Clinician Article

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

  • Hempel S
  • Newberry SJ
  • Maher AR
  • Wang Z
  • Miles JN
  • Shanman R, et al.
JAMA. 2012 May 9;307(18):1959-69. doi: 10.1001/jama.2012.3507. (Review)
PMID: 22570464
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  • Infectious Disease
    Relevance - 7/7
    Newsworthiness - 5/7
  • Internal Medicine
    Relevance - 6/7
    Newsworthiness - 6/7
  • Emergency Medicine
    Relevance - 6/7
    Newsworthiness - 5/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 6/7
    Newsworthiness - 5/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 6/7
    Newsworthiness - 5/7
  • Pediatric Emergency Medicine
    Relevance - 6/7
    Newsworthiness - 4/7
  • Pediatrics (General)
    Relevance - 6/7
    Newsworthiness - 4/7
  • Pediatric Hospital Medicine
    Relevance - 5/7
    Newsworthiness - 4/7


CONTEXT: Probiotics are live microorganisms intended to confer a health benefit when consumed. One condition for which probiotics have been advocated is the diarrhea that is a common adverse effect of antibiotic use.

OBJECTIVE: To evaluate the evidence for probiotic use in the prevention and treatment of antibiotic-associated diarrhea (AAD).

DATA SOURCES: Twelve electronic databases were searched (DARE, Cochrane Library of Systematic Reviews, CENTRAL, PubMed, EMBASE, CINAHL, AMED, MANTIS, TOXLINE, ToxFILE, NTIS, and AGRICOLA) and references of included studies and reviews were screened from database inception to February 2012, without language restriction.

STUDY SELECTION: Two independent reviewers identified parallel randomized controlled trials (RCTs) of probiotics (Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and/or Bacillus) for the prevention or treatment of AAD.

DATA EXTRACTION: Two independent reviewers extracted the data and assessed trial quality.

RESULTS: A total of 82 RCTs met inclusion criteria. The majority used Lactobacillus-based interventions alone or in combination with other genera; strains were poorly documented. The pooled relative risk in a DerSimonian-Laird random-effects meta-analysis of 63 RCTs, which included 11 811 participants, indicated a statistically significant association of probiotic administration with reduction in AAD (relative risk, 0.58; 95% CI, 0.50 to 0.68; P < .001; I(2), 54%; [risk difference, -0.07; 95% CI, -0.10 to -0.05], [number needed to treat, 13; 95% CI, 10.3 to 19.1]) in trials reporting on the number of patients with AAD. This result was relatively insensitive to numerous subgroup analyses. However, there exists significant heterogeneity in pooled results and the evidence is insufficient to determine whether this association varies systematically by population, antibiotic characteristic, or probiotic preparation.

CONCLUSIONS: The pooled evidence suggests that probiotics are associated with a reduction in AAD. More research is needed to determine which probiotics are associated with the greatest efficacy and for which patients receiving which specific antibiotics.

Clinical Comments

Emergency Medicine

This article reports that there is an association between decreased diarrhea and probiotic consumption. Importantly, there are references reporting rare but potentially severe adverse events with probiotics. The last line of the article states that future studies should assess this risk. This issue should have been addressed in the abstract of the article.

Family Medicine (FM)/General Practice (GP)

Most Physicians may appreciate the efficacy of Probiotics when antibiotics are given for active infections to prevent antibiotic associated diarrhea (AAD). Overall efficacy equates to a NNT = 13! Others: NNT = 25 to prevent one case of C. difficile; NNT = 11 for children to prevent one case of AAD. Some questions remain in regards to which antibiotics match best with which formulations of probiotics. Further studies are needed.

General Internal Medicine-Primary Care(US)

63 RCTs! Premature to conclude. "The pooled evidence suggests that probiotics are associated with...". Significant heterogeneity. NNT 13. "More research is needed..."

Infectious Disease

Good quality meta-analysis includes a lot of studies not included in a previous one on the same subject. Results are similar with the old meta analysis, however, they are much more robust.

Internal Medicine

Although, in general term, probiotics seem to reduce antibiotic associated diarrhea, more data on safety would be useful, specially in populations with high risk of bacterial translocation (such a patients with liver cirrhosis and patients with severe neutropenia).

Pediatric Emergency Medicine

This is a well conducted systematic review. However, getting into the specifics of use of probiotics in paediatrics (my area) only mirrors that which has already been published in a Cochrane review.

Pediatrics (General)

For a primary care paediatrician like me, could be useful to know the result of this meta-analysis (63 RCT, 11.811 participants): AAD is reduced with a statistically significant association with probiotic administration. However, there is a significant heterogeneity in pooled results therefore, to be more confident with the results, more research is needed to determine which probiotics are associated with the greatest efficacy, which kind of patients would benefit most from adjunct probiotics and the real possibility of adverse effects of probiotics.

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