Exploring the in situ evolution of nitrofurantoin resistance in clinically derived uropathogenic Escherichia coli isolates.

This article focuses on the in situ evolution and mechanisms of nitrofurantoin resistance (NitR) in Escherichia coli isolates from patients with urinary tract infections (UTIs) undergoing antibiotic prophylaxis. Nitrofurantoin resistance primarily arises through step-wise loss-of-function mutations in the nitroreductase genes nfsA and nfsB, with intermediate mutants (e.g., nfsA inactivation) showing a narrow selective growth advantage at sub-minimum inhibitory concentrations (sub-MIC) of nitrofurantoin. The study's genetic and growth analyses indicate no significant fitness cost associated with NitR mutations in the absence of antibiotic, suggesting that the low incidence of nitrofurantoin resistance in the community is driven by urinary drug concentrations that inhibit the establishment of intermediate resistant mutants. These findings highlight the role of pharmacokinetics and selective pressure in limiting the emergence of nitrofurantoin resistance among uro-associated E. coli.