Non-antibiotic strategies for preventing urinary tract infections in children, with an emphasis on vesicoureteral reflux: a narrative review

Context: Urinary tract infections (UTI) are among the most common bacterial infections in childhood. Children with vesicoureteral reflux (VUR) are at a higher risk for recurrent urinary tract infections (rUTI) and their sequelae. Long term antibiotic prophylaxis with rising antimicrobial resistance without preventing scarring prompted a search for alternatives. Objective: To systematically evaluate the evidence for non-antibiotic uroinfection prevention strategies in children, with primary focus on children with VUR. Data Sources: Databases PubMed, Cochrane Library, Scopus, Web of Science, Embase and ClinicalTrials.gov were searched up to June 2026. Study Selection: A systematic review of databases was conducted according to PRISMA 2020 guidelines. Pediatric studies of non-antibiotic uroinfection prevention strategies with VUR were prioritized. Narrative synthesis was performed to summarise and interpret findings. Data Extraction: Study design, population, intervention and outcomes were extracted for each study. Results: Thirty-six studies were included. Probiotics appear non-inferior to antibiotics in VUR specific trials, with multi-strain formulations showing greater potential. D-mannose is a promising candidate due to its pathogen specific mechanism and safety, although biomarker guided patient selection may be necessary. Cranberry is best used as an addition to standard prophylaxis in high risk populations. Vitamin D may enhance urinary immunological defense by inducing cathelicidin production. In high-grade VUR, altered intercalated cell function may impair cathelicidin production, potentially increasing susceptibility to recurrent infections. Immunoprophylaxis showed some potential for reducing uroinfection recurrence, but pediatric evidence remains limited. Conclusion: Antibiotic-induced dysbiosis may contribute to recurrent infections. Future prevention strategies should focus on preserving or restoring the urobiome.