Effectiveness and Safety of Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Children: A Systematic Review

Abstract

Background: Antibiotic-associated diarrhea (AAD) is a clinically important gastrointestinal complication of antibiotic therapy in children. Probiotic effects are biologically and clinically strain-specific, and differences in formulation, dose, outcome definition, and study setting can influence observed effectiveness. This systematic review evaluated the effectiveness and safety of probiotics for prevention of AAD in children receiving antibiotic therapy.

Methods: A systematic review was conducted in accordance with PRISMA 2020. PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library were searched using controlled vocabulary and free-text terms for children, probiotics, antibiotics, and AAD. Randomized controlled trials and prospective observational studies reporting comparative pediatric outcomes were eligible. The primary outcome was AAD incidence; secondary outcomes included diarrhea severity and duration, stool frequency and consistency, gastrointestinal symptoms, and adverse events. Randomized trials were assessed with Cochrane Risk of Bias 2 and the observational study with the Newcastle-Ottawa Scale. Because of substantial clinical and methodological heterogeneity, results were synthesized narratively rather than pooled.

Results: Five studies enrolled 1,224 children, of whom 1,104 were included in the final analyses reported by the individual studies; four studies were randomized controlled trials and one was prospective observational. Lactobacillus rhamnosus GG was associated with lower AAD incidence than placebo in Arvola et al. (5% vs 16%; treatment effect -11%, 95% CI -21% to 0%; p = 0.05) and Vanderhoof et al. (8% vs 26%; p < 0.001). A multi-strain probiotic yogurt reduced severe diarrhea (0% vs 16.7%; p = 0.025) and minor diarrhea (2.9% vs 58.3%; p < 0.001). Lactobacillus plantarum DSM 9843 did not significantly reduce AAD (2.8% vs 4.1%; p = 0.40). In the observational study, probiotic prophylaxis was associated with lower AAD incidence (12.4% vs 41.8%; RR 0.30, 95% CI 0.19-0.46). No consistent increase in reported adverse events was identified.

Conclusion: The included studies suggest that selected probiotic preparations, particularly Lactobacillus rhamnosus GG-containing interventions, may reduce pediatric AAD, whereas benefit was not demonstrated for all strains. The findings support strain-specific interpretation and cautious application because of heterogeneity in interventions, outcome definitions, study design, and sample size.

Keywords: Probiotics; antibiotic-associated diarrhea; children; pediatric patients; Lactobacillus rhamnosus GG; antibiotics; gastrointestinal symptoms; prevention