Comparative in vitro activity of furazidin and nitrofurantoin and assessment of resistance mechanisms in Escherichia coli isolates from urinary tract infections
摘要
To bridge the clinical and methodological gap created by Poland’s widespread OTC use of furazidin in empirical urinary tract infections (UTIs) management versus EUCAST’s reliance on nitrofurantoin for susceptibility testing, by comparing their activity against E. coli isolates and identifying nfsA mutations associated with reduced nitrofuran susceptibility.
Thirty-three E. coli isolates were obtained from outpatient urine samples. MICs for furazidin and nitrofurantoin were determined using broth microdilution, and MIC₅₀/MIC₉₀ values were calculated. Isolates with MIC ≥ 8 µg/ml underwent nfsA detection and Sanger sequencing of the examined nfsA gene. This analysis was performed as a targeted, exploratory assessment of genotype-phenotype associations, with results interpreted according to current EUCAST methodological standards.
Furazidin showed higher in vitro activity than nitrofurantoin (mean MIC: 6.05 µg/ml vs. 10.46 µg/ml; MIC₅₀: 2 µg/ml vs. 4 µg/ml; MIC₉₀: 16 µg/ml vs. 32 µg/ml). The nfsA gene was detected in 75% of isolates with elevated MICs. Gene sequencing revealed nonsense and frameshift mutations leading to truncated nitroreductase, consistent with reduced susceptibility, although none of the isolates met EUCAST clinical resistance breakpoints.
Nitrofurantoin MICs do not fully reflect the activity of furazidin, which is widely used in Poland and East European countries. These results underscore the need for region-specific evaluation of nitrofuran susceptibility and caution against extrapolating nitrofurantoin MICs to furazidin efficacy in clinical practice. Moreover, the findings highlight the need for improved standardization of nitrofuran susceptibility testing and further investigation of resistance mechanisms to guide optimal UTI therapy, particularly in outpatient populations where nitrofurans remain first-line empirical agents.