An in vitro experimental study of the effect of fosfomycin in combination with amikacin, ciprofloxacin or meropenem on biofilm formation by multidrug-resistant urinary isolates of Escherichia coli

Abstract

Background. This study was conducted to understand the effect of fosfomycin in combination with amikacin, ciprofloxacin or meropenem on biofilm formation by multidrug-resistant urinary isolates of Escherichia coli.Methods. Fifty urinary tract multidrug-resistant E. coli isolates that were known biofilm producers were studied. The MIC was determined using the agar dilution method for amikacin, ciprofloxacin, meropenem and fosfomycin. The fractional inhibitory concentration was determined for the combination of antibiotics followed by a time-kill assay. A tissue culture plate method was used to study the effect of the combination of antibiotics on biofilm formation.Results. The MICs of the isolates tested ranged from 0.25 to 32 µg ml^-1 for fosfomycin, 1 to 1024 µg ml^-1 for ciprofloxacin, 4 to 1024 µg ml^-1 for amikacin, and 0.25 to 512 µg ml^-1 for meropenem. The combination of fosfomycin with meropenem showed 68 % synergy, fosfomycin with amikacin 58 % synergy and fosfomycin with ciprofloxacin 6 % synergy. The combination also reduced the MIC of each antibiotic and none showed an antagonistic effect. Biofilm inhibition was best observed with the combination of fosfomycin with meropenem.Conclusion. The combination of fosfomycin with amikacin and fosfomycin with meropenem yielded a high percentage of synergy alongside an increased capacity to reduce biofilm formation when compared to combination with ciprofloxacin against multidrug-resistant E. coli. Fosfomycin in combination with other classes of antimicrobial agents has potential beneficial effects.

Keywords: FIC; MDR E.coli; MIC; biofilm; fosfomycin combination.