The Activity of Fosfomycin Against Extended-Spectrum Beta-Lactamase-Producing Isolates of Enterobacteriaceae Recovered from Urinary Tract Infections: A Single-Center Study over a Period of 12 Years

Abstract

Despite global efforts to tackle resistance in extended-spectrum beta-lactamase (ESBL)-producing isolates via old antibiotics, there are limited data on the efficacy of fosfomycin-an old oral antibiotic-against Enterobacteriaceae in the Middle East. The purpose of this study was to evaluate the in vitro activity of fosfomycin against urinary ESBL-producing isolates of Enterobacteriaceae. Between 2004 and 2015, 363 isolates of ESBL-producing Enterobacteriaceae were recovered from high-risk patients suffering from cardiac disorders and were subjected to polymerase chain reaction using specific primers for the blaTEM, blaSHV, and blaCTX-M genes. Antibiotic susceptibility testing was performed for fosfomycin and other antibiotic comparators. For the isolates considered nonsusceptible to fosfomycin by disk diffusion, the minimum inhibitory concentration (MIC) was determined. The susceptibility rate to fosfomycin remained almost steady (90-100%) over a 12-year period, although it fluctuated vis-à-vis ciprofloxacin (0-54%), trimethoprim/sulfamethoxazole (9.1-31.7%), and nitrofurantoin (41.7-100%). Of all the antibiotics tested, fosfomycin was the most active antimicrobial agent (97%) against the ESBL-positive isolates. Fosfomycin maintained higher activity against ESBL-Escherichia coli than against ESBL-Klebsiella pneumoniae. Only 11 (3%) isolates were not susceptible to fosfomycin according to disk diffusion and they had MICs greater than 1,024 mg/ml. All of the fosfomycin-nonsusceptible isolates were positive for the blaCTX-M gene (100%), while 5 (45.4%) and 3 (27.3%) of the isolates harbored the blaTEM and blaSHV genes, respectively. We showed that fosfomycin had a numerically higher susceptibility rate than the other antibiotics against the ESBL-producing isolates of the most common Enterobacteriaceae. Given its low resistance rate and oral administration, fosfomycin may be deemed a promising antibiotic for the treatment of urinary tract infections caused by ESBL-producing Enterobacteriaceae.