pH-dependent efficacy of nitrofurantoin against uropathogenic Escherichia coli: Implications for personalized urinary tract infection treatment

Introduction: Uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infections (UTIs). The urinary milieu, particularly the pH, may critically influence the efficacy of nitrofurantoin, a first-line oral agent for uncomplicated UTIs. This study aimed to investigate the impact of urinary pH on the susceptibility of nitrofurantoin in clinical UPEC isolates and to assess its implications for individualized therapy. Methods: A prospective study was conducted on 100 culture-confirmed UPEC isolates. Nitrofurantoin susceptibility was determined using the disk diffusion method, broth microdilution following Clinical and Laboratory Standards Institute (CLSI) guidelines, and the automated Vitek-2 system. The minimum bactericidal concentration (MBC) was evaluated in artificial urine at pH levels of 5.5 and 7.2, with estimated minimum inhibitory concentrations (MICs) derived as MBC ÷ 2. A subset of isolates underwent MIC validation in the pH-adjusted broth. Statistical analysis included Chi-square and Wilcoxon signed-rank tests. Results: Standard testing at pH 7.2 revealed an 85% susceptibility rate, concordant across both broth microdilution and Vitek-2. In contrast, acidic pH (5.5) markedly enhanced the activity of nitrofurantoin, reflected by significantly lower MBC and estimated MIC values compared to the neutral conditions ( χ 2 = 14.09, P < 0.001; Wilcoxon P < 0.05). Validation in selected isolates confirmed 4- to 16-fold reductions in MIC under acidic conditions. Conclusion: Nitrofurantoin exhibits pronounced pH-dependent activity, with acidic environments enhancing its bactericidal efficacy against UPEC. Current susceptibility testing at neutral pH may underestimate the in vivo performance. Integrating urinary pH considerations into antimicrobial susceptibility testing and patient management could optimize the treatment outcomes and support personalized UTI therapy.