Variety of β-Lactamases Produced by Amoxicillin-Clavulanate-Resistant
            <i>Escherichia coli</i>
            Isolated in the Northeastern United States

Kaye, Keith S.; Gold, Howard S.; Schwaber, Mitchell J.; Venkataraman, Lata; Qi, Youlin; Girolami, Paola C. De; Samore, Matthew H.; Anderson, Greg M.; Rasheed, J. Kamile; Tenover, Fred C.

doi:10.1128/aac.48.5.1520-1525.2004

Cited by 64 publications

(49 citation statements)

References 30 publications

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“…However, these mechanisms generally do not result in great increases in the MICs of extended-spectrum cephalosporins. We did not screen for OXA enzymes, which are usually clavulanate resistant and are only rarely found in E. coli or Klebsiella isolates (3,11,7). We also found a few isolates of both species, both confirming and nonconfirming, in which we were unable to detect any ␤-lactamase genes.…”

Section: Discussionmentioning

confidence: 87%

Prevalence and Significance of a Negative Extended-Spectrum β-Lactamase (ESBL) Confirmation Test Result after a Positive ESBL Screening Test Result for Isolates of Escherichia coli and Klebsiella pneumoniae : Results from the SENTRY Asia-Pacific Surveillance Program

et al. 2007

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A negative extended-spectrum ␤-lactamase (ESBL) confirmation test result obtained after a positive ESBL screening test result using Clinical and Laboratory Standards Institute methods has been a common occurrence among isolates of Escherichia coli and Klebsiella pneumoniae in the SENTRY Antimicrobial Surveillance Program in the Asia-Pacific region. Among isolates collected between 1998 and 2004 this screen-positive, nonconfirmed profile (failed to show clavulanate synergy) was observed in 8.9% of 4,515 E. coli isolates and 20.3% of 2,303 K. pneumoniae isolates. We then selected 52 E. coli isolates and 68 K. pneumoniae isolates with a negative ESBL confirmation test, as well as comparable number of isolates with confirmed ESBL-positive tests, and examined them for the presence of TEM, SHV, plasmid-borne ampC, and CTX-M genes. We found that 62% of nonconfirming E. coli isolates and 75% of nonconfirming K. pneumoniae harbored a plasmid-borne AmpC enzyme of the CIT or DHA type. The majority of nonconfirming E. coli and K. pneumoniae from the Asia-Pacific region harbor important ␤-lactamases, and a positive screening test alone should be sufficient grounds to report resistance to extended-spectrum cephalosporins in this region. Current Clinical and Laboratory Standards Institute (CLSI)standards recommend the use of a screening and confirmation test, in addition to standard susceptibility testing methods, to detect extended-spectrum ␤-lactamases (ESBLs) in the routine clinical laboratory among strains of Escherichia coli and Klebsiella pneumoniae (1,6). This method has proven reliable over many years at detecting the great majority of conventional ESBLs, particularly of variants of the TEM and SHV enzyme classes. The CLSI method, however, does not address the significance of strains that are positive on the screening test but negative on the confirmation test. By default, the result of the standard susceptibility test (e.g., broth microdilution or disk diffusion) is applied to organisms with this ESBL test profile. However, the MIC distributions for these wild-type gram-negative species suggest that strains for which the MICs of any of the ESBL screening agents are Ͼ1 g/ml are abnormal (8) and therefore likely to possess an acquired resistance mechanism. In particular, the emergence of plasmid-borne AmpC ␤-lactamases, which are not inhibited by clavulanic acid, in members of the Enterobacteriaceae (13) is likely to explain at least some of the strains that have a positive screening test but a negative confirmation test. It is important for both clinical and infection control reasons to detect strains harboring transmissible resistance mechanisms to extended-spectrum cephalosporins.The present study examined isolates for which the MICs of extended-spectrum cephalosporins and/or aztreonam are Ͼ1 g/ml, including strains that would be considered susceptible by routine susceptibility testing using CLSI broth microdilution. In particular, we focused on their overall frequency in a prospective collection of clinical isolates...

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Section: Discussionmentioning

confidence: 87%

Prevalence and Significance of a Negative Extended-Spectrum β-Lactamase (ESBL) Confirmation Test Result after a Positive ESBL Screening Test Result for Isolates of Escherichia coli and Klebsiella pneumoniae : Results from the SENTRY Asia-Pacific Surveillance Program

et al. 2007

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“…The lack of detection of these CTX-M variants in the clinical setting does not necessarily mean they are really absent, due to the predominant interpretation of similar phenotypes that are attributed to IRTs and IRSHVs (25). It is of note that in some national surveillance programs, nearly 5% of AMC-resistant E. coli isolates had unknown resistance mechanisms (26). Moreover, the complex effects, such as antagonistic pleiotropy, observed in IR-CTX-M enzymes, significantly reduce the oxyimino-cephalosporin MICs and result in unexpected phenotypes in which the possible mechanism(s) of resistance is even more difficult to infer (6,27,28).…”

Section: Discussionmentioning

confidence: 99%

Detection of Resistance to Beta-Lactamase Inhibitors in Strains with CTX-M Beta-Lactamases: a Multicenter External Proficiency Study Using a Well-Defined Collection of Escherichia coli Strains

et al. 2014

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␤-lactams and ␤-lactam-␤-lactamase inhibitor (BLBLI) combinations. The main objective of the study was to ascertain how these variants with reduced susceptibilities to BLBLIs are identified in clinical microbiology laboratories. CTX-M variants with high resistance to BLBLIs were mainly identified as inhibitor-resistant TEM (IRT) enzymes (68.0%); however, isogenic CTX-M mutant strains with reduced susceptibilities to BLBLIs and cephalosporins were mainly associated with extended-spectrum ␤-lactamase production alone (51 to 80%) or in combination with other mechanisms (14 to 31%). Concerning all ␤-lactams tested, the overall interpretative discrepancy rate was 11.5%, of which 38.1% were the consequence of postreading changes in the clinical categories when a resistance mechanism was inferred. Therefore, failure to recognize these complex phenotypes might contribute to an explanation of their apparent absence in the clinical setting and might lead to inadequate drug treatment selection. A proposal for improving recognition is to adhere strictly to the current CLSI or EUCAST guidelines for detecting reduced susceptibility to BLBLI combinations, without any interpretative modification. ␤-Lactamase production is the most important resistant mechanism to ␤-lactam antibiotics in Gram-negative bacteria (1). CTX-M extended-spectrum ␤-lactamases (ESBLs) are becoming one of the largest groups of ␤-lactamases, with a spectacular increase in the number of variants along the last years (147 variants; see www.lahey.org/Studies/other.asp). Isolates expressing these enzymes often confer resistance not only to oxyimino-cephalosporins but also to other antimicrobial agents, thus representing an important problem in therapeutics and public health (2-4).Single mutations in CTX-M ␤-lactamases that increase the spectrum of action against cefotaxime and ceftazidime have been selected in nature and under laboratory conditions. Although CTX-M mutants with single amino acid changes (such as S130G, S237G, and K234R) conferring reduced susceptibility to ␤-lactam-␤-lactamase inhibitor (BLBLI) combinations have been easily obtained under in vitro conditions (5), these variants have not yet been described in the clinical setting (6). This might be due to the limited exposure of the mutants to BLBLI combinations, as these agents are not usually recommended in infections due to ESBL-producing strains, and carbapenems remain the drugs of choice in empirical or oriented therapy (7). Treatment with BLBLI combinations is still controversial; however, recent studies suggest that BLBLI combinations might provide similar results to carbapenems in the treatment of infections caused by ESBL-producing organisms (8). Therefore, an expected increase in the consumption of BLBLI combinations might lead to the emergence and spread of strains with CTX-M variants with reduced susceptibilities to these compounds.The apparent absence of CTX-M variants with reduced susceptibilities to BLBLI combinations in the clinical setting might derive from the difficulties in t...

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“…Challenge isolate 39661 (E. coli) was shown to have ESBL production by the reference broth microdilution and MicroScan methods, but it did not show ESBL production with the BD BBL disks or Etest (8,14). A more recently recognized mechanism of extended-spectrum beta-lactam resistance results from mutated ESBL enzymes which are resistant to inactivation by CA.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Four Commercially Available Extended-Spectrum Beta-Lactamase Phenotypic Confirmation Tests

Linscott

Brown

2005

J Clin Microbiol

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Extended-spectrum beta-lactamase (ESBL) production in members of the Enterobacteriaceae can confer resistance to extended-spectrum cephalosporins, aztreonam, and penicillin. As such, the accurate detection of ESBL producers is essential for the appropriate selection of antibiotic therapy. Twenty previously characterized isolates and 49 clinical isolates suspected of ESBL production were tested by four ESBL phenotypic confirmatory methods for accuracy and ease of use.

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Variety of β-Lactamases Produced by Amoxicillin-Clavulanate-Resistant Escherichia coli Isolated in the Northeastern United States

Cited by 64 publications

References 30 publications

Prevalence and Significance of a Negative Extended-Spectrum β-Lactamase (ESBL) Confirmation Test Result after a Positive ESBL Screening Test Result for Isolates of Escherichia coli and Klebsiella pneumoniae : Results from the SENTRY Asia-Pacific Surveillance Program

Prevalence and Significance of a Negative Extended-Spectrum β-Lactamase (ESBL) Confirmation Test Result after a Positive ESBL Screening Test Result for Isolates of Escherichia coli and Klebsiella pneumoniae : Results from the SENTRY Asia-Pacific Surveillance Program

Detection of Resistance to Beta-Lactamase Inhibitors in Strains with CTX-M Beta-Lactamases: a Multicenter External Proficiency Study Using a Well-Defined Collection of Escherichia coli Strains

Evaluation of Four Commercially Available Extended-Spectrum Beta-Lactamase Phenotypic Confirmation Tests

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