Methenamine Hippurate Versus Low-Dose Nitrofurantoin for Recurrent Urinary Tract Infection Prophylaxis in Women

BACKGROUND: Recurrent urinary tract infections (rUTIs), a prevalent condition among women, substantially impair quality of life, underscoring the need for effective and safe preventive treatments. AIM: This study evaluated the efficacy, safety, and bacterial resistance rates of methenamine hippurate versus low-dose nitrofurantoin for rUTI prevention in women, to guide clinical prophylaxis choices. METHODS: We conducted a retrospective propensity score-matched cohort study involving female rUTI patients from our urology clinic between June 2021 and February 2024. After 1:1 matching, fifty patients each constituted the methenamine hippurate (MH) group and the low-dose nitrofurantoin (NFT) group . The treatment and follow-up period was 12 months, with assessments at 3, 6, and 12 months. A non-inferiority margin of Δ=0.5 episodes per person-year was defined. The primary endpoint was the 12-month symptomatic UTI recurrence rate. Secondary outcomes encompassed urine culture positivity, pathogen profile, antibiotic resistance, asymptomatic bacteriuria, international prostate symptom score (IPSS), quality of life score (SF-36), direct costs, compliance, and adverse events. RESULT: After propensity score matching (PSM), initial analysis showed no significant differences in the baseline characteristics between the two groups (P>0.05). The 12-month recurrence rates were 18.00% for MH and 20.00% for NFT, confirming non-inferiority (P=0.765). Urine culture positivity and pathogen profiles did not differ significantly. Notably, the MH group showed no detectable resistance, compared to 28.57% resistance in the NFT group (P=0.022), and a reduced rate of asymptomatic bacteriuria (8.00% vs. 22.00%; P=0.037). Compliance was similar between groups. At 12 months, MH resulted in significantly improved IPSS and SF-36 scores (P<0.001). Although drug costs were higher with MH, total management costs for recurrences and adverse events were lower (P<0.001), with fewer reported adverse events (P<0.05). CONCLUSIONS: Methenamine hippurate demonstrates noninferiority to low-dose nitrofurantoin for preventing rUTIs in women, with reduced resistance, adverse events, and asymptomatic bacteriuria. Despite higher cost, its superior long-term benefit supports its use as an alternative in NFT-intolerant or high-risk patients.