Introduction

The prevalence of urinary tract infections (UTIs) is quite common in women due to the anatomical factors. The recurrence of UTIs is a significant cause of concern, leading to clinical and economic burden. Although antibiotics are widely prescribed for the treatment of UTIs, their long-term use is associated with side effects and antimicrobial resistance. The physicians face challenges in selection of antibiotics, treatment duration and management of recurrent infections. Hence, non-antibiotic alternatives like methenamine hippurate are being explored as a preventive measure against recurrent UTIs.

Aim

To assess the efficacy of methenamine hippurate vs standard antibiotics and placebo in the prophylaxis of UTIs, by incorporating the latest research findings and employing trial sequential analysis.

Method

Study Design

• Systematic review and meta-analysis

Study Selection Criteria

• An extensive search of MEDLINE, Embase, Scopus, Cochrane, and Google Scholar databases was conducted to identify randomized controlled trials comparing methenamine hippurate with placebo or antibiotic in adult women with a history of recurrent or confirmed UTIs
• Studies including women with acute UTIs were excluded
• Asymptomatic UTIs with negative urine cultures was excluded from the meta-analysis as they were not adequately accounted for in the studies
• Adverse effects related to antibiotic resistance were not described in the studies, so only the adverse effects related to the medications were considered
• Trial sequential analysis was used as it helps to control random errors and can evaluate the robustness of the evidence

Endpoints

Primary Endpoint

• Recurrence of clinical UTIs

Secondary Endpoints

• Positive urine cultures associated with UTI symptoms
• Asymptomatic bacteriuria
• Adverse effects

Results

• The meta-analysis included 5 studies, comprising of 216 patients in the methenamine group and 205 patients in the control group (antibiotics/placebo)
• There were no significant differences in the incidence of symptomatic UTI episodes between the two groups (RR 1.15; p = 0.41)
• Both the clinical interventions demonstrated comparable rate of positive urine cultures (RR 1.20; p = 0.25), and adverse effects (RR 0.98; p = 0.35)
• Prophylaxis with methenamine hippurate was associated with a higher rate of asymptomatic bacteriuria as compared to the antibiotic group; RR 1.91; p = 0.0001
• In trial sequential analysis, existing studies were not able to attain the futility boundaries

Conclusion

• Methenamine hippurate is an effective, non-inferior and safe alternative to antibiotics in the prophylaxis of recurrent urinary tract infections in adult women
• However, more RCTs are warranted to achieve the futility boundaries in trial sequential analysis

BMC Urol. 2025 Feb: 25:30. Doi:10.1186/s12894-025-01708-8.