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Science Policy

Population Distribution of Beta-Lactamase Conferring Resistance to Third-Generation Cephalosporins in Human Clinical Enterobacteriaceae in The Netherlands
Published: Thursday, December 20, 2012
Author: Guido M. Voets et al.

by Guido M. Voets, Tamara N. Platteel, Ad C. Fluit, Jelle Scharringa, Claudia M. Schapendonk, James Cohen Stuart, Marc J. M. Bonten, Maurine A. L. Hall, National ESBL Surveillance Working Group

There is a global increase in infections caused by Enterobacteriaceae with plasmid-borne ß-lactamases that confer resistance to third-generation cephalosporins. The epidemiology of these bacteria is not well understood, and was, therefore, investigated in a selection of 636 clinical Enterobacteriaceae with a minimal inhibitory concentration >1 mg/L for ceftazidime/ceftriaxone from a national survey (75% E. coli, 11% E. cloacae, 11% K. pneumoniae, 2% K. oxytoca, 2% P. mirabilis). Isolates were investigated for extended-spectrum ß-lactamases (ESBLs) and ampC genes using microarray, PCR, gene sequencing and molecular straintyping (Diversilab and multi-locus sequence typing (MLST)). ESBL genes were demonstrated in 512 isolates (81%); of which 446 (87%) belonged to the CTX-M family. Among 314 randomly selected and sequenced isolates, blaCTX-M-15 was most prevalent (n?=?124, 39%), followed by blaCTX-M-1 (n?=?47, 15%), blaCTX-M-14 (n?=?15, 5%), blaSHV-12 (n?=?24, 8%) and blaTEM-52 (n?=?13, 4%). Among 181 isolates with MIC =16 mg/L for cefoxitin plasmid encoded AmpCs were detected in 32 and 27 were of the CMY-2 group. Among 102 E. coli isolates with MIC =16 mg/L for cefoxitin ampC promoter mutations were identified in 29 (28%). Based on Diversilab genotyping of 608 isolates (similarity cut-off >98%) discriminatory indices of bacteria with ESBL and/or ampC genes were 0.994, 0.985 and 0.994 for E. coli, K. pneumoniae and E. cloacae, respectively. Based on similarity cut-off >95% two large clusters of E. coli were apparent (of 43 and 30 isolates) and 21 of 21 that were typed by belonged to ST131 of which 13 contained blaCTX-M-15. Our findings demonstrate that blaCTX-M-15 is the most prevalent ESBL and we report a larger than previously reported prevalence of ampC genes among Enterobacteriaceae responsible for resistance to third-generation cephalosporins.