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


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


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


METHODS
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.


METHODS
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.


RESULTS
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%).


CONCLUSIONS
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.


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


BACKGROUND
None.
The Hospital for Sick Children Research Institute, Room 2420, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. bradley.johnston@sickkids.ca
Bradley C
BC
Johnston
Stephanie S Y
SS
Ma
Joshua Z
JZ
Goldenberg
Kristian
K
Thorlund
Per O
PO
Vandvik
Mark
M
Loeb
Gordon H
GH
Guyatt
D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002648:Child; D016360:Clostridioides difficile; D003967:Diarrhea / Q000453:epidemiology / Q000382:microbiology* / Q000517:prevention & control*; D004761:Enterocolitis, Pseudomembranous / Q000453:epidemiology / Q000517:prevention & control*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology*; D006801:Humans; D015994:Incidence; D019936:Probiotics / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors
D000900:Anti-Bacterial Agents