOR 2.23; 95% CI, 0.74 - 6.7). Conclusion: There is a high burden of MDR and carbapenem resistant gram negative bacteraemia, with a high mortality rate. (author)

  12. The distribution of carbapenem- and colistin-resistance in Gram-negative bacteria from the Tamil Nadu region in India.

    Science.gov (United States)

    Manohar, Prasanth; Shanthini, Thamaraiselvan; Ayyanar, Ramankannan; Bozdogan, Bulent; Wilson, Aruni; Tamhankar, Ashok J; Nachimuthu, Ramesh; Lopes, Bruno S

    2017-07-01

    The occurrence of carbapenem- and colistin-resistance among Gram-negative bacteria is increasing worldwide. The aim of this study was to understand the distribution of carbapenem- and colistin-resistance in two areas in Tamil Nadu, India. The clinical isolates (n=89) used in this study were collected from two diagnostic centres in Tamil Nadu, India. The bacterial isolates were screened for meropenem- and colistin-resistance. Further, resistance genes blaNDM-1, blaOXA-48-like, blaIMP, blaVIM, blaKPC, mcr-1 and mcr-2 and integrons were studied. The synergistic effect of meropenem in combination with colistin was assessed. A total of 89 bacterial isolates were studied which included Escherichia coli (n=43), Klebsiella pneumoniae (n=18), Pseudomonas aeruginosa (n=10), Enterobacter cloacae (n=6), Acinetobacter baumannii (n=5), Klebsiella oxytoca (n=4), Proteus mirabilis (n=2) and Salmonella paratyphi (n=1). MIC testing showed that 58/89 (65 %) and 29/89 (32 %) isolates were resistant to meropenem and colistin, respectively, whereas 27/89 (30 %) isolates were resistant to both antibiotics. Escherichia coli, K. pneumoniae, K. oxytoca, Pseudomonas aeruginosa, and Enterobacter cloacae isolates were blaNDM-1-positive (n=20). Some strains of Escherichia coli, K. pneumoniae and K. oxytoca were blaOXA-181-positive (n=4). Class 1, 2 and 3 integrons were found in 24, 20 and 3 isolates, respectively. Nine NDM-1-positive Escherichia coli strains could transfer carbapenem resistance via plasmids to susceptible Escherichia coli AB1157. Meropenem and colistin showed synergy in 10/20 (50 %) isolates by 24 h time-kill studies. Our results highlight the distribution of carbapenem- and colistin-resistance in Gram-negative bacteria isolated from the Tamil Nadu region in South India.

  13. SME-3, a Novel Member of the Serratia marcescens SME Family of Carbapenem-Hydrolyzing β-Lactamases

    Science.gov (United States)

    Queenan, Anne Marie; Shang, Wenchi; Schreckenberger, Paul; Lolans, Karen; Bush, Karen; Quinn, John

    2006-01-01

    Imipenem-resistant Serratia marcescens isolates were cultured from a lung transplant patient given multiple antibiotics over several months. The strains expressed SME-3, a β-lactamase of the rare SME carbapenem-hydrolyzing family. SME-3 differed from SME-1 by a single amino acid substitution of tyrosine for histidine at position 105, but the two β-lactamases displayed similar hydrolytic profiles. PMID:17005839

  14. SME-3, a novel member of the Serratia marcescens SME family of carbapenem-hydrolyzing beta-lactamases.

    Science.gov (United States)

    Queenan, Anne Marie; Shang, Wenchi; Schreckenberger, Paul; Lolans, Karen; Bush, Karen; Quinn, John

    2006-10-01

    Imipenem-resistant Serratia marcescens isolates were cultured from a lung transplant patient given multiple antibiotics over several months. The strains expressed SME-3, a beta-lactamase of the rare SME carbapenem-hydrolyzing family. SME-3 differed from SME-1 by a single amino acid substitution of tyrosine for histidine at position 105, but the two beta-lactamases displayed similar hydrolytic profiles.

  15. Whole-Genome Sequences of Two Carbapenem-Resistant Klebsiella quasipneumoniae Strains Isolated from a Tertiary Hospital in Johor, Malaysia.

    Science.gov (United States)

    Gan, Han Ming; Rajasekaram, Ganeswrie; Eng, Wilhelm Wei Han; Kaniappan, Priyatharisni; Dhanoa, Amreeta

    2017-08-10

    We report the whole-genome sequences of two carbapenem-resistant clinical isolates of Klebsiella quasipneumoniae subsp. similipneumoniae obtained from two different patients. Both strains contained three different extended-spectrum β-lactamase genes and showed strikingly high pairwise average nucleotide identity of 99.99% despite being isolated 3 years apart from the same hospital. Copyright © 2017 Gan et al.

  16. [Isolation of a carbapenem-resistant K1 serotype Klebsiella pneumonia strain and the study of resistance mechanism].

    Science.gov (United States)

    Zhang, Rong; Wang, Xuan; Lü, Jianxin

    2014-12-16

    To study the virulence and mechanism of carbapenem resistance of a clinical isolate of carbapenem-resistant K1 serotype Klebsiella pneumonia strain. Identification of isolate was carried out with VITEK-2 compact system. Antimicrobial susceptibility was determined by E-test; Metallo β-lactamases and carbapenemases screening were conducted by imipenem-EDTA double disc synergy test and modified Hodge test, respectively.Specific polymerehse chain reaction (PCR) and DNA sequencing were preformed to detect the virulence genes including K1, K2, K5, K20, K54, K57, magA, rmpA, wcaG and a series of β-lactamase resistence genes. Conjunction experiment was also performed. The plasmids of transconjugants were submitted to PCR-based replicon typing (PBRT) method. Molecular typing was performed by multilocus sequence typing (MLST). Antimicrobial susceptibility testing revealed that the Klebsiella pneumonia strain was resistant to most of the antibiotics used in clinic. Phynotype confirmary rest revealed the production of carbapanemases, while Metallo β-lactamases were negative; PCR and DNA sequencing confirmed the isolate was positive for blaKPC-2, blaCTX-M-15, blaTEM-1, blaSHV-1 and virulence genes K1, magA, rmpA, wcaG simultaneously; blaKPC-2 was transferred from donor to Escherichia EC600 by conjunction experiment, while no virulence genes were found in the transconjugants. PBRT revealed that Frep plasmid was found in transconjugants. MLST analysis revealed that this strain belonged to ST23. K1 serotype Klebsiella pneumonia strain carries virulence genes and carbapenem resistance gene blaKPC-2, noteworthily the carbapenem resistance genes can be transferred through horizontal transmission on plasmids.

  17. TITLE

    Directory of Open Access Journals (Sweden)

    Nisha K. M

    2016-01-01

    Full Text Available The new millennium is seen as an epoch of entrepreneurship with entrepreneurs perceiving novel opportunities, organizing resources, undertaking risks to pursue their goals in establishing innovative ventures for scaling new horizons. Women entrepreneurs have the potency to confront numerous challenges, such as creating equity, equilibrium, ensuring sustainable and inclusive socio economic development in divergent economies, by seizing tremendous business opportunities in the contemporary commercial world. Kerala, the southern State of India, is experiencing an economic renovation through technological transformation and, in particular, through the growth of women oriented Micro, Small and Medium Enterprises (MSMEs. The study aims to; identify the growth trends of women’s entrepreneurship in the micro enterprises of Kerala; examine whether women’s entrepreneurial activities significantly vary across the form of women owned enterprises, type of organization and nature of activity; and also explore the prospects and challenges faced by women entrepreneurs through micro entrepreneurial activities. Research methodology involves the application of descriptive quantitative analysis on the secondary data primarily collected from the database of Directorate of Industries and District Industries Centre for a period of 7 years extending from 2007-08 to 2013-14. Findings reveal that MSMEs spawn better income distribution, by operating in heterogeneous areas of the economy with limited capital and creating more employment opportunities, thereby reducing poverty and inequalities. The trend analysis reflects an escalation in the number of enterprises, investments, profits and employment opportunities generated especially through micro enterprises of women. They play a crucial role in the economy in terms of creating self employment and generating employment opportunities for others. A paradigm shift is seen in the role of women’s entrepreneurship in terms of innovation, attitudes, leadership qualities, competitiveness, entrepreneurial skill and absorbing new entrants to the job market, empowering marginalized women.

  18. TITLE

    Directory of Open Access Journals (Sweden)

    Abdolhamid Papzan

    2013-01-01

    Full Text Available This study investigated entrepreneurial intention among graduate students of USM Engineering Campus. Applying the Theory of Planned Behavior (TPB; Ajzen, we examined the empirical model of entrepreneurial intention determinants. Although research has been conducted in entrepreneurial intention, limited study has been done among Iranian graduate students who are studying abroad. This research aims to fill this gap using Entrepreneurial Intention Questionnaire (EIQ, version 3.1. Accordingly, a survey study was applied and Iranian graduate students of the USM Engineering Campus were studied using the census method. The authors propose an empirical model and tested its reliability and validity using structural equation modeling. Data was analyzed using Spss16 and Amos18 software. Results revealed that the level of knowledge about business sources of assistance for entrepreneurs in addition to components of the TPB, affected entrepreneurial intention. Empirical model ‘s goodness of fit indices indicated good model fit x2=1.047, df=2, probability 0.592; NFI= 0.981; CFI= 1.000; RMSEA=0.000. It seems that current empirical model could be a guide for future research on this important topic.

  19. Spread of carbapenem-resistant Acinetobacter baumannii global clone 2 in Asia and AbaR-type resistance islands.

    Science.gov (United States)

    Kim, Dae Hun; Choi, Ji-Young; Kim, Hae Won; Kim, So Hyun; Chung, Doo Ryeon; Peck, Kyong Ran; Thamlikitkul, Visanu; So, Thomas Man-Kit; Yasin, Rohani M D; Hsueh, Po-Ren; Carlos, Celia C; Hsu, Li Yang; Buntaran, Latre; Lalitha, M K; Song, Jae-Hoon; Ko, Kwan Soo

    2013-11-01

    In this surveillance study, we identified the genotypes, carbapenem resistance determinants, and structural variations of AbaR-type resistance islands among carbapenem-resistant Acinetobacter baumannii (CRAB) isolates from nine Asian locales. Clonal complex 92 (CC92), corresponding to global clone 2 (GC2), was the most prevalent in most Asian locales (83/108 isolates; 76.9%). CC108, or GC1, was a predominant clone in India. OXA-23 oxacillinase was detected in CRAB isolates from most Asian locales except Taiwan. blaOXA-24 was found in CRAB isolates from Taiwan. AbaR4-type resistance islands, which were divided into six subtypes, were identified in most CRAB isolates investigated. Five isolates from India, Malaysia, Singapore, and Hong Kong contained AbaR3-type resistance islands. Of these, three isolates harbored both AbaR3- and AbaR4-type resistance islands simultaneously. In this study, GC2 was revealed as a prevalent clone in most Asian locales, with the AbaR4-type resistance island predominant, with diverse variants. The significance of this study lies in identifying the spread of global clones of carbapenem-resistant A. baumannii in Asia.

  20. Colistin- and Carbapenem-Resistant Escherichia coli Harboring mcr-1 and blaNDM-5, Causing a Complicated Urinary Tract Infection in a Patient from the United States.

    Science.gov (United States)

    Mediavilla, José R; Patrawalla, Amee; Chen, Liang; Chavda, Kalyan D; Mathema, Barun; Vinnard, Christopher; Dever, Lisa L; Kreiswirth, Barry N

    2016-08-30

    Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene blaNDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1- and blaNDM-5-harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized. Colistin has become the last line of defense for the treatment of infections caused by Gram-negative bacteria resistant to multiple classes of antibiotics, in particular carbapenem-resistant Enterobacteriaceae (CRE). Resistance to colistin, encoded by the plasmid-borne gene mcr-1, was first identified in animal and clinical samples from China in November 2015 and has subsequently been reported from numerous other countries. In April 2016, mcr-1 was identified in a carbapenem-susceptible Escherichia coli strain from a clinical sample in the United States, followed by a second report from a carbapenem-susceptible E. coli strain originally isolated in May 2015. We report the isolation and identification of

  1. 24 CFR 202.12 - Title II.

    Science.gov (United States)

    2010-04-01

    ... INSTITUTIONS AND MORTGAGEES Title I and Title II Specific Requirements § 202.12 Title II. (a) Tiered pricing—(1... rate up to two percentage points under the mortgagee's customary lending practices must be based on... after accounting for the value of servicing rights generated by making the loan and other income to the...

  2. Biochemical and Structural Characterization of Mycobacterium tuberculosis beta-Lactamase with the Carbapenems Ertapenem and Doripenem

    Energy Technology Data Exchange (ETDEWEB)

    L Tremblay; F Fan; J Blanchard

    2011-12-31

    Despite the enormous success of {beta}-lactams as broad-spectrum antibacterials, they have never been widely used for the treatment of tuberculosis (TB) due to intrinsic resistance that is caused by the presence of a chromosomally encoded gene (blaC) in Mycobacterium tuberculosis. Our previous studies of TB BlaC revealed that this enzyme is an extremely broad-spectrum {beta}-lactamase hydrolyzing all {beta}-lactam classes. Carbapenems are slow substrates that acylate the enzyme but are only slowly deacylated and can therefore act also as potent inhibitors of BlaC. We conducted the in vitro characterization of doripenem and ertapenem with BlaC. A steady-state kinetic burst was observed with both compounds with magnitudes proportional to the concentration of BlaC used. The results provide apparent K{sub m} and k{sub cat} values of 0.18 {micro}M and 0.016 min{sup -1} for doripenem and 0.18 {micro}M and 0.017 min{sup -1} for ertapenem, respectively. FTICR mass spectrometry demonstrated that the doripenem and ertapenem acyl-enzyme complexes remain stable over a time period of 90 min. The BlaC-doripenem covalent complex obtained after a 90 min soak was determined to 2.2 {angstrom}, while the BlaC-ertapenem complex obtained after a 90 min soak was determined to 2.0 {angstrom}. The 1.3 {angstrom} diffraction data from a 10 min ertapenem-soaked crystal revealed an isomerization occurring in the BlaC-ertapenem adduct in which the original {Delta}2-pyrroline ring was tautomerized to generate the {Delta}1-pyrroline ring. The isomerization leads to the flipping of the carbapenem hydroxyethyl group to hydrogen bond to carboxyl O2 of Glu166. The hydroxyethyl flip results in both the decreased basicity of Glu166 and a significant increase in the distance between carboxyl O2 of Glu166 and the catalytic water molecule, slowing hydrolysis.

  3. Clinical and Molecular Epidemiology of Carbapenem-Resistant Enterobacteriaceae Among Adult Inpatients in Singapore.

    Science.gov (United States)

    Marimuthu, Kalisvar; Venkatachalam, Indumathi; Khong, Wei Xin; Koh, Tse Hsien; Cherng, Benjamin Pei Zhi; Van La, My; De, Partha Pratim; Krishnan, Prabha Unny; Tan, Thean Yen; Choon, Raymond Fong Kok; Pada, Surinder Kaur; Lam, Choong Weng; Ooi, Say Tat; Deepak, Rama Narayana; Smitasin, Nares; Tan, Eng Lee; Lee, Jia Jun; Kurup, Asok; Young, Barnaby; Sim, Nancy Tee Wen; Thoon, Koh Cheng; Fisher, Dale; Ling, Moi Lin; Peng, Brenda Ang Sze; Teo, Yik-Ying; Hsu, Li Yang; Lin, Raymond Tzer Pin; Ong, Rick Twee-Hee; Teo, Jeanette; Ng, Oon Tek

    2017-05-15

    Since 2010, the incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing in Singapore. We analyzed the clinical and molecular epidemiology of CRE among adult inpatients in Singapore. Quarterly incidence of unique subjects (per 100000 patient-days) with positive clinical and surveillance cultures for CRE were estimated based on mandatory data submitted to the National Public Health Laboratory by public hospitals between 2010 and 2015. CRE-positive adult inpatients were prospectively recruited from 6 public sector hospitals between December 2013 and April 2015. Subjects answered a standardized epidemiologic questionnaire and provided samples for this study. Further clinical information was extracted from subjects' electronic medical records. Whole-genome sequencing was performed on study isolates to determine transmission clusters. Incidence of CRE clinical cultures among adult inpatients plateaued from 2013 (range: 7.73 to 10.32 per 100000 patient-days) following an initial increase between 2010 and end-2012. We prospectively recruited 249 subjects. Their median age was 65 years, 108 (43%) were female, and 161 (64.7%) had carbapenemase-producing Enterobacteriaceae (CPE). On multivariate analysis, prior carbapenem exposure (OR: 3.23; 95% CI: 1.67-6.25) and hematological malignancies (OR: 2.85; 95% CI: 1.10-7.41) were associated with non-carbapenemase-producing CRE (NCPE) (n = 88) compared with CPE (n = 161) subjects. Among 430 CRE isolates from the 249 subjects, 307(71.3%) were CPE, of which 154(50.2%) were blaKPC-positive, 97(31.6%) blaNDM-positive, and 42 (13.7%) blaOXA-positive. Klebsiella pneumoniae (n = 180, 41.9%), Escherichia coli (n = 129, 30.0%) and Enterobacter cloacae (n = 62, 14.4%) were the main Enterobacteriaceae species. WGS (n = 206) revealed diverse bacterial strain type (STs). The predominant blaKPC-positive plasmid was pHS102707 (n = 62, 55.4%) and the predominant blaNDM-positive plasmid was pNDM-ECS01 (n = 46, 48.9%). Five

  4. Performance evaluation of three automated identification systems in detecting carbapenem-resistant Enterobacteriaceae.

    Science.gov (United States)

    He, Qingwen; Chen, Weiyuan; Huang, Liya; Lin, Qili; Zhang, Jingling; Liu, Rui; Li, Bin

    2016-06-21

    Carbapenem-resistant Enterobacteriaceae (CRE) is prevalent around the world. Rapid and accurate detection of CRE is urgently needed to provide effective treatment. Automated identification systems have been widely used in clinical microbiology laboratories for rapid and high-efficient identification of pathogenic bacteria. However, critical evaluation and comparison are needed to determine the specificity and accuracy of different systems. The aim of this study was to evaluate the performance of three commonly used automated identification systems on the detection of CRE. A total of 81 non-repetitive clinical CRE isolates were collected from August 2011 to August 2012 in a Chinese university hospital, and all the isolates were confirmed to be resistant to carbapenems by the agar dilution method. The potential presence of carbapenemase genotypes of the 81 isolates was detected by PCR and sequencing. Using 81 clinical CRE isolates, we evaluated and compared the performance of three automated identification systems, MicroScan WalkAway 96 Plus, Phoenix 100, and Vitek 2 Compact, which are commonly used in China. To identify CRE, the comparator methodology was agar dilution method, while the PCR and sequencing was the comparator one to identify CPE. PCR and sequencing analysis showed that 48 of the 81 CRE isolates carried carbapenemase genes, including 23 (28.4 %) IMP-4, 14 (17.3 %) IMP-8, 5 (6.2 %) NDM-1, and 8 (9.9 %) KPC-2. Notably, one Klebsiella pneumoniae isolate produced both IMP-4 and NDM-1. One Klebsiella oxytoca isolate produced both KPC-2 and IMP-8. Of the 81 clinical CRE isolates, 56 (69.1 %), 33 (40.7 %) and 77 (95.1 %) were identified as CRE by MicroScan WalkAway 96 Plus, Phoenix 100, and Vitek 2 Compact, respectively. The sensitivities/specificities of MicroScan WalkAway, Phoenix 100 and Vitek 2 were 93.8/42.4 %, 54.2/66.7 %, and 75.0/36.4 %, respectively. The MicroScan WalkAway and Viteck2 systems are more reliable in clinical identification of

  5. Community-onset carbapenem-resistant Klebsiella pneumoniae urinary tract infections in infancy following NICU hospitalisation.

    Science.gov (United States)

    Vergadi, Eleni; Bitsori, Maria; Maraki, Sofia; Galanakis, Emmanouil

    2017-10-01

    Urinary tract infection (UTI) is a common bacterial infection in childhood with favourable outcome. However, the recent emergence of UTI caused by multidrug-resistant pathogens, such as carbapenem-resistant Enterobacteriaceae (CRE), has become a great concern worldwide. CRE are mainly responsible for nosocomial infections and community-onset CRE infections in healthy individuals are rare. In this study, we report a series of infants without substantial genitourinary abnormalities that were admitted with community-onset urinary tract infections (UTIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) and we discuss their aetiology. We retrospectively reviewed the medical records of nine infants who presented from community to the paediatric ward with CRKP urinary tract infections, as well as all affected neonates of a concomitant CRKP outbreak that occurred in the neonatal intensive care unit (NICU) in a tertiary hospital (period from April 2009 to July 2012). We further retrieved all culture-proven CRKP infections of any site from 2007 to 2015 in our paediatric department. Over a 33-month period, nine infants, all males, aged 0.9-19.3 (median 4.0) months, were admitted to the Department of Paediatrics with UTI caused by CRKP. Three of them were diagnosed with urinary tract abnormalities but only one had vesicoureteral reflux (VUR), which was a UTI-associated one. History revealed that they had all been hospitalised in the same NICU during a concurrent long-lasting CRKP outbreak for a median of 17 (2-275) days and thereafter presented with CRKP UTI 15 to 207 (median 41) days after NICU discharge. The antibiotic susceptibility and phenotypic characteristics were identical among all isolates in NICU and the paediatric ward. The summary Figure shows a timeline of NICU hospitalisation indicative of its duration and subsequent CRKP UTI of study participants is presented. These cases illustrate that UTI caused by multidrug-resistant pathogens does not

  6. A Five-Year Experience of Carbapenem Resistance in Enterobacteriaceae Causing Neonatal Septicaemia: Predominance of NDM-1

    Science.gov (United States)

    Datta, Saswati; Roy, Subhasree; Chatterjee, Somdatta; Saha, Anindya; Sen, Barsha; Pal, Titir; Som, Tapas; Basu, Sulagna

    2014-01-01

    Treatment of neonatal sepsis has become a challenge with the emergence of carbapenemase-producing bacteria. This study documents the trend of carbapenem susceptibility in Enterobacteriaceae that caused septicaemia in neonates over a five year period (2007–2011) and the molecular characterisation of Enterobacteriaceae resistant to carbapenems and cephalosporins. Hundred and five Enterobacteriaceae including Escherichia coli (n = 27), Klebsiella pneumoniae (n = 68) and Enterobacter spp. (n = 10) were isolated from blood of septicaemic neonates followed by antibiotic susceptibility tests, determination of MIC values, phenotypic and genotypic detection of β-lactamases. Carbapenem was the most active antimicrobial tested after tigecycline. CTX-M type was the most prevalent ESBL throughout the period (82%). New Delhi Metallo-β-lactamase-1 (NDM-1), which is a recent addition to the carbapenemase list, was the only carbapenemase identified in our setting. Fourteen percent of the isolates possessed bla NDM-1. Carbapenem non-susceptibility was first observed in 2007 and it was due to loss of Omp F/Ompk36 in combination with the presence of ESBLs/AmpCs. NDM-1 first emerged in E. coli during 2008; later in 2010, the resistance was detected in K. pneumoniae and E. cloacae isolates. NDM-1-producing isolates were resistant to other broad-spectrum antibiotics and possessed ESBLs, AmpCs, 16S-rRNA methylases, AAC(6′)-Ib-cr, bleomycin resistant gene and class 1 integron. Pulsed field gel electrophoresis of the NDM-1-producing isolates indicated that the isolates were clonally diverse. The study also showed that there was a significantly higher incidence of sepsis caused by NDM-1-harbouring isolates in the male sex, in neonates with low birth weight and neonates born at an extramural centre. However, sepsis with NDM-1-harbouring isolates did not result in a higher mortality rate. The study is the first to review the carbapenem resistance patterns in neonatal sepsis

  7. 42 CFR 476.86 - Correlation of Title XI functions with Title XVIII functions.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Correlation of Title XI functions with Title XVIII functions. 476.86 Section 476.86 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF...) Qio Review Functions § 476.86 Correlation of Title XI functions with Title XVIII functions. (a...

  8. In vitro activity of colistin in antimicrobial combination against carbapenem-resistant Acinetobacter baumannii isolated from patients with ventilator-associated pneumonia in Vietnam.

    Science.gov (United States)

    Le Minh, Vien; Thi Khanh Nhu, Nguyen; Vinh Phat, Voong; Thompson, Corinne; Huong Lan, Nguyen Phu; Thieu Nga, Tran Vu; Thanh Tam, Pham Thi; Tuyen, Ha Thanh; Hoang Nhu, Tran Do; Van Hao, Nguyen; Thi Loan, Huynh; Minh Yen, Lam; Parry, Christopher M; Trung Nghia, Ho Dang; Campbell, James I; Hien, Tran Tinh; Thwaites, Louise; Thwaites, Guy; Van Vinh Chau, Nguyen; Baker, Stephen

    2015-10-01

    Acinetobacter baumannii has become one of the major infection threats in intensive care units (ICUs) globally. Since 2008, A. baumannii has been the leading cause of ventilator-associated pneumonia (VAP) in our ICU at an infectious disease hospital in southern Vietnam. The emergence of this pathogen in our setting is consistent with the persistence of a specific clone exhibiting resistance to carbapenems. Antimicrobial combinations may be a strategy to treat infections caused by these carbapenem-resistant A. baumannii. Therefore, we assessed potential antimicrobial combinations against local carbapenem-resistant A. baumannii by measuring in vitro interactions of colistin with four antimicrobials that are locally certified for treating VAP. We first performed antimicrobial susceptibility testing and multilocus variable number tandem repeat analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal aspirates from patients with VAP over an 18-month period. These 74 isolates could be subdivided into 21 main clusters by MLVA and >80 % were resistant to carbapenems. We selected 56 representative isolates for in vitro combination synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and 38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone, imipenem and meropenem, respectively. Notably, more carbapenem-resistant A. baumannii isolates (36/43; 84 %) exhibited synergistic activity with a combination of colistin and meropenem than carbapenem-susceptible A. baumannii isolates (2/13; 15 %) (P = 0.023; Fisher's exact test). Our findings suggest that combinations of colistin and meropenem should be considered when treating carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical trials investigating combination therapy for VAP.

  9. Development of carbapenem resistance in Pseudomonas aeruginosa is associated with OprD polymorphisms, particularly the amino acid substitution at codon 170.

    Science.gov (United States)

    Shu, Jwu-Ching; Kuo, An-Jing; Su, Lin-Hui; Liu, Tsui-Ping; Lee, Ming-Hsun; Su, I-Ning; Wu, Tsu-Lan

    2017-09-01

    Pan-susceptible Pseudomonas aeruginosa (PSPA) clinical isolates carrying an OprD with loop 7 shortening (the group-1A allele) were found to rapidly develop carbapenem resistance under continuous selection pressure. We further studied whether OprD polymorphisms are associated with the potential to develop carbapenem resistance. OprD amino acid sequences of 126 PSPA clinical isolates were analysed to determine their STs using P. aeruginosa strain PAO1 as the control strain. Site-directed mutagenesis was performed in PAO1 to generate polymorphisms of interest. A disc diffusion method was used to select carbapenem-resistant variants from the mutant strains. Expression levels of oprD were determined by quantitative RT-PCR. MICs of carbapenems were determined by Etest. Forty-eight (38.1%) of the tested isolates carried the group-1A allele. Another two major STs, C1 and C2, both of which harboured an F170L polymorphism, were found in 21 (16.7%) and 39 (31.0%) isolates, respectively. The PAO1 type was also found in 14 (11.1%) isolates. Under continuous selective pressure, isolates of most STs developed carbapenem resistance at different numbers of passaging events; only those belonging to the PAO1 type remained susceptible. However, PAO1 mutants carrying either the oprD group-1A allele or the OprD-F170L polymorphism were able to develop carbapenem resistance. Reduced oprD expression triggered by continuous imipenem challenge was found in PAO1 mutants, but not in the PAO1 WT strain. OprD polymorphisms, particularly the F170L substitution and the specific shortening in loop 7, appear to determine the potential for P. aeruginosa to develop carbapenem resistance. © 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  11. Screening of nursing home residents for colonization with carbapenem-resistant Enterobacteriaceae admitted to acute care hospitals: Incidence and risk factors.

    Science.gov (United States)

    Cunha, Cheston B; Kassakian, Steven Z; Chan, Ryan; Tenover, Fred C; Ziakas, Panos; Chapin, Kimberle C; Mermel, Leonard A

    2016-02-01

    There are increasing reports of multidrug-resistant gram-negative bacilli in nursing homes and acute care hospitals. We performed a point prevalence survey to detect fecal carriage of gram-negative bacteria carrying carbapenem resistance genes or which were otherwise resistant to carbapenem antibiotics among 500 consecutive admissions from local nursing homes to 2 hospitals in Providence, Rhode Island. We performed a case-control study to identify risk factors associated with carriage of carbapenem-resistant Enterobacteriaceae (CRE). There were 404 patients with 500 hospital admissions during which they had rectal swab samples cultured. Fecal carriage of any carbapenem-resistant or carbapenemase- producing gram-negative bacteria was found in 23 (4.6%) of the 500 hospital admissions, including 7 CRE (1.4%), 2 (0.4%) of which were Klebsiella pneumoniae carbapenemase (ie, blaKPC) producing (CPE) Citrobacter freundii, 1 of which was carbapenem susceptible by standard testing methods. Use of a gastrostomy tube was associated with CRE carriage (P = .04). We demonstrated fecal carriage of carbapenem-resistant or carbapenemase-producing gram-negative bacteria in 4.6% of nursing home patients admitted to 2 acute care hospitals, but only 0.4% of such admissions were patients with fecal carriage of CPE. Use of gastrostomy tubes was associated with fecal carriage of gram-negative bacteria with detectable carbapenem resistance. CRE fecal carriage is uncommon in our hospital admissions from nursing homes. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  12. Heterogeneity of Carbapenem Resistance Mechanisms Among Gram-Negative Pathogens in Lebanon: Results of the First Cross-Sectional Countrywide Study.

    Science.gov (United States)

    Hammoudi Halat, Dalal; Moubareck, Carole Ayoub; Sarkis, Dolla Karam

    2017-09-01

    Carbapenem-resistant Gram-negative pathogens have progressively disseminated to different countries worldwide, presenting a serious public health concern. The aims of this study were to determine the prevalence of carbapenem resistance in Gram-negative bacteria in Lebanon, to elucidate molecular mechanisms, and to identify genetic relatedness of incriminated strains. Carbapenem nonsusceptible Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas were collected from 11 Lebanese hospitals in 2012. Antimicrobial susceptibility was assessed with phenotypic tests, genes encoding carbapenemases were screened via PCR-sequencing, and genetic relatedness was examined by PGFE and ERIC-PCR. A total of 398 nonrepetitive carbapenem nonsusceptible isolates were studied, of which 44 were Enterobacteriaceae, 142 were A. baumannii, and 212 were Pseudomonas. Among Enterobacteriaceae, 70.4% carried bla OXA-48-like gene on IncL/M-type plasmids, while acquired AmpC cephalosporinases, extended-spectrum-β-lactamases, and efflux-pump were additional contributors to carbapenem resistance. Among A. baumannii, 90% produced OXA-23 and GES-11 and carried insertion sequence ISAba1 upstream and adjacent to bla OXA-23 and bla Acinetobacter -derived cephalosporinases . Among Pseudomonas, 16% harbored VIM-2, 4.2% IMP-2, and 1.4% IMP-1 metallo-β-lactamases. Fingerprint analysis indicated that the spread of OXA-48-like carbapenemases was mostly mediated by horizontal transfer, while OXA-23 and GES-11 diffusion in A. baumannii and VIM-2 diffusion in P. aeruginosa were primarily due to clonal dissemination. This study is the first nationwide investigation of carbapenem resistance in Lebanon, showing low level of resistance in Enterobacteriaceae, and higher levels in A. baumannii and Pseudomonas. With current changes in the region, continuous surveillance of carbapenem resistance is crucial.

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

    Directory of Open Access Journals (Sweden)

    Vanessa Cristine Kobs

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

  14. Risk factors for infections due to carbapenem-resistant Klebsiella pneumoniae after open heart surgery.

    Science.gov (United States)

    Salsano, Antonio; Giacobbe, Daniele Roberto; Sportelli, Elena; Olivieri, Guido Maria; Brega, Carlotta; Di Biase, Carlo; Coppo, Erika; Marchese, Anna; Del Bono, Valerio; Viscoli, Claudio; Santini, Francesco

    2016-11-01

    Patients undergoing major surgery are at increased risk of developing infections due to resistant organisms, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp). In this study, we assessed risk factors for CR-Kp infections after open heart surgery in a teaching hospital in northern Italy. A retrospective study was conducted from January to December 2014. The primary outcome measure was postoperative CR-Kp infection, defined as a time-to-event end-point. The effect of potentially related variables was assessed by univariable and multivariable analyses. Secondary end-points were in-hospital mortality and 180-day postoperative mortality. Among 553 patients undergoing open heart surgery, 32 developed CR-Kp infections (6%). In the final multivariable model, CR-Kp colonization [hazard ratio (HR) 227.45, 95% confidence intervals (CI) 67.13-1225.20, P open heart surgery. CR-Kp infection after surgery significantly affected survival. Preventing colonization is conceivably the most effective current strategy to reduce the impact of CR-Kp. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  15. Wide Distribution of Carbapenem Resistant Acinetobacter baumannii in Burns Patients in Iran

    Directory of Open Access Journals (Sweden)

    zahra eFarshadzadeh

    2015-10-01

    Full Text Available Antimicrobial resistance in carbapenem non-susceptible Acinetobacter baumannii (CNSAb is a major public health concern globally. This study determined the antibiotic resistance and molecular epidemiology of CNSAb isolates from a referral burn center in Tehran, Iran.Sixty-nine CNSAb isolates were tested for susceptibility to antimicrobial agents using the E-test methodology. Multiple locus variable number tandem repeat analysis (MLVA, Multilocus sequence typing and multiplex PCR were performed. PCR assays tested for ambler classes A, B, and D β-lactamases. Detection of ISAba1, characterization of integrons, and biofilm formation were investigated.Fifty-three (77% isolates revealed XDR phenotypes. High prevalence of blaOXA-23-like (88% and blaPER-1 (54% were detected. ISAba1 was detected upstream of blaADC, blaOXA-23-like and blaOXA51-like genes in, 97, 42 and 26% of isolates, respectively. Thirty-one (45% isolates were assigned to International Clone (IC variants. MLVA identified 56 distinct types with 6 clusters and 53 singleton genotypes. Forty previously known MLST sequence types forming 5 clonal complexes were identified. The Class 1 integron (class 1 integrons gene was identified in 84% of the isolates. The most prevalent (33% cassette combination was aacA4-catB8-aadA1. The IC variants were predominant in the A. baumannii lineage with the ability to form strong biofilms.The XDR-CNSAb from burned patients

  16. Emergence of Oxacillinases in Environmental Carbapenem-Resistant Acinetobacter baumannii Associated with Clinical Isolates.

    Science.gov (United States)

    Goic-Barisic, Ivana; Hrenovic, Jasna; Kovacic, Ana; Musić, Martina Šeruga

    2016-10-01

    Six carbapenem-resistant isolates of Acinetobacter baumannii were recovered from untreated and treated municipal wastewater of the capital city of Zagreb, Croatia. Molecular identification of environmental isolates of A. baumannii was performed by amplification, sequencing, and phylogenetic analyses of rpoB gene. The presence of bla OXA genes encoding OXA-type carbapenemases (OXA-51-like, OXA-23, and OXA-40-like) was confirmed by multiplex PCR and sequencing. Phylogenetic analyses corroborated the affiliation of detected bla OXA genes to three different clusters and showed association of environmental OXAs with those described from clinical isolates. This result suggests that isolates recovered from municipal wastewater are most probably of clinical origin. Furthermore, the presence of OXA-40-like (OXA-72) in an environmental A. baumannii isolate is reported for the first time. Persistence of A. baumannii harboring the clinically important OXAs in the wastewater treatment process poses a potentially significant source for horizontal gene transfer and implications for wider spread of antibiotic resistance genes.

  17. High-dose Sulbactam Treatment for Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant

    Directory of Open Access Journals (Sweden)

    In Beom Jeong

    2016-11-01

    Full Text Available Background Several antibiotics can be used to treat ventilator-associated pneumonia caused by carbapenem-resistant A. baumannii (CRAB-VAP including high-dose sulbactam. However, the effectiveness of high-dose sulbactam therapy is not well known. We report our experience with high-dose sulbactam for treatment of CRAB-VAP. Methods Medical records of patients with CRAB-VAP who were given high-dose sulbactam between May 2013 and June 2015 were reviewed. Results Fifty-eight patients with CRAB-VAP were treated with high-dose sulbactam. The mean age was 72.0 ± 15.2 years, and the acute physiology and chronic health evaluation II (APACHE II score was 15.1 ± 5.10 at the time of CRAB-VAP diagnosis. Early clinical improvement was observed in 65.5% of patients, and 30-day mortality was 29.3%. Early clinical failure (odds ratio [OR]: 8.720, confidence interval [CI]: 1.346-56.484; p = 0.023 and APACHE II score ≥ 14 at CRAB-VAP diagnosis (OR: 10.934, CI: 1.047-114.148; p = 0.046 were associated with 30-day mortality. Conclusions High-dose sulbactam therapy may be effective for the treatment of CRAB-VAP. However, early clinical failure was observed in 35% of patients and was associated with poor outcome.

  18. A systematic review of the epidemiology of carbapenem-resistant Enterobacteriaceae in the United States.

    Science.gov (United States)

    Livorsi, Daniel J; Chorazy, Margaret L; Schweizer, Marin L; Balkenende, Erin C; Blevins, Amy E; Nair, Rajeshwari; Samore, Matthew H; Nelson, Richard E; Khader, Karim; Perencevich, Eli N

    2018-01-01

    Carbapenem-resistant Enterobacteriaceae (CRE) pose an urgent public health threat in the United States. An important step in planning and monitoring a national response to CRE is understanding its epidemiology and associated outcomes. We conducted a systematic literature review of studies that investigated incidence and outcomes of CRE infection in the US. We performed searches in MEDLINE via Ovid, CDSR, DARE, CENTRAL, NHS EED, Scopus, and Web of Science for articles published from 1/1/2000 to 2/1/2016 about the incidence and outcomes of CRE at US sites. Five studies evaluated incidence, but many used differing definitions for cases. Across the entire US population, the reported incidence of CRE was 0.3-2.93 infections per 100,000 person-years. Infection rates were highest in long-term acute-care (LTAC) hospitals. There was insufficient data to assess trends in infection rates over time. Four studies evaluated outcomes. Mortality was higher in CRE patients in some but not all studies. While the incidence of CRE infections in the United States remains low on a national level, the incidence is highest in LTACs. Studies assessing outcomes in CRE-infected patients are limited in number, small in size, and have reached conflicting results. Future research should measure a variety of clinical outcomes and adequately adjust for confounders to better assess the full burden of CRE.

  19. Infections by carbapenem-resistant Klebsiella pneumoniae in SCT recipients: a nationwide retrospective survey from Italy.

    Science.gov (United States)

    Girmenia, C; Rossolini, G M; Piciocchi, A; Bertaina, A; Pisapia, G; Pastore, D; Sica, S; Severino, A; Cudillo, L; Ciceri, F; Scimè, R; Lombardini, L; Viscoli, C; Rambaldi, A

    2015-02-01

    Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) represent a challenging problem after SCT. A retrospective survey (January 2010 to July 2013) involving 52 Italian centers was performed to assess the epidemiology and the prognostic factors of CRKp infections in auto- and allo-SCT. Cases of CRKp infection were reported in 53.4% of centers. CRKp infections were documented in 25 auto-SCTs and 87 allo-SCTs, with an incidence of 0.4% (from 0.1% in 2010 to 0.7% in 2013) and 2% (from 0.4% in 2010 to 2.9% in 2013), respectively. A CRKp colonization documented before or after transplant was followed by an infection in 25.8% of auto-SCT and 39.2% of allo-SCT patients. The infection-related mortality rates were 16% and 64.4%, respectively. A pre-transplant CRKp infection (hazard ratio (HR) 0.33, 95% confidence intervals (CIs) 0.15-0.74; P=0.007) and a not CRKp-targeted first-line treatment (HR 2.67, 95% CI 1.43-4.99; P=0.002) were independent factors associated with an increased mortality in allo-SCT patients who developed a CRKp infection. Our study shows challenging findings of CRKp infections in SCT patients in Italy particularly after allo-SCT. The detection of carriers and the definition of early therapeutic strategies represent critical aspects of the management of CRKp infections after SCT.

  20. Molecular insight on the non-covalent interactions between carbapenems and uc(l,d)-transpeptidase 2 from Mycobacterium tuberculosis: ONIOM study

    Science.gov (United States)

    Ntombela, Thandokuhle; Fakhar, Zeynab; Ibeji, Collins U.; Govender, Thavendran; Maguire, Glenn E. M.; Lamichhane, Gyanu; Kruger, Hendrik G.; Honarparvar, Bahareh

    2018-05-01

    Tuberculosis remains a dreadful disease that has claimed many human lives worldwide and elimination of the causative agent Mycobacterium tuberculosis also remains elusive. Multidrug-resistant TB is rapidly increasing worldwide; therefore, there is an urgent need for improving the current antibiotics and novel drug targets to successfully curb the TB burden. uc(l,d)-Transpeptidase 2 is an essential protein in Mtb that is responsible for virulence and growth during the chronic stage of the disease. Both uc(d,d)- and uc(l,d)-transpeptidases are inhibited concurrently to eradicate the bacterium. It was recently discovered that classic penicillins only inhibit uc(d,d)-transpeptidases, while uc(l,d)-transpeptidases are blocked by carbapenems. This has contributed to drug resistance and persistence of tuberculosis. Herein, a hybrid two-layered ONIOM (B3LYP/6-31G+(d): AMBER) model was used to extensively investigate the binding interactions of LdtMt2 complexed with four carbapenems (biapenem, imipenem, meropenem, and tebipenem) to ascertain molecular insight of the drug-enzyme complexation event. In the studied complexes, the carbapenems together with catalytic triad active site residues of LdtMt2 (His187, Ser188 and Cys205) were treated at with QM [B3LYP/6-31+G(d)], while the remaining part of the complexes were treated at MM level (AMBER force field). The resulting Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) for all complexes showed that the carbapenems exhibit reasonable binding interactions towards LdtMt2. Increasing the number of amino acid residues that form hydrogen bond interactions in the QM layer showed significant impact in binding interaction energy differences and the stabilities of the carbapenems inside the active pocket of LdtMt2. The theoretical binding free energies obtained in this study reflect the same trend of the experimental observations. The electrostatic, hydrogen bonding and Van der Waals interactions between the carbapenems and Ldt

  1. INIS: Authority list for journal titles

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-03-01

    This is the twenty-ninth revision of the INIS: Authority List for Journal Titles (IAEA-INIS-11). It lists the titles of 12 990 journals which have contained articles within the scope of INIS. The purpose of this report is to provide descriptive cataloguers with a standard entry for the full title of a journal. In addition to the full journal title, the ISSN (International Standard Serial Number), administered by the ISSN International Centre, Paris, France, and/or CODEN, assigned by Chemical Abstracts Service, USA, are given in this manual. In order to help the reader to find titles easily, the list is divided into two parts. In Part I, the full journal titles are grouped by country or international organization responsible for coverage and ordered alphabetically. In Part II, the full journal titles of all countries or international organizations are arranged alphabetically. The country name or the international organization name responsible for coverage of the journal title to INIS is entered in parentheses. Journal titles marked with an asterisk are regularly scanned by INIS. Titles that have been identified by INIS Centres as 'Key Journals' are marked with the hash sign.

  2. INIS: Authority list for journal titles

    International Nuclear Information System (INIS)

    2003-01-01

    This is the twenty-ninth revision of the INIS: Authority List for Journal Titles (IAEA-INIS-11). It lists the titles of 12 990 journals which have contained articles within the scope of INIS. The purpose of this report is to provide descriptive cataloguers with a standard entry for the full title of a journal. In addition to the full journal title, the ISSN (International Standard Serial Number), administered by the ISSN International Centre, Paris, France, and/or CODEN, assigned by Chemical Abstracts Service, USA, are given in this manual. In order to help the reader to find titles easily, the list is divided into two parts. In Part I, the full journal titles are grouped by country or international organization responsible for coverage and ordered alphabetically. In Part II, the full journal titles of all countries or international organizations are arranged alphabetically. The country name or the international organization name responsible for coverage of the journal title to INIS is entered in parentheses. Journal titles marked with an asterisk are regularly scanned by INIS. Titles that have been identified by INIS Centres as 'Key Journals' are marked with the hash sign

  3. Land Titles and Rice Production in Vietnam

    DEFF Research Database (Denmark)

    Van Den Broeck, Katleen; Newman, Carol; Tarp, Finn

    In most of the empirical literature on land titling, the household is regarded as unitary, and land rights are found to have ambiguous effects on land allocation, investment and productivity. Using data from 12 provinces in Vietnam, we diversify land titles, and show in a household fixed effects...... analysis of plot level rice yields that land titles are indeed important. Only exclusively held titles have the expected positive effects, and the positive effect on yields is found in male headed households. Furthermore, a household level rice yield function reveals that exclusive user rights...... are inefficiency decreasing, while jointly held user rights have no efficiency effects. Finally, once the gender of the head of household is controlled for, exclusively held female titles have a greater positive effect on the efficiency of the household than that of male held titles...

  4. Photochemical degradation of the carbapenem antibiotics imipenem and meropenem in aqueous solutions under solar radiation.

    Science.gov (United States)

    Reina, Alejandro Cabrera; Martínez-Piernas, Ana B; Bertakis, Yannis; Brebou, Christina; Xekoukoulotakis, Nikolaos P; Agüera, Ana; Sánchez Pérez, José Antonio

    2018-01-01

    This paper deals with the photochemical fate of two representative carbapenem antibiotics, namely imipenem and meropenem, in aqueous solutions under solar radiation. The analytical method employed for the determination of the target compounds in various aqueous matrices, such as ultrapure water, municipal wastewater treatment plant effluents, and river water, at environmentally relevant concentrations, was liquid chromatography coupled with hybrid triple quadrupole-linear ion trap-mass spectrometry. The absorption spectra of both compounds were measured in aqueous solutions at pH values from 6 to 8, and both compounds showed a rather strong absorption band centered at about 300 nm, while their molar absorption coefficient was in the order from 9 × 10 3 -10 4  L mol -1  cm -1 . The kinetics of the photochemical degradation of the target compounds was studied in aqueous solutions under natural solar radiation in a solar reactor with compound parabolic collectors. It was found that the photochemical degradation of both compounds at environmentally relevant concentrations follows first order kinetics and the quantum yield was in the order of 10 -3  mol einsten -1 . Several parameters were studied, such as solution pH, the presence of nitrate ions and humic acids, and the effect of water matrix. In all cases, it was found that the presence of various organic and inorganic constituents in the aqueous matrices do not contribute significantly, either positively or negatively, to the photochemical degradation of both compounds under natural solar radiation. In a final set of photolysis experiments, the effect of the level of irradiance was studied under simulated solar radiation and it was found that the quantum yield for the direct photodegradation of both compounds remained practically constant by changing the incident solar irradiance from 28 to 50 W m -2 . Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Evaluation of carriage and environmental contamination by carbapenem-resistant Acinetobacter baumannii.

    Science.gov (United States)

    Nutman, A; Lerner, A; Schwartz, D; Carmeli, Y

    2016-11-01

    We evaluated the sensitivity of surveillance cultures for carbapenem-resistant Acinetobacter baumannii (CRAB) in patients and in their environment. Patients with a CRAB-positive clinical culture were sampled within 7 days; the buccal mucosa and rectum were sampled using swabs, and skin was sampled using pre-moistened sterile sponges. Sponges were also used to sample the surrounding environment. Specimens were inoculated onto CHROMagar MDR Acinetobacter plates both directly and after overnight enrichment. CRAB load was scored semi-quantitatively and composite scores for patient colonization and environmental contamination were calculated. Thirty-four patients were included. Screening sensitivity was 28/34 (82%) for buccal mucosa, 30/34 (88%) for skin, and 25/34 (74%) for rectum. Combined sensitivity was 32/34 (94%). Among patients with CRAB-positive respiratory cultures, sensitivity for buccal mucosa was 20/20 (100%). Direct inoculation had excellent sensitivity: 25/28 (89%) for all three sites combined. In the subgroup of patients who did not have a respiratory source for CRAB, direct inoculation sensitivity was lower than among patients with CRAB-positive respiratory cultures: 5/8 (63%) versus 20/20 (100%). The environment of all patients was contaminated with CRAB. There was a positive correlation between the patient colonization score and the environmental contamination score (r = 0.63, p Environmental contamination is common and can be monitored. Implementing screening may facilitate infection control efforts to limit the spread of CRAB. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. Molecular characterization of β-lactamase genes in clinical isolates of carbapenem-resistant Acinetobacter baumannii.

    Science.gov (United States)

    Raible, Kevin M; Sen, Bhaswati; Law, Nancy; Bias, Tiffany E; Emery, Christopher L; Ehrlich, Garth D; Joshi, Suresh G

    2017-11-16

    Acinetobacter baumannii is a nosocomial pathogen which is establishing as a major cause of morbidity and mortality within the healthcare community. The success of this pathogen is largely due to its ability to rapidly gain resistance to antimicrobial therapies and its capability to persist in an abiotic environment through the production of a biofilm. Our tertiary-care hospital has showed high incidence of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. In this study we explore both genotypic and phenotypic properties of 26 CRAB isolates: 16 isolates were collected from January 2010 to March 2011, and 10 were collected between February and May 2015. We determined that all 26 CRAB isolates possessed multiple β-lactamase genes, including genes from Groups A, C, and D. Specifically, 42% of the isolates possesses the potentially plasmid-borne genes of OXA-23-like or OXA-40-like β-lactamase. The presence of mobile gene element integron cassettes and/or integrases in 88% of the isolates suggests a possible mechanism of dissemination of antibiotic resistance genes. Additionally, the location of insertion sequence (IS) ISAba1 in promotor region of of the OXA-51-like, ADC-7, and ampC genes was confirmed. Multilocus sequence typing (MLST) demonstrated that all 26 CRAB isolates were either sequence type (ST)-229 or ST-2. Interestingly, ST-2 went from being the minority CRAB strain in the 2010-2011 isolates to the predominant strain in the 2015 isolates (from 32 to 90%). We show that the ST-2 strains have an enhanced ability to produce biofilms in comparison to the ST-229 strains, and this fact has potentially led to more successful colonization of the clinical environment over time. This study provides a longitudinal genetic and phenotypic survey of two CRAB sequence types, and suggests how their differing phenotypes may interact with the selective pressures of a hospital setting effecting strain dominance over a 5-year period.

  7. Clinical epidemiology and resistance mechanisms of carbapenem-resistant Acinetobacter baumannii, French Guiana, 2008-2014.

    Science.gov (United States)

    Mahamat, Aba; Bertrand, Xavier; Moreau, Brigitte; Hommel, Didier; Couppie, Pierre; Simonnet, Christine; Kallel, Hatem; Demar, Magalie; Djossou, Felix; Nacher, Mathieu

    2016-07-01

    This study investigated the clinical epidemiology and resistance mechanisms of Acinetobacter baumannii and characterised the clonal diversity of carbapenem-resistant A. baumannii (CRAB) during an ICU-associated outbreak at Cayenne Hospital, French Guiana. All non-duplicate A. baumannii isolates from 2008 to 2014 were tested for antibiotic susceptibility by disk diffusion. Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on CRAB. Of the 441 A. baumannii isolates, most were from males (54.0%) and were detected mainly from the ICU (30.8%) and medicine wards (21.8%). In the ICU, strains were mainly isolated from the respiratory tract (44.1%) and bloodstream (14.0%), whereas in medicine wards they mainly were from wound/drainage (36.5%) and bloodstream (25.0%). A. baumannii showed the greatest susceptibility to piperacillin/tazobactam (92.7%), imipenem (92.5%), colistin (95.6%) and amikacin (97.2%), being lower in the ICU and medicine wards compared with other wards. An outbreak of OXA-23-producing CRAB occurred in the 13-bed ICU in 2010. CRAB strains were more co-resistant to other antimicrobials compared with non-CRAB. Molecular genetics analysis revealed five sequence types [ST78, ST107 and ST642 and two new STs (ST830 and ST831)]. Analysis of PFGE profiles indicated cross-transmissions of CRAB within the ICU, between the ICU and one medicine ward during transfer of patients, and within that medicine ward. This study provides the first clinical and molecular data of A. baumannii from French Guiana and the Amazon basin. The ICU was the highest risk unit of this nosocomial outbreak of OXA-23-producing CRAB, which could subsequently disseminate within the hospital. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  8. Potential economic burden of carbapenem-resistant Enterobacteriaceae (CRE) in the United States.

    Science.gov (United States)

    Bartsch, S M; McKinnell, J A; Mueller, L E; Miller, L G; Gohil, S K; Huang, S S; Lee, B Y

    2017-01-01

    The Centers for Disease Control and Prevention considers carbapenem-resistant Enterobacteriaceae (CRE) an urgent public health threat; however, its economic burden is unknown. We developed a CRE clinical and economics outcomes model to determine the cost of CRE infection from the hospital, third-party payer, and societal, perspectives and to evaluate the health and economic burden of CRE to the USA. Depending on the infection type, the median cost of a single CRE infection can range from $22 484 to $66 031 for hospitals, $10 440 to $31 621 for third-party payers, and $37 778 to $83 512 for society. An infection incidence of 2.93 per 100 000 population in the USA (9418 infections) would cost hospitals $275 million (95% CR $217-334 million), third-party payers $147 million (95% CR $129-172 million), and society $553 million (95% CR $303-1593 million) with a 25% attributable mortality, and would result in the loss of 8841 (95% CR 5805-12 420) quality-adjusted life years. An incidence of 15 per 100 000 (48 213 infections) would cost hospitals $1.4 billion (95% CR $1.1-1.7 billion), third-party payers $0.8 billion (95% CR $0.6-0.8 billion), and society $2.8 billion (95% CR $1.6-8.2 billion), and result in the loss of 45 261 quality-adjusted life years. The cost of CRE is higher than the annual cost of many chronic diseases and of many acute diseases. Costs rise proportionally with the incidence of CRE, increasing by 2.0 times, 3.4 times, and 5.1 times for incidence rates of 6, 10, and 15 per 100 000 persons. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Imipenem/cilastatin encapsulated polymeric nanoparticles for destroying carbapenem-resistant bacterial isolates.

    Science.gov (United States)

    Shaaban, Mona I; Shaker, Mohamed A; Mady, Fatma M

    2017-04-11

    Carbapenem-resistance is an extremely growing medical threat in antibacterial therapy as the incurable resistant strains easily develop a multi-resistance action to other potent antimicrobial agents. Nonetheless, the protective delivery of current antibiotics using nano-carriers opens a tremendous approach in the antimicrobial therapy, allowing the nano-formulated antibiotics to beat these health threat pathogens. Herein, we encapsulated imipenem into biodegradable polymeric nanoparticles to destroy the imipenem-resistant bacteria and overcome the microbial adhesion and dissemination. Imipenem loaded poly Ɛ-caprolactone (PCL) and polylactide-co-glycolide (PLGA) nanocapsules were formulated using double emulsion evaporation method. The obtained nanocapsules were characterized for mean particle diameter, morphology, loading efficiency, and in vitro release. The in vitro antimicrobial and anti adhesion activities were evaluated against selected imipenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa clinical isolates. The obtained results reveal that imipenem loaded PCL nano-formulation enhances the microbial susceptibility and antimicrobial activity of imipenem. The imipenem loaded PCL nanoparticles caused faster microbial killing within 2-3 h compared to the imipenem loaded PLGA and free drug. Successfully, PCL nanocapsules were able to protect imipenem from enzymatic degradation by resistant isolates and prevent the emergence of the resistant colonies, as it lowered the mutation prevention concentration of free imipenem by twofolds. Moreover, the imipenem loaded PCL eliminated bacterial attachment and the biofilm assembly of P. aeruginosa and K. pneumoniae planktonic bacteria by 74 and 78.4%, respectively. These promising results indicate that polymeric nanoparticles recover the efficacy of imipenem and can be considered as a new paradigm shift against multidrug-resistant isolates in treating severe bacterial infections.

  10. Genomic Analysis of Hospital Plumbing Reveals Diverse Reservoir of Bacterial Plasmids Conferring Carbapenem Resistance

    Directory of Open Access Journals (Sweden)

    Rebecca A. Weingarten

    2018-02-01

    Full Text Available The hospital environment is a potential reservoir of bacteria with plasmids conferring carbapenem resistance. Our Hospital Epidemiology Service routinely performs extensive sampling of high-touch surfaces, sinks, and other locations in the hospital. Over a 2-year period, additional sampling was conducted at a broader range of locations, including housekeeping closets, wastewater from hospital internal pipes, and external manholes. We compared these data with previously collected information from 5 years of patient clinical and surveillance isolates. Whole-genome sequencing and analysis of 108 isolates provided comprehensive characterization of blaKPC/blaNDM-positive isolates, enabling an in-depth genetic comparison. Strikingly, despite a very low prevalence of patient infections with blaKPC-positive organisms, all samples from the intensive care unit pipe wastewater and external manholes contained carbapenemase-producing organisms (CPOs, suggesting a vast, resilient reservoir. We observed a diverse set of species and plasmids, and we noted species and susceptibility profile differences between environmental and patient populations of CPOs. However, there were plasmid backbones common to both populations, highlighting a potential environmental reservoir of mobile elements that may contribute to the spread of resistance genes. Clear associations between patient and environmental isolates were uncommon based on sequence analysis and epidemiology, suggesting reasonable infection control compliance at our institution. Nonetheless, a probable nosocomial transmission of Leclercia sp. from the housekeeping environment to a patient was detected by this extensive surveillance. These data and analyses further our understanding of CPOs in the hospital environment and are broadly relevant to the design of infection control strategies in many infrastructure settings.

  11. Impact of ethylene oxide gas sterilization of duodenoscopes after a carbapenem-resistant Enterobacteriaceae outbreak.

    Science.gov (United States)

    Naryzhny, Igor; Silas, Dean; Chi, Kenneth

    2016-08-01

    Carbapenem-resistant Enterobacteriaceae (CRE) outbreaks have been implicated at several medical institutions involving gastroenterology laboratories and, specifically, duodenoscopes. Currently, there are no specific guidelines to eradicate or prevent the outbreak of this bacteria. We describe ethylene oxide (ETO) gas sterilizations of duodenoscopes to address this issue. A complete investigation of the gastroenterology laboratory and an evaluation by the Centers for Disease Control and Prevention concluded that no lapses were found in the reprocessing of the equipment. With no deficiencies to address, we began a novel cleaning process using surgical ETO gas sterilizers in addition to standard endoscope reprocessing recommendations and guidelines, all while trying to eradicate the CRE contamination and prevent future recurrences. We also instituted a surveillance system for recurrence of CRE contamination via monthly cultures of the duodenoscopes. Between October 2013 and April 2014, 589 ERCPs were performed with 645 ETO gas sterilizations of 6 duodenoscopes. Given the extra 16 hours needed to sterilize the duodenoscopes, our institution incurred costs resulting from purchasing additional equipment and surveillance cultures. Four duodenoscopes sustained damage during this period; however, this could not be directly attributed to the sterilization process. Furthermore, after an 18-month success period we encountered a positive CRE culture after sterilization, albeit of a different strain than originally detected during the outbreak. The duodenoscope underwent additional ETO gas sterilization, with a negative repeated culture; all potentially exposed individuals screened negative for CRE. Proper use of high-level disinfection alone may not eliminate multidrug-resistant organisms from duodenoscopes. In this single-center study, the addition of ETO sterilization and frequent monitoring with cultures reduced duodenoscope contamination and eliminated clinical infections

  12. Carbapenem Susceptibility and Multidrug-Resistance in Pseudomonas aeruginosa Isolates in Egypt.

    Science.gov (United States)

    Hashem, Hany; Hanora, Amro; Abdalla, Salah; Shawky, Alaa; Saad, Alaa

    2016-11-01

    Resistant Pseudomonas aeruginosa is a serious concern for antimicrobial therapy, as the common isolates exhibit variable grades of resistance, involving beta-lactamase enzymes, beside native defense mechanisms. The present study was designed to determine the occurrence of Metallo-β- Lactamases (MBL) and Amp C harboring P. aeruginosa isolates from Suez Canal university hospital in Ismailia, Egypt. A total of 147 P. aeruginosa isolates, recovered from 311 patients during a 10-month period, were collected between May 2013 and February 2014; the isolates were collected from urine, wound and sputum. Minimum inhibitory concentration (MIC) determined by agar dilution methods was ≥2 μg/mL for meropenem and imipenem. Identification of P. aeruginosa was confirmed using API 20NE. Metallo-β- Lactamases and Amp C were detected based on different phenotypic methods. Overall, 26.5% of P. aeruginosa isolates (39/147) were carbapenem resistant isolates. Furthermore, 64.1% (25/39) were MBL producers, these isolates were screened by the combined disc and disc diffusion methods to determine the ability of MBL production. Both MBL and Amp C harbored P. aeruginosa isolates were 28% (7/25). Sixty-four percent of P. aeruginosa isolates were multidrug resistant (MDR) (16/25). The sensitivity toward polymyxin, imipenem, norfloxacin, piperacillin-tazobactam and gentamicin was 99%, 91%, 88%, 82% and 78%, respectively. The resistance rate towards cefotaxime, ceftazidime, cefepime, aztreonam and meropenem was 98.6%, 86%, 71.4%, 34% and 30%, respectively. Multidrug resistance was significantly associated with MBL production in P. aeruginosa . Early detection of MBL-producing P. aeruginosa and hospital antibiotic policy prescription helps proper antimicrobial therapy and avoidance of dissemination of these multidrug resistance isolates.

  13. In vitro activity of tigecycline and comparators against carbapenem-susceptible and resistant Acinetobacter baumannii clinical isolates in Italy

    Directory of Open Access Journals (Sweden)

    Carattoli Alessandra

    2008-02-01

    Full Text Available Abstract Background In a recent multi-centre Italian survey (2003–2004, conducted in 45 laboratories throughout Italy with the aim of monitoring microorganisms responsible for severe infections and their antibiotic resistance, Acinetobacter baumannii was isolated from various wards of 9 hospitals as one of the most frequent pathogens. One hundred and seven clinically significant strains of A. baumannii isolates were included in this study to determine the in vitro activity of tigecycline and comparator agents. Methods Tests for the susceptibility to antibiotics were performed by the broth microdilution method as recommended by CLSI guidelines. The following antibiotics were tested: aztreonam, piperacillin/tazobactam, ampicillin/sulbactam, ceftazidime, cefepime, imipenem, meropenem tetracycline, doxycycline, tigecycline, gentamicin, amikacin, ciprofloxacin, colistin, and trimethoprim/sulphametoxazole. The PCR assay was used to determine the presence of OXA, VIM, or IMP genes in the carbapenem resistant strains. Results A. baumannii showed widespread resistance to ceftazidime, ciprofloxacin and aztreonam in more than 90% of the strains; resistance to imipenem and meropenem was 50 and 59% respectively, amikacin and gentamicin were both active against about 30% of the strains and colistin about 99%, with only one strain resistant. By comparison with tetracyclines, tigecycline and doxycycline showed a higher activity. In particular, tigecycline showed a MIC90 value of 2 mg/L and our strains displayed a unimodal distribution of susceptibility being indistinctly active against carbapenem-susceptible and resistant strains, these latter possessed OXA-type variant enzymes. Conclusion In conclusion, tigecycline had a good activity against the MDR A. baumannii strains while maintaining the same MIC90 of 2 mg/L against the carbapenem-resistant strains.

  14. Retrospective and prospective evaluation of the Carbapenem inactivation method for the detection of carbapenemase-producing Enterobacteriaceae

    Science.gov (United States)

    Gauthier, Lauraine; Dortet, Laurent; Naas, Thierry

    2017-01-01

    Background There is an urgent need for accurate and rapid diagnostic tests to identify carbapenemase producing enterobacteria (CPE). Here, we have evaluated the Carbapenem Inactivation Method (CIM) test to detect CPEs from cultured colonies. Methods A total of 256 enterobacterial isolates were used to evaluate the performance of the CIM in comparison to Carba NP test and molecular detection used a reference method. Ninety three well-characterized isolates (including 29 non-CPE and 63 CPEs of worldwide origin) with decreased susceptibility to at least one carbapenem were used to (i) evaluate the efficacy of CIM test and (ii) to compare it to the Carba NP test. We also tested different carbapenems to determine the best substrate for this test. Finally, the CIM test was then evaluated prospectively against 164 isolates referred to the French National Reference Center (NRC) for Antimicrobial Resistance from may 2016 to july 2016. Results Based on the results of this retrospective study, sensitivity and specificity of the CIM and the Carba NP test were 92.1% and 100%, respectively. We demonstrated that the meropenem was the best substrate to perform the CIM test since sensitivity and specificity were 81.1% and 100% using ertapenem disk, and 100% and 65,6% using imipenem disk, and respectively. Taking in account the results of retrospective and prospective studies, CIM and Carba NP tests have similar sensitivity, specificity, positive predictive value and negative predictive values being 96.3%, 98.9%, 99.0% and 98.4% for the CIM test versus 96.9%, 100%, 100% and 100% for the Carba NP test. Conclusions Our results confirm that the CIM test may be a useful tool for the reliable confirmation of carbapenemase-activity in enterobacterial isolates, especially in clinical microbiological laboratories with limited resources, no trained personnel, and no specialized equipment. PMID:28158310

  15. 24 CFR 200.61 - Title.

    Science.gov (United States)

    2010-04-01

    ... Commissioner. (c) Endorsement of the credit instrument for insurance shall evidence the acceptability of title... GENERAL INTRODUCTION TO FHA PROGRAMS Requirements for Application, Commitment, and Endorsement Generally...

  16. In vitro Evaluation of the Colistin-Carbapenem Combination in Clinical Isolates of A. baumannii Using the Checkerboard, Etest, and Time-Kill Curve Techniques.

    Science.gov (United States)

    Soudeiha, Micheline A H; Dahdouh, Elias A; Azar, Eid; Sarkis, Dolla K; Daoud, Ziad

    2017-01-01

    The worldwide increase in the emergence of carbapenem resistant Acinetobacter baumannii (CRAB) calls for the investigation into alternative approaches for treatment. This study aims to evaluate colistin-carbapenem combinations against Acinetobacter spp., in order to potentially reduce the need for high concentrations of antibiotics in therapy. This study was conducted on 100 non-duplicate Acinetobacter isolates that were collected from different patients admitted at Saint George Hospital-University Medical Center in Beirut. The isolates were identified using API 20NE strips, which contain the necessary agents to cover a panel of biochemical tests, and confirmed by PCR amplification of bla OXA-51-like . Activities of colistin, meropenem and imipenem against Acinetobacter isolates were determined by ETEST and microdilution methods, and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. In addition, PCR amplifications of the most common beta lactamases contributing to carbapenem resistance were performed. Tri locus PCR-typing was also performed to determine the international clonality of the isolates. Checkerboard, ETEST and time kill curves were then performed to determine the effect of the colistin-carbapenem combinations. The synergistic potential of the combination was then determined by calculating the Fractional Inhibitory Concentration Index (FICI), which is an index that indicates additivity, synergism, or antagonism between the antimicrobial agents. In this study, 84% of the isolates were resistant to meropenem, 78% to imipenem, and only one strain was resistant to colistin. 79% of the isolates harbored bla OXA-23-like and pertained to the International Clone II. An additive effect for the colistin-carbapenem combination was observed using all three methods. The combination of colistin-meropenem showed better effects as compared to colistin-imipenem ( p carbapenems could be a promising antimicrobial strategy in

  17. Risk factors for and role of OprD protein in increasing minimal inhibitory concentrations of carbapenems in clinical isolates of Pseudomonas aeruginosa.

    Science.gov (United States)

    Hirabayashi, Aki; Kato, Daizo; Tomita, Yuka; Iguchi, Mitsutaka; Yamada, Keiko; Kouyama, Yuichi; Morioka, Hiroshi; Tetsuka, Nobuyuki; Yagi, Tetsuya

    2017-11-01

    This study examined the risk factors for, and molecular mechanisms underlying, the increase in carbapenem minimum inhibitory concentrations (MICs) in clinical isolates of Pseudomonas aeruginosa. Consecutive clinical isolates of P. aeruginosa were collected. The MicroScan WalkAway system detected more than fourfold increases in the MICs of carbapenems in P. aeruginosa isolates serially recovered from some patients during their clinical course. The clinical risk factors associated with this increase were examined by multiple logistic regression analysis. Western blot analysis and nucleotide sequencing of the oprD gene of 19 clonally related and paired P. aeruginosa isolates from the same patients were undertaken to examine the mechanisms underlying the increase in MICs. The results showed that prior use of carbapenems (OR, 2.799; 95 % CI, 1.088-7.200; P=0.033) and the use of ventilators or tracheostomies (OR, 2.648; 95 % CI, 1.051-6.671; P=0.039) were risk factors for increased carbapenem MICs. Analysis of the underlying mechanisms revealed that loss of functional OprD protein due to mutation of the oprD gene tended to occur in P. aeruginosa isolates with imipenem MICs of more than 8 µg ml -1 ; a reduction in OprD expression was observed in P. aeruginosa isolates with imipenem MICs of 4 or 8 µg ml -1 . This difference in the resistance mechanism was not correlated with the MICs of meropenem. This difference in the resistance mechanism of P. aeruginosa indicates a critical breakpoint at an imipenem MIC of 8 µg ml -1 , in accordance with EUCAST criteria. Reducing carbapenem use will prevent P. aeruginosa clinical isolates from developing resistance to carbapenems.

  18. Antibacterial activity of exogenous glutathione and its synergism on antibiotics sensitize carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

    Science.gov (United States)

    Alharbe, Roaa; Almansour, Ayidh; Kwon, Dong H

    2017-10-01

    A major clinical impact of A. baumannii is hospital-acquired infections including ventilator-associated pneumonia. The treatment of this pathogen is often difficult due to its innate and acquired resistance to almost all commercially available antibiotics. Infections with carbapenem-associated multidrug resistant A. baumannii is the most problematic. Glutathione is a tripeptide thiol-antioxidant and antibacterial activity of exogenous glutathione was reported in some bacteria. However, clinical relevance and molecular details of the antibacterial activity of glutathione are currently unclear. Seventy clinical isolates of A. baumannii including 63 carbapenem-associated multidrug resistant isolates and a type strain A. baumannii ATCC 19606 were used to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Fractional inhibitory concentration (FIC) and time-killing activity with meropenem and/or glutathione were also determined in the carbapenem-associated multidrug resistant isolates. In addition, the roles of exogenous glutathione in multidrug efflux pumps and β-lactamase production were examined. Levels of MIC and MBC were ranged from 10 to 15mM of exogenous glutathione. All tested carbapenem-associated multidrug resistant isolates were sensitized by all tested antibiotics in combination with subinhibitory concentrations of glutathione. FIC levels of glutathione with carbapenem (meropenem) were allcarbapenem-associated multidrug resistant isolates were killed by subinhibitory concentrations of both glutathione and meropenem at>2log10 within 12h, suggesting glutathione synergistically interacts with meropenem. The roles of multidrug efflux pumps and β-lactamase production were excluded for the glutathione-mediated antibiotic susceptibility. Overall results demonstrate that the antibacterial activity of glutathione is clinically relevant and its synergism on antibiotics sensitizes clinical isolates of A. baumannii regardless

  19. Treatment Outcomes in Infections Caused by "SPICE" (Serratia, Pseudomonas, Indole-positive Proteus, Citrobacter, and Enterobacter) Organisms: Carbapenem versus Noncarbapenem Regimens.

    Science.gov (United States)

    Moy, Stanley; Sharma, Roopali

    2017-01-01

    Techniques used to identify AmpC β-lactamases in SPICE (Serratia, Pseudomonas, indole-positive Proteus, Citrobacter, and Enterobacter) organisms are not yet optimized for the clinical laboratory and are not routinely used. Clinicians are often left with an uncertainty on the choice of antibiotic when a SPICE organism is isolated. The purpose of this study was to evaluate the outcomes of carbapenem versus noncarbapenem regimens in treating bacteremia or urinary tract infection from a SPICE organism in clinical practice. This single-center, retrospective, cohort study analyzed data from adult patients who had clinical infection with a SPICE organism isolated from blood or urine cultures. Patients were assigned to a carbapenem- or noncarbapenem-treated group. The primary end point was clinical response, defined as a resolution of signs and symptoms of infection at the end of therapy. A total of 332 patients were assessed, and 145 patients met the inclusion criteria for the study. There were 20 patients who received a carbapenem, while 125 received a noncarbapenem regimen. The percentage of patients who were bacteremic was 46.2%. Clinical response overall was achieved in 80% of patients on a carbapenem versus 90.3% of patients on a noncarbapenem regimen (P = 0.24). The rate of microbiologic cure was 90% in patients on a carbapenem versus 91.2% in patients on a noncarbapenem regimen (P = 1). In this study in patients treated for infection with a SPICE organism in clinical practice, the rates of clinical response did not differ significantly between the carbapenem and noncarbapenem groups. Current CLSI breakpoints set for SPICE organisms may still be reliable and may not require additional testing for AmpC β-lactamases. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  20. Efficacy of non-carbapenem antibiotics for pediatric patients with first febrile urinary tract infection due to extended-spectrum beta-lactamase-producing Escherichia coli.

    Science.gov (United States)

    Abe, Yoshifusa; Inan-Erdogan, Işil; Fukuchi, Kunihiko; Wakabayashi, Hitomi; Ogawa, Yasuha; Hibino, Satoshi; Sakurai, Shunsuke; Matsuhashi, Kazuhiko; Watanabe, Yoshitaka; Hashimoto, Kaori; Ugajin, Kazuhisa; Itabashi, Kazuo

    2017-08-01

    Although carbapenem is the recommended for urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms, non-carbapenems have been reported to be effective for adult patients with UTI caused by ESBL-producing organisms. The purpose of this study was to evaluate the efficacy of non-carbapenems for pediatric patients with UTI due to ESBL-producing Escherichia coli (E. coli) based on the microbiologic and clinical outcomes. Fifteen children, who were treated for first febrile UTI caused by ESBL-producing E. coli were enrolled in this study. Antimicrobial susceptibilities and ESBL production were determined according to the Clinical and Laboratory Standards Institute guidelines. To detect CTX-M genes, polymerase chain reaction was performed with specific primers for bla CTX-M detection. Of the 15 enrolled patients, 10 (66.7%) were boys and 5 (33.3%) were girls, with a median age of four months. VUR was detected in six patients (40%). For detection of bla CTX-M by PCR, CTX-M-3, CTX-M-8, CTX-M-14, and CTX-M-15 were detected in five, one, eight, and one patient, respectively. Overall, 14 of the 15 isolates (93.3%) were susceptible for fosfomycin (FOM), and all isolates were susceptible for cefmetazole (CMZ), flomoxef (FMOX), and imipenem/cilastatin (IPM/CS). Of the 15 patients, 12 (80%) clinically improved without the use of carbapenems. In conclusion, even if isolates of ESBL-producing E. coli are multidrug resistant based on MIC assessment, clinical susceptibility to non-carbapenems, such as CMZ, FMOX, and FOM, is possible. Accordingly, carbapenems may not be required all the time for treatment of pediatric UTI in clinical practice. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. RpoN Modulates Carbapenem Tolerance in Pseudomonas aeruginosa through Pseudomonas Quinolone Signal and PqsE

    Science.gov (United States)

    Murakami, Keiji; Amoh, Takashi; Ono, Tsuneko; Miyake, Yoichiro

    2016-01-01

    The ability of Pseudomonas aeruginosa to rapidly modulate its response to antibiotic stress and persist in the presence of antibiotics is closely associated with the process of cell-to-cell signaling. The alternative sigma factor RpoN (σ54) is involved in the regulation of quorum sensing (QS) and plays an important role in the survival of stationary-phase cells in the presence of carbapenems. Here, we demonstrate that a ΔrpoN mutant grown in nutrient-rich medium has increased expression of pqsA, pqsH, and pqsR throughout growth, resulting in the increased production of the Pseudomonas quinolone signal (PQS). The link between pqsA and its role in carbapenem tolerance was studied using a ΔrpoN ΔpqsA mutant, in which the carbapenem-tolerant phenotype of the ΔrpoN mutant was abolished. In addition, we demonstrate that another mechanism leading to carbapenem tolerance in the ΔrpoN mutant is mediated through pqsE. Exogenously supplied PQS abolished the biapenem-sensitive phenotype of the ΔrpoN ΔpqsA mutant, and overexpression of pqsE failed to alter the susceptibility of the ΔrpoN ΔpqsA mutant to biapenem. The mutations in the ΔrpoN ΔrhlR mutant and the ΔrpoN ΔpqsH mutant led to susceptibility to biapenem. Comparison of the changes in the expression of the genes involved in QS in wild-type PAO1 with their expression in the ΔrpoN mutant and the ΔrpoN mutant-derived strains demonstrated the regulatory effect of RpoN on the transcript levels of rhlR, vqsR, and rpoS. The findings of this study demonstrate that RpoN negatively regulates the expression of PQS in nutrient-rich medium and provide evidence that RpoN interacts with pqsA, pqsE, pqsH, and rhlR in response to antibiotic stress. PMID:27431228

  2. Community-acquired carbapenem-resistant Acinetobacter baumannii urinary tract infection just after marriage in a renal transplant recipient.

    Science.gov (United States)

    Solak, Y; Atalay, H; Turkmen, K; Biyik, Z; Genc, N; Yeksan, M

    2011-12-01

    Urinary tract infection (UTI) is common in renal transplant recipients and may worsen allograft and patient survival. Many risk factors such as age, female gender, immunosuppression, comorbidity, deceased-donor kidney transplantation, and uretheral catheterization are involved in development of UTI. Acinetobacter baumannii has rarely been reported as a causative agent for development of UTI. Here, we present an unusual case of a renal transplant recipient who developed community-acquired carbapenem-resistent A. baumannii UTI. © 2011 John Wiley & Sons A/S.

  3. Phenotypic and genotypic characteristics of carbapenem-resistant Enterobacteriaceae in a tertiary-level reference hospital in Turkey.

    Science.gov (United States)

    Baran, Irmak; Aksu, Neriman

    2016-04-06

    Enterobacteriaceae are among the most common pathogens that are responsible for serious community-acquired, hospital-acquired, and health-care associated infections. The emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) have become an increasing concern for healthcare services worldwide. Infections caused by these bacteria have been associated with significant morbidity and mortality and treatment options have been limited. The rapid and accurate detection of carbapenem resistance in these bacteria is important for infection control. The aim of this study was to investigate the phenotypic and genotypic features of CRE strains isolated in a tertiary-level reference hospital in Turkey. A total of 181 CRE strains were included in the study. Antimicrobial susceptibility rates were tested using Vitek 2 system. Modified Hodge test (MHT) was performed using meropenem and ertapenem discs. Metallo-β-lactamase antimicrobial gradient test (E-test MBL strips) were used for evaluation of metallo-β-lactamase production. A multiplex PCR was used for detection of carbapenems resistance genes (IMP, VIM, KPC, NDM-1 and OXA-48). The OXA-48 gene was detected in 86 strains, NDM-1 gene in six strains, VIM gene in one strain. IMP and KPC genes were not identified. Three strains produced both OXA-48 and NDM-1 and one strain produced both OXA-48 and VIM. In two patients more than one genus of OXA-48 positive CREs was isolated. Ninety-two of the isolates were multidrug-resistant. One hundred and ten isolates were MHT with meropenem (MEM-MHT) positive and 109 isolates were MHT with ertapenem (ERT-MHT) positive. Nine of the isolates were positive with E-test MBL strips. The sensitivity of MEM-MHT and ERT-MHT for detection of OXA-48 was 70.9 and 70.6 %, respectively. MEM-MHT was found highly discriminative for OXA-48 Escherichia coli (p Enterobacteriaceae in the hospital environment. While OXA-48 is still the most common source of carbapenem resistance in

  4. Is This the Carbapenemase Test We've Been Waiting for? A Multicenter Evaluation of the Modified Carbapenem Inactivation Method.

    Science.gov (United States)

    Butler-Wu, Susan M; Abbott, April N

    2017-08-01

    A plethora of phenotypic methods exist for the detection of carbapenemases; however, clinical laboratories have struggled for years with accurate, objective phenotypic detection of carbapenemase activity in Enterobacteriaceae In this issue of the Journal of Clinical Microbiology , V. M. Pierce et al. (J Clin Microbiol 55:2321-2333, 2017, https://doi.org/10.1128/JCM.00193-17) report on a multicenter evaluation of the modified carbapenem inactivation method (mCIM). The high sensitivity, specificity, reproducibility, and ease of interpretation associated with the mCIM for Enterobacteriaceae will likely lead to its adoption by clinical laboratories. Copyright © 2017 American Society for Microbiology.

  5. Reduction in Fluoroquinolone Use following Introduction of Ertapenem into a Hospital Formulary Is Associated with Improvement in Susceptibility of Pseudomonas aeruginosa to Group 2 Carbapenems: a 10-Year Study▿

    Science.gov (United States)

    Cook, Paul P.; Gooch, Michael; Rizzo, Shemra

    2011-01-01

    We examined the effect of the addition of ertapenem to our hospital formulary on the resistance of nosocomial Pseudomonas aeruginosa to group 2 carbapenems (imipenem, meropenem, and doripenem). This was a retrospective, observational study conducted between 1 January 2000 and 31 January 2009 at a large, tertiary-care hospital. Autoregressive integrated moving average (ARIMA) regression models were used to evaluate the effect of ertapenem use on the susceptibility of Pseudomonas aeruginosa to group 2 carbapenems as well as on the use of the group 2 carbapenems, ciprofloxacin, and other antipseudomonal drugs (i.e., tobramycin, cefepime, and piperacillin-tazobactam). Resistance was expressed as a percentage of total isolates as well as the number of carbapenem-resistant bacterial isolates per 10,000 patient days. Pearson correlation was used to assess the relationship between antibiotic use and carbapenem resistance. Following the addition of ertapenem to the formulary, there was a statistically significant decrease in the percentage of Pseudomonas aeruginosa isolates resistant to the group 2 carbapenems (P = 0.003). Group 2 carbapenem use and the number of carbapenem-resistant Pseudomonas aeruginosa isolates per 10,000 patient days did not change significantly over the time period. There was a large decrease in the use of ciprofloxacin (P = 0.0033), and there was a correlation of ciprofloxacin use with the percentage of isolates resistant to the group 2 carbapenems (ρ = 0.47, P = 0.002). We suspect that the improvement in susceptibility of Pseudomonas aeruginosa to group 2 carbapenems was related to a decrease in ciprofloxacin use. PMID:21968357

  6. Reduction in fluoroquinolone use following introduction of ertapenem into a hospital formulary is associated with improvement in susceptibility of Pseudomonas aeruginosa to group 2 carbapenems: a 10-year study.

    Science.gov (United States)

    Cook, Paul P; Gooch, Michael; Rizzo, Shemra

    2011-12-01

    We examined the effect of the addition of ertapenem to our hospital formulary on the resistance of nosocomial Pseudomonas aeruginosa to group 2 carbapenems (imipenem, meropenem, and doripenem). This was a retrospective, observational study conducted between 1 January 2000 and 31 January 2009 at a large, tertiary-care hospital. Autoregressive integrated moving average (ARIMA) regression models were used to evaluate the effect of ertapenem use on the susceptibility of Pseudomonas aeruginosa to group 2 carbapenems as well as on the use of the group 2 carbapenems, ciprofloxacin, and other antipseudomonal drugs (i.e., tobramycin, cefepime, and piperacillin-tazobactam). Resistance was expressed as a percentage of total isolates as well as the number of carbapenem-resistant bacterial isolates per 10,000 patient days. Pearson correlation was used to assess the relationship between antibiotic use and carbapenem resistance. Following the addition of ertapenem to the formulary, there was a statistically significant decrease in the percentage of Pseudomonas aeruginosa isolates resistant to the group 2 carbapenems (P = 0.003). Group 2 carbapenem use and the number of carbapenem-resistant Pseudomonas aeruginosa isolates per 10,000 patient days did not change significantly over the time period. There was a large decrease in the use of ciprofloxacin (P = 0.0033), and there was a correlation of ciprofloxacin use with the percentage of isolates resistant to the group 2 carbapenems (ρ = 0.47, P = 0.002). We suspect that the improvement in susceptibility of Pseudomonas aeruginosa to group 2 carbapenems was related to a decrease in ciprofloxacin use.

  7. Novel ambler class A carbapenem-hydrolyzing beta-lactamase from a Pseudomonas fluorescens isolate from the Seine River, Paris, France.

    Science.gov (United States)

    Girlich, Delphine; Poirel, Laurent; Nordmann, Patrice

    2010-01-01

    A Pseudomonas fluorescens isolate (PF-1) resistant to carbapenems was recovered during an environmental survey performed with water from the Seine River (Paris). It expressed a novel Ambler class A carbapenemase, BIC-1, sharing 68 and 59% amino acid identities with beta-lactamases SFC-1 from Serratia fonticola and the plasmid-encoded KPC-2, respectively. beta-Lactamase BIC-1 hydrolyzed penicillins, carbapenems, and cephalosporins except ceftazidime and monobactams. The bla(BIC-1) gene was chromosomally located and was also identified in two other P. fluorescens strains isolated from the Seine River 3 months later.

  8. Comparing the characteristics of highly cited titles and highly alted titles

    Energy Technology Data Exchange (ETDEWEB)

    Didegah, F.; Bowman, T.D.; Bowman, S.; Hartley, J.

    2016-07-01

    This study examines differences in the types of titles for articles that show high altmetric activity (highly alted articles) versus highly cited articles. This work expands on previous research on document titles in combination with a grounded theory approach to develop a codebook in which articles were manually coded based on 11 characteristics. The results show that there are differences and similarities in titles across many of the examined characteristics; highly cited titles and highly mentioned titles on Wikipedia have some similar characteristics such as they have the the highest percentage of substantive words; in addition, there are no or very few titles referencing outside or with humor/lightness on both platforms. Twitter and Facebook also showed some similarities having the highest percentage of humorous/light titles and lowest percentage of substantive words in their titles. (Author)

  9. Getting to one from title 10 + title 32 unity of effort in the homeland

    OpenAIRE

    Prosch, Caroline Ross.

    2011-01-01

    CHDS State/Local Approved for public release; distribution is unlimited This thesis bridges the knowledge gap between Title 10 Active Duty and Title 32 National Guard in order to breakdown cultural barriers and reach unity of effort for response operations in the homeland. Regrettably, a unified response was missing among Title 10 Active Duty and Title 32 National Guard members following Hurricane Katrina. Since then, initiatives based in doctrine, statutes and formal recommendations...

  10. How property title impacts urban consolidation

    DEFF Research Database (Denmark)

    Easthope, Hazel; Warnken, Jan; Sherry, Cathy

    2014-01-01

    Continuing urbanisation is triggering an increase in multi-titled housing internationally. This trend has given rise to a substantial research interest in the social consequences of higher density living. Little enquiry, however, has been directed to examining how property title subdivisions gene...

  11. 31 CFR 505.01 - Short title.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Short title. 505.01 Section 505.01 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN... CERTAIN MERCHANDISE BETWEEN FOREIGN COUNTRIES § 505.01 Short title. The regulations in this part may be...

  12. 33 CFR 401.1 - Short title.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Short title. 401.1 Section 401.1 Navigation and Navigable Waters SAINT LAWRENCE SEAWAY DEVELOPMENT CORPORATION, DEPARTMENT OF TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations § 401.1 Short title. These regulations may be cited as the...

  13. 18 CFR 415.1 - Short title.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Short title. 415.1 Section 415.1 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Generally § 415.1 Short title. This part shall be known...

  14. 25 CFR 151.13 - Title examination.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Title examination. 151.13 Section 151.13 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER LAND ACQUISITIONS § 151.13 Title examination. If the Secretary determines that he will approve a request for the acquisition of land from...

  15. Student Achievement in Title I Schools

    Science.gov (United States)

    Diaz, Abby T.

    2017-01-01

    This researcher seeks to answer the following question: How did two elementary Title I schools, identified as "high performing" on the first Smarter Balanced assessment, address elements of Maslow's hierarchy of needs when developing school-wide initiatives to enhance student achievement? Many students in Title I schools face barriers to…

  16. Land Titles and Rice Production in Vietnam

    DEFF Research Database (Denmark)

    Van Den Broeck, Katleen; Newman, Carol; Tarp, Finn

    analysis of plot level rice yields that land titles are indeed important. Only exclusively held titles have the expected positive effects, and the positive effect on yields is found in male headed households. Furthermore, a household level rice yield function reveals that exclusive user rights...

  17. 24 CFR 202.11 - Title I.

    Science.gov (United States)

    2010-04-01

    ... in 24 CFR 25.5. Civil money penalties may be imposed against Title I lenders and mortgagees pursuant... unacceptable risk to the Department; or (iv) Transfer of a Title I loan to a party that does not have a valid...

  18. Characterization of resistance mechanisms and genetic relatedness of carbapenem-resistant Acinetobacter baumannii isolated from blood, Italy.

    Science.gov (United States)

    Migliavacca, Roberta; Espinal, Paula; Principe, Luigi; Drago, Monica; Fugazza, Giulia; Roca, Ignasi; Nucleo, Elisabetta; Bracco, Silvia; Vila, Jordi; Pagani, Laura; Luzzaro, Francesco

    2013-02-01

    The aim of this study was to characterize the resistance mechanisms and genetic relatedness of 21 carbapenem-resistant Acinetobacter baumannii blood isolates collected in Italy during a 1-year multicenter prospective surveillance study. Genes coding for carbapenemase production were identified by polymerase chain reaction (PCR) and sequencing. Pulsed-field gel electrophoresis (PFGE), multiplex PCRs for group identification, and multilocus sequence typing (MLST) were used to determine genetic relationships. Carbapenem resistance was consistently related to the production of oxacillinases, mostly the plasmid-mediated OXA-58 enzyme. Strains producing the OXA-23 enzyme (chromosomally mediated) were also detected. Seven PFGE clones were identified, some of which being related to international (ICL- I and ICL-II) or national clonal lineages. Multiplex PCRs identified 4 different groups (group 2 being dominant), further distinguishable in 6 sequence types by MLST. The heterogeneity of profiles highlights the diffusion of international and national clonal lineages in Italy. Continuous surveillance is needed for monitoring the spread of these worrisome strains equipped with multiple drug resistance mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Trapping and Characterization of a Reaction Intermediate in Carbapenem Hydrolysis by B. cereus Metallo-β-lactamase

    Science.gov (United States)

    Tioni, Mariana F.; Llarrull, Leticia I.; Poeylaut-Palena, Andrés A.; Martí, Marcelo A.; Saggu, Miguel; Periyannan, Gopal R.; Mata, Ernesto G.; Bennett, Brian; Murgida, Daniel H.; Vila, Alejandro J.

    2009-01-01

    Metallo-β-lactamases hydrolyze most β-lactam antibiotics. The lack of a successful inhibitor for them is related to the previous failure to characterize a reaction intermediate with a clinically useful substrate. Stopped-flow experiments together with rapid freeze-quench EPR and Raman spectroscopies were used to characterize the reaction of Co(II)-BcII with imipenem. These studies show that Co(II)-BcII is able to hydrolyze imipenem both in the mono- and dinuclear forms. In contrast to the situation met for penicillin, the species that accumulates during turnover is an enzyme-intermediate adduct in which the β-lactam bond has already been cleaved. This intermediate is a metal-bound anionic species, with a novel resonant structure, that is stabilized by the metal ion at the DCH or Zn2 site. This species has been characterized based on its spectroscopic features. This represents a novel, previously unforeseen intermediate, that is related to the chemical nature of carbapenems, as confirmed by the finding of a similar intermediate for meropenem. Since carbapenems are the only substrates cleaved by B1, B2 and B3 lactamases, the identification of this intermediate could be exploited as a first step towards the design of transition state based inhibitors for all three classes of metallo-β-lactamases. PMID:18980308

  20. Novel Aminoglycoside Resistance Transposons and Transposon-Derived Circular Forms Detected in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates

    Science.gov (United States)

    Dwibedi, Chinmay Kumar; Sjöström, Karin; Edquist, Petra; Wai, Sun Nyunt; Uhlin, Bernt Eric

    2016-01-01

    Acinetobacter baumannii has emerged as an important opportunistic pathogen equipped with a growing number of antibiotic resistance genes. Our study investigated the molecular epidemiology and antibiotic resistance features of 28 consecutive carbapenem-resistant clinical isolates of A. baumannii collected throughout Sweden in 2012 and 2013. The isolates mainly belonged to clonal complexes (CCs) with an extensive international distribution, such as CC2 (n = 16) and CC25 (n = 7). Resistance to carbapenems was related to blaOXA-23 (20 isolates), blaOXA-24/40-like (6 isolates), blaOXA-467 (1 isolate), and ISAba1-blaOXA-69 (1 isolate). Ceftazidime resistance was associated with blaPER-7 in the CC25 isolates. Two classical point mutations were responsible for resistance to quinolones in all the isolates. Isolates with high levels of resistance to aminoglycosides carried the 16S rRNA methylase armA gene. The isolates also carried a variety of genes encoding aminoglycoside-modifying enzymes. Several novel structures involved in aminoglycoside resistance were identified, including Tn6279, ΔTn6279, Ab-ST3-aadB, and different assemblies of Tn6020 and TnaphA6. Importantly, a number of circular forms related to the IS26 or ISAba125 composite transposons were detected. The frequent occurrence of these circular forms in the populations of several isolates indicates a potential role of these circular forms in the dissemination of antibiotic resistance genes. PMID:26824943

  1. Treatment Options for Infections Caused by Carbapenem-resistant Enterobacteriaceae: Can We Apply “Precision Medicine” to Antimicrobial Chemotherapy?

    Science.gov (United States)

    Perez, Federico; El Chakhtoura, Nadim G.; Papp-Wallace, Krisztina; Wilson, Brigid M; Bonomo, Robert A.

    2016-01-01

    Introduction For the past three decades, carbapenems played a central role in our antibiotic armamentarium, trusted to effectively treat infections caused by drug-resistant bacteria. The utility of this class of antibiotics has been compromised by the emergence of resistance especially among Enterobacteriaceae. Areas covered We review the current mainstays of pharmacotherapy against infections caused by carbapenem-resistant Enterobacteriaceae (CRE) including tigecycline, aminoglycosides, and rediscovered 'old' antibiotics such as fosfomycin and polymyxins, and discuss their efficacy and potential toxicity. We also summarize the clinical experience treating CRE infections with antibiotic combination therapy. Finally, we review ceftazidime/avibactam and imipenem/relebactam, a new generation of beta-lactamase inhibitors, which may offer alternatives to treat CRE infections. We critically evaluate the published literature, identify relevant clinical trials and review documents submitted to the United States Food and Drug Administration. Expert Opinion It is essential to define the molecular mechanisms of resistance and to apply insights about pharmacodynamic and pharmacokinetic properties of antibiotics, in order to maximize the impact of old and new therapeutic approaches against infections caused by CRE. A concerted effort is needed to carry out high-quality clinical trials that: i) establish the superiority of combination therapy vs. monotherapy; ii) confirm the role of novel beta-lactam/beta-lactamase inhibitor combinations as therapy against KPC- and OXA-48 producing Enterobacteriaceae; and, iii) evaluate new antibiotics active against CRE as they are introduced into the clinic. PMID:26799840

  2. Phenotypic Detection of Metallo-Beta-Lactamases in Carbapenem Resistant Acinetobacter baumannii Isolated from Pediatric Patients in Pakistan

    Directory of Open Access Journals (Sweden)

    Muneeza Anwar

    2016-01-01

    Full Text Available Multidrug resistant A. baumannii has emerged as an important and problematic human pathogen as it is the causative agent of several types of infections especially in neonates and immunocompromised patients because they have least capacity to fight against infections. Carbapenems are used as last resort antibiotics for treating these infections but currently resistance against carbapenems due to MBL production is on the rise. The objective of this study was to determine the frequency of antibiotic resistance in A. baumannii and also to compare the efficacy of combined disk test and double disk synergy test for detection of metallo-beta-lactamases. A total of 112 A. baumannii were identified from various clinical samples and antibiotic susceptibility profile was determined by Kirby-Bauer Disk Diffusion method. Out of 112, 66 (58.9% isolates were resistant to both imipenem and meropenem (OXOID. These resistant isolates were tested for carbapenemase production, and 55 (83.3% were carbapenemase producers by Modified Hodge Test. These isolates were further tested for MBL production by combined disk test and double disk synergy test. Out of 66, 49 isolates were positive by both methods, CDT and DDST, and only one isolate was detected as negative (with kappa value = 0.038. All MBL producing strains showed remarkable resistance to cephalosporins, fluoroquinolones, aminoglycosides, and piperacillin/tazobactam (OXOID. The antibiotic resistance was very high in A. baumannii which were isolated from children in Pakistan specially attending a nephrology unit.

  3. 24 CFR 203.385 - Types of satisfactory title evidence.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Types of satisfactory title... Title Waivers § 203.385 Types of satisfactory title evidence. The following types of title evidence shall be satisfactory to the Commissioner: (a) Fee or owner's title policy. A fee or owner's policy of...

  4. Quarterly title list for the period ending June 1980

    International Nuclear Information System (INIS)

    1980-01-01

    The title list contains: a) 17 titles and abstracts of laboratory reports, b) 36 titles of publications (32 with abstracts), c) 13 titles of articles submitted for publication (12 with abstracts), and d) 72 titles of lectures (52 with abstracts.) (GG) [de

  5. Polyvinylpyrrolidone-Capped Silver Nanoparticle Inhibits Infection of Carbapenem-Resistant Strain of Acinetobacter baumannii in the Human Pulmonary Epithelial Cell

    Directory of Open Access Journals (Sweden)

    Vishvanath Tiwari

    2017-08-01

    Full Text Available Acinetobacter baumannii, an opportunistic ESKAPE pathogen, causes respiratory and urinary tract infections. Its prevalence increases gradually in the clinical setup. Pathogenicity of Acinetobacter is significantly influenced by its ability to infect and survive in human pulmonary cells. Therefore, it is important to study the infection of A. baumannii in human pulmonary host cell (A-549, monitoring surface interacting and internalized bacteria. It was found that during infection of A. baumannii, about 40% bacteria adhered to A-549, whereas 20% got internalized inside pulmonary cell and induces threefold increase in the reactive oxygen species production. We have synthesized polyvinylpyrrolidone (PVP-capped AgNPs using chemical methods and tested its efficacy against carbapenem-resistant strain of A. baumannii. PVP-capped silver nanoparticles (PVP-AgNPs (30 µM have shown antibacterial activity against carbapenem-resistant strain of A. baumannii and this concentration does not have any cytotoxic effect on the human pulmonary cell line (IC50 is 130 µM. Similarly, PVP-AgNPs treatment decreases 80% viability of intracellular bacteria, decreases adherence of A. baumannii to A-549 (40 to 2.2%, and decreases intracellular concentration (20 to 1.3% of A. baumannii. This concludes that PVP-AgNPs can be developed as a substitute for carbapenem to control the infection caused by carbapenem-resistant A. baumannii.

  6. Informing Antibiotic Treatment Decisions: Evaluating Rapid Molecular Diagnostics To Identify Susceptibility and Resistance to Carbapenems against Acinetobacter spp. in PRIMERS III.

    Science.gov (United States)

    Evans, Scott R; Hujer, Andrea M; Jiang, Hongyu; Hill, Carol B; Hujer, Kristine M; Mediavilla, Jose R; Manca, Claudia; Tran, Thuy Tien T; Domitrovic, T Nicholas; Higgins, Paul G; Seifert, Harald; Kreiswirth, Barry N; Patel, Robin; Jacobs, Michael R; Chen, Liang; Sampath, Rangarajan; Hall, Thomas; Marzan, Christine; Fowler, Vance G; Chambers, Henry F; Bonomo, Robert A

    2017-01-01

    The widespread dissemination of carbapenem-resistant Acinetobacter spp. has created significant therapeutic challenges. At present, rapid molecular diagnostics (RMDs) that can identify this phenotype are not commercially available. Two RMD platforms, PCR combined with electrospray ionization mass spectrometry (PCR/ESI-MS) and molecular beacons (MB), for detecting genes conferring resistance/susceptibility to carbapenems in Acinetobacter spp. were evaluated. An archived collection of 200 clinical Acinetobacter sp. isolates was tested. Predictive values for susceptibility and resistance were estimated as a function of susceptibility prevalence and were based on the absence or presence of beta-lactamase (bla) NDM, VIM, IMP, KPC, and OXA carbapenemase genes (e.g., bla OXA-23 , bla OXA-24/40 , and bla OXA-58 found in this study) against the reference standard of MIC determinations. According to the interpretation of MICs, 49% (n = 98) of the isolates were carbapenem resistant (as defined by either resistance or intermediate resistance to imipenem). The susceptibility sensitivities (95% confidence interval [CI]) for imipenem were 82% (74%, 89%) and 92% (85%, 97%) for PCR/ESI-MS and MB, respectively. Resistance sensitivities (95% CI) for imipenem were 95% (88%, 98%) and 88% (80%, 94%) for PCR/ESI-MS and MB, respectively. PRIMERS III establishes that RMDs can discriminate between carbapenem resistance and susceptibility in Acinetobacter spp. In the context of a known prevalence of resistance, SPVs and RPVs can inform clinicians regarding the best choice for empiric antimicrobial therapy against this multidrug-resistant pathogen. Copyright © 2016 American Society for Microbiology.

  7. The Carbapenem Inactivation Method (CIM), a Simple and Low-Cost Alternative for the Carba NP Test to Assess Phenotypic Carbapenemase Activity in Gram-Negative Rods

    NARCIS (Netherlands)

    Zwaluw, K. van der; Haan, A. de; Pluister, G.N.; Bootsma, H.J.; Neeling, A.J. de; Schouls, L.M.

    2015-01-01

    A new phenotypic test, called the Carbapenem Inactivation Method (CIM), was developed to detect carbapenemase activity in Gram-negative rods within eight hours. This method showed high concordance with results obtained by PCR to detect genes coding for the carbapenemases KPC, NDM, OXA-48, VIM, IMP

  8. Emergence of carbapenem-resistant Acinetobacter baumannii ST787 in clinical isolates from blood in a tertiary teaching hospital in Northern Taiwan

    Directory of Open Access Journals (Sweden)

    Yi-Fan Hu

    2017-10-01

    Conclusion: To the best of our knowledge, this study is the first to describe the microbiological characteristics of CRAB ST787, which carried high genetic resistance to carbapenem, but remained susceptible to colistin. CRAB ST787 was the predominant clone in our hospital in the study period.

  9. Carbapenem-Resistant E. cloacae in Southwest China: Molecular Analysis of Resistance and Risk Factors for Infections Caused by NDM-1-Producers

    Directory of Open Access Journals (Sweden)

    Xiaojiong Jia

    2018-04-01

    Full Text Available Carbapenem-resistant Enterobacteriaceae (CRE has been considered a serious global threat, but carbapenem resistance remains relatively uncommon in E. cloacae, especially in China. The aim of this study was to characterize carbapenem-resistant E. cloacae (CR-ECL isolates from 2012 to 2016 in Southwest China. Our study revealed that 20 (15.2% of the 132 CR-ECL isolates obtained from patients were identified as NDM-1, with most isolates carrying the IncFIIA plasmids. Notably, we initially observed that the E. cloacae strain co-harbored NDM-1 and IMP-8 carbapenemases simultaneously. Analysis of the genetic environment of these two genes has revealed that the highly conserved regions (blaNDM-1-bleMBL-trpF-tat are associated with the dissemination of NDM-1, while IS26, intI1, and tniC could be involved in the spread of IMP-8. Molecular epidemiology studies showed the nosocomial outbreak caused by NDM-1-producing E. cloacae ST88. Transferring from another hospital and previous carbapenem exposure were identified as independent risk factors for the acquisition of NDM-1-producing E. cloacae. These findings emphasize the need for intensive surveillance and precautions to monitor the further spread of NDM-1 in China.

  10. Endemic carbapenem-nonsusceptible Acinetobacter baumannii-calcoaceticus complex in intensive care units of the national referral hospital in Jakarta, Indonesia

    NARCIS (Netherlands)

    Saharman, Y.R. (Yulia Rosa); Karuniawati, A. (Anis); Sedono, R. (Rudyanto); Aditianingsih, D. (Dita); Sudarmono, P. (Pratiwi); W.H.F. Goessens (Wil); Klaassen, C.H.W. (Corné H.W.); H.A. Verbrugh (Henri); J.A. Severin (Juliëtte)

    2018-01-01

    textabstractBackground: Carbapenem-nonsusceptible A. baumannii-calcoaceticus complex have emerged worldwide, but the epidemiology in Indonesian hospitals has not been studied. Methods: A prospective observational study was performed on the intensive care units (ICUs) of the national referral

  11. Colistin- and Carbapenem-Resistant Escherichia coli Harboring mcr-1 and blaNDM-5, Causing a Complicated Urinary Tract Infection in a Patient from the United States

    Directory of Open Access Journals (Sweden)

    José R. Mediavilla

    2016-08-01

    Full Text Available Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene blaNDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1- and blaNDM-5-harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized.

  12. SURVEILLANCE of CARBAPENEM NON-SUSCEPTIBLE GRAM NEGATIVE STRAINS and CHARACTERIZATION of CARBAPENEMASES of CLASSES A, B and D in a LEBANESE HOSPITAL.

    Science.gov (United States)

    Hammoudi, Dalal; Moubareck, Carole Ayoub; Kanso, Abeer; Nordmann, Patrice; Sarkis, Dolla Karam

    2015-01-01

    The production of carbapenem-hydrolyzing enzymes has been recognized as one of the most currently relevant resistance mechanisms in gram negative bacterial isolates, and is being detected in various countries. In Lebanon, carbapenem resistance was studied among gram negative pathogens collected from a university hospital from January to June of years 2011 and 2012. All isolates were subjected to phenotypic tests including antibiotic susceptibility, cloxacillin effect, modified Hodge test, and Etest for metallo-β-lactamase detection. They were also subjected to genotyping by PCR sequencing to characterize β-lactamases. Between January and June 2011, 48 carbapenem non-susceptible strains were collected. Of these, one Klebsiella pneumoniae harbored OXA-48 and insertion sequence IS 1999; four Acinetobacter baumanni harbored simultaneously OXA-23 and GES-11, and three Pseudomonas harbored VIM-2 carbapenemase. Between January and June 2012, 100 carbapenem non-susceptible strains were collected. Of these, one K. pneumoniae harbored simultaneously OXA-48, IS 1999, and an acquired AmpC of the ACC group; four Serratia marcescens harbored OXA-48, while among eight A. baumannii, one strain co-harbored OXA-23 and GES-11, six harbored OXA-23 and one OXA-24. Fifteen P, aeruginosa and two Pseudomonas species harbored VIM-2; two P. aeruginosa strains produced IMP-1 and two others IMP-2. This epidemiological survey demonstrates the presence of carbapenemases of Ambler classes A, B, and D in a Lebanese hospital and indicates increase in the number and variety of such enzymes.

  13. The emergence of carbapenem-resistant Klebsiella pneumoniae isolates producing OXA-48 and NDM in the Southern (Asir) province, Saudi Arabia.

    Science.gov (United States)

    Al-Zahrani, Ibrahim A; Alsiri, Bander A

    2018-01-01

    To identify the prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) and the most common types of cabapenemases among CRKP in the Southern (Asir) province hospitals, Saudi Arabia. Methods: The cross-sectional study was conducted between late April and September in 2015. A total of 54 Klebsiella pneumoniae (K. pneumoniae) isolates with reduced sensitivity to carbapenems were obtained from various clinical specimens of the 2 largest hospitals in the Southern province. Minimum inhibitory concentrations (MICs) of carbapenems were confirmed using E-test. Molecular detection of the most common carbapenemase genes (blaIMP, bla-carbapenem-hydrolyzing oxacillinase [OXA-48], blaVIM, bla-New Delhi metallo-ß-lactamas [NDM], and blaKPC) was performed using multiplex-polymerase chain reaction. Results: The current study found that increasing age and intensive care unit admission were associated with CRKP isolation. The major type of carbapenemases was OXA-48 with 81.5% (n=44) and it seems to reach an endemic level. New Delhi metallo-ß-lactamas (NDM) was the second most frequent carbapenemase by 7.4% (n=4) of isolates while Verona integron-encoded metallo-ß-lactamase (VIM) was reported only in one isolate. Conclusion: Saudi Arabia receives large numbers of visitors and migrant workers from OXA-48 and NDM endemic countries such as Turkey, India, and Pakistan every year.

  14. The emergence of carbapenem-resistant Klebsiella pneumoniae isolates producing OXA-48 and NDM in the Southern (Asir province, Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Ibrahim A. Al-Zahrani

    2018-01-01

    Full Text Available Objectives: To identify the prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP and the most common types of cabapenemases among CRKP in the Southern (Asir province hospitals, Saudi Arabia. Methods: The cross-sectional study was conducted between late April and September in 2015. A total of 54 Klebsiella pneumoniae (K. pneumoniae isolates with reduced sensitivity to carbapenems were obtained from various clinical specimens of the 2 largest hospitals in the Southern province. Minimum inhibitory concentrations (MICs of carbapenems were confirmed using E-test. Molecular detection of the most common carbapenemase genes (blaIMP, bla-carbapenem-hydrolyzing oxacillinase [OXA-48], blaVIM, bla-New Delhi metallo-ß-lactamas [NDM], and blaKPC was performed using multiplex-polymerase chain reaction. Results: The current study found that increasing age and intensive care unit admission were associated with CRKP isolation. The major type of carbapenemases was OXA-48 with 81.5% (n=44 and it seems to reach an endemic level. New Delhi metallo-ß-lactamas (NDM was the second most frequent carbapenemase by 7.4% (n=4 of isolates while Verona integron-encoded metallo-ß-lactamase (VIM was reported only in one isolate. Conclusion: Saudi Arabia receives large numbers of visitors and migrant workers from OXA-48 and NDM endemic countries such as Turkey, India, and Pakistan every year.

  15. Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study.

    Science.gov (United States)

    Cheng, Aristine; Chuang, Yu-Chung; Sun, Hsin-Yun; Sheng, Wang-Huei; Yang, Chia-Jui; Liao, Chun-Hsing; Hsueh, Po-Ren; Yang, Jia-Ling; Shen, Ni-Jiin; Wang, Jann-Tay; Hung, Chien-Ching; Chen, Yee-Chun; Chang, Shan-Chwen

    2015-06-01

    Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations. Prospective, observational, multicenter study. Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia. Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p=0.105) and 69% versus 50% (p=0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p=0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline

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

    Science.gov (United States)

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

    2015-01-01

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

  17. INIS: Authority list for journal titles

    International Nuclear Information System (INIS)

    2005-01-01

    This is the 31st revision of the INIS: Authority List for Journal Titles (IAEA-INIS-11). This list is published annually and includes the titles of all journals which have contained articles submitted to INIS at the time of publication. The current list contains 13,104 journal titles, 2,078 regularly scanned journals and 561 key journals. It was last updated in February 2005. The purpose of this report is to provide descriptive cataloguers with a standard entry for the full title of a journal. In addition to the full journal title, the ISSN (International Standard Serial Number), administered by the ISSN International Centre, Paris, France, and/or CODEN, assigned by Chemical Abstracts Service, USA, are given in this manual. In order to help the user find titles easily, the list is arranged in six parts, followed by summary statistics: In Part I, all key journals are grouped under the name of the country or international organization responsible for their input in INIS, then sorted alphabetically under their title. In Part II, all key journals are sorted alphabetically under their title. The name of the country or international organization responsible for their input in INIS is entered in parentheses within the body of the entry. In Part III, all journals that are regularly scanned by INIS Centers are grouped under the name of the country or international organization responsible for their input in INIS, then sorted alphabetically under their title. In Part IV, all journals that are regularly scanned by INIS Centers are sorted alphabetically under their title. The name of the country or international organization responsible for their input in INIS is entered in parentheses within the body of the entry. In Part V, all journals are grouped under the name of the country or international organization responsible for their input in INIS, then sorted alphabetically under their title. In Part VI, all journals are sorted alphabetically under their title. The name of the

  18. INIS: Authority list for journal titles

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-03-01

    This is the 31st revision of the INIS: Authority List for Journal Titles (IAEA-INIS-11). This list is published annually and includes the titles of all journals which have contained articles submitted to INIS at the time of publication. The current list contains 13,104 journal titles, 2,078 regularly scanned journals and 561 key journals. It was last updated in February 2005. The purpose of this report is to provide descriptive cataloguers with a standard entry for the full title of a journal. In addition to the full journal title, the ISSN (International Standard Serial Number), administered by the ISSN International Centre, Paris, France, and/or CODEN, assigned by Chemical Abstracts Service, USA, are given in this manual. In order to help the user find titles easily, the list is arranged in six parts, followed by summary statistics: In Part I, all key journals are grouped under the name of the country or international organization responsible for their input in INIS, then sorted alphabetically under their title. In Part II, all key journals are sorted alphabetically under their title. The name of the country or international organization responsible for their input in INIS is entered in parentheses within the body of the entry. In Part III, all journals that are regularly scanned by INIS Centers are grouped under the name of the country or international organization responsible for their input in INIS, then sorted alphabetically under their title. In Part IV, all journals that are regularly scanned by INIS Centers are sorted alphabetically under their title. The name of the country or international organization responsible for their input in INIS is entered in parentheses within the body of the entry. In Part V, all journals are grouped under the name of the country or international organization responsible for their input in INIS, then sorted alphabetically under their title. In Part VI, all journals are sorted alphabetically under their title. The name of the

  19. INIS: Authority list for journal titles

    International Nuclear Information System (INIS)

    2006-01-01

    This is the 32nd revision of the INIS: Authority List for Journal Titles (IAEA-INIS-11). This list is published annually and includes the titles of all journals which have contained articles submitted to INIS at the time of publication. The current list contains 13,231 journal titles, 2,125 regularly scanned journals and 555 key journals. It was last updated in February 2006. The purpose of this report is to provide descriptive cataloguers with a standard entry for the full title of a journal. In addition to the full journal title, the ISSN (International Standard Serial Number), administered by the ISSN International Centre, Paris, France, and/or CODEN, assigned by Chemical Abstracts Service, USA, are given in this manual. In order to help the user find titles easily, the list is arranged in six parts, followed by summary statistics: In Part I, all key journals are grouped under the name of the country or international organization responsible for their input in INIS, then sorted alphabetically under their title. In Part II, all key journals are sorted alphabetically under their title. The name of the country or international organization responsible for their input in INIS is entered in parentheses within the body of the entry. In Part III, all journals that are regularly scanned by INIS Centres are grouped under the name of the country or international organization responsible for their input in INIS, then sorted alphabetically under their title. In Part IV, all journals that are regularly scanned by INIS Centres are sorted alphabetically under their title. The name of the country or international organization responsible for their input in INIS is entered in parentheses within the body of the entry. In Part V, all journals are grouped under the name of the country or international organization responsible for their input in INIS, then sorted alphabetically under their title. In Part VI, all journals are sorted alphabetically under their title. The name of the

  20. 20 CFR 404.535 - How much will we withhold from your title VIII and title XVI benefits to recover a title II...

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false How much will we withhold from your title... Officer § 404.535 How much will we withhold from your title VIII and title XVI benefits to recover a title II overpayment? (a) If past-due benefits are payable to you, we will withhold the lesser of the...

  1. High mortality of bloodstream infection outbreak caused by carbapenem-resistant P. aeruginosa producing SPM-1 in a bone marrow transplant unit.

    Science.gov (United States)

    Chaves, Lucas; Tomich, Lísia Moura; Salomão, Matias; Leite, Gleice Cristina; Ramos, Jessica; Martins, Roberta Ruedas; Rizek, Camila; Neves, Patricia; Batista, Marjorie Vieira; Amigo, Ulysses; Guimaraes, Thais; Levin, Anna Sara; Costa, Silvia Figueiredo

    2017-12-01

    Carbapenem resistance in P. aeruginosa is increasing worldwide. In Brazil, SPM-1 is the main P. aeruginosa carbapenemase identified. Little is known about the virulence factor in SPM-1 clones.Methodolgy. We describe a carbapenem-resistant P. aeruginosa bloodstream infection (CRPa-BSI) outbreak in a bone marrow transplant Unit (BMT). Twenty-nine CRPa-BSI cases were compared to 58 controls. Microbiological characteristics of isolates, such as sensitivity, carbapenemase gene PCR for P. aeruginosa, and PFGE are described, as well as the whole-genome sequence (WGS) of three strains.Results/Key findings. The cultures from environmental and healthcare workers were negative. Some isolates harboured KPC and SPM. The WGS showed that the 03 strains belonged to ST277, presented the same mutations in outer membrane protein, efflux pump, and virulence genes such as those involved in adhesion, biofilm, quorum-sensing and the type III secretion system, but differ regarding the carbapenemase profile. A predominant clone-producing SPM harbouring Tn 4371 was identified and showed cross-transmission; no common source was found. Overall mortality rate among cases was 79 %. The first multivariate analysis model showed that neutropenia (P=0.018), GVHD prophylaxis (P=0.016) and prior use of carbapenems (P=0.0089) were associated with CRPa-BSI. However, when MASCC>21 points and platelets were added in the final multivariate analysis, only prior use of carbapenems remained as an independent risk factor for CRPa-BSI (P=0.043). The predominant clone belonging to ST277 showed high mortality. Carbapenem use was the only risk factor associated with CRPa-BSI. This finding is a wake-up call for the need to improve management in BMT units.

  2. Antibacterial activity of epigallocatechin-3-gallate (EGCG) and its synergism with β-lactam antibiotics sensitizing carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

    Science.gov (United States)

    Lee, Spencer; Razqan, Ghaida Saleh Al; Kwon, Dong H

    2017-01-15

    Infections caused by Acinetobacter baumannii were responsive to conventional antibiotic therapy. However, recently, carbapenem-associated multidrug resistant isolates have been reported worldwide and present a major therapeutic challenge. Epigallocatechin-3-Gallate (EGCG) extracted from green tea exhibits antibacterial activity. We evaluated the antibacterial activity of EGCG and possible synergism with antibiotics in carbapenem-associated multidrug resistant A. baumannii. A potential mechanism for synergism was also explored. Seventy clinical isolates of A. baumannii collected from geographically different areas were analyzed by minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of EGCG. Checkerboard and time-killing assays were performed to exam the synergism between EGCG and antibiotics. The effects of EGCG on a multidrug efflux pump inhibitor (1-[1-naphthylmethyl] piperazine; NMP) and β-lactamase production were also examined in A. baumannii. Sixty-three of 70 clinical isolates of A. baumannii carried carbapenemase-encoding genes with carbapenem-associated multidrug resistance. Levels of MIC and MBC of EGCG ranged from 64 to 512µg/ml and from 128 to ≥1024µg/ml, respectively among the clinical isolates. MIC 90 and MBC 86 levels were 256µg/ml and 512µg/ml of EGCG, respectively. Subinhibitory concentration of EGCG in combination with all antibiotics tested, including carbapenem, sensitized (MICs fall≤1.0µg/ml) all carbapenem-associated multidrug resistant isolates. Checkerboard and time-killing assays showed synergism between EGCG and meropenem (or carbenicillin) counted as fractional inhibitory concentration of 2log10 within 12h, respectively. EGCG significantly increased the effect of NMP but was unrelated to β-lactamase production in A. baumannii, suggesting EGCG may be associated with inhibition of efflux pumps. Overall we suggest that EGCG-antibiotic combinations might provide an alternative approach to treat

  3. Carbapenems and SHV-1 β-Lactamase Form Different Acyl-Enzyme Populations in Crystals and Solution

    Science.gov (United States)

    Kalp, Matthew; Carey, Paul R.

    2009-01-01

    The reactions between single crystals of the SHV-1 β-lactamase enzyme and the carbapenems, meropenem, imipenem and ertapenem, have been studied by Raman microscopy. Aided by quantum mechanical calculations, major populations of two acyl-enzyme species, a labile Δ2-pyrroline and a more tightly bound Δ1-pyrroline, have been identified for all three compounds. These isomers differ only in the position of the double bond about the carbapenem nucleus. This discovery is consonant with X-ray crystallographic findings that also identified two populations for meropenem bound in SHV-1: one with the acyl C=O group in the oxyanion hole and the second with the acyl group rotated 180 degrees compared to its expected position [Nukaga, M., Bethel, C. R., Thomson, J. M., Hujer, A. M., Distler, A. M., Anderson, V. E., Knox, J. R., and Bonomo, R. A. (2008) Journal of the American Chemical Society]. When crystals of the Δ1 and Δ2 containing acyl-enzymes were exposed to solutions with no carbapenem, rapid deacylation of the Δ2 species was observed by kinetic Raman experiments. However, no change in the Δ1 population was observed over 1 hour, the effective lifetime of the crystal. These observations lead to the hypothesis that the stable Δ1 species is due to the form seen by X-ray with the acyl carbonyl outside the oxyanion hole, while the Δ2 species corresponds to the form with the carbonyl inside the oxyanion hole. Soak-in and soak-out Raman experiments also demonstrated that tautomeric exchange between the Δ1 and Δ2 forms does not occur on the crystalline enzyme. When meropenem or ertapenem were reacted with SHV-1 in solution, the Raman difference spectra demonstrated that only a major population corresponding to the Δ1 acyl-enzyme could be detected. The 1003 cm-1 mode of the phenyl ring positioned on the C3 side chain of ertapenem acts as an effective internal Raman intensity standard and the ratio of its intensity to that of the 1600 cm-1 feature of Δ1 provides an

  4. 12 CFR 5.42 - Corporate title.

    Science.gov (United States)

    2010-01-01

    ... 18 U.S.C. 709, regarding false advertising and the misuse of names to indicate a Federal agency, and... the appropriate district office if it changes its corporate title. The notice must contain the old and...

  5. Code of Federal Regulations Title 21

    Data.gov (United States)

    U.S. Department of Health & Human Services — This database contains the most recent revision from the Government Printing Office (GPO) of the Code of Federal Regulations (CFR) Title 21 - Food and Drugs.

  6. The Need for Conciliation under Title VII

    Science.gov (United States)

    Pollard, William E.

    1975-01-01

    The AFL-CIO is committed to the task of eliminating discrimination and injustice in the workplace and is making efforts to expand the Equal Employment Opportunity Commission's conciliation efforts under Title Seven. (MW)

  7. Service Locator - Family Planning Title X

    Data.gov (United States)

    U.S. Department of Health & Human Services — This locator tool will help you find Title X family planning centers that provide high quality and cost-effective family planning and related preventive health...

  8. Carbapenem susceptibilities and non-susceptibility concordance to different carbapenems amongst clinically important Gram-negative bacteria isolated from intensive care units in Taiwan: results from the Surveillance of Multicentre Antimicrobial Resistance in Taiwan (SMART) in 2009.

    Science.gov (United States)

    Jean, Shio-Shin; Hsueh, Po-Ren; Lee, Wen-Sen; Yu, Kwok-Woon; Liao, Chun-Hsing; Chang, Feng-Yi; Ko, Wen-Chien; Wu, Jiunn-Jong; Chen, Yen-Hsu; Chen, Yao-Shen; Liu, Jien-Wei; Lu, Min-Chi; Liu, Cheng-Yi; Lam, Carlos; Chen, Ray-Jade

    2013-05-01

    To investigate the in vitro susceptibilities to various carbapenems amongst clinical Gram-negative bacteria isolated from patients in intensive care units of ten major teaching hospitals in Taiwan in 2009, a survey was conducted to determine the minimum inhibitory concentrations (MICs) of ertapenem, imipenem, meropenem and doripenem against isolates of Enterobacteriaceae (n = 594), Pseudomonas aeruginosa (n = 185), Acinetobacter baumannii (n = 192) and Burkholderia cepacia (n = 23) using the agar dilution method. Susceptibilities were determined according to 2009, 2011 and 2012 MIC breakpoints recommended by the CLSI as well as 2012 MIC breakpoints recommended by EUCAST. Based on CLSI 2012 criteria, the ertapenem susceptible rate was 93%, 81%, 68% and 92% for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Serratia marcescens, respectively. All Proteus mirabilis and Morganella morganii isolates were susceptible to ertapenem; however, 64% of P. mirabilis and all M. morganii isolates were non-susceptible to imipenem. Meropenem and doripenem had better activities than imipenem against ertapenem-non-susceptible Enterobacteriaceae isolates. E. coli, K. pneumoniae and E. cloacae with ertapenem MICs≥4 mg/L were synchronously not susceptible to imipenem, meropenem and doripenem. Imipenem susceptibility was 65% and 29% for P. aeruginosa and A. baumannii, respectively. Additionally, P. aeruginosa and A. baumannii isolates with imipenem MICs≥8 mg/L were also not susceptible to meropenem and doripenem. These data provide a better understanding of choosing appropriate carbapenem agents to treat infections caused by ertapenem-non-susceptible Enterobacteriaceae as well as P. aeruginosa and A. baumannii isolates with imipenem MICs≥4 mg/L. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  9. Outbreak of carbapenem-resistant Klebsiella pneumoniae: two-year epidemiologic follow-up in a tertiary hospital

    Directory of Open Access Journals (Sweden)

    Graziella Hanna Pereira

    2013-02-01

    Full Text Available This study describes a carbapenem-resistant Klebsiella pneumoniae (CRKP outbreak that occurred from October 2008-December 2010. Polymerase chain reaction assays were performed to detect the blaKPC gene and molecular typing was performed using pulsed-field gel electrophoresis (PFGE. There were 33 CRKP infections; PFGE revealed five genotypes: genotype A in five (15%, B in 18 (55%, C in eight (24% and two unique profiles. Genotype B was disseminated in all hospital units and belonged to the same clone identified in 11 different hospitals in the state of São Paulo. Sixteen (48% patients died. Seven isolates (21% were resistant to polymyxin B and 45% were resistant to tigecycline and amikacin.

  10. Outbreak of carbapenem-resistant Acinetobacter baumannii in the intensive care unit: a multi-level strategic management approach.

    Science.gov (United States)

    Molter, G; Seifert, H; Mandraka, F; Kasper, G; Weidmann, B; Hornei, B; Öhler, M; Schwimmbeck, P; Kröschel, P; Higgins, P G; Reuter, S

    2016-02-01

    An outbreak of carbapenem-resistant Acinetobacter baumannii (CRAb) occurred in an interdisciplinary intensive care unit, affecting 10 patients. Within hours of recognition of the spread of CRAb an intervention team was instituted for collection of available data, decision-making, communication and monitoring of all interventions performed, including cohorting, temporary stop of admissions, staff education, and enforcement of infection control measures. An area was defined for cohortation of patients colonized with CRAb, with a separate nursing team and a second set of mobile equipment. New transmissions were no longer observed after only four days into the institution of enhanced infection control measures. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  11. INIS: Authority list for journal titles

    International Nuclear Information System (INIS)

    2008-01-01

    This is the 34th revision of the INIS: Authority List for Journal Titles (IAEA-INIS-11). This list is published annually and includes the titles of all journals which have contained articles submitted to INIS at the time of publication. The current list contains 13 538 journal titles, 2 106 regularly scanned journals and 613 key journals. It was last updated in February 2008. A journal - or periodical - is a continuing publication issued in a succession of discrete parts, usually bearing numbering and/or chronological designations and intended to be continued indefinitely. It is generally published within a defined, fixed interval between issues and normally appears more than once per year. It includes a mixture of articles, letters, summaries, etc. Within this definition, annuals such as the Annual Review of Nuclear Science are included, but series titles such as the McGraw-Hill Series in Nuclear Engineering are not. The purpose of this document is to provide descriptive cataloguers with standard elements to include in bibliographic level 'S' of the INIS record. These elements include field (tag) 229 (Full Journal Title), 320 (ISSN) and 321 (CODEN). The full journal title is mandatory, and either the ISSN or the CODEN must be included (both may appear). Instructions on how to use this and other elements of the INIS record format are found in INIS: Guide to Bibliographic Description (IAEA-INIS-1). In order to help the user find titles easily, the list is arranged in six parts, followed by summary statistics: - In Part I, all key journals are grouped under the name of the country or international organization responsible for their input in INIS, then sorted alphabetically under their title. - In Part II, all key journals are sorted alphabetically under their title. The name of the country or international organization responsible for their input in INIS is entered in parentheses within the body of the entry. - In Part III, all journals that are regularly scanned by

  12. INIS: Authority list for journal titles

    International Nuclear Information System (INIS)

    2009-01-01

    This is the 35th revision of the INIS: Authority List for Journal Titles (IAEA-INIS-11). This list is published annually and includes the titles of all journals which have contained articles submitted to INIS at the time of publication. The current list contains 13 750 journal titles, 1 965 regularly scanned journals and 593 key journals. It was last updated in March 2009. A journal - or periodical - is a continuing publication issued in a succession of discrete parts, usually bearing numbering and/or chronological designations and intended to be continued indefinitely. It is generally published within a defined, fixed interval between issues and normally appears more than once per year. It includes a mixture of articles, letters, summaries, etc. Within this definition, annuals such as the Annual Review of Nuclear Science are included, but series titles such as the McGraw-Hill Series in Nuclear Engineering are not. The purpose of this document is to provide descriptive cataloguers with standard elements to include in bibliographic level 'S' of the INIS record. These elements include field (tag) 229 (Full Journal Title), 320 (ISSN) and 321 (CODEN). The full journal title is mandatory, and either the ISSN or the CODEN must be included (both may appear). Instructions on how to use this and other elements of the INIS record format are found in INIS: Guide to Bibliographic Description (IAEA-INIS-1). In order to help the user find titles easily, the list is arranged in six parts, followed by summary statistics: - In Part I, all key journals are grouped under the name of the country or international organization responsible for their input in INIS, then sorted alphabetically under their title. - In Part II, all key journals are sorted alphabetically under their title. The name of the country or international organization responsible for their input in INIS is entered in parentheses within the body of the entry. - In Part III, all journals that are regularly scanned by the

  13. INIS: Authority list for journal titles

    International Nuclear Information System (INIS)

    2007-01-01

    This is the 33rd revision of the INIS: Authority List for Journal Titles (IAEA-INIS-11). This list is published annually and includes the titles of all journals which have contained articles submitted to INIS at the time of publication. The current list contains 13 396 journal titles, 2 170 regularly scanned journals and 578 key journals. It was last updated in February 2007. A journal - or periodical - is a continuing publication issued in a succession of discrete parts, usually bearing numbering and/or chronological designations and intended to be continued indefinitely. It is generally published within a defined, fixed interval between issues and normally appears more than once per year. It includes a mixture of articles, letters, summaries, etc. Within this definition, annuals such as the Annual Review of Nuclear Science are included, but series titles such as the McGraw-Hill Series in Nuclear Engineering are not. The purpose of this document is to provide descriptive cataloguers with standard elements to include in bibliographic level 'S' of the INIS record. These elements include field (tag) 229 (Full Journal Title), 320 (ISSN) and 321 (CODEN). The full journal title is mandatory, and either the ISSN or the CODEN must be included (both may appear). Instructions on how to use this and other elements of the INIS record format are found in INIS: Guide to Bibliographic Description (IAEA-INIS-1). In order to help the user find titles easily, the list is arranged in six parts, followed by summary statistics: - In Part I, all key journals are grouped under the name of the country or international organization responsible for their input in INIS, then sorted alphabetically under their title. - In Part II, all key journals are sorted alphabetically under their title. The name of the country or international organization responsible for their input in INIS is entered in parentheses within the body of the entry. - In Part III, all journals that are regularly scanned by

  14. High prevalence of the PER-1 gene among carbapenem-resistant Acinetobacter baumannii in Riyadh, Saudi Arabia.

    Science.gov (United States)

    Aly, M M; Abu Alsoud, N M; Elrobh, M S; Al Johani, S M; Balkhy, H H

    2016-11-01

    The prevalence of carbapenem-resistant Acinetobacter baumannii in Saudi Arabia and their resistance genetic mechanisms are yet to be identified. We studied the prevalence and genetic diversity of extended-spectrum beta-lactamase genes, particularly the PER-1 gene, among carbapenem-resistant A. baumannii strains from patients at a tertiary care hospital in Riyadh, Saudi Arabia between 2006 and 2014. Fresh subcultured samples were tested for antimicrobial susceptibility minimum inhibitory concentration (MIC). Total genomic DNA was extracted from each isolate and further used for polymerase chain reaction (PCR) genotyping, sequence-based typing (SBT) of PER-1 and OXA-51-like gene, and multilocus sequence typing (MLST) of positive isolates. Randomly selected clinical isolates (n = 100) were subjected to MLST. A total of 503 isolates were characterized as multidrug-resistant (MDR) using the MIC. Isolates were further PCR tested for bla -TEM and bla -PER-1 resistance genes (n = 503). The genotyping results showed that 68/503 (14 %) isolates were positive to bla TEM. The genotyping results of PER-1-like genes showed that 384/503 (76.3 %) were positive among MDR Acinetobacter isolates. Based on SBT, the majority of these isolates were clustered into three main groups including isolates harboring PER-1: AB11 (bla -PER-1 ), isolate AB16 (bla -PER-1 ), and, finally, the plasmid pAB154 (bla -PER-7 ). Remarkably, many isolates were concealing the PER-1 gene and harboring the TEM resistance genes as well. MLST results for selected isolates (n = 100) identified four main sequence types (STs: 2, 19, 20, and 25) and four novel isolates (ST 486-489). We report 76.3 % prevalence of the PER-1 resistance gene among Acinetobacter clinical isolates from Riyadh, Saudi Arabia. Further work is needed to explore the clinical risks and patient outcome with such resistance related to healthcare-associated infections and investigate the genetic and molecular mechanisms that confer the MDR

  15. Carbapenem-resistant Enterobacteriaceae colonization and infection in critically ill patients: a retrospective matched cohort comparison with non-carriers.

    Science.gov (United States)

    Dickstein, Y; Edelman, R; Dror, T; Hussein, K; Bar-Lavie, Y; Paul, M

    2016-09-01

    To examine whether carbapenem-resistant Enterobacteriaceae (CRE) carriage is associated with incidence of clinical infection as a means of assessing whether the morbidity and mortality associated with these bacteria are mediated by underlying conditions or intrinsic properties of CRE. This retrospective matched cohort study compared the incidence of invasive infections in CRE-colonized patients and matched non-carriers in the intensive care unit (ICU). The primary outcome was infection caused by CRE of the same species as the colonizing strain among CRE carriers, and infections caused by carbapenem-sensitive strains of the same organism in non-carriers. Hospital discharge and death were considered as competing events. Competing-risks hazard analysis was performed for the entire cohort and for a nested cohort matched by Acute Physiology and Chronic Health Evaluation (APACHE) II scores, stratified by matching. In total, 146 CRE carriers were compared with 292 non-carriers. Patients were well matched for most risk factors for Enterobacteriaceae infection, including age, renal failure, previous invasive infection, previous hospitalization, APACHE II score, length of mechanical ventilation, length of hospitalization and CRE carriage. On regression analysis, colonization with CRE was independently associated with Enterobacteriaceae infection {cause-specific hazard ratio (CSHR) 2.06 [95% confidence interval (CI) 1.03-4.09]}. On regression analysis of the APACHE-II-matched cohort (N=284), colonization with CRE remained significantly associated with Enterobacteriaceae infection [CSHR 3.32 (95% CI 1.31-8.43)]. Colonization with CRE was associated with at least a two-fold increased risk of infection by the colonizing strain amongst ICU patients. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  16. Ventilator-associated pneumonia caused by carbapenem-resistant Enterobacteriaceae carrying multiple metallo-beta-lactamase genes

    Directory of Open Access Journals (Sweden)

    Dwivedi Mayank

    2009-07-01

    Full Text Available Context: Ventilator-associated pneumonia (VAP is a leading nosocomial infection in the intensive care unit (ICU. Members of Enterobacteriaceae are the most common causative agents and carbapenems are the most commonly used antibiotics. Metallo-beta-lactamase (MBL production leading to treatment failure may go unnoticed by routine disc diffusion susceptibility testing. Moreover, there is not much information on association of MBL-producing Enterobacteriaceae with ICU-acquired VAP. Therefore, a study was undertaken to find out the association of MBL-producing Enterobacteriaceae with VAP. Settings: This study was conducted in a large tertiary care hospital of North India with an eight-bed critical care unit. Materials and Methods: The respiratory samples (bronchoalveolar lavage, protected brush catheter specimens and endotracheal or transtracheal aspirates obtained from VAP patients (during January 2005-December 2006 were processed, isolated bacteria identified and their antibiotic susceptibilities tested as per standard protocols. The isolates of Enterobacteriaceae resistant to carbapenem were subjected to phenotypic and genotypic tests for the detection of MBLs. Results: Twelve of 64 isolates of Enterobacteriaceae were detected as MBL producers, bla IMP being the most prevalent gene. Additionally, in three strains, simultaneous coexistence of multiple MBL genes was detected. Conclusion: The coexistence of multiple MBL genes in Enterobacteriaceae is an alarming situation. As MBL genes are associated with integrons that can be embedded in transposons, which in turn can be accommodated on plasmids thereby resulting in a highly mobile genetic apparatus, the further spread of these genes in different pathogens is likely to occur.

  17. Screening for synergistic activity of antimicrobial combinations against carbapenem-resistant Enterobacteriaceae using inkjet printer-based technology.

    Science.gov (United States)

    Brennan-Krohn, Thea; Truelson, Katherine A; Smith, Kenneth P; Kirby, James E

    2017-10-01

    Synergistic combination antimicrobial therapy may provide new options for treatment of MDR infections. However, comprehensive in vitro synergy data are limited and facile methods to perform synergy testing in a clinically actionable time frame are unavailable. To systematically investigate a broad range of antibiotic combinations for evidence of synergistic activity against a collection of carbapenem-resistant Enterobacteriaceae (CRE) isolates. We made use of an automated method for chequerboard array synergy testing based on inkjet printer technology in the HP D300 digital dispenser to test 56 pairwise antimicrobial combinations of meropenem, aztreonam, cefepime, colistin, gentamicin, levofloxacin, chloramphenicol, fosfomycin, trimethoprim/sulfamethoxazole, minocycline and rifampicin, as well as the double carbapenem combination of meropenem and ertapenem. In a screening procedure, we tested these combinations against four CRE strains and identified nine antibiotic combinations that showed potential clinically relevant synergy. In confirmatory testing using 10 CRE strains, six combinations demonstrated clinically relevant synergy with both antimicrobials at the minimum fractional inhibitory concentration (FICI-MIN) in the susceptible or intermediate range in at least one trial. These included two novel combinations: minocycline plus colistin and minocycline plus meropenem. In 80% of strains at least one combination demonstrated clinically relevant synergy, but the combinations that demonstrated synergy varied from strain to strain. This work establishes the foundation for future systematic, broad-range investigations into antibiotic synergy for CRE, emphasizes the need for individualized synergy testing and demonstrates the utility of inkjet printer-based technology for the performance of automated antimicrobial synergy assays. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights

  18. Act Fast as Time Is Less: High Faecal Carriage of Carbapenem-Resistant Enterobacteriaceae in Critical Care Patients.

    Science.gov (United States)

    Saseedharan, Sanjith; Sahu, Manisa; Pathrose, Edwin Joseph; Shivdas, Sarita

    2016-09-01

    Carbapenem-resistant Enterobacteriaceae (CRE) are drug-resistant Gram-negative bacteria that are present in the community as well as in hospitals. Their infection and colonisation puts critically ill patients at high risk due to the drug-resistant nature of the strains and possible spreading of these organisms, even in a hospital environment. To examine the presence and types of Enterobacteriaceae species in patients admitted directly from the community. The present study was a one-month pilot conducted in the ICU of a tertiary care hospital in Mumbai, India in 2015. Faecal samples of patients admitted from the community directly to the ICU were analysed using tests like MHT (Modified Hodge) and EDTA for the presence of IMP (action on Imipenem) and KPC ( Klebsiella Test Pneumoniae Carbapenemase) producing strains of Enterobacteriaceae . Polymerase Chain Reaction (PCR) was performed to look for VIM , IMP , NDM 1, OXA , and KPC genes. Antibiotic Sensitivity Test was carried out as per CLSI guidelines. The results showed an alarming level of faecal carriage rates in adult ICU patients. Klebsiella pneumonia was the most common carbapenem-resistant isolate, closely followed by Escherichia coli . PCR results revealed nine strains were positive for bla (KPC) gene, from which 7 were Klebsiella pneumoniae and one each of Escherichia coli and Klebsiella oxytoca was observed. Antibiotic Sensitivity Test results showed that the isolates had maximum sensitivity to Colistin (100%) and Tigecycline (95%). These levels indicate that in the absence of CRE screenings, proper isolation of carrier patients is not possible, leading to possible spreading of these resistant bacteria strains in ICUs. A longer period of study is required to obtain more substantial data to validate the results of this pilot.

  19. Safety and clinical outcomes of carbapenem de-escalation as part of an antimicrobial stewardship programme in an ESBL-endemic setting.

    Science.gov (United States)

    Lew, Kaung Yuan; Ng, Tat Ming; Tan, Michelle; Tan, Sock Hoon; Lew, Ee Ling; Ling, Li Min; Ang, Brenda; Lye, David; Teng, Christine B

    2015-04-01

    To evaluate the safety and clinical outcomes of patients who received carbapenem de-escalation as guided by an antimicrobial stewardship programme (ASP) in a setting where ESBL-producing Enterobacteriaceae are endemic. Patients receiving meropenem or imipenem underwent a prospective ASP review for eligibility for de-escalation according to defined institutional guidelines. Patients in whom carbapenem was de-escalated or not de-escalated, representing the acceptance and rejection of the ASP recommendation, respectively, were compared. The primary outcome was the clinical success rate; secondary outcomes included the 30 day readmission and mortality rates, the duration of carbapenem therapy, the incidence of adverse drug reactions due to antimicrobials, the acquisition of carbapenem-resistant Gram-negative bacteria and the occurrence of Clostridium difficile-associated diarrhoea (CDAD). The de-escalation recommendations for 300 patients were evaluated; 204 (68.0%) were accepted. The patient demographics and disease severity were similar. The clinical success rates were similar [de-escalated versus not de-escalated, 183/204 (89.7%) versus 85/96 (88.5%), P=0.84], as was the survival at hospital discharge [173/204 (84.8%) versus 79/96 (82.3%), P=0.58]. In the de-escalated group, the duration of carbapenem therapy was shorter (6 versus 8 days, Pcarbapenem-resistant Acinetobacter baumannii acquisition [4/204 (2.0%) versus 7/96 (7.3%), P=0.042] and there was a lower incidence of CDAD [2/204 (1.0%) versus 4/96 (4.2%), P=0.081]. This study suggests that the ASP-guided de-escalation of carbapenems led to comparable clinical success, fewer adverse effects and a lower incidence of the development of resistance. This approach is safe and practicable, and should be a key component of an ASP. © 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.

  20. In vitro Evaluation of the Colistin-Carbapenem Combination in Clinical Isolates of A. baumannii Using the Checkerboard, Etest, and Time-Kill Curve Techniques

    Directory of Open Access Journals (Sweden)

    Micheline A. H. Soudeiha

    2017-05-01

    Full Text Available The worldwide increase in the emergence of carbapenem resistant Acinetobacter baumannii (CRAB calls for the investigation into alternative approaches for treatment. This study aims to evaluate colistin-carbapenem combinations against Acinetobacter spp., in order to potentially reduce the need for high concentrations of antibiotics in therapy. This study was conducted on 100 non-duplicate Acinetobacter isolates that were collected from different patients admitted at Saint George Hospital-University Medical Center in Beirut. The isolates were identified using API 20NE strips, which contain the necessary agents to cover a panel of biochemical tests, and confirmed by PCR amplification of blaOXA−51−like. Activities of colistin, meropenem and imipenem against Acinetobacter isolates were determined by ETEST and microdilution methods, and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. In addition, PCR amplifications of the most common beta lactamases contributing to carbapenem resistance were performed. Tri locus PCR–typing was also performed to determine the international clonality of the isolates. Checkerboard, ETEST and time kill curves were then performed to determine the effect of the colistin-carbapenem combinations. The synergistic potential of the combination was then determined by calculating the Fractional Inhibitory Concentration Index (FICI, which is an index that indicates additivity, synergism, or antagonism between the antimicrobial agents. In this study, 84% of the isolates were resistant to meropenem, 78% to imipenem, and only one strain was resistant to colistin. 79% of the isolates harbored blaOXA−23−like and pertained to the International Clone II. An additive effect for the colistin-carbapenem combination was observed using all three methods. The combination of colistin-meropenem showed better effects as compared to colistin-imipenem (p < 0.05. The colistin-meropenem and

  1. Characterization of the etiological structure and genotypically determined phenotypic resistance to carbapenems of infectious complications leading pathogens in critically ill patients

    Directory of Open Access Journals (Sweden)

    O. A. Nazarchuk

    2018-06-01

    Full Text Available The aim is to investigate the genotypically determined phenotypic resistance to carbapenems of gram-negative microorganisms isolated from patients with critical states. Material and methods. Microbiological etiology of infectious complications in critically ill patients (n = 726 was investigated. In total, during the years 2011–2016, 933 clinical strains of infectious complications pathogens from patients with severe burns (n = 435 and from patients treated in intensive care units (n = 291 were isolated and identified. The sensitivity of microorganisms clinical isolates to antibiotics was investigated by means of the standard microbiological methods. In gram-negative bacteria resistant to carbapenems, a molecular genetic study of mechanisms of resistance, determined by the presence of VIM genes, was carried out using the method of real-time polymerase chain reaction. Results. Studies have shown that gram-negative microorganisms (Acinetobacter spp. – 36.3 %, P. aeruginosa – 31.7 %, Enterobacter spp. – 13.5 %, Proteus spp. – 7.9 %, E. coli – 3.8 %; K. pneumoniae – 3.6 %, etc. account for a significant part of infectious complications pathogens structure in critically ill patients. A. baumannii strains (67 % have expressed phenotypic resistance to most antibiotics, in particular to carbapenems (up to 63.2 %. Poly-antibiotic resistance was also found in P. aeruginosa (72 %, and above one the 3rd part of strains of this pathogen was found to have phenotypic resistance to carbapenems. In-depth study of molecular genetic determinants of the resistance mechanism to β-lactam antibiotics among clinical strains of gram-negative bacteria there was proved VIM-induced resistance to carbapenems in A. baumannii, P. aeruginosa, P. mirabilis. Conclusions. Enterobacteriaceae and non-fermenting gram-negative microorganisms (P. aeruginosa, P. mirabilis, A. baumannii, which are the leading causative agents of infectious complications in patients with

  2. 7 CFR 1927.55 - Title clearance services.

    Science.gov (United States)

    2010-01-01

    ... REGULATIONS TITLE CLEARANCE AND LOAN CLOSING Real Estate Title Clearance and Loan Closing § 1927.55 Title clearance services. (a) Responsibilities of closing agents. Services to be provided to the agency and the borrower by a closing agent in connection with the transaction vary depending on whether a title insurance...

  3. Title of the paper goes here second line

    Indian Academy of Sciences (India)

    %%Please download if these packages are not included %%in your local TeX distribution %%txfonts,balance,textcase,float %% \\begin{document} %%paper title %%For line breaks, \\\\ can be used within title \\title{Title of the paper goes here\\\\ second line} %%author names are separated by comma (,) %%use \\and before ...

  4. Roadmap Through Title XX. Financing Services for Children Through Title XX and Other Programs: Manual 5.

    Science.gov (United States)

    Copeland, William C.; Iversen, Iver A.

    This manual, part of a Hecht Institute four-manual series entitled Financing Children's Services Through Title XX and Related Programs, teaches what Title XX regulations are, what they mean, and what actions and procedures are commanded by them. The first section covers the necessity of rule systems, the characteristics of a good rule system and…

  5. Title List of documents made publicly available

    International Nuclear Information System (INIS)

    1982-07-01

    The Title List of Documents Made Publicly Available is a monthly publication. It contains descriptions of the information received and generated by the US Nuclear Regulatory Commission (NRC). This information includes: (1) docketed material associated with civilian nuclear power plants and other uses of radioactive materials and (2) nondocketed material received and generated by NRC pertinent to its role as a regulatory agency. As used here, docketed does not refer to Court dockets; it refers to the system by which NRC maintains its regulatory records. This series of documents is indexed by a Personal Author Index, a Corporate Source Index, and a Report Number Index. The docketed information contained in the Title List includes the information formerly issued through the Department of Energy publication Power Reactor Docket Information, last published in January 1979. Microfiche of the docketed information listed in the Title List is available for sale on a subscription basis from the National Technical Information Service (NTIS)

  6. Title List of documents made publicly available

    International Nuclear Information System (INIS)

    1982-06-01

    The Title List of Documents Made Publicly Available is a monthly publication. It contains descriptions of the information received and generated by the US Nuclear Regulatory Commission (NRC). This information includes: (1) docketed material associated with civilian nuclear power plants and other uses of radioactive materials and (2) nondocketed material received and generated by NRC pertinent to its role as a regulatory agency. As used here, docketed does not refer to Court dockets; it refers to the system by which NRC maintains its regulatory records. This series of documents is indexed by a Personal Author Index, a Corporate Source Index, and a Report Number Index. The docketed information contained in the Title List includes the information formerly issued throught the Department of Energy publication Power Reactor Docket Information, last published in January 1979. Microfiche of the docketed information listed in the Title List is available for sale on a subscription basis from the National Technical Information Service (NTIS)

  7. Changing the epidemiology of carbapenem-resistant Pseudomonas aeruginosa in a Brazilian teaching hospital: the replacement of São Paulo metallo-β-lactamase-producing isolates

    Directory of Open Access Journals (Sweden)

    Felipe Lira de Sá Cavalcanti

    2012-05-01

    Full Text Available In Brazil, carbapenem-resistant Pseudomonas aeruginosa isolates are closely related to the São Paulo metallo-β-lactamase (SPM Brazilian clone. In this study, imipenem-resistant isolates were divided in two sets, 2002/2003 and 2008/2009, analysed by pulsed field gel electrophoresis and tested for the Ambler class B metallo-β-lactamase (MBL genes blaSPM-1, blaIMP and blaVIM. The results show a prevalence of one clone related to the SPM Brazilian clone in 2002/2003. In 2008/2009, P. aeruginosa isolates were mostly MBL negative, genetically diverse and unrelated to those that had been detected earlier. These findings suggest that the resistance to carbapenems by these recent P. aeruginosa isolates was not due to the spread of MBL-positive SPM-related clones, as often observed in Brazilian hospitals.

  8. Quarterly title list for the period ending September 1976

    International Nuclear Information System (INIS)

    1976-01-01

    The title list of the Max-Planck-Institut fuer Plasmaphysik and the Projektgruppe fuer Laserforschung of the MPG is concerned with the period from July until September 1976, and it contains: a) 12 titles and abstracts of laboratory reports, b) 37 titles of publications (30 abstracts), c) 20 titles of articles submitted for publication (16 abstracts), and d) 25 titles of lectures (12 abstracts). (GG) [de

  9. Energy Information Data Base: serial titles

    International Nuclear Information System (INIS)

    1980-06-01

    The Department of Energy Technical Information Center (TIC) is responsible for creating bibliographic data bases that are used in the announcement and retrieval of publications dealing with all phases of energy. The TIC interactive information processing system makes use of a number of computerized authorities so that consistency can be maintained and indexes can be produced. One such authority is the Energy Information Data Base: Serial Titles. This authority contains the full and abbreviated journal title, country of publication, CODEN, and certain codes. This revision replaces previous revisions of this document

  10. Title list of documents made publicly available

    International Nuclear Information System (INIS)

    1991-01-01

    The Title List of Documents Made Publicly Available is a monthly publication. It contains descriptions of the information received and generated by the US Nuclear Regulatory Commission (NRC). This information includes docketed material associated with civilian nuclear power plants and other uses of radioactive materials and nondocketed material received and generated by NRC pertinent to its role as a regulatory agency. This series of documents is indexed by a Personal Author Index, a Corporate Source Index, and a Report Number Index. The docketed information contained in the Title List includes the information formerly issued though the Department of Energy publication Power Reactor Docket Information, last published in January 1979

  11. Role of the interplay between quorum sensing regulator VqsR and the Pseudomonas quinolone signal in mediating carbapenem tolerance in Pseudomonas aeruginosa.

    Science.gov (United States)

    Viducic, Darija; Murakami, Keiji; Amoh, Takashi; Ono, Tsuneko; Miyake, Yoichiro

    2017-06-01

    Pseudomonas aeruginosa coordinates its response to environmental conditions through activation of a quorum sensing (QS) system. In this study, we investigated the regulatory interaction between the QS transcriptional regulator VqsR and the Pseudomonas quinolone signal (PQS) through integration of sigma factor RpoS, and we addressed whether one of the pathways controlling carbapenem tolerance can be attributed to VqsR. We demonstrate that vqsR expression at the transcriptional level is regulated by pqsA, pqsR, and pqsE. Assessment of the transcriptional expression of vqsR, lasI, rhlI, and qscR in ΔpqsA and ΔpqsAΔrpoS mutants provided insight into pqsA- and rpoS-dependent regulation of vqsR and vqsR-controlled genes. Exogenously supplemented PQS reversed expression of vqsR and vqsR-controlled genes in the ΔpqsA mutant to wild-type levels, but failed to increase expression levels of lasI and qscR in the ΔpqsAΔrpoS mutant to levels observed in wild-type PAO1. The ΔvqsR mutant showed reduced survival when challenged with carbapenems compared to wild-type PAO1. Introduction of a pqsA mutation into the ΔvqsR mutant completely abolished its carbapenem-sensitive phenotype. We conclude that a regulatory link between PQS and vqsR exists, and that RpoS is important in their interaction. We also demonstrate that VqsR affects carbapenem tolerance. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  12. Carbapenems and piperacillin/tazobactam for the treatment of bacteremia caused by extended-spectrum β-lactamase-producing Proteus mirabilis.

    Science.gov (United States)

    Tsai, Hsih-Yeh; Chen, Yen-Hsu; Tang, Hung-Jen; Huang, Chi-Chang; Liao, Chun-Hsing; Chu, Fang-Yeh; Chuang, Yin-Ching; Sheng, Wang-Huei; Ko, Wen-Chien; Hsueh, Po-Ren

    2014-11-01

    This study was intended to delineate the role of carbapenems and piperacillin/tazobactam in treating bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Proteus mirabilis. We performed a multicenter and retrospective study of the patients with ESBL-producing P. mirabilis bacteremia. The outcomes of the patients treated by piperacillin/tazobactam or a carbapenem for at least 48 hours and the MICs of the prescribed drugs for these isolates were analyzed. Forty-seven patients with available clinical data were included. The overall 30-day mortality rate was 29.8%. All available isolates (n = 44) were susceptible to ertapenem, meropenem, and doripenem, and 95.6% were susceptible to piperacillin/tazobactam; however, only 11.4% of the isolates were susceptible to imipenem. Among the 3 patients infected with isolates exhibiting non-susceptibility to imipenem (MIC ≥2 mg/L) who were treated with imipenem, none died within 28 days. The 30-day (14.3% versus 23.1%, P = 0.65) or in-hospital (19.1% versus 30.8%, P = 0.68) mortality rate of 21 patients treated by a carbapenem was lower than that of 13 treated by piperacillin/tazobactam. However, among those treated by piperacillin/tazobactam, the mortality rate of those infected by the isolates with lower piperacillin/tazobactam MICs (≤0.5/4 mg/L) was lower than that of the isolates with MICs of ≥1/4 mg/L (0%, 0/7 versus 60%, 3/5; P = 0.045). ESBL-producing P. mirabilis bacteremia is associated with significant mortality, and carbapenem therapy could be regarded as the drugs of choice. The role of piperacillin/tazobactam, especially for the infections due to the isolates with an MIC ≤0.5/4 mg/L, warrants more clinical studies. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. High minimum inhibitory concentration of imipenem as a predictor of fatal outcome in patients with carbapenem non-susceptible Klebsiella pneumoniae.

    Science.gov (United States)

    Wu, Ping-Feng; Chuang, Chien; Su, Chin-Fang; Lin, Yi-Tsung; Chan, Yu-Jiun; Wang, Fu-Der; Chuang, Yin-Ching; Siu, L Kristopher; Fung, Chang-Phone

    2016-09-02

    Carbapenem resistance in Klebsiella pneumoniae is important because of its increasing prevalence and limited therapeutic options. To investigate the clinical and microbiological characteristics of patients infected or colonized with carbapenem non-susceptible K. pneumoniae (CnsKP) in Taiwan, we conducted a retrospective study at Taipei Veterans General Hospital from January 2012 to November 2013. Carbapenem non-susceptibility was defined as a minimum inhibitory concentration (MIC) of ≥2 mg/L for imipenem or meropenem. A total of 105 cases with CnsKP were identified: 49 patients with infection and 56 patients with colonization. Thirty-one isolates had genes that encoded carbapenemases (29.5%), including K. pneumoniae carbapenemase (KPC)-2 (n = 27), KPC-3 (n = 1), VIM-1 (n = 1) and IMP-8 (n = 2). The in-hospital mortality among patients with CnsKP was 43.8%. A MIC for imipenem ≥16 μg/mL, nasogastric intubation and Acute Physiology and Chronic Health Evaluation II score were independent risk factors for in-hospital mortality for all patients with CnsKP. A MIC for imipenem ≥16 μg/mL was also an independent risk factor for 14-day mortality in patients with CnsKP. In conclusion, a positive culture for CnsKP was associated with high in-hospital mortality. A high imipenem MIC of CnsKP can predispose a patient to a poor prognosis.

  14. The stationary phase sigma factor, RpoS, regulates the production of a carbapenem antibiotic, a bioactive prodigiosin and virulence in the enterobacterial pathogen Serratia sp. ATCC 39006.

    Science.gov (United States)

    Wilf, Nabil M; Salmond, George P C

    2012-03-01

    Serratia sp. ATCC 39006 (S39006) is a Gram-negative bacterium that is virulent in plant (potato) and invertebrate animal (Caenorhabditis elegans) models. It produces two secondary metabolite antibiotics, a prodigiosin and a carbapenem, and the exoenzymes pectate lyase and cellulase. We showed previously that deletion of the RNA chaperone Hfq abolished antibiotic production and attenuated virulence in both animal and plant hosts. Hfq and dependent small RNAs (sRNAs) are known to regulate the post-transcriptional expression of rpoS, which encodes σ(S), the stationary phase sigma factor subunit of RNA polymerase. An S39006 hfq deletion mutant showed decreased transcript levels of rpoS. Therefore, in this study we investigated whether the phenotypes regulated by Hfq were mediated through its control of rpoS. Whereas loss of Hfq abolished prodigiosin and carbapenem production and attenuated virulence in both C. elegans and potato, characterization of an S39006 rpoS mutant showed unexpectedly elevated prodigiosin and carbapenem production. Furthermore, the rpoS mutant exhibited attenuated animal pathogenesis, but not plant pathogenesis. Additionally, a homologue of the Hfq-dependent sRNA, RprA, was identified and shown to regulate prodigiosin production in a manner consistent with its role in positively regulating translation of rpoS mRNA. Combined, these results demonstrate that Hfq regulation of secondary metabolism and plant pathogenesis is independent of RpoS and establishes RpoS and RprA as regulators of antibiotic production.

  15. Resistencia a los antibióticos beta-lactámicos Carbapenems mediada por el gen blaKPC en Klebsiella pneumoniae

    Directory of Open Access Journals (Sweden)

    Aura Dayana del Carmen Falco Restrepo

    2015-12-01

    Full Text Available  Los carbapenems son antibióticos â-lactamicos de amplio espectro que se utilizan como terapia de primera línea para tratar pacientes con infecciones graves. Actualmente, la resistencia a carbapenems se asocia con la presencia de â-lactamasas capaces de hidrolizar estos antibióticos. La carbapenemasa de clase A más común es KPC, la cual es codificada por el gen blaKPC que generalmente, se encuentra ubicado en plásmidos. La selección y la rápida propagación de aislados de Klebsiella pneumoniae portadores de estas carbapenemasas se ha convertido en un problema de salud pública a nivel mundial. Esta mini-revision describe uno de los mecanismos más frecuentes de resistencia a carbapenems como lo son las enzimas carbapenemasas tipo KPC. Además se describen las variantes del gen blaKPC asi como el elemento genético móvil, el transposon Tn4401, el principal responsable de su diseminación entre géneros y especies bacterianas diferentes. Finalmente se hace una pequeña revisión cronológica de los reportes de la enzima KPC a nivel mundial.

  16. Outbreak by Hypermucoviscous Klebsiella pneumoniae ST11 Isolates with Carbapenem Resistance in a Tertiary Hospital in China

    Directory of Open Access Journals (Sweden)

    Lingling Zhan

    2017-05-01

    Full Text Available Hypervirulent and multidrug resistant Klebsiella pneumoniae strains pose a significant threat to the public health. In the present study, 21 carbapenem-resistant K. pneumoniae isolates (CRKP were determined by the string test as hypermucoviscous K. pneumoniae (HMKP, with the prevalence of 15.0% (21/140 among CRKP, and 1.1% (21/1838 among all K. pneumoniae isolates. Among them, 7 (33.3%, and 1 (4.76% isolate belonged to capsular serotype K20 and K2 respectively, while 13 (61.9%, 13/21 weren't successfully typed by capsular serotyping. All the 21 isolates were carbapenemase-producers and were positive for blaKPC-2. In addition to blaKPC-2, all the 21 isolates except one harbor blaSHV-11, and 15 carry extended-spectrum β-lactamase gene blaCTX-M-65. The virulence-associated genes with more than 90% of positive rates among 21 isolates included ureA (100%, 21/21, wabG (100%, 21/21, fimH (95.2%, 20/21, entB (95.2%, 20/21, ycf (95.2%, 20/21, ybtS (95.2%, 20/21, and iutA (90.5%, 19/21. rmpA and aerobactin were found in 57.1% (12/21 isolates. Five sequence types (STs were identified by multilocus sequence typing (MLST, including ST11 (11 K-non capsule typable and 5 K20 isolates, ST268 (1 K20 isolate and 1 K-non capsule typable isolate, ST65 (1 K2 isolate, ST692 (1 K-non capsule typable isolate, and ST595, a novel sequence type (1 K-non capsule typable isolate. Pulsed-field gel electrophoresis (PFGE results showed two major PFGE clusters, of which cluster A accounts for 6 ST11 isolates (28.6% and cluster B includes 8 ST11 isolates (38.1%, 8/21. Ten and six ST11 isolates were isolated from 2014 and 2015, respectively, while 8 were isolated from the same month of December in 2014. Ten isolates were collected from the intensive care unit (ICU, and all except one belonged to ST11. Additional 4 ST11 isolates were collected from patients in non-ICU wards, who had more than 10 days of ICU stay history in 2014 prior to transfer to their current wards where the

  17. 20 CFR 408.931 - How much will we withhold from your title II and title XVI benefits to recover a title VIII...

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false How much will we withhold from your title II... and Overpayments Adjustment of Title II Benefits § 408.931 How much will we withhold from your title...-due benefits. (b)(1) We will collect the overpayment from current monthly benefits due in a month...

  18. Factors Influencing Title VII Bilingual Program Institutionalization.

    Science.gov (United States)

    Lewis, Gerald R.; And Others

    1985-01-01

    This study of the primary restraining and driving forces that influence Title VII bilingual education programs found the external environment, the local community, to be the main factor influencing institutionalization and self-renewal. The internal environment--the local school, and the local school's organization or central office, school board,…

  19. What Difference Does a Title Make

    DEFF Research Database (Denmark)

    Balle, Søren Hattesen

    out by Gerard Genette, by naming and “designat[ing] it as precisely as possible and without too much risk of confusion” (Genette, 1997). In accordance with its title the poem thus represents the discourse of a newsreader neutrally reporting the events of war scenario. However, each section of the poem...

  20. 76 FR 60593 - Title VI; Proposed Circular

    Science.gov (United States)

    2011-09-29

    ..., several of them related to ambiguous language in the existing Circular. The proposed Circular reorganizes... regional entity, and inclusive of public and private entities. This term is used exclusively in Chapter IV... revisions to the Title VI Circular. The section that addresses the existing requirement for a Language...

  1. Browse Title Index - African Journals Online

    African Journals Online (AJOL)

    Items 801 - 850 of 1006 ... Issue, Title. Vol 59, No 4 (2017), Spatial patterns and determinants of fertility levels among women of childbearing age in Nigeria, Abstract PDF. Oluwayemisi O. Alaba, Olusanya E. Olubusoye, J.O. Olaomi. Vol 55, No 1 (2013), Spirit(ed) away: preventing foetal alcohol syndrome with motivational ...

  2. 36 CFR 254.15 - Title standards.

    Science.gov (United States)

    2010-07-01

    ...) Conveyances of lands from the United States are made by patent, quitclaim deed, or deed and without express or implied warranties, except as to hazardous substances pursuant to § 254.3 of this subpart. (c) Title... of the existing use(s) authorized under the terms of the grant, permit, easement, or lease. The non...

  3. Providing Transparency to the Title IX Process

    Science.gov (United States)

    Hartle, Terry

    2017-01-01

    When U.S. Secretary of Education Betsy DeVos announced Sept. 7, 2017, that her department would revisit how Title IX rules are enforced with respect to campus sexual assault, she said the first step would be a "transparent notice and comment process" to replace the 2011 "guidance" (and follow up 2014 guidance) that has been…

  4. Software Development Framework For Electronic Land Titles ...

    African Journals Online (AJOL)

    Record keeping is a fundamental activity of public administration. Land Titles management in Nigeria, by virtue of the Land use act 1990, is one of the functions of government. Most of the records hitherto used in managing the records of lands are documented on paper. We carried out an investigation into the suitability of ...

  5. Browse Title Index - African Journals Online

    African Journals Online (AJOL)

    Items 151 - 200 of 771 ... Issue, Title. Vol 33, No 4 (2013), Community-researcher liaisons: the Pathways to Resilience Project Advisory Panel, Abstract PDF. LC Theron. Vol 37, No 3 (2017), Comparing the achievement goal orientation of mathematics learners with and without attention-deficit hyperactivity disorder, Abstract ...

  6. Molecular epidemiology and drug resistant mechanism in carbapenem-resistant Klebsiella pneumoniae isolated from pediatric patients in Shanghai, China.

    Science.gov (United States)

    Zhang, Xingyu; Chen, Di; Xu, Guifeng; Huang, Weichun; Wang, Xing

    2018-01-01

    Infection by carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a public health challenge worldwide, in particular among children, which was associated with high morbidity and mortality rates. There was limited data in pediatric populations, thus this study aimed to investigate molecular epidemiology and drug resistant mechanism of CR-KP strains from pediatric patients in Shanghai, China. A total of 41 clinical CR-KP isolates from sputum, urine, blood or drainage fluid were collected between July 2014 and May 2015 in Shanghai Children's Medical Center. Multilocus sequence typing (MLST), antibiotic susceptibility testing, PCR amplification and sequencing of the drug resistance associated genes were applied to all these isolates. MLST analysis revealed 16 distinct STs identified within the 41 isolates, among which the most frequently represented were ST11(19.5%),ST25(14.6%),ST76(14.6%),ST37(9.8%).One new ST was first identified. All CR-KP isolates showed MDR phenotypes and were resistance to ceftazidime, imipenem, piperacillin / tazobactam, ceftriaxone, ampicillin /sulbactam, aztreonam. They were confirmed as carbapenemase producer, NDM-1 (56.1%, 23/41), IMP (26.8%, 11/41), KPC-2 (22.0%, 9/41) were detected. Of note, two isolates carried simultaneously both NDM-1 and IMP-4. All CR-KP strains contained at least one of extended spectrum β-lactamase genes tested(TEM, SHV, OXA-1, CTX-M group) and six isolates carried both ESBL and AmpC genes(DHA-1). Among the penicllinase and β-lactamase genes, the most frequently one is SHV(92.7%,38/41), followed by TEM-1(68.3%,28/41), CTX-M-14(43.9%,18/41), CTX-M-15(43.9%,14/41), OXA-1(14.6%,6/41). In the present study, NDM-1-producing isolates was the predominant CR-KP strains in children, follow by IMP and KPC-producing strains. NDM-1and IMP-4 were more frequent than KPC-2 and showed a multiclonal background. Those suggested carbapenem-resistant in children is diverse, and certain resistance mechanisms differ from prevalent

  7. Insertional inactivation of oprD in carbapenem-resistant Pseudomonas aeruginosa strains isolated from burn patients in Tehran, Iran.

    Science.gov (United States)

    Shariati, A; Azimi, T; Ardebili, A; Chirani, A S; Bahramian, A; Pormohammad, A; Sadredinamin, M; Erfanimanesh, S; Bostanghadiri, N; Shams, S; Hashemi, A

    2018-01-01

    In this study, we report the insertion sequence IS Ppu 21 in the opr D porin gene of carbapenem-resistant Pseudomonas aeruginosa isolates from burn patients in Tehran, Iran. Antibiotic susceptibility tests for P. aeruginosa isolates were determined. Production of metallo-β-lactamases (MBLs) and carbapenemase was evaluated and the β-lactamase-encoding and aminoglycoside-modifying enzyme genes were investigated by PCR and sequencing methods. The mRNA transcription level of oprD and mex efflux pump genes were evaluated by real-time PCR. The outer membrane protein profile was determined by SDS-PAGE. The genetic relationship between the P. aeruginosa isolates was assessed by random amplified polymorphic DNA PCR. In all, 10.52% (10/95) of clinical isolates of P. aeruginosa harboured the IS Ppu 21 insertion element in the opr D gene. The extended-spectrum β-lactamase-encoding gene in IS Ppu 21-carrying isolates was bla TEM . PCR assays targeting MBL and carbapenemase-encoding genes were also negative in all ten isolates. The rmt A, aad A, aad B and arm A genes were positive in all IS Ppu 21 harbouring isolates. The relative expression levels of the mex X, mex B, mex T and mex D genes in ten isolates ranged from 0.1- to 1.4-fold, 1.1- to 3.68-fold, 0.3- to 8.22-fold and 1.7- to 35.17-fold, respectively. The relative expression levels of the oprD in ten isolates ranged from 0.57- to 35.01-fold, which was much higher than those in the control strain P. aeruginosa PAO1. Evaluation of the outer membrane protein by SDS-PAGE suggested that opr D was produced at very low levels by all isolates. Using random amplified polymorphic DNA PCR genotyping, eight of the ten isolates containing IS Ppu 21 were shown to be clonally related. The present study describes a novel molecular mechanism, IS Ppu 21 insertion of the opr D gene, associated with carbapenem resistance in clinical P. aeruginosa isolates.

  8. Comparative Genomics of Two ST 195 Carbapenem-Resistant Acinetobacter baumannii with Different Susceptibility to Polymyxin Revealed Underlying Resistance Mechanism

    Science.gov (United States)

    Lean, Soo-Sum; Yeo, Chew Chieng; Suhaili, Zarizal; Thong, Kwai-Lin

    2016-01-01

    Acinetobacter baumannii is a Gram-negative nosocomial pathogen of importance due to its uncanny ability to acquire resistance to most antimicrobials. These include carbapenems, which are the drugs of choice for treating A. baumannii infections, and polymyxins, the drugs of last resort. Whole genome sequencing was performed on two clinical carbapenem-resistant A. baumannii AC29 and AC30 strains which had an indistinguishable ApaI pulsotype but different susceptibilities to polymyxin. Both genomes consisted of an approximately 3.8 Mbp circular chromosome each and several plasmids. AC29 (susceptible to polymyxin) and AC30 (resistant to polymyxin) belonged to the ST195 lineage and are phylogenetically clustered under the International Clone II (IC-II) group. An AbaR4-type resistance island (RI) interrupted the comM gene in the chromosomes of both strains and contained the blaOXA−23 carbapenemase gene and determinants for tetracycline and streptomycin resistance. AC29 harbored another copy of blaOXA−23 in a large (~74 kb) conjugative plasmid, pAC29b, but this gene was absent in a similar plasmid (pAC30c) found in AC30. A 7 kb Tn1548::armA RI which encodes determinants for aminoglycoside and macrolide resistance, is chromosomally-located in AC29 but found in a 16 kb plasmid in AC30, pAC30b. Analysis of known determinants for polymyxin resistance in AC30 showed mutations in the pmrA gene encoding the response regulator of the two-component pmrAB signal transduction system as well as in the lpxD, lpxC, and lpsB genes that encode enzymes involved in the biosynthesis of lipopolysaccharide (LPS). Experimental evidence indicated that impairment of LPS along with overexpression of pmrAB may have contributed to the development of polymyxin resistance in AC30. Cloning of a novel variant of the blaAmpC gene from AC29 and AC30, and its subsequent expression in E. coli also indicated its likely function as an extended-spectrum cephalosporinase. PMID:26779129

  9. Molecular epidemiology of carbapenem resistant gram-negative bacilli from infected pediatric population in tertiary - care hospitals in Medellín, Colombia: an increasing problem.

    Science.gov (United States)

    Vanegas, Johanna M; Parra, O Lorena; Jiménez, J Natalia

    2016-09-01

    Gram-negative bacilli are a cause of serious infections in the pediatric population. Carbapenem are the treatment of choice for infections caused by multidrug-resistant Gram-negative bacilli, but the emergence of carbapenem resistance has substantially reduced access to effective antimicrobial regimens. Children are a population vulnerable to bacterial infections and the emergence of resistance can worsen prognosis. The aim of this study is to describe the clinical and molecular characteristics of infections caused by carbapenem-resistant Gram-negative bacilli in pediatric patients from five tertiary-care hospitals in Medellín, Colombia. A cross-sectional study was conducted in five tertiary-care hospitals from June 2012 to June 2014. All pediatric patients infected by carbapenem-resistant Gram-negative bacilli were included. Clinical information for each patient was obtained from medical records. Molecular analyses included PCR for detection of bla VIM, bla IMP bla NDM, bla OXA-48 and bla KPC genes and PFGE and MLST for molecular typing. A total of 59 patients were enrolled, most of them less than 1 year old (40.7 % n = 24), with a previous history of antibiotic use (94.9 %; n = 56) and healthcare-associated infections - predominately urinary tract infections (31.0 %; n = 18). Klebsiella pneumoniae was the most frequent bacteria (47.4 %), followed by Enterobacter cloacae (40.7 %) and Pseudomonas aeruginosa (11.9 %). For K. pneumoniae, KPC was the predominant resistance mechanism (85.7 %; n = 24) and ST14 was the most common clone (39.3 % n = 11), which included strains closely related by PFGE. In contrast, E. cloacae and P. aeruginosa were prevailing non-carbapenemase-producing isolates (only KPC and VIM were detected in 1 and 3 isolates, respectively) and high genetic diversity according to PFGE and MLST was found in the majority of the cases. In recent years, increasing carbapenem-resistant bacilli in children has become in a matter

  10. Outcome of Transplantation Using Organs From Donors Infected or Colonized With Carbapenem-Resistant Gram-Negative Bacteria.

    Science.gov (United States)

    Mularoni, A; Bertani, A; Vizzini, G; Gona, F; Campanella, M; Spada, M; Gruttadauria, S; Vitulo, P; Conaldi, P; Luca, A; Gridelli, B; Grossi, P

    2015-10-01

    Donor-derived infections due to multidrug-resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2-year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem-resistant gram-negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor-derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high-risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high-risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug-resistant bacteria requires intra- and inter-institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  11. Frequency of Carbapenem, Colistin and Tigecycline Resistant Enterobacteriacae in Medical ICU of a Tertiary Care Hospital in Karachi

    Directory of Open Access Journals (Sweden)

    Shobha Luxmi

    2018-01-01

    Full Text Available BACKGROUND: Resistance to antibiotics among Enterobacteriacae represents a serious therapeutic and infection control challenge. The objective of this study was to determine the frequency of carbapenem, colistin and tigecycline resistant Enterobacteriaceae isolates obtained from patients admitted in medical intensive care unit (ICU of a tertiary care hospital in Karachi, Pakistan. METHODS: This was a descriptive cross sectional study that was conducted at Liaquat National Postgraduate Medical Centre, Karachi, Pakistan during December 2015 to May 2016. Patients admitted in the medical ICU with systemic inflammatory response syndrome were included. The culture positive samples were analyzed for further identification and antimicrobial sensitivity was performed according to clinical laboratory standard institute (CLSI 2014 guidelines. RESULTS: Of the 748 samples, 177 were positive for Enterobactericae. Most samples were taken from blood 75(42.2% or tracheal secretions 67(37.9%. Most common organism isolated were Klebsiella pneumoniae 77(43.5% and Escherichia coli 71(40.1%. Out of these 10.7% organisms were resistant to meropenem, while 2.8% and 20.3% were resistant to colistin and tigecycline respectively. CONCLUSION: Increasing spread of drug resistance among Enterobacteriacae reflects an important problem that can be controlled with effective policies of infection control, surveillance and antimicrobial stewardship.

  12. The Effect of Different Carbapenem Antibiotics (Ertapenem, Imipenem/Cilastatin, and Meropenem) on Serum Valproic Acid Concentrations.

    Science.gov (United States)

    Wu, Chien-Chih; Pai, Tsung-Yu; Hsiao, Fei-Yuan; Shen, Li-Jiuan; Wu, Fe-Lin Lin

    2016-10-01

    Carbapenem antibiotics (CBPMs) may significantly reduce the serum concentration of valproic acid (VPA), but the extent of this effect among various CBPMs is unknown. This study compared the extent and onset of the interactions among ertapenem, imipenem/cilastatin, and meropenem. A 5-year retrospective study was performed. Hospitalized patients over 18 years old who received VPA and a CBPM concurrently were enrolled via the pharmacy computer system. Patients who lacked VPA serum concentration measurements before or during CBPMs' use, had concurrent medication(s) that might interfere with VPA metabolism, or had a history of liver cirrhosis were excluded. Total VPA serum concentrations before and during CBPMs' use and after its discontinuation were recorded, and differences among various CBPMs were analyzed. Fifty-two patients were included in this analysis. Irrespective of the route of administration, VPA serum concentrations were subtherapeutic in 90% of the subjects during CBPMs' use. There was a significant decrease (P imipenem/cilastatin (N = 17), and meropenem (N = 26) groups, respectively. The effect of ertapenem and meropenem on VPA was significantly more expressed than that of imipenem/cilastatin (P imipenem/cilastatin. Because of the dramatic reduction of VPA serum concentration during CBPMs' use, concomitant use of VPA and CBPMs should be avoided.

  13. A carbapenem antibiotic imipenem/cilastatin induces an oxidative stress-status and gonadotoxic effects in « wistar » rats.

    Science.gov (United States)

    Tahri, Amal; Ksouda, Kamilia; Kallel, Rim; Daoud, Salima; Boudawara, Tahia; Zeghal, Khaled Mounir; Sahnoun, Zouheir

    2017-11-01

    Imipenem is a carbapenem antibiotic largely used to treat infection diseases. The present study was designed to investigate the effects of imipenem/cilastatin (IMP) on oxidative stress, antioxidant levels, testicular structure and sperm parameters in rats. Adult Wistar rats (84days old; N=8/group) were treated intraperitoneally with physiological serum containing 0mg/kg, 30mg/kg, 50mg/kg and 80mg/kg of IMP for one week. The results revealed that exposure to IMP especially at high doses, significantly decreased sexual organs weights (testis, epididymis, seminal vesicle and prostate), sperm characteristics (motility, viability and count) and plasma testosterone level while increased sperm abnormality. In addition, the testicular tissue level of lipid peroxidation (LPO) was significantly increased while the level of activities of superoxide dismutase (SOD), catalase (CAT) and glutathion peroxidase (GPx) decreased compared to the control group. Severe testicular lesions were recorded in the seminiferous tubules as well as a significant impairment in sperm characteristics. In conclusion, IMP induced an oxidative stress-status and histopathological changes in the testis and altered spermatogenesis in particular at both 50 and 80mg/kg dose-levels (p<0.001). Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis.

    Science.gov (United States)

    Zilberberg, Marya D; Nathanson, Brian H; Sulham, Kate; Fan, Weihong; Shorr, Andrew F

    2017-04-17

    Drug resistance among gram-negative pathogens is a risk factor for inappropriate empiric treatment (IET), which in turn increases the risk for mortality. We explored the impact of carbapenem-resistant Enterobacteriaceae (CRE) on the risk of IET and of IET on outcomes in patients with Enterobacteriaceae infections. We conducted a retrospective cohort study in Premier Perspective database (2009-2013) of 175 US hospitals. We included all adult patients with community-onset culture-positive urinary tract infection (UTI), pneumonia, or sepsis as a principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, treated with antibiotics within 2 days of admission. We employed regression modeling to compute adjusted association of presence of CRE with risk of receiving IET, and of IET on hospital mortality, length of stay (LOS) and costs. Among 40,137 patients presenting to the hospital with an Enterobacteriaceae UTI, pneumonia or sepsis, 1227 (3.1%) were CRE. In both groups, the majority of the cases were UTI (51.4% CRE and 54.3% non-CRE). Those with CRE were younger (66.6+/-15.3 vs. 69.1+/-15.9 years, p pneumonia or sepsis was comparable to other national estimates. Infection with CRE was associated with a four-fold increased risk of receiving IET, which in turn increased mortality, LOS and costs.

  15. 24 CFR 203.386 - Coverage of title evidence.

    Science.gov (United States)

    2010-04-01

    ... SINGLE FAMILY MORTGAGE INSURANCE Contract Rights and Obligations Property Title Transfers and Title... the public records, there are not, at such date, any outstanding prior liens, including any past-due...

  16. 14 CFR 1245.109 - Assignment of title to NASA.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Assignment of title to NASA. 1245.109... INTELLECTUAL PROPERTY RIGHTS Patent Waiver Regulations § 1245.109 Assignment of title to NASA. (a) The instrument of waiver set forth in § 1245.115(c) shall be voided by NASA with respect to the domestic title to...

  17. Title IX: With New Opportunities, Girls' Interest Rises

    Science.gov (United States)

    Toporek, Bryan

    2012-01-01

    On June 23, 1972, President Richard M. Nixon signed into law Title IX of the Education Amendments of 1972, which prohibits gender discrimination in any federally financed education program or activity. Title IX is far-reaching, but the law is most often associated with school and college athletics. Title IX allows schools to prove their athletic…

  18. Exploring New Directions: Title I in the Year 2000.

    Science.gov (United States)

    Puma, Michael J.; Drury, Darrel W.

    This report takes stock of the present Title I program, identifies the most promising approaches to educating the nation's disadvantaged children, and offers guidance to policymakers seeking to improve Title I's effectiveness. The report draws upon hundreds of studies, evaluations, and other documents, and details the evolution of the Title I…

  19. 40 CFR 300.220 - Related Title III issues.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Related Title III issues. 300.220 Section 300.220 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY... PLAN Planning and Preparedness § 300.220 Related Title III issues. Other related Title III requirements...

  20. Formulating the Right Title for a Research Article.

    Science.gov (United States)

    Bavdekar, Sandeep B

    2016-02-01

    Title is an important part of the article. It condenses article content in a few words and captures readers' attention. A good title for a research article is the one which, on its own, is able to introduce the research work to the fullest extent, but in a concise manner. Writing scientific titles that are informative and attractive is a challenging task. This communication describes the importance of titles and the methods of creating appropriate titles for research papers. © Journal of the Association of Physicians of India 2011.

  1. Carbapenem non-susceptible enterobacteriaceae in Quebec, Canada: results of a laboratory surveillance program (2010-2012.

    Directory of Open Access Journals (Sweden)

    Brigitte Lefebvre

    Full Text Available The emergence and spread of carbapenemase-producing Enterobacteriaceae (CPE represent a major public health concern because these bacteria are usually extensively resistant to most antibiotics. In order to evaluate their dissemination in Quebec, a surveillance program was introduced in 2010. We report the molecular and epidemiological profiles of CPE isolates collected. Between August 2010 and December 2012, a total of 742 non-duplicate isolates non-susceptible to carbapenems were analysed. AmpC β-lactamase and metallo-β-lactamase production were detected by Etest and carbapenemase production by the modified Hodge test (MHT. Antibiotic susceptibility profiles were determined using broth microdilution or Etest. Clonality of Klebsiella pneumoniae carbapenemase (KPC strains was analyzed by pulsed-field gel electrophoresis (PFGE. The presence of genes encoding carbapenemases as well as other β-lactamases was detected using PCR. Of the 742 isolates tested, 169 (22.8% were CPE. Of these 169 isolates, 151 (89.3% harboured a blaKPC gene while the remaining isolates carried blaSME (n = 9, blaOXA-48 (n = 5, blaNDM (n = 3, and blaNMC (n = 1 genes. Among the 93 KPC strains presenting with a unique pattern (unique PFGE pattern and/or unique antibiotics susceptibility profile, 99% were resistant to ertapenem, 95% to imipenem, 87% to meropenem, 97% to aztreonam, 31% to colistin and 2% to tigecycline. In 19 patients, 2 to 5 KPC strains from different species or with a different PFGE pattern were isolated. CPE strains were present in the province of Quebec with the majority of strains harbouring KPC. Alternately, SME, OXA-48 and NMC containing strains were rarely found.

  2. Clonal relatedness and biofilm formation of OXA-23-producing carbapenem resistant Acinetobacter baumannii isolates from hospital environment.

    Science.gov (United States)

    Aliramezani, Amir; Douraghi, Masoumeh; Hajihasani, Azade; Mohammadzadeh, Mona; Rahbar, Mohammad

    2016-10-01

    Carbapenem-resistant Acinetobacter baumannii (CRAB) is a serious threat for hospitalized patients and it can survive for long periods in hospital settings, particularly on inanimate surfaces. The environment occupied by these resistant and resilient isolates may act as a reservoir for cross-colonization and outbreaks. Here, we aimed to determine the distribution of CRAB in the hospital environment and to characterize their clonal relatedness, susceptibility profile, carriage of bla OXA genes, and biofilm formation. A total of 1080 samples were collected from various environmental surfaces and equipment of two referral hospitals in Tehran, Iran. The A. baumannii isolates were subjected to gyrB multiplex PCR, antibiotic susceptibility testing, biofilm formation assay, pulsed field gel electrophoresis (PFGE), and multiplex PCR for bla OXA-58 , bla OXA-24 , and bla OXA-23 genes. Eighteen Acinetobacter spp. were isolated; 8 were identified as A. baumannii and 10 as A. lwoffii. Five of A. baumannii isolates were CRAB and exhibited the multidrug-resistant (MDR) phenotype as well. All CRAB isolates produced biofilm, albeit with different levels. Four of CRAB isolates harbored the bla OXA-23 . The CRAB isolates were clustered into 3 distinct pulsotypes (PTs). The CRAB isolates belonging to PT1 were detected in two geographically distinct hospitals whereas those belonging to PT3 were found in two different units of same hospital. This study revealed the presence of clonally related OXA-23-producing CRAB in high risk units of referral hospitals as inter- or intra-hospital dissemination. The distribution of multiresistant A. baumannii on several surfaces and areas may increase the risk of transmission of resistant isolates to vulnerable patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Fecal carriage of carbapenem-resistant Enterobacteriaceae and risk factor analysis in hospitalised patients: A single centre study from India

    Directory of Open Access Journals (Sweden)

    Balvinder Mohan

    2017-01-01

    Full Text Available Purpose: Carbapenem-resistant Enterobacteriaceae (CRE have emerged and disseminated widely causing a variety of infections. In India, the carriage of CRE in hospitalised patients has not been well-studied. Therefore, we conducted the present study to observe gut carriage rate of CRE in patients admitted to our tertiary care hospital. Methods: A total of 232 faecal swabs collected from consecutive stool samples from admitted patients were inoculated on ChromID extended spectrum β-lactamase plates and members of Enterobacteriaceae family were subjected to antibiotic susceptibility as per the Clinical Laboratory Standards Institute guidelines. Polymerase chain reaction for blaVIM, blaKPC, blaIMPand blaNDM-1 genes was performed. CRE was identified if the isolates showed resistance to either imipenem or meropenem or showed the presence of resistant genes. Risk factors of patients with or without CRE colonisation were also analysed. Results: A total of 232 faecal swabs yielded 252 Enterobacteriaceae isolates, of which 49 isolates from 42 patients showed the presence of CRE (occurrence 42/232; 18.1%; 27 isolates from 22 patients carried blaNDM-1, whereas 20 isolates from 17 patients possessed blaVIMgene. No isolate was positive for blaKPCand blaIMPgenes. The CRE was common in both intensive care units (38.4% and wards (46% which may reflect the excessive use of broad-spectrum antibiotics in both these settings. The CRE was also found to have a significantly higher antimicrobial resistance as compared to non-CRE isolates. The logistic regression analysis of significance showed the presence of any indwelling device (P = 0.049 and nasogastric tube (P = 0.043 as independent risk factors for acquiring gut colonisation. Conclusions: The study is the first from India to show high CRE carriage in patients admitted to a tertiary care centre and emphasises the need of strict antimicrobial stewardship implementation in hospitals to prevent dissemination of

  4. A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome.

    Science.gov (United States)

    de Maio Carrilho, Claudia M D; de Oliveira, Larissa Marques; Gaudereto, Juliana; Perozin, Jamile S; Urbano, Mariana Ragassi; Camargo, Carlos H; Grion, Cintia M C; Levin, Anna Sara S; Costa, Silvia F

    2016-11-03

    To describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death. A prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7.0 (CDC, Atlanta, GA, USA) and SPSS (Chicago, IL, USA). One hundred and twenty-seven patients were evaluated. Pneumonia, 52 (42 %), and urinary tract infections (UTI), 51 (40.2 %), were the most frequent sites of infection. The isolates were polyclonal; the Bla KPC gene was found in 75.6 % of isolates, and 27 % of isolates were resistant to colistin. Mortality related to infection was 34.6 %, and was higher among patients with pneumonia (61.4 %). Combination therapy was used in 98 (77.2 %), and monotherapy in 22.8 %; 96.5 % of them were UTI patients. Shock, age, and dialysis were independent risk factors for death. There was no difference in infection-related death comparing colistin-susceptible and colistin-resistant infections (p = 0.46); neither in survival rate comparing the use of combination therapy with two drugs or more than two drugs (p = 0.32). CRE infection mortality was higher among patients with pneumonia. Infections caused by colistin-resistant isolates did not increase mortality. The use of more than two drugs on combination therapy did not show a protective effect on outcome. The isolates were polyclonal, and the bla KPC gene was the only carbapenemase found. Shock, dialysis, and age over 60 years were independent risk factors for death.

  5. Use of Monte Carlo Simulations to Determine Optimal Carbapenem Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Lewis, Susan J; Kays, Michael B; Mueller, Bruce A

    2016-10-01

    Pharmacokinetic/pharmacodynamic analyses with Monte Carlo simulations (MCSs) can be used to integrate prior information on model parameters into a new renal replacement therapy (RRT) to develop optimal drug dosing when pharmacokinetic trials are not feasible. This study used MCSs to determine initial doripenem, imipenem, meropenem, and ertapenem dosing regimens for critically ill patients receiving prolonged intermittent RRT (PIRRT). Published body weights and pharmacokinetic parameter estimates (nonrenal clearance, free fraction, volume of distribution, extraction coefficients) with variability were used to develop a pharmacokinetic model. MCS of 5000 patients evaluated multiple regimens in 4 different PIRRT effluent/duration combinations (4 L/h × 10 hours or 5 L/h × 8 hours in hemodialysis or hemofiltration) occurring at the beginning or 14-16 hours after drug infusion. The probability of target attainment (PTA) was calculated using ≥40% free serum concentrations above 4 times the minimum inhibitory concentration (MIC) for the first 48 hours. Optimal doses were defined as the smallest daily dose achieving ≥90% PTA in all PIRRT combinations. At the MIC of 2 mg/L for Pseudomonas aeruginosa, optimal doses were doripenem 750 mg every 8 hours, imipenem 1 g every 8 hours or 750 mg every 6 hours, and meropenem 1 g every 12 hours or 1 g pre- and post-PIRRT. Ertapenem 500 mg followed by 500 mg post-PIRRT was optimal at the MIC of 1 mg/L for Streptococcus pneumoniae. Incorporating data from critically ill patients receiving RRT into MCS resulted in markedly different carbapenem dosing regimens in PIRRT from those recommended for conventional RRTs because of the unique drug clearance characteristics of PIRRT. These results warrant clinical validation. © 2016, The American College of Clinical Pharmacology.

  6. Frequency of colistin and fosfomycin resistance in carbapenem-resistant Enterobacteriaceae from a tertiary care hospital in Karachi

    Directory of Open Access Journals (Sweden)

    Qamar S

    2017-07-01

    Full Text Available Salima Qamar, Najma Shaheen, Sadia Shakoor, Joveria Farooqi, Kauser Jabeen, Rumina Hasan Clinical Microbiology, Department of Pathology And Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan Introduction: Management of infections with carbapenem-resistant Enterobacteriaceae (CRE is challenging. In recent times, agents such as colistin and fosfomycin have been used in combination with other antibiotics to treat such infections. In this study, we aim to seek frequency of colistin and fosfomycin resistance in CRE from Pakistan.Methods: This study was conducted at clinical laboratories, Aga Khan University Hospital. In total, 251 CRE were included in the study. Colistin minimum inhibitory concentrations (MICs were performed using broth microdilution (BMD method and VITEK® 2 system, whereas fosfomycin susceptibility was performed using Kirby–Bauer method. MIC50 and MIC90 were calculated for colistin and agreement between VITEK and BMD was also calculated.Results: Out of 251 strains colistin MIC of ≥4 µg/mL was seen in 40 (15.9%. Of these strains 20 (50% were Klebsiella pneumoniae. Colistin MIC50 and MIC90 were found to be 0.5 and 16 µg/mL, respectively. BMD and VITEK 2 showed 100% categorical agreement. Essential agreement was 88.5% with kappa score 0.733 indicating strong agreement between VITEK and BMD. 31 out of 251 (12.3% CREs were resistant to fosfomycin.Conclusion: Study shows frequency of colistin and fosfomycin resistance to be 15.9% and 12.3%, respectively. In countries where rate of CREs is high, emerging resistance against these last resort antibiotics is alarming as it leaves clinicians with almost no options to manage such multidrug resistant and extensively drug resistant infections. Keywords: emerging drug resistance, colistin resistance, fosfomycin resistance, carbapenam resistant enterobacteriaceae, salvage antibiotics 

  7. Expanding the Repertoire of Carbapenem-Hydrolyzing Metallo-ß-Lactamases by Functional Metagenomic Analysis of Soil Microbiota.

    Science.gov (United States)

    Gudeta, Dereje D; Bortolaia, Valeria; Pollini, Simona; Docquier, Jean-Denis; Rossolini, Gian M; Amos, Gregory C A; Wellington, Elizabeth M H; Guardabassi, Luca

    2016-01-01

    Carbapenemases are bacterial enzymes that hydrolyze carbapenems, a group of last-resort β-lactam antibiotics used for treatment of severe bacterial infections. They belong to three β-lactamase classes based amino acid sequence (A, B, and D). The aim of this study was to elucidate occurrence, diversity and functionality of carbapenemase-encoding genes in soil microbiota by functional metagenomics. Ten plasmid libraries were generated by cloning metagenomic DNA from agricultural ( n = 6) and grassland ( n = 4) soil into Escherichia coli . The libraries were cultured on amoxicillin-containing agar and up to 100 colonies per library were screened for carbapenemase production by CarbaNP test. Presumptive carbapenemases were characterized with regard to DNA sequence, minimum inhibitory concentration (MIC) of β-lactams, and imipenem hydrolysis. Nine distinct class B carbapenemases, also known as metallo-beta-lactamases (MBLs), were identified in six soil samples, including two subclass B1 (GRD23-1 and SPN79-1) and seven subclass B3 (CRD3-1, PEDO-1, GRD33-1, ESP-2, ALG6-1, ALG11-1, and DHT2-1). Except PEDO-1 and ESP-2, these enzymes were distantly related to any previously described MBLs (33 to 59% identity). RAIphy analysis indicated that six enzymes (CRD3-1, GRD23-1, DHT2-1, SPN79-1, ALG6-1, and ALG11-1) originated from Proteobacteria , two (PEDO-1 and ESP-2) from Bacteroidetes and one (GRD33-1) from Gemmatimonadetes . All MBLs detected in soil microbiota were functional when expressed in E. coli , resulting in detectable imipenem-hydrolyzing activity and significantly increased MICs of clinically relevant ß-lactams. Interestingly, the MBLs yielded by functional metagenomics generally differed from those detected in the same soil samples by antibiotic selective culture, showing that the two approaches targeted different subpopulations in soil microbiota.

  8. The Soil Microbiota Harbors a Diversity of Carbapenem-Hydrolyzing β-Lactamases of Potential Clinical Relevance.

    Science.gov (United States)

    Gudeta, Dereje Dadi; Bortolaia, Valeria; Amos, Greg; Wellington, Elizabeth M H; Brandt, Kristian K; Poirel, Laurent; Nielsen, Jesper Boye; Westh, Henrik; Guardabassi, Luca

    2016-01-01

    The origin of carbapenem-hydrolyzing metallo-β-lactamases (MBLs) acquired by clinical bacteria is largely unknown. We investigated the frequency, host range, diversity, and functionality of MBLs in the soil microbiota. Twenty-five soil samples of different types and geographical origins were analyzed by antimicrobial selective culture, followed by phenotypic testing and expression of MBL-encoding genes in Escherichia coli, and whole-genome sequencing of MBL-producing strains was performed. Carbapenemase activity was detected in 29 bacterial isolates from 13 soil samples, leading to identification of seven new MBLs in presumptive Pedobacter roseus (PEDO-1), Pedobacter borealis (PEDO-2), Pedobacter kyungheensis (PEDO-3), Chryseobacterium piscium (CPS-1), Epilithonimonas tenax (ESP-1), Massilia oculi (MSI-1), and Sphingomonas sp. (SPG-1). Carbapenemase production was likely an intrinsic feature in Chryseobacterium and Epilithonimonas, as it occurred in reference strains of different species within these genera. The amino acid identity to MBLs described in clinical bacteria ranged between 40 and 69%. Remarkable features of the new MBLs included prophage integration of the encoding gene (PEDO-1), an unusual amino acid residue at a key position for MBL structure and catalysis (CPS-1), and overlap with a putative OXA β-lactamase (MSI-1). Heterologous expression of PEDO-1, CPS-1, and ESP-1in E. coli significantly increased the MICs of ampicillin, ceftazidime, cefpodoxime, cefoxitin, and meropenem. Our study shows that MBL producers are widespread in soil and include four genera that were previously not known to produce MBLs. The MBLs produced by these bacteria are distantly related to MBLs identified in clinical samples but constitute resistance determinants of clinical relevance if acquired by pathogenic bacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, against Carbapenem-Nonsusceptible and Multidrug-Resistant Isolates of Gram-Negative Bacilli Collected Worldwide in 2014 to 2016.

    Science.gov (United States)

    Hackel, Meredith A; Tsuji, Masakatsu; Yamano, Yoshinori; Echols, Roger; Karlowsky, James A; Sahm, Daniel F

    2018-02-01

    The in vitro activity of the investigational siderophore cephalosporin, cefiderocol (formerly S-649266), was determined against a 2014-2016, 52-country, worldwide collection of clinical isolates of carbapenem-nonsusceptible Enterobacteriaceae ( n = 1,022), multidrug-resistant (MDR) Acinetobacter baumannii ( n = 368), MDR Pseudomonas aeruginosa ( n = 262), Stenotrophomonas maltophilia ( n = 217), and Burkholderia cepacia ( n = 4) using the Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution method. Iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB), prepared according to a recently approved (2017), but not yet published, CLSI protocol, was used to test cefiderocol; all other antimicrobial agents were tested using CAMHB. The concentration of cefiderocol inhibiting 90% (MIC 90 ) of isolates of carbapenem-nonsusceptible Enterobacteriaceae was 4 μg/ml; cefiderocol MICs ranged from 0.004 to 32 μg/ml, and 97.0% (991/1,022) of isolates demonstrated cefiderocol MICs of ≤4 μg/ml. The MIC 90 s for cefiderocol for MDR A. baumannii , MDR P. aeruginosa , and S. maltophilia were 8, 1, and 0.25 μg/ml, respectively, with 89.7% (330/368), 99.2% (260/262), and 100% (217/217) of isolates demonstrating cefiderocol MICs of ≤4 μg/ml. Cefiderocol MICs for B. cepacia ranged from 0.004 to 8 μg/ml. We conclude that cefiderocol demonstrated potent in vitro activity against a 2014-2016, worldwide collection of clinical isolates of carbapenem-nonsusceptible Enterobacteriaceae , MDR A. baumannii , MDR P. aeruginosa , S. maltophilia , and B. cepacia isolates as 96.2% of all (1,801/1,873) isolates tested had cefiderocol MICs of ≤4 μg/ml. Copyright © 2018 Hackel et al.

  10. Molecular epidemiology of bla OXA-23 -producing carbapenem-resistant Acinetobacter baumannii in a single institution over a 65-month period in north China.

    Science.gov (United States)

    Ning, Nian-Zhi; Liu, Xiong; Bao, Chun-Mei; Chen, Su-Ming; Cui, En-Bo; Zhang, Ju-Ling; Huang, Jie; Chen, Fang-Hong; Li, Tao; Qu, Fen; Wang, Hui

    2017-01-05

    Carbapenem-resistant Acinetobacter baumannii poses a significant threat to hospitalized patients, as few therapeutic options remain. Thus, we investigated the molecular epidemiology and mechanism of resistance of carbapenem-resistant A.baumannii isolates in Beijing, China. Carbapenem-resistant A.baumannii isolates (n = 101) obtained between June 2009 and November 2014 were used. Multilocus sequence typing (MLST) and PCR assays for class C and D β-lactamase were performed on all isolates. S1 nuclease pulsed-field gel electrophoresis (PFGE) and Southern blot hybridization were performed to identify the resistance gene location. All 101 A.baumannii isolates were highly resistant to frequently used antimicrobials, and were considered multidrug resistant. A total of 12 sequence types (STs) were identified, including 10 reported STs and 2 novel STs. Eighty-seven isolates were classified to clonal complex 92 (CC92), among which ST191 and ST195 were the most common STs. The bla OXA-23 gene was positive in most (n = 95) of the A.baumannii isolates. Using S1-nuclease digestion PFGE and Southern blot hybridization, 3 patterns of plasmids carrying bla OXA-23 were confirmed. ST191 and ST195 (both harboring bla OXA-23 ) caused outbreaks during the study period, and this is the first report of outbreaks caused by ST191 and ST195 in north China. bla OXA-23 -producing A.baumannii ST191 and ST 195 isolates can disseminate in a hospital and are potential nosocomial outbreak strains. Surveillance of imipenem-resistant A.baumannii and antimicrobial stewardship should be strengthened.

  11. Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States

    Science.gov (United States)

    Chen, Liang; Patel, Gopi; Gomez-Simmonds, Angela; Weston, Gregory; Kim, Angela C.; Seo, Susan K.; Rosenthal, Marnie E.; Sperber, Steven J.; Jenkins, Stephen G.; Hamula, Camille L.; Uhlemann, Anne-Catrin; Levi, Michael H.; Fries, Bettina C.; Juretschko, Stefan; Rojtman, Albert D.; Hong, Tao; Mathema, Barun; Jacobs, Michael R.; Walsh, Thomas J.; Bonomo, Robert A.; Kreiswirth, Barry N.

    2017-01-01

    ABSTRACT Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics. PMID:28167547

  12. Comparison of synergism between colistin, fosfomycin and tigecycline against extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates or with carbapenem resistance

    Directory of Open Access Journals (Sweden)

    Yee-Huang Ku

    2017-12-01

    Full Text Available Purpose: To investigate the synergistic and bactericidal effects of antimicrobial combinations of any two of colistin, fosfomycin and tigecycline against the nine extended-spectrum β-lactamase (ESBL-producing Klebsiella pneumoniae (KP clinical isolates, including 4 carbapenem-susceptible strains and five imipenem and/or meropenem-resistant strains. Methods: In vitro synergism and bactericidal activity of combination of colistin, fosfomycin and tigecycline were evaluated by time-kill studies in standard inoculum of bacterial densities of a suspension containing 5 × 105 CFU/mL by using 1/2× MIC for each alone, and both 1/2× and 1/4× MIC for any two drugs. The settings of low MIC dosing were allowed to rapidly survey the most active drug combination. Results: The most active combination group was colistin plus tigecycline, showing synergy in 8 isolates and bactericidal activities in 6 isolates by using concentrations of 1/2× MIC and 1/4× MIC, respectively. The least active combination was tigecycline plus fosfomycin, which showed synergy in only 4 isolates and no bactericidal activities by using concentrations of 1/2× MIC and 1/4× MIC, respectively. Conclusions: The combination of tigecycline and colistin may be considered as a last-resort approach to the ESBL-producing KP infections, especially those isolates with carbapenem resistance. Keywords: Carbapenem resistance, Colistin, ESBL, Fosfomycin, Tigecycline

  13. Carbapenem and cefoxitin resistance of Klebsiella pneumoniae strains associated with porin OmpK36 loss and DHA-1 β-lactamase production

    Directory of Open Access Journals (Sweden)

    Weifeng Shi

    2013-01-01

    Full Text Available Clinical isolates of carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae strains are being increased worldwide. Five pan-resistant K. pneumoniae strains have been isolated from respiratory and ICU wards in a Chinese hospital, and reveal strong resistance to all β-lactams, fluoroquinolones and aminoglycosides. Totally 27 β-lactamase genes and 2 membrane pore protein (porin genes in 5 K. pneumoniae strains were screened by polymerase chain reaction (PCR. The results indicated that all of 5 K. pneumoniae strains carried blaTEM-1 and blaDHA-1 genes, as well as base deletion and mutation of OmpK35 or OmpK36 genes. Compared with carbapenem-sensitive isolates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE, the resistant isolates markedly lacked the protein band of 34-40 kDa, which might be the outer membrane proteins of OmpK36 according to the electrophoresis mobility. In addition, the conjugation test was confirmed that blaDHA-1 mediated by plasmids could be transferred between resistant and sensitive strains. When reserpine (30 µg/mL and carbonyl cyanide m-chlorophenylhydrazone (CCCP (50 µg/mL were added in imipenem and meropenem, the MICs had no change against K. pneumoniae strains. These results suggest that both DHA-1 β-lactamase and loss or deficiency of porin OmpK36 may be the main reason for the cefoxitin and carbapenem resistance in K. pneumoniae strains in our hospital.

  14. WCK 4234, a novel diazabicyclooctane potentiating carbapenems against Enterobacteriaceae, Pseudomonas and Acinetobacter with class A, C and D β-lactamases.

    Science.gov (United States)

    Mushtaq, Shazad; Vickers, Anna; Woodford, Neil; Livermore, David M

    2017-06-01

    Several diazabicyclooctanes (DBOs) are under development as inhibitors of class A and C β-lactamases. Inhibition of OXA (class D) carbapenemases is variable, with those of Acinetobacter spp. remaining notably resistant. We describe a novel DBO, WCK 4234 (Wockhardt), with distinctive activity against OXA carbapenemases. MICs of imipenem and meropenem were determined by CLSI agar dilution with WCK 4234 added at 4 or 8 mg/L. Test organisms were clinical Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa with carbapenemases or carbapenem resistance via porin loss plus AmpC or ESBL activity. AmpC mutants were also tested. WCK 4234, which lacked direct antibacterial activity, strongly potentiated imipenem and meropenem against Enterobacteriaceae with OXA-48/OXA-181 or KPC enzymes, or with combinations of impermeability and AmpC or ESBL activity, with MICs reduced to ≤2 mg/L in almost all cases. Carbapenems likewise were potentiated against P. aeruginosa ( n  =   2) with OXA-181 enzyme, with MICs reduced from 64-128 to 2-8 mg/L and against A. baumannii with OXA carbapenemases, particularly OXA-23 or hyperproduced OXA-51, with MICs reduced to ≤2 mg/L for 9/10 acinetobacters with OXA-23 enzyme. Carbapenems were not potentiated against Enterobacteriaceae or non-fermenters with metallo-β-lactamases. WCK 4234 distinctively overcame resistance mediated by OXA-type carbapenemases, including those of A. baumannii . It behaved similarly to other DBOs against strains with KPC carbapenemases or combinations of impermeability and ESBL or AmpC activity. © 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.

  15. Alterations of OprD in Carbapenem-Intermediate and -Susceptible Strains of Pseudomonas aeruginosa Isolated from Patients with Bacteremia in a Spanish Multicenter Study

    Science.gov (United States)

    Cabot, Gabriel; Rodríguez, Cristina; Roman, Elena; Tubau, Fe; Macia, María D.; Moya, Bartolomé; Zamorano, Laura; Suárez, Cristina; Peña, Carmen; Domínguez, María A.; Moncalián, Gabriel; Oliver, Antonio; Martínez-Martínez, Luis

    2012-01-01

    We investigated the presence of OprD mutations in 60 strains of metallo-ß-lactamase-negative Pseudomonas aeruginosa intermediately susceptible (IS [n = 12]; MIC = 8 μg/ml) or susceptible (S [n = 48]; MICs ≤ 1 to 4 μg/ml) to imipenem and/or meropenem that were isolated from patients with bacteremia in order to evaluate their impact on carbapenem susceptibility profiles. The presence of mutations in oprD was detected by sequencing analysis. OprD expression was assessed by both outer membrane protein (OMP) analysis and real-time PCR (RT-PCR). Fourteen (23%) isolates had an OprD identical to that of PAO1, and OprD modifications were detected in 46 isolates (77%). Isolates were classified as OprD “full-length types” (T1 [n = 40, including both wild-type OprD and variants showing several polymorphisms]) and OprD “deficient types” (T2 [n = 3 for OprD frameshift mutations] and T3 [n = 17 for premature stop codons in oprD]). RT-PCR showed that 5 OprD type T1 isolates presented reduced transcription of oprD (0.1- to 0.4-fold compared to PAO1), while oprD levels increased more than 2-fold over that seen with PAO1 in 4 OprD type T1 isolates. A total of 50% of the isolates belonging to OprD “deficient types” were susceptible to both carbapenems, and 40% were susceptible to meropenem and intermediately susceptible to imipenem. Only one isolate (5%) within this group was intermediately susceptible to both carbapenems, and one (5%) was susceptible to imipenem and intermediately susceptible to meropenem. We concluded that OprD inactivating mutations in clinical isolates of P. aeruginosa are not restricted only to carbapenem-resistant isolates but are also found in isolates with imipenem or meropenem MICs of only 0.06 to 4 μg/ml. PMID:22290967

  16. The Impact of a Carbapenem-Resistant Enterobacteriaceae Outbreak on Facilitating Development of a National Infrastructure for Infection Control in Israel.

    Science.gov (United States)

    Schwaber, Mitchell J; Carmeli, Yehuda

    2017-11-29

    In 2006 the Israeli healthcare system faced an unprecedented outbreak of carbapenem-resistant Enterobacteriaceae, primarily involving KPC-producing Klebsiella pneumoniae clonal complex CC258. This public health crisis exposed major gaps in infection control. In response, Israel established a national infection control infrastructure. The steps taken to build this infrastructure and benefits realized from its creation are described here. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  17. In vitro activity of ACH-702, a new isothiazoloquinolone, against Nocardia brasiliensis compared with econazole and the carbapenems imipenem and meropenem alone or in combination with clavulanic acid.

    Science.gov (United States)

    Vera-Cabrera, Lucio; Campos-Rivera, Mayra Paola; Escalante-Fuentes, Wendy G; Pucci, Michael J; Ocampo-Candiani, Jorge; Welsh, Oliverio

    2010-05-01

    The in vitro activities of ACH-702 and other antimicrobials against 30 Nocardia brasiliensis isolates were tested. The MIC(50) (MIC for 50% of the strains tested) and MIC(90) values of ACH-702 were 0.125 and 0.5 microg/ml. The same values for econazole were 2 and 4 microg/ml. The MIC(50) and MIC(90) values of imipenem and meropenem were 64 and >64 microg/ml and 2 and 8 microg/ml, respectively; the addition of clavulanic acid to the carbapenems had no effect.

  18. Investigation of a possible outbreak of carbapenem-resistant Acinetobacter baumannii in Odense, Denmark using PFGE, MLST and whole-genome-based SNPs

    DEFF Research Database (Denmark)

    Hammerum, Anette M; Hansen, Frank; Skov, Marianne N

    2015-01-01

    carbapenem-resistant A. baumannii were detected at Odense University Hospital, Odense, Denmark. These isolates were typed by PFGE, with ApaI and SmaI, respectively, and subjected to WGS. The WGS data were used for in silico extraction of MLST types using two different schemes, resistance genes and SNPs......, to which 31 publicly available A. baumannii genomes were added. RESULTS: Using ApaI, the eight isolates had four different PFGE profiles, which were further differentiated using SmaI, separating one of the profiles into two distinct PFGE types. Five ST2 (Pasteur MLST) OXA-23-producing isolates, two ST1 OXA...

  19. Title list of documents made publicly available

    International Nuclear Information System (INIS)

    1979-12-01

    This monthly publication contains descriptions of the information received and generated by the US Nuclear Regulatory Commission (NRC). This information includes docketed material associated with civilian nuclear power plants and other uses of radioactive materials, and nondocketed material received and generated by NRC pertinent to its role as a regulatory agency. This series of documents is indexed by a Personal Author Index, a Corporate Source Index, and a Report Number Index. The docketed information includes the inforation formerly issued through the Department of Energy's Technical Information Center under the title Power Reactor Docket Information (PRDI) and, in addition, information received or generated on other uses of radioactive materials

  20. Title list of documents made publicly available

    International Nuclear Information System (INIS)

    1994-06-01

    The Title List of Documents Made Publicly Available is a monthly publication. It contains descriptions of the information received and generated by the US Nuclear Regulatory Commission (NRC). This information includes (1) docketed material associated with civilian nuclear power plants and other uses of radioactive materials and (2) nondocketed material received and generated by NRC pertinent to its role as a regulatory agency. As used here, docketed does not refer to Court dockets; it refers to the system by which NRC maintains its regulatory records. This series of documents is indexed by a Personal Author Index, a Corporate Source Index, and a Report Number Index

  1. Title list of documents made publicly available

    International Nuclear Information System (INIS)

    1982-03-01

    The Title List of Documents Made Publicly Available is a monthly publication. It contains descriptions of the information received and generated by the US Nuclear Regulatory Commission (NRC). This information includes (1) docketed material associated with civilian nuclear power plants and other uses of radioactive materials and (2) nondocketed material received and generated by NRC pertinent to its role as a regulatory agency. As used here, docketed does not refer to Court dockets; it refers to the system by which NRC maintains its regulatory records. This series of documents is indexed by a Personal Author Index, a Corporate Source Index, and a Report Number Index

  2. Wisconsin Public Service, Weston Generating Station; Petition to Object to Issuance of Title V Operating Permit

    Science.gov (United States)

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database.

  3. Tennessee Valley Authority, Paradise Fossil Plant; Petition to Object to Title V Operating Permit

    Science.gov (United States)

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database.

  4. Tennessee Valley Authority, Paradise Fossil Plant; Order Responding Petition to Object to Title V Operating Permit

    Science.gov (United States)

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database.

  5. 20 CFR 416.573 - How much will we withhold from your title II and title VIII benefits to recover a title XVI...

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false How much will we withhold from your title II... Payment of Benefits, Overpayments, and Underpayments § 416.573 How much will we withhold from your title...-due benefits. (b)(1) We will collect the overpayment from current monthly benefits due in a month by...

  6. Title XX and CETA. A Coordination Guide for Title XX Administrators.

    Science.gov (United States)

    Urban Management Consultants of San Francisco, Inc., CA.

    Written for the social service (Title XX) administrator at the State or sub-State level, this guide is intended to serve four major purposes: (1) Provide selected insights into what the Comprehensive Employment and Training Act (CETA) is and how it works; (2) point out potential areas for coordination which, from study or field experience, hold…

  7. New chiral phosphinephosphinite ligands: Application to stereoselective synthesis of a key intermediate of 1{beta}-methyl carbapenems by Rh(I)-catalyzed asymmetric hydroformylation

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Takao; Yoshida, Akifumi; Matsumura, Kazuhiko [Takasago International Corp., Kanagawa (Japan)] [and others

    1995-12-31

    Transition metal catalyzed asymmetric hydroformylation is an attractive and highly useful homologation process for organic synthesis. Recently, the authors reported that the Rh(I) complexes of phosphinephosphite BINAPHOS are highly efficient catalysts for enantioselective hydroformylation of a variety of olefins. This time, the authors have designed and synthesized new chiral phosphinephosphinite ligands having binaphthyl backbone, (R)-2-diarylphosphino-2{prime}-diarylphosphinoxy-1,1{prime}-binaphthy1 (hereafter abbreviated (R)-BIPNITE). The Rh(I) complexes of these ligands are effective catalysts for the asymmetric hydroformylation of 4-vinylazetidin-2-one to give the corresponding oxo-aldehyde 3{beta} as the major product in very high diastereoselectivities and in good regioselectivities. Interestingly, modifications of the aryl substituents in phosphine and phosphinite moieties afforded higher selectivities. Aldehyde 3{beta} was easily oxidized with NaClO{sub 2} to 4, a key intermediate of 1{beta}-methyl carbapenems. Thus, the present method provides a new practical route to a versatile key intermediate for the synthesis of carbapenem antibiotics.

  8. Complete nucleotide sequence of pGA45, a 140,698-bp incFIIY plasmid encoding blaIMI-3-mediated carbapenem resistance, from river sediment

    Directory of Open Access Journals (Sweden)

    Bingjun eDang

    2016-02-01

    Full Text Available Plasmid pGA45 was isolated from the sediment of Haihe River using E. coli CV601 (gfp-tagged as recipients and indigenous bacteria from sediment as donors. This plasmid confers reduced susceptibility to imipenem which belongs to carbapenem group. Plasmid pGA45 was fully sequenced on an Illumina HiSeq 2000 sequencing system. The complete sequence of plasmid pGA45 was 140,698 bp in length with an average G+C content of 52.03%. Sequence analysis shows that pGA45 belongs to incFIIY group and harbors a backbone region shares high homology and gene synteny to several other incF plasmids including pNDM1_EC14653, pYDC644, pNDM-Ec1GN574, pRJF866, pKOX_NDM1 and pP10164-NDM. In addition to the backbone region, plasmid pGA45 harbors two notable features including one blaIMI-3-containing region and one type VI secretion system region. The blaIMI-3-containing region is responsible for bacteria carbapenem resistance and the type VI secretion system region is probably involved in bacteria virulence, respectively. Plasmid pGA45 represents the first complete nucleotide sequence of the blaIMI-harboring plasmid from environment sample and the sequencing of this plasmid provided insight into the architecture used for the dissemination of blaIMI carbapenemase genes.

  9. In vitro activity of tigecycline and comparators against carbapenem-resistant Enterobacteriaceae in Africa-Middle East countries: TEST 2007-2012.

    Science.gov (United States)

    Renteria, M I; Biedenbach, D J; Bouchillon, S K; Hoban, D J; Raghubir, N; Sajben, P

    2014-09-01

    Multidrug-resistant (MDR) Enterobacteriaceae are an emerging concern for healthcare providers. Infections caused by MDR pathogens are associated with increased costs, length of hospital stay, and morbidity and mortality rates. Carbapenem-resistant Enterobacteriaceae (CRE) continue to increase, and infections with these organisms are observed worldwide not only as hospital-acquired infections but also as community-acquired infections. Increasing antimicrobial resistance dictates the need for continued surveillance studies of common and MDR pathogens. The Tigecycline Evaluation Surveillance Trial (TEST) examined the susceptibility of pathogens isolated in Africa and the Middle East from 2007 to 2012. A total of 4155 Enterobacteriaceae isolates were evaluated to determine the in vitro activity and changes in resistance patterns for tigecycline and comparators. Carbapenem resistance was found in 191 (4.6%) of the isolates tested. Klebsiella pneumoniae was the most common CRE (64.9%), followed by Enterobacter cloacae (14.1%) and Escherichia coli (9.9%). Tigecycline MIC 90 values (minimum inhibitory concentration required to inhibit 90% of the isolates) were 2μg/mL against all of these enteric species, with susceptibility rates of 96.8%, 92.6% and 100%, respectively. Tigecycline had in vitro activity against CRE, with a 95.3% susceptibility rate. Copyright © 2014 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  10. Citation Oil and Gas Corporation... Title V Applicability Determination

    Science.gov (United States)

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  11. Comparative effectiveness of flomoxef versus carbapenems in the treatment of bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae with emphasis on minimum inhibitory concentration of flomoxef: a retrospective study.

    Science.gov (United States)

    Lee, Chen-Hsiang; Su, Lin-Hui; Chen, Fang-Ju; Tang, Ya-Feng; Li, Chia-Chin; Chien, Chun-Chih; Liu, Jien-Wei

    2015-12-01

    This study compared treatment outcomes of adult patients with bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae (ESBL-EK) receiving flomoxef versus those receiving a carbapenem as definitive therapy. In propensity score matching (PSM) analysis, case patients receiving flomoxef shown to be active in vitro against ESBL-EK were matched with controls who received a carbapenem. The primary endpoint was 30-day crude mortality. The flomoxef group had statistically significantly higher sepsis-related mortality (27.3% vs. 10.5%) and 30-day mortality (28.8% vs. 12.8%) than the carbapenem group. Of the bacteraemic episodes caused by isolates with a MICflomoxef of ≤1 mg/L, sepsis-related mortality rates were similar between the two treatment groups (8.7% vs. 6.4%; P=0.73). The sepsis-related mortality rate of the flomoxef group increased to 29.6% and 50.0% of episodes caused by isolates with a MICflomoxef of 2-4 mg/L and 8 mg/L, respectively, which was significantly higher than the carbapenem group (12.3%). In the PSM analysis of 86 case-control pairs infected with strains with a MICflomoxef of 2-8 mg/L, case patients had a significantly higher 30-day mortality rate (38.4% vs. 18.6%). Multivariate regression analysis revealed that flomoxef therapy for isolates with a MICflomoxef of 2-8 mg/L, concurrent pneumonia or urosepsis, and a Pitt bacteraemia score ≥4 were independently associated with 30-day mortality. Definitive flomoxef therapy appears to be inferior to carbapenems in treating ESBL-EK bacteraemia, particularly for isolates with a MICflomoxef of 2-8 mg/L, even though the currently suggested MIC breakpoint of flomoxef is ≤8 mg/L. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  12. Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States.

    Science.gov (United States)

    Satlin, Michael J; Chen, Liang; Patel, Gopi; Gomez-Simmonds, Angela; Weston, Gregory; Kim, Angela C; Seo, Susan K; Rosenthal, Marnie E; Sperber, Steven J; Jenkins, Stephen G; Hamula, Camille L; Uhlemann, Anne-Catrin; Levi, Michael H; Fries, Bettina C; Tang, Yi-Wei; Juretschko, Stefan; Rojtman, Albert D; Hong, Tao; Mathema, Barun; Jacobs, Michael R; Walsh, Thomas J; Bonomo, Robert A; Kreiswirth, Barry N

    2017-04-01

    Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types ( cps ), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae , Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC- Kp ). The wzi154 allele, corresponding to cps-2 , was present in 93% of KPC-3- Kp , whereas KPC-2- Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3- Kp had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3- Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics. Copyright © 2017 American Society for Microbiology.

  13. Whole genome sequencing for the molecular characterization of carbapenem-resistant Klebsiella pneumoniae strains isolated at the Italian ASST Fatebenefratelli Sacco Hospital, 2012-2014.

    Science.gov (United States)

    Rimoldi, Sara Giordana; Gentile, Bernardina; Pagani, Cristina; Di Gregorio, Annamaria; Anselmo, Anna; Palozzi, Anna Maria; Fortunato, Antonella; Pittiglio, Valentina; Ridolfo, Anna Lisa; Gismondo, Maria Rita; Rizzardini, Giuliano; Lista, Florigio

    2017-10-10

    The emergence of carbapenem-resistant Klebsiella pneumoniae strains is threatening antimicrobial treatment. Sixty-eight carbapenemase-producing K. pneumoniae strains isolated at Luigi Sacco University Hospital-ASST Fatebenefratelli Sacco (Milan, Italy) between 2012 and 2014 were characterised microbiologically and molecularly. They were tested for drug susceptibility and carbapenemase phenotypes, investigated by means of repetitive extra-genic palindromic polymerase chain reaction (REP-PCR), and fully sequenced by means of next-generation sequencing for the in silico analysis of multi-locus sequence typing (MLST), their resistome, virulome and plasmid content, and their core single nucleotide polymorphism (SNP) genotypes. All of the samples were resistant to carbapenems, other β-lactams and ciprofloxacin; many were resistant to aminoglycosides and tigecycline; and seven were resistant to colistin. Resistome analysis revealed the presence of blaKPC genes and, less frequently blaSHV, blaTEM, blaCTX-M and blaOXA, which are related to resistance to carbapenem and other β-lactams. Other genes conferring resistance to aminoglycoside, fluoroquinolone, phenicol, sulphonamide, tetracycline, trimethoprim and macrolide-lincosamide-streptogramin were also detected. Genes related to AcrAB-TolC efflux pump-dependent and pump-independent tigecycline resistance mechanisms were investigated, but it was not possible to clearly correlate the genomic features with tigecycline resistance because of the presence of a common mutation in susceptible, intermediate and resistant strains. Concerning colistin resistance, the mgrB gene was disrupted by an IS5-like element, and the mobile mcr-1 and mcr-2 genes were not detected in two cases. The virulome profile revealed type-3 fimbriae and iron uptake system genes, which are important during the colonisation stage in the mammalian host environment. The in silico detected plasmid replicons were classified as IncFIB(pQil), IncFIB(K), Col

  14. Molecular epidemiological survey of the quinolone- and carbapenem-resistant genotype and its association with the type III secretion system in Pseudomonas aeruginosa.

    Science.gov (United States)

    Ferreira, Melina Lorraine; Dantas, Raquel Cavalcanti; Faria, Ana Luiza Souza; Gonçalves, Iara Rossi; Silveira de Brito, Cristiane; Queiroz, Lícia Ludendorff; Gontijo-Filho, Paulo P; Ribas, Rosineide Marques

    2015-03-01

    This study evaluated the predictors of mortality and the impact of inappropriate therapy on the outcomes of patients with bacteraemia and ventilator-associated pneumonia (VAP). Additionally, we evaluated the correlation of the type III secretion system (TTSS) effector genotype with resistance to carbapenems and fluoroquinolones, mutations in the quinolone resistance-determining regions (QRDRs), metallo-β-lactamase and virulence factors. A retrospective cohort was conducted at a tertiary hospital in patients with multidrug-resistant (MDR) P. aeruginosa bacteraemia (157 patients) and VAP (60 patients). The genes for blaIMP, blaVIM, blaSIM, blaGIM and blaSPM and virulence genes (exoT, exoS, exoY, exoU, lasB, algD and toxA) were detected; sequencing was conducted for QRDR genes on fluoroquinolone-resistant strains. The multivariate analyses showed that the predictors independently associated with death in patients with bacteraemia were cancer and inappropriate therapy. Carbapenem resistance was more frequent among strains causing VAP (53.3 %), and in blood we observed the blaSPM genotype (66.6 %) and blaVIM genotype (33.3 %). The exoS gene was found in all isolates, whilst the frequency was low for exoU (9.4 %). Substitution of threonine to isoleucine at position 83 in gyrA was the most frequent mutation among fluoroquinolone-resistant strains. Our study showed a mutation at position 91 in the parC gene (Glu91Lys) associated with a mutation in gyrA (Thre83Ile) in a strain of extensively drug-resistant P. aeruginosa, with the exoT(+)exoS(+)exoU(+) genotype, that has not yet been described in Brazil to the best of our knowledge. This comprehensive analysis of resistance mechanisms to carbapenem and fluoroquinolones and their association with TTSS virulence genes, covering MDR P. aeruginosa in Brazil, is the largest reported to date. © 2015 The Authors.

  15. The ties that bind: what's in a title?

    Science.gov (United States)

    Neuhaus, Susan J

    2018-03-01

    Many Australian and New Zealand surgeons use the title 'Mister' rather than 'Doctor', a practice dating back to traditions established over 600 years ago. The Royal Australasian College of Surgeons is currently undergoing a period of critical self-reflection, embodied by its 'Respect' campaign. Active measures to embrace diversity and encourage women into surgery are underway. This paper reviews the historical basis to the use of gendered titles and their current use amongst fellows. De-identified demographic data from the college register of active fellows was searched by self-identified title, country or state, and gender. Data were further reviewed by surgical sub-specialty and year of fellowship. The college dataset suggests that there is significant variance in the preference for gendered titles, determined predominantly by geography rather than specialty. The highest use of gendered titles (by male and female surgeons) was in Victoria/Tasmania (58% male, 22% female) and New Zealand (81% male, 17% female). By contrast, only 2% of female surgeons in other states elected a gendered title (Miss/Mrs/Ms). Surgery is the only profession that continues to use gendered titles. As the College of Surgeons moves towards greater equity and diversity, consideration should be given to phasing out the use of gendered titles, which serve to divide rather than unite our profession. © 2017 Royal Australasian College of Surgeons.

  16. 24 CFR 232.595 - Eligibility of title.

    Science.gov (United States)

    2010-04-01

    ... URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES MORTGAGE INSURANCE FOR NURSING HOMES, INTERMEDIATE CARE FACILITIES, BOARD AND CARE HOMES, AND ASSISTED... Fire Safety Equipment Title § 232.595 Eligibility of title. In order for the property which is to be...

  17. Title IX--Beyond Compliance to Personal Commitment and Leadership

    Science.gov (United States)

    Peterson, Barbara

    1976-01-01

    In order to move beyond legal compliance to real equality of opportunity, every educational leader must develop some systematic means of extending his or her personal knowledge and skills with respect to Title IX. Provides a check list for self evaluation of educational leaders and a guide for developing an implementation plan for Title IX.…

  18. Comprehensive Social Service Programs for Handicapped Citizens through Title XX.

    Science.gov (United States)

    Roten, Shelby Jean

    Reviewed are present and potential services and social programs for handicapped children in Mississippi through purchase of service contracts under Title XX of the Social Security Act. Sections cover the following topics: background and purpose of Title XX which gives states greater control over social service programs, planning state supported…

  19. Pocketguide to Title XX: Social Services to Children & Youth.

    Science.gov (United States)

    Mueller, Candace

    This brief guide to Title XX contains the following chapter headings: (1) Historical Overview of the Social Services Program, (2) The Provisions of Title XX at a Glance, (3) Implications for Services to Children and Youth, (4) The Planning Process, (5) Publication of the Proposed Plan and the Public Comment Period, (6) After the Final Plan is…

  20. A License for Bias: Sex Discrimination, Schools, and Title IX.

    Science.gov (United States)

    Morse, Susan Ed.

    This report discusses non-sports-related Title IX complaints filed with the Department of Education's Office for Civil Rights (OCR) from 1993-1997. Its purpose is to dispel the popular belief that Title IX is a sports-equity law and to determine the effectiveness of the legislation. The document examines the kinds of complaints filed, the status…