Fosfomycin and Comparator Activity Against Select Enterobacteriaceae, Pseudomonas, and Enterococcus Urinary Tract Infection Isolates from the United States in 2012

Abstract

Introduction

Fosfomycin is a broad-spectrum cell wall active agent that inhibits the MurA enzyme involved in peptidoglycan synthesis and is FDA-approved for treatment of uncomplicated urinary tract infections (UTIs) caused by Escherichia coli and Enterococcus faecalis in women. Data regarding the susceptibility of recent UTI isolates to fosfomycin are limited.

Methods

This study compared the fosfomycin susceptibility of 658 US UTI isolates with susceptibility to ciprofloxacin, levofloxacin, nitrofurantoin, and trimethoprim/sulfamethoxazole (SXT). Isolates included E. coli ( n = 257), Klebsiella spp. ( n = 156), Enterobacter spp. ( n = 79), Pseudomonas aeruginosa ( n = 60), E. faecalis ( n = 54), and Proteus spp. ( n = 52). Extended-spectrum β-lactamase (ESBL)-producing E. coli, Klebsiella spp., and Proteus mirabilis, ceftazidime-nonsusceptible P. aeruginosa and Enterobacter spp., and vancomycin-nonsusceptible E. faecalis were included.

Results

Overall, the minimum concentration inhibiting 50% of isolates (MIC ₅₀) and 90% of isolates (MIC ₉₀) for fosfomycin were 4 and 64 µg/mL, respectively. Of the 257 E. coli isolates, 99.6% were susceptible to fosfomycin. Ciprofloxacin, levofloxacin, SXT, and nitrofurantoin susceptibility rates were 65.4%, 65.8%, 59.9%, and 90.3%, respectively. The fosfomycin-susceptibility rate for E. faecalis (94.4%) was comparable with the nitrofurantoin-susceptibility rate (98.1%). Among the 144 ESBL-producing isolates, the fosfomycin MIC ₅₀ and MIC ₉₀ values were 2 and 32 µg/mL, respectively. Fosfomycin MIC ₅₀ and MIC ₉₀ values were 16 and 128 µg/mL for the 38 ceftazidime-nonsusceptible Enterobacter isolates and 64 and 128 µg/mL for the 15 ceftazidime-nonsusceptible P. aeruginosa isolates, respectively.

Conclusion

These results demonstrate that fosfomycin has in vitro activity against many US UTI isolates, including drug-resistant isolates, and may provide another therapeutic option for treatment of UTIs caused by antibiotic-resistant pathogens.