Bradley C. Johnston, PhD; Stephanie S.Y. Ma, MD; Joshua Z. Goldenberg, BSc; Kristian Thorlund, PhD; Per O. Vandvik, MD, PhD; Mark Loeb, MD; Gordon H. Guyatt, MD
Acknowledgment: The authors thank Jane Saxton for conducting the literature search.
Grant Support: Dr. Johnston was supported in part by a postdoctoral fellowship from the SickKids Foundation. Mr. Goldenberg is supported by grants BUCSR-Y2-005 and BUCSR-Y2-019 from the Bastyr Center for Student Research.
Potential Conflicts of Interest: Dr. Johnston: Grants/grants pending (money to institution): Biocodex. Mr. Goldenberg: Grant: Bastyr Center for Student Research; Support for travel to meetings for the study or other purposes: Bastyr Center for Student Research. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-1183.
Requests for Single Reprints: Bradley C. Johnston, PhD, The Hospital for Sick Children Research Institute, Room 2420, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Johnston: The Hospital for Sick Children Research Institute, Room 2420, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Dr. Ma: Division of Plastic and Reconstructive Surgery, McMaster University, Health Sciences Center 4E9, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
Mr. Goldenberg: Bastyr University, 14500 Juanita Drive NE, Kenmore, WA 98028-4966.
Drs. Thorlund and Guyatt: Department of Clinical Epidemiology and Biostatistics, McMaster University, Health Sciences Centre 3N48, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
Dr. Vandvik: Department of Medicine, Innlandet Hospital Trust–Division Gjøvik, Kyrre Greppsgt 13, 2819 Gjøvik, Norway.
Dr. Loeb: Division of Infectious Diseases, McMaster University, Michael G. DeGroote Center for Learning, Room 3200, 1200 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
Author Contributions: Conception and design: B.C. Johnston, G.H. Guyatt.
Analysis and interpretation of the data: B.C. Johnston, S.S.Y. Ma, J.Z. Goldenberg, K. Thorlund, P.O. Vandvik, M. Loeb, G.H. Guyatt.
Drafting of the article: B.C. Johnston, S.S.Y. Ma, J.Z. Goldenberg.
Critical revision of the article for important intellectual content: B.C. Johnston, K. Thorlund, P.O. Vandvik, M. Loeb, G.H. Guyatt.
Final approval of the article: B.C. Johnston, S.S.Y. Ma, K. Thorlund, P.O. Vandvik, M. Loeb, G.H. Guyatt.
Provision of study materials or patients: B.C. Johnston.
Statistical expertise: B.C. Johnston, K. Thorlund, P.O. Vandvik.
Administrative, technical, or logistic support: B.C. Johnston.
Collection and assembly of data: B.C. Johnston, S.S.Y. Ma, J.Z. Goldenberg, P.O. Vandvik.
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]; I2 = 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]; I2 = 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.
Bradley C. Johnston, Stephanie S.Y. Ma, Joshua Z. Goldenberg, Kristian Thorlund, Per O. Vandvik, Mark Loeb, et al. Probiotics for the Prevention of Clostridium difficile–Associated Diarrhea: A Systematic Review and Meta-analysis. Ann Intern Med. 2012;157:878–888. doi: 10.7326/0003-4819-157-12-201212180-00563
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Published: Ann Intern Med. 2012;157(12):878-888.
Diarrhea, Gastroenterology/Hepatology, Hospital-Acquired Infections, Infectious Disease, Prevention/Screening.
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