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Background: The prevalence of extended-spectrum -lactamase (ESBL)-producing Escherichia coli in Norway has been steadily increasing during the last 10-15 years as part of a global pandemic. ESBL producers frequently express co-res...
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Background: The prevalence of extended-spectrum -lactamase (ESBL)-producing Escherichia coli in Norway has been steadily increasing during the last 10-15 years as part of a global pandemic. ESBL producers frequently express co-resistance to other important antimicrobial drug classes, limiting therapeutic options. This has led to regained interest in older antimicrobial agents. The aim of this study was to evaluate the antimicrobial activity of mecillinam, nitrofurantoin, temocillin and fosfomycin, as well as to perform a comparative analysis of resistance patterns in a nationwide collection of ESBL-producing E. coli. Methods: A nationwide collection of all 105 clinical isolates of ESBL-producing E. coli from the Norwegian Organisation for Surveillance of Antimicrobial Resistance (NORM) during 2010-2011 was analyzed. Detection and identification of ESBL-encoding genes were performed by PCR and sequencing for confirmation of ESBL variants of bla(TEM) and bla(SHV) (2010) or microarray (2011). Minimum inhibitory concentrations (MICs) or MIC correlates were determined using MIC gradient tests or VITEK 2, respectively. Comparative analysis of resistance patterns was performed. Results: All isolates were susceptible to fosfomycin, temocillin (urinary tract breakpoint) and meropenem. For mecillinam and nitrofurantoin, 6% and 9% of the isolates, respectively, were non-susceptible. A high level of susceptibility was also observed for amikacin (95%). In contrast, the non-susceptibility proportions to ampicillin (100%), cefotaxime (97%), ceftazidime (77%), aztreonam (87%), gentamicin (42%), tobramycin (52%), ciprofloxacin (76%) and trimethoprim-sulfamethoxazole (71%) were higher. Conclusions: Overall, the in vitro susceptibility to nitrofurantoin, fosfomycin, mecillinam and temocillin was high, indicating that these drugs are good options for treating uncomplicated urinary tract infections caused by ESBL-producing E. coli.
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We evaluated the in vitro effectiveness of temocillin and several commonly used antimicrobials against Enterobacterales bacteria in isolates from Polish patients. We tested 400 isolates: 260 extended-spectrum β-lactamase (ESBL)- ...
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We evaluated the in vitro effectiveness of temocillin and several commonly used antimicrobials against Enterobacterales bacteria in isolates from Polish patients. We tested 400 isolates: 260 extended-spectrum β-lactamase (ESBL)- and/or ampC β-lactamase (AmpC)-producing isolates; 40 Klebsiella pneumoniae carbapenemase (KPC)-producing isolates; and 100 ESBL-, AmpC-, and KPC-negative isolates. The minimal inhibitory concentrations (MICs) of temocillin and 16 other antimicrobials were determined by reference microdilution. We also determined the activities of fosfomycin and ceftazidime/avibactam in KPC-producing isolates. The antibiotic sensitivities were interpreted according to EUCAST, BSAC, and CLSI criteria. Overall, 91% of the isolates were susceptible to temocillin using the urinary tract infection breakpoint (≤32 mg/L), and 61.8% were susceptible using the systemic infection breakpoint (≤ 8 mg/L). Meropenem and imipenem were the most active drugs (MIC_(50) values of 0.06 and 0.5 mg/L, respectively). Colistin and ertapenem (both MIC_(50) = 0.12 mg/L) were less active than meropenem or imipenem, but some strains were 77% susceptible to each of them. Among the KPC-producing isolates, 42.5% had MIC values of ≤ 32 mg/L (urinary tract infection breakpoint), but 100% were resistant to temocillin (systemic infection breakpoint). Ceftazidime/avibactam was active against 100% ofthe KPC-producing isolates, and fosfomycin was active against 40%. The empirical susceptibility rate observed among the urinary isolates suggests that temocillin may be considered as an alternative to carbapenems in the absence of KPC-producing bacteria. With regard to isolates from other sources, temocillin might be useful as a documented therapy agent or an empirical treatment in hospitals with a low prevalence of ESBL/AmpC-producing strains.
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Recently there has been a renewed interest in reviving older antimicrobial agents, particularly those with activity against multidrug-resistant Gram-negative bacilli. Because many such antimicrobials are not licensed in all countr...
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Recently there has been a renewed interest in reviving older antimicrobial agents, particularly those with activity against multidrug-resistant Gram-negative bacilli. Because many such antimicrobials are not licensed in all countries, there is a paucity of international surveillance data, and none of these agents is part of any antimicrobial resistance surveillance on the level of the EU. Some of the agents are used in lower urinary tract infection, whereas most available supranational surveillance data pertain to severe infections such as bloodstream infections. Among old antimicrobial agents, the most interesting compounds from a clinical perspective are the two intravenous agents colistin and temocillin, the two oral agents pivmecillinam and nitrofurantoin, and fosfomycin, which is available both for intravenous and oral use. The most interesting target microorganisms are Enterobacteriaceae, although colistin also has good activity against Pseudomonas aeruginosa and Acinetobacter species. Recent European surveillance data point to approximately 5% resistance to colistin in general among Klebsiella pneumoniae, whereas resistance in carbapenemase-producing Enterobacteriaceae may be up to 15% to 20% in some settings. Temocillin is stable against many extended-spectrum beta-lactamase producing Enterobacteriaceae and some carbapenemase producers, but low-level resistance is not uncommon in extended-spectrum B-lactamase producers, and high-level resistance is always seen with OXA-48 group carbapenemases. Fosfomycin resistance is rare in areas with limited use but increasing is in countries with higher usage. Resistance levels to mecillinam and nitrofurantoin are generally low in EU countries, but clinical data supporting treatment efficacy of multidrug-resistant strains are few. Systematic surveillance of the above-mentioned agents will be important, particularly for those agents used in severe infections. Clinical Microbiology and Infection (C) 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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AIM: To evaluate the diagnostic performance of MDI and temocillin disk (30 μg) for detection of carbapenem-resistant Enterobacteriaceae in comparison to real-time PCR. MATERIAL AND METHODS: Fifty specimens submitted to the Microb...
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AIM: To evaluate the diagnostic performance of MDI and temocillin disk (30 μg) for detection of carbapenem-resistant Enterobacteriaceae in comparison to real-time PCR. MATERIAL AND METHODS: Fifty specimens submitted to the Microbiology Laboratory of Ain Shams University Hospitals and showed resistance to carbapenem drugs through routine culture and susceptibility testing, were assessed by both temocillin disk (30 μg) and MDI set to detect carbapenem-resistant Enterobacteriaceae . Results were compared to real-time PCR for detection of carbapenemase genes blaKPC, blaNDM, blaOXA –48- like , blaVIM , and blaIMP . RESULTS: Our work revealed that most of the CPE isolates were Klebsiella species (62%) followed by E. coli (24%), Serratia (10%) and Citrobacter (4%). Phenotypic detection of carbapenem-resistant classes revealed OXA - 48 in 96% of isolates, followed by MBLs (82%), and KPC (34%). All isolates were negative for AmpC . Detection of the genes by real-time PCR showed that the predominance was for the blaOXA-48 gene (96%) then blaVIM (94%) followed by blaNDM (54%), blaKPC (46%) and finally blaIMP (40%). Evaluation of the MDI set against PCR showed sensitivity (82.1%) and specificity (70%). The temocillin disk had 97.9% sensitivity and 50% specificity. The evaluation of Temocillin disk and MDI in combination for detection of carbapenem-resistant Enterobacteriaceae showed 99.7% sensitivity and 35% specificity. CONCLUSION: Adding Temocillin disk to Mastdisks ID inhibitor combination set provides a simple, easy, rapid and highly sensitive test that can be used for screening and classification of carbapenem-resistant Enterobacteriaceae . However, it still needs confirmation by molecular techniques.
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With rising antibiotic resistance, alternatives to carbapenems are needed for acute cholangitis (AC). Temocillin reaches high biliary concentrations with limited impact on microbiota. We retrospectively included 140 AC episodes an...
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With rising antibiotic resistance, alternatives to carbapenems are needed for acute cholangitis (AC). Temocillin reaches high biliary concentrations with limited impact on microbiota. We retrospectively included 140 AC episodes and assessed the efficacy of temocillin using microbiology susceptibility testing from blood cultures. Considering all bacteria collected by episode, resistance to temocillin, PIP/TAZ and 3GC occurred in 27/140 (26%), 32 (22.8%) and 31 (22%) episodes, respectively (p = 0.7). After documentation, temocillin could have spared PIP/TAZ or carbapenems in 14/26 and 4/11 episodes. Temocillin may constitute an alternative treatment after microbiological documentation by sparing carbapenems and/or PIP/TAZ, but not as an empirical therapeutic option.
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Background: Carbapenemase-producing Enterobacterales (CPE) represent a serious threat to public health. Clinical microbiology laboratories (CMLs) need effective protocols for screening and confirmation of CPE.
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To evaluate the ground susceptibility of urinary Escherichia coli and Klebsiella pneumoniae to temocillin, the susceptibility of temocillin and comparators against 500 clinical isolates (231 E. coli and 269 K. pneumoniae) was test...
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To evaluate the ground susceptibility of urinary Escherichia coli and Klebsiella pneumoniae to temocillin, the susceptibility of temocillin and comparators against 500 clinical isolates (231 E. coli and 269 K. pneumoniae) was tested. Temocillin was either found as the most active antibiotic (susceptibility rate of 92%) or the fourth most active antibiotic (65%), as per its urinary and systemic breakpoint, respectively. No difference of activity was observed in isolates expressing ESBL/AmpC enzymes. Considering the percentage of isolates expressing beta-lactamases and the need to spare broad-spectrum antibiotics, temocillin seems promising for treating urinary tract infections.
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We note the concerns expressed by Batura and Gopal Rao1 regarding infections post-transrectal ultrasound-guided needle biopsy. They correctly point out that current guidelines issued by the European Association of Urology and Amer...
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We note the concerns expressed by Batura and Gopal Rao1 regarding infections post-transrectal ultrasound-guided needle biopsy. They correctly point out that current guidelines issued by the European Association of Urology and American Urological Association recommend fluoroquinolones as prophylaxis for this procedure. This has more recently been echoed, albeit with a caveat that local resistance patterns should be evaluated, by the Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery issued this year by the American Society of Health-System Pharmacists.
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In this study, an ertapenem-nonsusceptible Escherichia coli isolate was investigated to determine the genetic basis for its carbapenem resistance phenotype. This clinical strain was recovered from a patient that received, 1 year p...
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In this study, an ertapenem-nonsusceptible Escherichia coli isolate was investigated to determine the genetic basis for its carbapenem resistance phenotype. This clinical strain was recovered from a patient that received, 1 year previously, ertapenem to treat a cholangitis due to a carbapenem-susceptible extended-spectrum-beta-lactamase (ESBL)-producing E. coli isolate. Whole-genome sequencing of these strains was performed using Illumina and single-molecule real-time sequencing technologies. It revealed that they belonged to the ST131 clonal group, had the predicted O25b:H4 serotype, and produced the CTX-M-15 and TEM-1 beta-lactamases. One nucleotide substitution was identified between these strains. It affected the ompR gene, which codes for a regulatory protein involved in the control of OmpC/OmpF porin expression, creating a Gly-63-Val substitution. The role of OmpR alteration was confirmed by a complementation experiment that fully restored the susceptibility to ertapenem of the clinical isolate. A modeling study showed that the Gly-63-Val change displaced the histidine-kinase phosphorylation site. SDS-PAGE analysis revealed that the ertapenem-nonsusceptible E. coli strain had a decreased expression of OmpC/OmpF porins. No significant defect in the growth rate or in the resistance to Dictyostelium discoideum amoeba phagocytosis was found in the ertapenem-nonsusceptible E. coli isolate compared to its susceptible parental strain. Our report demonstrates for the first time that ertapenem resistance may emerge clinically from ESBL-producing E. coli due to mutations that modulate the OmpR activity.
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A new phenotypic method for detecting carbapenemases has been adapted (assembling of two MAST kits, including one that contains faropenem to which a temocillin disk has been added) then assessed using 101 bacterial strains (Entero...
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A new phenotypic method for detecting carbapenemases has been adapted (assembling of two MAST kits, including one that contains faropenem to which a temocillin disk has been added) then assessed using 101 bacterial strains (Enterobacteriaceae with assays on Pseudomonas aeruginosa and Acinetobacter baumannii) including 62 which produce genetically identified carbapenemases. Concerning Carbapenemase-Producing Enterobacteriaceae (CPE), there is 100% sensitivity for Klebsiella pneumoniae carbapenemase (KPC, Ambler class A) and OXA-48 (Ambler class D), and 91% for metallo-beta-lactamase (MBL, Ambler class B), with a 97% sensitivity for all carbapenemases, with a specificity of 100%. The test is also efficient for detecting Pseudomonas aeruginosa carbapenemases (sensitivity between 82 and 100% and 100% specificity). The major innovation is the combined use of faropenem and temocillin for reliable detection (excellent performance with 100% sensitivity and specificity) of OXA-48. This study has led to the development of a new algorithm to detect the different classes of carbapenemases, for first-line diagnosis, by combining this modified MAST test with immunochromatographic methods and molecular biology techniques.
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