Biological cost of resistance to fosfomycin in Escherichia coli isolates

Abstract number: 1733_380

Alós J.I., García-Peña P., Tamayo J.

Fosfomycin is a bactericidal antibiotic that acts by inhibiting the cell wall, and which is used mainly in the treatment of uncomplicated urinary tract infections (UTI). Resistance to fosfomycin develops rapidly in experimental conditions, although despite its frequent use in UTI, resistance in E. coli, the main uropathogen, is very low (1–3%), and has remained so for many years. The objective of this study was to ascertain whether E. coli fosfomycin-resistant strains have less fitness than those that are fosfomycin-sensitive in competing, and would therefore tend to disappear in their competition with fosfomycin-sensitive strains in the absence of antibiotics.

Methods: Fosfomycin-resistant strains (n = 8) with different phenotypes of resistance to other antibiotics. All but one were lactose (+). Fosfomycin-resistant strains (n = 13) that had same phenotypes of resistance to other antibiotics as the resistant strains and which furthermore had the opposite pattern of lactose fermentation.

Thirty-three (33) competition experiments by pairs of strains were conducted (Fosfomycin-R versus Fosfomycin-S with the rest of resistance determinants being equal and with a different lactose fermentation capacity to perform the differential counts in MacConkey agar). The experiments were performed in nutrient broth (NB). Equal amounts of the strains were challenged (approx. 50% and approx. 50%) for 4 days, with a daily change to a new medium. Five differential counts were performed (days 0, 1, 2, 3, and 4). The 33 experiments were performed in duplicate, and the mean of both results are presented below.

Results: In 20 experiments (60.6%) there was a relative increase in the fosfomycin-sensitive strain that translated into a count of >60% (between 65%-99%) on the fourth day. In 6 experiments (18.2%) there was a relative increase in the fosfomycin-resistant strain that translated into a count of >60% (between 65%-75%) on the fourth day. In 7 experiments (21.2%), on the fourth day none of the strains reached 60%. When the data of the 26 (20+6) experiments in which there were changes were analysed by the Chi2 test there was an statistically significant difference (P = 0.044).

Conclusions:

• Resistance to fosfomycin entails a biological cost (less fitness) for the majority of the E. coli strains assayed.

• This biological cost hinders their competition with fosfomycin-sensitive strains in the normal intestinal flora, which would make them less likely to cause UTI.