Continuous Antibiotic Prophylaxis for Vesicoureteral Reflux: Impact on the Pediatric Microbiome—A Systematic Review

Background: Continuous antibiotic prophylaxis (CAP) is widely used in infants with vesicoureteral reflux (VUR) to prevent recurrent urinary tract infections and renal scarring. However, this practice entails prolonged low-dose antibiotic exposure during a critical period of microbiome establishment, potentially influencing long-term microbial and immune development. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched up to September 2025 for studies evaluating gut or urinary microbiome changes in children receiving CAP for VUR. Eligible studies included human participants under 18 years with microbiome outcomes assessed by sequencing or culture-based methods. Results: Twenty-one records were identified, and four studies met inclusion criteria—three observational microbiome studies and one randomized controlled trial. CAP preserved overall microbial alpha diversity but induced compositional changes, notably enrichment of Enterobacteriaceae and reduction in Bifidobacteriaceae. The included RCT confirmed reduced UTI recurrence but increased antimicrobial resistance and non–E. coli infections. Conclusions: CAP in early life maintains microbial diversity but alters microbiota composition and resistance profiles. Identifying these shifts may support individualized prophylaxis strategies and microbiome-preserving interventions to balance infection prevention with ecological safety in infancy.