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Probiotics prevent C. diff-associated diarrhea in patients taking antibiotics

Clinical question

Does the use of probiotics prevent Clostridium difficile-associated diarrhea in patients taking antibiotics?

Bottom line

Moderate-quality evidence suggests that probiotic administration reduces the incidence of C. difficile-associated diarrhea (CDAD) in patients who are taking antibiotics. LOE = 1a-


Johnston BC, Ma SS, Goldenberg JZ, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Ann Intern Med 2012 Nov 13. [Epub ahead of print]

Study Design

Meta-analysis (other)

Funding Source



Various (meta-analysis)


These investigators searched multiple databases, including the Cochrane Register, MEDLINE, EMBASE, as well as reviewed bibliographies of relevant articles and spoke to experts in the field, to find randomized controlled trials that compared probiotics with placebo in reducing the incidence of CDAD in patients taking antibiotics. Two reviewers independently selected the articles, extracted data, and assessed study quality. Half of the 20 studies selected had either an unclear or high risk of bias; 7 studies had an overall low risk of bias. Patients included in the individual studies (N = 3818) varied in age and baseline risk of CDAD. Meta-analysis of the data showed that probiotics, as compared with placebo, reduced the incidence of CDAD in patients taking antibiotics (relative risk = 0.34; 95% CI, 0.24-0.49). Subgroup analyses showed similar results in adults and children, with lower and higher doses of probiotics, and with different probiotic species. There was no evidence of an increased risk of adverse events in the probiotics group. The majority of the studies excluded immunocompromised patients, thus limiting the generalizability of the results. Addtionally, the authors downrated the level of evidence to moderate quality because the overall sample size was smaller than what would be required for an optimally powered single study, which decreases the precision of the results.

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