Comparative Efficacy and Safety of Nitrofurantoin Versus Fosfomycin for Acute Uncomplicated Lower Urinary Tract Infection: A Systematic Review and Meta-Analysis.

Abstract

Introduction and hypothesis: Nitrofurantoin and fosfomycin are first-line oral agents for acute uncomplicated lower urinary tract infection (u-UTI) in women, yet direct comparative evidence remains limited. This study compared clinical and microbiological outcomes of multi-day nitrofurantoin versus single-dose fosfomycin trometamol for u-UTI, including pregnant and nonpregnant women.

Methods: Databases were searched from inception through 9 May 2025, for RCTs comparing oral nitrofurantoin with single-dose fosfomycin trometamol (3g) for u-UTI. Primary outcomes were clinical and microbiological cure; secondary outcomes were 14-day relapse and adverse drug reactions (ADRs). Pooled risk ratios (RRs) with 95% CIs were calculated. Risk of bias was assessed using Cochrane RoB 2.0, and evidence certainty was graded using GRADE.

Results: Six RCTs (n = 1762; mean age 36.49±15.29) were included. Clinical cure at ≤7, 7-10, 14, and ≥28 days was comparable (RR 0.98, 0.99, 1.05, 1.02). Nitrofurantoin 300 mg/day was associated with higher clinical cure at 14 and ≥28 days (RR 1.14 and 1.22), whereas no significant difference was observed with 200 mg/day. In pregnant women, fosfomycin was associated with higher clinical cure at ≤7 days (RR 0.87; 95% CI 0.76-0.98). Microbiological cure showed no significant overall difference between treatments (RR 0.99; 95% CI 0.92-1.08), including at 14 and ≥28 days. Nitrofurantoin was associated with higher 14-day relapse (RR 1.71; 95% CI 1.13-2.59). Overall ADR rates were not significantly different (RR 1.27; 95% CI 0.95-1.70), although ADRs were higher with nitrofurantoin 300 mg/day (RR 1.63; 95% CI 1.07-2.49).

Conclusions: Nitrofurantoin and single-dose fosfomycin are both effective treatment options for uncomplicated cystitis. Treatment choice may be influenced by pregnancy, dosing regimen, and adherence considerations. Further well-designed trials are needed to clarify differences between treatment regimens.