Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 64, Issue 4, Pages 712-717Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkp288
Keywords
urinary tract infections; antibiotic consumption; extended-spectrum beta-lactamases
Funding
- Ministerio de Sanidad y Consumo
- Instituto de Salud Carlos III
- Spanish Network for Research in Infectious Diseases [REIPI C03/14, REIPI RD06/0008]
- Direccion General de Salud Publica, Ministry of Health, Spain [1429/05-11]
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Objectives: To describe trends in fosfomycin resistance in urinary isolates of Escherichia coli producing extended-spectrum beta-lactamases (ESBLs) in relation to fosfomycin consumption and to characterize representative fosfomycin-resistant isolates. Methods: In 2007-08, an unexpected increase in fosfomycin resistance in ESBL-producing urinary E. coli was observed. Laboratory records were reviewed and a prospective surveillance study was initiated on all urinary tract infections caused by ESIBL-producing, fosfomycin-resistant E. coli. bla(ESBL) types, phylogroups, genetic environment and afa/dra operon were determined by PCR and sequencing. Molecular epidemiology was analysed by PFGE and multilocus sequence typing. To elucidate possible mechanisms of fosfomycin resistance, uhpT, glpT, uhpA, ptsl, cyaA and murA genes were analysed. Fosfomycin consumption was determined as recommended by WHO, Results: From 2004 to 2008, fosfomycin consumption increased by 50%, while fosfomycin resistance in ESBL producers increased from 2.2% to 21.7%. Of 26 isolates studied, 24 produced CTX-M-15 and belonged to the O25b-ST131-phylogroup 132 clonal strain. PFGE revealed two clusters. Cluster I included 18 isolates, 16 of them indistinguishable from strains producing CTX-M-15 previously described in Madrid. The five isolates of Cluster 11 had the IS26 linked to bla(CTX-M-15) and the afa/dra, operon. In Cluster I isolates, no mutations in glpT, uhpT, uhpA, ptsl, cyaA and murA were detected. Cluster II isolates showed a 15 bp deletion (A(169)-C-183) in uhpA. Conclusions: Fosfomycin resistance in urinary E. coli has increased due to the acquisition of this resistance by a previously circulating CTX-M-15-producing E. coli O25b-ST131-phylogroup 132 strain. This happened during a period when the use of fosfomycin increased by 50%.
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