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

Recurrent urinary tract infections (rUTIs), a prevalent condition among women, substantially impair quality of life, underscoring the need for effective and safe preventive treatments.

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.

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.

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).

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.