Trends in production of extended-spectrum  -lactamases among Enterobacteriaceae of clinical interest: results of a nationwide survey in Belgian hospitals

Rodríguez-Villalobos, Hector; Bogaerts, Pierre; Berhin, Catherine; Bauraing, Caroline; Deplano, Ariane; Montesinos, Isabel; Mendonça, Ricardo De; Jans, Béatrice; Glupczynski, Youri

doi:10.1093/jac/dkq388

Cited by 61 publications

(43 citation statements)

References 39 publications

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“…Although the prevalence of ertapenem nonsusceptibility in the Enterobacteriaceae family is relatively lower than that in Pseudomonas aeruginosa and Acinetobacter baumannii, the current trend of rising ertapenem resistance of the Enterobacteriaceae has become a great concern (13,19,27). Surveillance of antimicrobial susceptibility by the Study for Monitoring Antimicrobial Resistance Trends (SMART) reported that the rate of susceptibility of E. cloacae strains to ertapenem decreased from 100% (2002) to 89.7% (2009) in China (27).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Ertapenem-Resistant Enterobacter cloacae in a Taiwanese University Hospital

et al. 2012

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The emergence of carbapenem resistance in Enterobacteriaceae has become a great concern. The aim of this study was to characterize ertapenem-resistant Enterobacter cloacae isolates from a Taiwanese university hospital. A total of 355 nonduplicated E. cloacae isolates collected in 2007 were analyzed by antimicrobial susceptibility testing with and without an inhibitor of efflux pumps and AmpC ␤-lactamase. The phenotype of extended-spectrum ␤-lactamase (ESBL), profile of outer membrane proteins (OMPs), and clonal relatedness were investigated by the double-disk synergy test, urea/SDS-PAGE, and pulsed-field gel electrophoresis (PFGE), respectively. ␤-Lactamase genes were examined by PCR and sequencing, and the expression of efflux pump gene acrB was evaluated by reverse transcription-PCR. The contribution of porin deficiency to resistance was investigated by restoring functional porin genes on plasmids. We demonstrated that ertapenem resistance was prevalent (53/355; 14.9%) in E. cloacae. Among the strains, IMP-8, SHV-12, and TEM-1 ␤-lactamases were identified in 3 (5.7%), 40 (75.5%), and 46 (86.8%) isolates, respectively. PFGE showed clonal diversity among these isolates. Phenotypes of ESBL, AmpC ␤-lactamase overproduction, an active efflux pump, and change in the expression of OMPs were found in 18 (34%), 11 (20.8%), 51 (96.2%), and 23 (43.4%) of ertapenem-resistant strains, respectively. Ertapenem MICs were restored in strains with OmpC and OmpF expression plasmids. This study suggests that ESBL, AmpC ␤-lactamase overproduction, and decreased OMP expression combined with an active efflux pump contribute to the ertapenem resistance of E. cloacae. The presence of IMP-8 may also play a partial role in ertapenem resistance in Taiwan.

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Section: Discussionmentioning

confidence: 99%

Characterization of Ertapenem-Resistant Enterobacter cloacae in a Taiwanese University Hospital

et al. 2012

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“…First, despite the extended use of AMC and TZP in areas in which CTX-M enzymes are prevalent (14,18,53), IR-CTX-Ms have never been described in clinical isolates (6). Second, several widespread CTX-Ms, such as CTX-M-15, are frequently coselected in the same bacterial host with other ␤-lactamases, as those of the OXA type (10,60), conferring variable degrees of resistance to BBLIs (32).…”

Section: Discussionmentioning

confidence: 99%

“…The present epidemiological situation has forced a reexamination of the therapeutic possibilities of BBLIs, some of which suggest a positive effect both in severe and in uncomplicated infections (50,56). The current resistance rates to BBLIs in Europe account for 12% and 25% of ESBL-producing Escherichia coli and Klebsiella strains, respectively (12,53). In a number of CTX-M-producing Enterobacteriaceae, as frequently happens for CTX-M-15 producers, BBLI resistance is associated with the coproduction of OXA-1 ␤-lactamase (10) or porin loss (59), whereas no natural CTX-M enzyme has been found to confer resistance to BBLIs (6).…”

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In VitroSelection of Variants Resistant to β-Lactams plus β-Lactamase Inhibitors in CTX-M β-Lactamases: Predicting theIn VivoScenario?

Ripoll

Baquero

Novais

et al. 2011

Antimicrob Agents Chemother

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CTX-M ␤-lactamases are the most prevalent group of enzymes within the extended-spectrum ␤-lactamases (ESBL). The therapeutic options for CTX-M-carrying isolates are scarce, forcing the reexamination of the therapeutic possibilities of ␤-lactams plus ␤-lactamase inhibitors (BBLIs). Inhibitor-resistant CTX-M ␤-lactamases (IR-CTX-M) have not hitherto been described in natural isolates. In this study, 168 cultures of the hypermutagenic Escherichia coli GB20 strain carrying plasmid pBGS18 with different bla CTX-M genes were submitted to parallel experimental evolution assays in the presence of increasing concentrations of a combination of amoxicillin and clavulanate. Fourteen CTX-M ␤-lactamases belonging to the three most representative clusters (CTX-M-1, -2, and -9) and the two main phenotypes (cefotaxime resistance and cefotaximeceftazidime resistance) were studied. Three types of IR-CTX-M mutants were detected, having mutations S130G, K234R, and S237G, which are associated with different resistance patterns. The most frequently recovered mutation was S130G, which conferred the highest resistance levels to BBLIs (reaching 12 g/ml for amoxicillin-clavulanate and 96 g/ml for piperacillin-tazobactam when acquired by CTX-M-1 cluster enzymes). The S130G change also provided a clear antagonistic pleiotropy effect, strongly decreasing the enzyme's activity against all cephalosporins tested. A double mutation, S130G L169S, partially restored the resistance against cephalosporins. A complex pattern observed in CTX-M-58, carrying P167S and S130G or K234R changes, conferred ESBL and IR phenotypes simultaneously. The K234R and S237G changes had a smaller effect in providing inhibitor resistance. In summary, IR-CTX-M enzymes might evolve under exposure to BBLIs, and the probability is higher for enzymes belonging to the CTX-M-1 cluster. However, this process could be delayed by antagonistic pleiotropy.

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“…All the carbapenemases encountered during this study were correctly detected by the BC-GN assay. Along with the detection of carbapenemase, the BC-GN assay also detects the presence of the CTX-M type, which is rapidly spreading among Enterobacteriaceae worldwide, replacing the TEM and SHV types as the predominant ESBLs in many countries (10,11). Out of the nine ESBLs detected by the phenotypic method, all but one were the CTX-M type.…”

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confidence: 99%

Performance of the Verigene Gram-Negative Blood Culture Assay for Rapid Detection of Bacteria and Resistance Determinants

et al. 2014

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Nonduplicate blood cultures that were positive for Gram-negative bacilli (n ‫؍‬ 125) were tested by the Verigene Gram-negative blood culture (BC-GN) assay; 117 (90.7%) isolates were members of the panel. For identification and resistance markers, the agreements with routine methods were 97.4% (114/117) and 92.3% (12/13). The BC-GN assay is a rapid and accurate tool for the detection of pathogens from blood cultures and could be integrated alongside conventional systems to enable faster patient management, but the clinical benefits should be further evaluated. The Verigene Gram-positive blood culture (BC-GP) and Gramnegative blood culture (BC-GN) nucleic acid tests (Nanosphere, Inc., Northbrook, IL) are microarray-based assays designed to rapidly identify multiple bacterial species and their associated resistance markers directly from positive blood cultures. Two separate panels dedicated for Gram-positive (1-3) and Gram-negative (4, 5) organisms are currently available. The system instrumentation supplies random access test processing that is easy to perform and requires no personnel trained in molecular approaches. The major advantages of these tests are the short turnaround time (TAT) following positivity and the ease of use, which allows testing 24 hours a day. These assays provide results in Յ3 h and may significantly impact patient management by reducing the time needed for laboratory processing.The targets of the BC-GN assay are Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Serratia marcescens, Proteus spp., Citrobacter spp., Enterobacter spp., Pseudomonas aeruginosa, and Acinetobacter spp. In addition, the BC-GN assay detects resistance markers, including the extended-spectrum ␤-lactamase (ESBL) CTX-M and the carbapenemases KPC, NDM, VIM, IMP, and OXA groups. Several studies on the BC-GP assay were published, but so far, only a few studies evaluated the BC-GN test, particularly in a European epidemiology context (4, 5). The aim of this study was to evaluate the diagnostic performance of the BC-GN assay and the TAT for positive blood cultures, with the results of culture and antimicrobial susceptibility testing (AST) considered the gold standard.A total of 125 nonduplicate blood cultures that were positive for Gram-negative bacilli (Bactec FX, Becton, Dickinson) were consecutively enrolled from patients admitted to Erasme Hospital from March 2013 to September 2013. An aliquot of 700 l was used for the testing of each blood culture flagging positive within 12 h, as recommended by the manufacturer. All samples which were not tested within 12 h were stored at Ϫ20°C to be analyzed retrospectively with the BC-GN assay. Verigene provides a qualitative result for the presence ("detected") or absence ("not detected") of the bacterial targets and resistance markers. Tests generating invalid results (reported as "no call") were repeated. Identification was performed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonics, Bremen, Germany) and AS...

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Trends in production of extended-spectrum -lactamases among Enterobacteriaceae of clinical interest: results of a nationwide survey in Belgian hospitals

Abstract: the rapid emergence of multiresistant CTX-M-15-producing E. coli isolates is of major concern and highlights the need for further surveillance in Belgium.

Cited by 61 publications

References 39 publications

Characterization of Ertapenem-Resistant Enterobacter cloacae in a Taiwanese University Hospital

Characterization of Ertapenem-Resistant Enterobacter cloacae in a Taiwanese University Hospital

In VitroSelection of Variants Resistant to β-Lactams plus β-Lactamase Inhibitors in CTX-M β-Lactamases: Predicting theIn VivoScenario?

Performance of the Verigene Gram-Negative Blood Culture Assay for Rapid Detection of Bacteria and Resistance Determinants

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