In vitro effect of fosfomycin on multi-drug resistant gram-negative bacteria causing urinary tract infections

Abstract

Background: Rising rates of resistance to antimicrobial drugs among Enterobacteriaceae limit the choice of therapeutic agents to treat urinary tract infections. In this context we assessed the in-vitro effect of fosfomycin against extended-spectrum beta-lactamases, AmpC beta-lactamases and carbapenemase-producing strains of Escherichia coli, Klebsiella pneumoniae, Enterobacter spp, and Pseudomonas aeruginosa isolated from the patients with urinary tract infection (UTI) and also studied the effect of fosfomycin on their biofilm formation. Materials and methods: A total of 326 multidrug-resistant (MDR) isolates comprising of Escherichia coli, Klebsiella pneumoniae, Enterobacter spp, and Pseudomonas aeruginosa from the urine samples of the patients with a diagnosis of UTI were included in the study. MIC 50 and MIC 90 were detected by agar dilution method and the capacity to form biofilm in the presence of fosfomycin by these MDR isolates was assessed by the tissue culture plate method. Results: The MIC50 for meropenem (0.5 µgm/mL) and nitrofurantoin (32 µgm/mL) was within the susceptible range only for E. coli. Fosfomycin was the only antibiotic that inhibited 100% E.coli, 70% Klebsiella spp, and 50% Pseudomonas spp and 40% Enterobacter spp which included the extended-spectrum beta-lactamases producers. It showed a similar effect on carbapenemase producers and AmpC producers. Fosfomycin disrupted biofilm in 67% (n=141) E.coli, 74% (n=50) Klebsiella spp, 88% (n=27) Pseudomonas spp and 36% (n=23) Enterobacter spp at 24 hrs of incubation with a concentration of 2 fold dilution lower than that of the MIC. Conclusion: Fosfomycin showed a good inhibitory effect on the biofilms produced by the MDR organisms studied here.