title: High rates of susceptibility to ceftazidime among globally prevalent CTX-M-producing Escherichia coli: potential clinical implications of the revised CLSI interpretive criteria.
abstract: The CTX-M family of extended-spectrum β-lactamases (ESBLs) is a significant global public health threat. The prevalence of specific bla (CTX-M) genes varies geographically, but bla (CTX-M-15) and bla (CTX-M-14) dominate in most countries. We applied the latest Clinical Laboratory Standards Institute (CLSI) interpretive criteria (M100-S20) to a diverse collection of ESBL-producing Escherichia coli strains obtained from clinical specimens in our laboratory. Whereas under previous CLSI recommendations all isolates in this strain collection would have been reported as ceftazidime-resistant, under the new recommendations, approximately 11% of CTX-M-15-producing E. coli and 93% of CTX-M-14-producing E. coli respectively tested as ceftazidime-susceptible. We also found that, whilst many CTX-M-14-producers had minimum inhibitory concentrations (MICs) less than the breakpoint of 4 mg/L, the MIC distribution for these strains was higher than that of wild-type E. coli, with one CTX-M-14-producing isolate having an MIC of >64 mg/L. Although the new CLSI recommendations imply that ceftazidime can be safely used to treat serious infections due to CTX-M-producing E. coli, clinical outcome data are lacking. Consequently, the widespread use of ceftazidime in this setting could have profound clinical implications.
authors: Department of Clinical Microbiology, Auckland City Hospital, Auckland, New Zealand.
authors: D A
authors: DA
authors: Williamson
authors: S A
authors: SA
authors: Roberts
authors: M
authors: M
authors: Smith
authors: H
authors: H
authors: Heffernan
authors: A
authors: A
authors: Tiong
authors: C
authors: C
authors: Pope
authors: J T
authors: JT
authors: Freeman
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology* / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D002442:Ceftazidime; D001618:beta-Lactamases