Clinician Article

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

  • Johnston BC
  • Ma SS
  • Goldenberg JZ
  • Thorlund K
  • Vandvik PO
  • Loeb M, et al.
Ann Intern Med. 2012 Dec 18;157(12):878-88. doi: 10.7326/0003-4819-157-12-201212180-00563. (Review)
PMID: 23362517
Read abstract Read evidence summary Read full text
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 7/7
    Newsworthiness - 6/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 7/7
    Newsworthiness - 6/7
  • Hospital Doctor/Hospitalists
    Relevance - 7/7
    Newsworthiness - 6/7
  • Internal Medicine
    Relevance - 7/7
    Newsworthiness - 6/7
  • Pediatrics (General)
    Relevance - 6/7
    Newsworthiness - 7/7
  • Infectious Disease
    Relevance - 6/7
    Newsworthiness - 5/7
  • Pediatric Hospital Medicine
    Relevance - 6/7
    Newsworthiness - 5/7
  • Pediatric Neonatology
    Relevance - 4/7
    Newsworthiness - 5/7


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.


Clinical Comments

General Internal Medicine-Primary Care(US)

I suspect that many of my colleagues are open to the idea of recommending probiotics to their patients taking antibiotics, but given the minimal side effects, low cost, and potential upside outlined in this article, I would hope that general internists would strongly consider changing their practice to recommend these agents when prescribing antibiotics.

General Internal Medicine-Primary Care(US)

Nice synthesis on available data for probiotics in prevention of C. difficile. The main problem with this meta-analysis is, although it makes a valid argument that multiple different probiotic regimens are probably helpful for prevention of C. difficile, it doesn`t test a specific regimen. Based on the internal figures and tables, it looks like lactobacilli (acidophilus and casei) are most promising.

General Internal Medicine-Primary Care(US)

This is a very helpful meta-analysis since this question often arises during my clinical practice. Many patients are now asking about whether to take probiotics when they take antibiotics. The review suggests that probiotics may be helpful. While the absolute benefit is relatively modest, the risks appear to be very low. This review, therefore, has the potential to change clinical practice to more commonly prescribe probiotics when prescribing antibiotics. A major question that remains is what type of probiotic cocktail is best.

General Internal Medicine-Primary Care(US)

Patients will ask clinicians how to get probiotics that most closely resemble the ones used in these RCTs.

Hospital Doctor/Hospitalists

This is likely a practice-changing article for many hospitalists.

Internal Medicine

Not completely new but more definitive and quite useful that this seems to be a class effect.

Internal Medicine

Careful and thorough review and meta-analysis of probiotics to prevent antibiotic-associated C. difficile diarrhea concludes significant benefit with minimal adverse effects. Given the potentially severe consequences of C. difficile, the information in this paper might reasonably lead individual physicians or care units to developing a standard protocol for treating patients who receive antibiotics concurrently with a probiotic.

Pediatric Hospital Medicine

This is a thorough review and meta-analysis of ALL probiotic studies to prevent C. difficle. A small minority of total patients were pediatric (300 each in treatment and control) and the effect is less than that of adults, so the total results must be considered in light of the small pediatric representation. The pediatric results, however, are consistent with the adult findings and there do not appear to be any negative effects of probiotic treatment.

Pediatric Neonatology

Probiotics reduce C. difficile.

Pediatrics (General)

This systematic review and meta-analysis provides strong evidence that an intervention I believe to be infrequently utilized is highly efficacious in preventing a common and highly morbid condition.

Register for free access to all Professional content