Activity of fosfomycin against extended-spectrum β-lactamase producing Escherichia coli and Klebsiella pneumoniae

INTRODUCTION. Infection due to extended-spectrum P-lactamase (ESBL)-producing microorganisms is an emerging problem in the community; a high proportion of these microorganisms have been isolated from urine samples of women with uncomplicated urinary tract infections (UTI). The options for oral treatment of uncomplicated UTI are limited because of the multiple drug resistance typical of ESBL-producing strains. METHODS. The in vitro activity of fosfomycin (FOS) was determined against 428 ESBL-producing strains, including 290 (68%) E. coli and 138 (32%) K. pneumoniae. Activity of fosfomycin was compared with that of amoxicillin-clavulanate (AMC), ciprofloxacin (CIP) and cotrimoxazole (SxT). MICs of AMC, CIP, and SxT, and detection of ESBL production were tested by the broth microdilution method, whereas FOS MICs were determined by the agar dilution method. ESBLs were characterized by isoelectric focusing, polymerase chain reaction (PCR) and direct sequencing of encoding genes. The genetic relationship among the isolates was determined by REP-PCR. RESULTS. Among the 428 ESBL-producing isolates studied, 417 (97.4%) were susceptible to FOS (MIC <= 64 mu g/mL). The resistance rate of E. coli to FOS was 0.3%, and was lower than resistance to AMC (111.7%), whereas the resistance rate of K. pneumoniae was 7.2% and was equal to resistance to AMC. SxT and CIP were the least active antibiotic agents against ESBL-producing isolates (sensitivity < 50%). There were no differences in fosfomycin activity against strains expressing different types of ESBLs. CONCLUSION. Fosfomycin showed maintained activity against ESBL-producing strains and did not present co-resistance with other antimicrobial groups.