Which probiotic has the best effect on preventing Clostridium difficile-associated diarrhea? A systematic review and network meta-analysis

J Dig Dis. 2020 Feb;21(2):69-80. doi: 10.1111/1751-2980.12839.


Objective: Clostridium difficile-associated diarrhea (CDAD) accounts for up to 25% of patients with antibiotic-associated diarrhea (AAD). We aimed to determine which probiotic is most effective in preventing CDAD using a network meta-analysis.

Methods: Studies were identified by searching PubMed, EMBASE and the Cochrane Library databases for randomized controlled trials (RCTs) that evaluated the efficacy of probiotic interventions for CDAD. Primary outcomes were the incidence rates of AAD and CDAD, and secondary outcomes were the duration of diarrhea and the time until onset of diarrhea. The PROSPERO registered number of this study is CRD42018106115.

Results: Ten RCTs including 11 analyses and including 4 692 patients were identified. Compared with the control group, probiotic intervention reduced the incidence rates of CDAD (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.17-0.61) and AAD (OR 0.39, 95% CI 0.23-0.66). Similar results were observed regarding the duration of diarrhea and the time until onset of diarrhea. Meta-regression analysis showed a correlation between the type of probiotic used and the incidence of CDAD and AAD. All nine kinds of probiotic interventions were statistically more effective than the placebo, with Lactobacillus casei ranking as the best intervention (OR 0.19, 95% credible interval [CrI] 0.06-0.63) for decreasing the incidence rate of CDAD. L. casei also ranked the highest in reducing the incidence rate of AAD (OR 0.32, 95% CrI 0.14-0.74).

Conclusion: Lactobacilli strains, especially L. casei, have a good effect on the prevention of CDAD and AAD.

Keywords: Clostridium difficile; antibiotic-associated diarrhea; network meta-analysis; prevention; probiotics.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / adverse effects*
  • Child
  • Clostridioides difficile*
  • Clostridium Infections / drug therapy*
  • Clostridium Infections / microbiology
  • Diarrhea / chemically induced
  • Diarrhea / microbiology
  • Diarrhea / prevention & control*
  • Enterocolitis, Pseudomembranous / drug therapy*
  • Enterocolitis, Pseudomembranous / microbiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Network Meta-Analysis
  • Odds Ratio
  • Probiotics / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Anti-Bacterial Agents