Probiotics for the Prevention of Clostridium difficile–Associated Diarrhea: A Systematic Review and Meta-analysis
Ann Intern Med. 2012;157(12):878-888.
Question: What are the efficacy and safety of probiotics for the prevention of Clostridium difficile–associated disease (CDAD) in adults and children receiving antibiotics?
Data Sources: Six primary scientific databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine Database, and Web of Science), as well as 12 gray-literature resources covering additional abstracts and reports, were reviewed for studies dated 1945 to 2012. Of 1435 citations initially identified through database searches, 101 articles underwent full text review.
Study Selection: Included studies were randomized clinical trials involving patients treated with antibiotics that (1) compared the effect of any dose of any specified probiotic with placebo or no treatment and (2) reported the incidence of diarrhea with associated stool cytotoxin assay or culture positive for C difficile.
Data Extraction and Synthesis: Data were extracted by 2 reviewers using standardized extraction forms. Reviewers independently assessed risk of biases. Each outcome was individually rated using Grading of Recommendations Assessment, Development and Evaluation criteria. Data were pooled using random-effects modeling for calculation of relative risks and 95% confidence intervals.
Main Outcomes and Measures: Incidence of CDAD and incidence of adverse effects in participants treated with probiotics versus placebo or no treatment.
Results: Twenty trials including 3818 participants were included for analysis. Probiotic use was associated with a 66% reduction in the incidence of CDAD (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]). Subgroup analyses did not demonstrate significant differences. Of patients treated with probiotics, 9.3% experienced adverse events, compared with 12.6% of control patients (relative risk, 0.82 [CI, 0.65 to 1.05]), on the basis of the 17 included studies reporting adverse event rates.
Authors’ Conclusions: The authors estimate that in a population with 5% incidence of antibiotic-associated CDAD, probiotic prophylaxis would prevent 33 episodes per 1000 persons without significant increase in adverse events. The overall confidence of effect estimates was rated as moderate for both CDAD and adverse event incidence.