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

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).

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

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

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.

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.

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%).

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.

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

None.