Biological cost associated with fosfomycin resistance in Escherichia coli isolates from urinary tract infections

: 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. Fosfomycin-resistant strains (n=11) with different phenotypes of resistance to other antibiotics were used. All but one were lactose (+). Fosfomycin-susceptible strains (n=15) that had the same phenotypes of resistance to other antibiotics as the resistant strains and which had the opposite pattern of lactose fermentation were also used. Thirty-three (33) competition experiments by pairs of strains were conducted in nutrient broth. 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 on days 0, 1, 2, 3 and 4. In 20 experiments (60.6%) there was a relative increase in the fosfomycin-sensitive strain. In 6 experiments (18.2%) there was a relative increase in the fosfomycin-resistant strain. 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 analyzed by the chi2 test there was a statistically significant difference (p=0.044). Resistance to fosfomycin could entail a biological cost (less fitness) for the majority of the E. coli strains assayed.