CTX-M-15-producing urinary Escherichia coli O25b-ST131-phylogroup B2 has acquired resistance to fosfomycin.
OBJECTIVE
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 ESBL-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, ptsI, 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 B2 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 II had the IS26 linked to bla(CTX-M-15) and the afa/dra operon. In Cluster I isolates, no mutations in glpT, uhpT, uhpA, ptsI, 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 B2 strain. This happened during a period when the use of fosfomycin increased by 50%.
Oteo
Jesús
J
Antibiotic Laboratory, Bacteriology, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Orden
Beatriz
B
Bautista
Verónica
V
Cuevas
Oscar
O
Arroyo
Margarita
M
Martínez-Ruiz
Rocío
R
Pérez-Vázquez
María
M
Alcaraz
Marta
M
García-Cobos
Silvia
S
Campos
José
J
D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015373:Bacterial Typing Techniques; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000453:epidemiology / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics; D005578:Fosfomycin / Q000494:pharmacology* / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D016133:Polymerase Chain Reaction; D015995:Prevalence; D017422:Sequence Analysis, DNA; D014552:Urinary Tract Infections / Q000453:epidemiology / Q000382:microbiology*; D001618:beta-Lactamases / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D005578:Fosfomycin; C473109:beta-lactamase CTX-M-15; D001618:beta-Lactamases