Lactobacillus probiotics in the prevention of diarrhea associated with Clostridium difficile: a systematic review and Bayesian hierarchical meta-analysis

Abstract

Recent meta-analyses of the efficacy of probiotics for preventing diarrhea associated with Clostridium difficile have concluded there is a large effect favouring probiotics. We reexamined this evidence, which contradicts the results of a more recent large randomized controlled trial that found no benefit of Lactobacillus probiotics for preventing C. difficile-associated diarrhea. We performed a systematic review of the efficacy of treatment with Lactobacillus probiotics for preventing nosocomial C. difficile-associated diarrhea in adults and carried out a meta-analysis using a Bayesian hierarchical model. We used credibility analysis and meta-regression to characterize the heterogeneity between studies. Ten studies met our inclusion criteria. The pooled risk ratio was highly statistically significant, at 0.25 (95% credible interval 0.08-0.47). However, the 95% prediction interval for the risk ratio in a future study, 0.02-1.34, was wider than the credible interval, owing to heterogeneity between studies. Furthermore, a credibility analysis showed that the strength of the evidence was weaker than the observed number of cases of C. difficile-associated diarrhea across studies would suggest. Meta-regression suggested that the beneficial effect of probiotics was more likely to be reported in studies with an increased risk of C. difficile-associated diarrhea in the control group, although this association was not statistically significant. Accounting for between-study heterogeneity showed that there is considerable uncertainty regarding the apparently large efficacy estimate associated with Lactobacillus probiotic treatment in preventing C. difficile-associated diarrhea. Most studies to date have been carried out in populations with a low risk of C. difficile-associated diarrhea, such that the evidence is inconclusive and inadequate to support a policy concerning routine use of probiotics in to prevent this condition.