Fosfomycin: In vitro efficacy against multidrug-resistant isolates beyond urinary isolates.

Abstract

Fosfomycin (FOF) is a bactericidal antimicrobial agent active against a range of Gram-negative bacteria, including multidrug-resistant (MDR) and metallo-β-lactamase (MBL)-producing Enterobacteriaceae. However, data are scarce regarding use of the drug beyond urinary tract infections (UTIs). In this study, susceptibility rates to FOF among 290 MDR Enterobacteriaceae isolates were analysed by gradient and disk diffusion tests and the results were compared with agar dilution according to the Clinical and Laboratory Standards Institute (CLSI). Minimum inhibitory concentrations (MICs) of imipenem (IPM) for isolates IPM-resistant/intermediate-susceptible isolates were determined by gradient test. In addition, the gradient test was used to determine MBL production. Of the 290 extended-spectrum β-lactamase (ESBL)-positive isolates, 60 (20.7%) were resistant to FOF, with rates of 9.5% for Escherichia coli, 28.0% for Enterobacter spp., 35.7% for Klebsiella spp. and 50.0% for Morganella spp. Among the 290 ESBL-positive isolates, 19 (6.6%) were resistant/intermediate-susceptible to IPM. In addition, 72.2% of extensively drug-resistant (XDR) and 61.1% of carbapenem-resistant isolates were resistant to FOF. In vitro FOF activity was higher among blood (86.9%) and genitourinary (91.7%) isolates. FOF showed excellent activity for a wide range of infections; however, further trials are necessary to evaluate its clinical efficacy. FOF presented good activity even against carbapenem-resistant isolates and may be a treatment alternative for non-UTI isolates, but should be used with caution for infections related to ESBL-producing Klebsiella spp.