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Introduction and Hypothesis <p>Recurrent urinary tract infections (rUTIs) are a prevalent condition in women, historically managed with continuous low-dose antibiotic prophylaxis. However, the global rise in antimicrobial resistance (AMR) necessitates the evaluation of non-antibiotic alternatives. This study was aimed at evaluating the efficacy and safety of non-antibiotic therapies, specifically D-mannose, cranberry products, probiotics, topical estrogen, methenamine hippurate, and immunoprophylaxis in preventing rUTIs in adult women.</p> Methods <p>A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We searched PubMed, Europe PMC, Science Direct, and the Cochrane Library for randomized controlled trials (RCTs) and high-quality observational studies published up to 31 January 2025. Studies were assessed for risk of bias using the Cochrane RoB 2 tool and the Newcastle–Ottawa Scale. The primary outcome was the reduction in UTI recurrence rates.</p> Results <p>Twelve studies met the inclusion criteria (10 RCTs, 2 observational studies). Methenamine hippurate was found to be non-inferior to daily antibiotic prophylaxis in preventing rUTIs. Immunoprophylaxis with the sublingual vaccine MV140 significantly reduced recurrence compared with placebo, with 56–58% of women remaining UTI free in a large RCT. Vaginal estrogen proved effective for postmenopausal women, significantly reducing recurrence, despite small sample sizes in recent trials. D-mannose demonstrated efficacy equivalent to antibiotics in specialist settings, but showed no benefit over placebo in a broad primary care population. Cranberry products were generally less effective than antibiotics but prevented the development of resistant fecal flora. Probiotics significantly prolonged the time to first recurrence.</p> Conclusions <p>Non-antibiotic therapies offer viable, safe, and effective alternatives to long-term antibiotics. The evidence supports a stratified approach: methenamine hippurate and vaginal estrogen (in postmenopausal women) are supported by level 1 evidence as first-line non-antibiotic alternatives. MV140 immunoprophylaxis demonstrates high efficacy in recurrent phenotypes. D-mannose and cranberry show mixed efficacy and should be reserved for selected patient populations, particularly in specialist settings.</p>

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Effectiveness of Non-Antibiotic Therapies in the Management of Recurrent Urinary Tract Infections in Women: A Systematic Review

  • 期刊论文

  • 发表日期：

    2026年5月14日

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  • Abdaal Munir,
  • Tasnuva Tarannum,
  • Nayab Saad,
  • Maham Abdaal

摘要

Introduction and Hypothesis

Recurrent urinary tract infections (rUTIs) are a prevalent condition in women, historically managed with continuous low-dose antibiotic prophylaxis. However, the global rise in antimicrobial resistance (AMR) necessitates the evaluation of non-antibiotic alternatives. This study was aimed at evaluating the efficacy and safety of non-antibiotic therapies, specifically D-mannose, cranberry products, probiotics, topical estrogen, methenamine hippurate, and immunoprophylaxis in preventing rUTIs in adult women.

Methods

A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We searched PubMed, Europe PMC, Science Direct, and the Cochrane Library for randomized controlled trials (RCTs) and high-quality observational studies published up to 31 January 2025. Studies were assessed for risk of bias using the Cochrane RoB 2 tool and the Newcastle–Ottawa Scale. The primary outcome was the reduction in UTI recurrence rates.

Results

Twelve studies met the inclusion criteria (10 RCTs, 2 observational studies). Methenamine hippurate was found to be non-inferior to daily antibiotic prophylaxis in preventing rUTIs. Immunoprophylaxis with the sublingual vaccine MV140 significantly reduced recurrence compared with placebo, with 56–58% of women remaining UTI free in a large RCT. Vaginal estrogen proved effective for postmenopausal women, significantly reducing recurrence, despite small sample sizes in recent trials. D-mannose demonstrated efficacy equivalent to antibiotics in specialist settings, but showed no benefit over placebo in a broad primary care population. Cranberry products were generally less effective than antibiotics but prevented the development of resistant fecal flora. Probiotics significantly prolonged the time to first recurrence.

Conclusions

Non-antibiotic therapies offer viable, safe, and effective alternatives to long-term antibiotics. The evidence supports a stratified approach: methenamine hippurate and vaginal estrogen (in postmenopausal women) are supported by level 1 evidence as first-line non-antibiotic alternatives. MV140 immunoprophylaxis demonstrates high efficacy in recurrent phenotypes. D-mannose and cranberry show mixed efficacy and should be reserved for selected patient populations, particularly in specialist settings.