Prevalence, mechanisms and comparison of detection methods of fosfomycin resistance in E. coli from urinary tract infections

Abstract

As numbers of bacterial isolates resistant to first line antibiotics rise there has been a revival in the use of older drugs such as fosfomycin. Fosfomycin is a cell wall inhibitor with a unique mode of action, increasingly used in the treatment of urinary tract infections. In this study, the prevalence of fosfomycin resistant E. coli in a panel of 1000 urine isolates was investigated. Three different clinically used fosfomycin susceptibility testing methods were assessed and genome sequencing used to characterise resistant isolates.\n\nOf the 1000 isolates, 676 were E. coli of which initial susceptibility testing with the MAST Uri(R)system suggested 81 (12%) were fosfomycin resistant. Of these, 62 were subsequently confirmed as being E. coli. However, using micro-broth dilution, agar dilution and E-test strips, a lower rate of 1.3% (8/62) of E. coli isolates were robustly identified as being truly fosfomycin resistant; a prevalence comparable with other similar studies. The use of E-test and 96-well breakpoint plates gave results that were inconsistent and hard to interpret. Resistant isolates of E. coli belonged to diverse MLST types and each had a unique set of chromosomal alterations in genes associated with fosfomycin resistance. Changes in GlpT and UhpT/UhpA transport systems were commonly identified, with 6/8 of the resistant isolates possessing amino-acid changes or deletions absent in susceptible strains. Fosfomycin resistant isolates were not multiply drug resistance and did not carry plasmidic fosfomycin resistance genes. Therefore, the use of fosfomycin may be unlikely to drive selection of a particular clone or movement of transferrable resistance genes.\n\nFosfomycin remains a viable option for the treatment of E. coli in uncomplicated UTIs, different susceptibility testing platforms can give very different results regarding the prevalence of fosfomycin resistance with false positives a potential problem that may unnecessarily limit use of this agent.