Preventing pediatric antibiotic-associated diarrhea and Clostridium difficile infections with probiotics: A meta-analysis

Abstract

AIM: To assess the efficacy and safety of probiotics for preventing pediatric: (1) antibiotic associated diarrhea and (2) Clostridium difficile (C. difficile) infections.

METHODS: On June 3, 2013, we searched PubMed (1960-2013), EMBASE (1974-2013), Cochrane Database of Systematic Reviews (1990-2013), CINAHL (1981-2013), AMED (1985-2013), and ISI Web of Science (2000-2013). Additionally, we conducted an extensive grey literature search including contact with National Institutes of Health Clinical Trials Registry, abstracts from annual infectious disease and gastroenterology meetings, experts in the field and correspondence with authors. The primary outcomes were the incidence of antibiotic-associated diarrhea (AAD) and C. difficile infections (CDI). Dichotomous outcomes (e.g., incidence of AAD or CDI) were pooled using a random-effects model to calculate the relative risk and corresponding 95% confidence interval (95%CI) and weighted on study quality. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic strain type, daily dose, quality of study and safety of probiotics. The overall quality of the evidence supporting each outcome was assessed using the grading of recommendations, assessment, development and evaluation criteria.

RESULTS: A total of 1329 studies were identified with 22 trials (23 treatment arms and 4155 participants) meeting eligibility requirements for our review of prevention of AAD and 5 trials (1211 participants) for the prevention of CDI. Trials in adult populations, trials of uncertain antibiotic exposure or studies which did not provide incidence of AAD were excluded. We found 12 trials testing a single strain of probiotic and 10 trials testing a mixture of probiotic strains. Probiotics (all strains combined) significantly reduced the incidence of pediatric AAD (pooled RR = 0.42, 95%CI: 0.33-0.53) and significantly reduced pediatric CDI (pooled RR = 0.35, 95%CI: 0.13-0.92). Of the two strains with multiple trials, both significantly reduced pediatric AAD: Saccharomyces boulardii lyo (pooled RR = 0.43, 95%CI: 0.32-0.60) and Lactobacillus rhamnosus GG (pooled RR = 0.36, 95%CI: 0.19-0.69). There was no significant effect by type of antibiotic, or by duration or dose of probiotic. No adverse events associated were found in the 22 controlled trials relating to the use of probiotics.

CONCLUSION: This meta-analysis found that probiotics significantly prevented pediatric antibiotic associated diarrhea and pediatric CDI, but the efficacy varies significantly by the strain of the probiotic.

Keywords: Probiotics; Pediatric; Antibiotic-associated diarrhea; Clostridium difficile; Saccharomyces boulardii; Lactobacillus rhamnosus; Safety; Meta-analysis; Randomized clinical trials

Core tip: A meta-analysis was conducted (1985-2013) for clinical trials testing probiotics for the prevention of pediatric antibiotic-associated diarrhea (AAD) or Clostridium difficile infections (CDI). Overall, probiotics significantly reduced the incidence of pediatric AAD (pooled from 22 trials RR = 0.42, 95%CI: 0.33-0.53) and significantly reduced pediatric CDI (pooled from five trials RR = 0.35, 95%CI: 0.13-0.92). Of the two strains with multiple trials, both significantly reduced pediatric AAD: Saccharomyces boulardii lyo (RR = 0.43, 95%CI: 0.32-0.60) and Lactobacillus rhamnosus GG (RR = 0.36, 95%CI: 0.19-0.69). There was no significant effect by type of antibiotic, or by duration or dose of probiotic.