JOURNAL ARTICLE
REVIEW

Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis

Bradley C Johnston, Stephanie S Y Ma, Joshua Z Goldenberg, Kristian Thorlund, Per O Vandvik, Mark Loeb, Gordon H Guyatt
Annals of Internal Medicine 2012 December 18, 157 (12): 878-88
23362517

BACKGROUND: Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization. This may result in complications, the most serious of which is Clostridium difficile–associated diarrhea (CDAD).

PURPOSE: To assess the efficacy and safety of probiotics for the prevention of CDAD in adults and children receiving antibiotics.

DATA SOURCES: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine Database, Web of Science, and 12 gray-literature sources.

STUDY SELECTION: Randomized, controlled trials including adult or pediatric patients receiving antibiotics that compared any strain or dose of a specified probiotic with placebo or with no treatment control and reported the incidence of CDAD.

DATA EXTRACTION: Two reviewers independently screened potentially eligible articles; extracted data on populations, interventions, and outcomes; and assessed risk of bias. The Grading of Recommendations Assessment, Development and Evaluation guidelines were used to independently rate overall confidence in effect estimates for each outcome.

DATA SYNTHESIS: Twenty trials including 3818 participants met the eligibility criteria. Probiotics reduced the incidence of CDAD by 66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]; I(2) = 0%). In a population with a 5% incidence of antibiotic-associated CDAD (median control group risk), probiotic prophylaxis would prevent 33 episodes (CI, 25 to 38 episodes) per 1000 persons. Of probiotic-treated patients, 9.3% experienced adverse events, compared with 12.6% of control patients (relative risk, 0.82 [CI, 0.65 to 1.05]; I(2) = 17%).

LIMITATIONS: In 13 trials, data on CDAD were missing for 5% to 45% of patients. The results were robust to worst-plausible assumptions regarding event rates in studies with missing outcome data.

CONCLUSION: Moderate-quality evidence suggests that probiotic prophylaxis results in a large reduction in CDAD without an increase in clinically important adverse events.

PRIMARY FUNDING SOURCE: None.

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