Comparison of increased hydration, D-mannose, and antibiotic prophylaxis for recurrent urinary tract infection prevention in premenopausal women: a three-arm randomized-controlled study.

PURPOSE

Recurrent urinary tract infections (rUTIs) are a common and impactful clinical challenge in premenopausal women, significantly affecting quality of life and imposing high healthcare costs. Despite their prevalence, robust comparative studies evaluating preventive strategies are scarce, and growing antimicrobial resistance necessitates exploring non-antibiotic alternatives. The aim of this study is to compare the efficacy and safety of increased hydration, D-mannose, and antibiotic prophylaxis in preventing recurrent UTIs in premenopausal women.

METHODS

This 12-month, prospective, randomized, controlled, multicenter, three-arm parallel study enrolled 75 premenopausal women (18-49 years) with ≥ 3 UTIs/year. Participants were randomized (1:1:1) to increased hydration, D-mannose, or low-dose antibiotic prophylaxis. Primary endpoints were number of UTI episodes/year. Secondary endpoints included time to first UTI and adverse events. Statistical analysis utilized ANOVA and Kaplan-Meier methods.

RESULTS

All three groups demonstrated some degree of UTI prevention. The antibiotic prophylaxis group showed the lowest rUTI incidence (mean 0.2 episodes/year, median 0), significantly lower than the increased hydration group (mean 1.08 episodes/year, median 1; p < 0.05). D-mannose showed intermediate efficacy (mean 0.32 episodes/year, median 0), trending toward significance compared to increased hydration. Mean time to first UTI was longest in the antibiotic group (4.5 months) vs. D-mannose (2.5 months) and hydration (1 month). Minor adverse events (e.g., mild gastrointestinal issues) were more frequent with antibiotics; no severe adverse events occurred.

CONCLUSION

Low-dose antibiotic prophylaxis remains the most effective strategy for rUTI prevention in premenopausal women. However, D-mannose emerges as a promising, safe non-antibiotic alternative, demonstrating notable efficacy in reducing episodes. Increased hydration, while less effective, remains a safe, economical, and easily implementable baseline measure. These findings advocate for a personalized approach to rUTI prevention, balancing efficacy, safety profile, and patient preference, particularly to mitigate antibiotic use and combat antimicrobial resistance.