Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Review: Probiotics are effective for prevention of antibiotic-associated diarrhea and treatment of Clostridium difficile disease

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ACP J Club. 2006 Sep-Oct;145:46. doi:10.7326/ACPJC-2006-145-2-046


Clinical Impact Ratings

GIM/FP/GP: 6 stars

Hospitalists: 6 stars

Gastroenterology: 6 stars


Source Citation

McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficiledisease. Am J Gastroenterol. 2006;101:812-22. [PubMed ID: 16635227]


Abstract

Question

Are probiotics effective for preventing antibiotic-associated diarrhea (AAD) and treating or preventing Clostridium difficile disease (CDD)?

Methods

Data sources: MEDLINE and Google Scholar (2005), Cochrane Central Register of Controlled Trials, metaRegister of Controlled Trials, National Institutes of Health clinical trial register, conference abstracts, and bibliographies of relevant studies and books.

Study selection and assessment: Randomized, blinded, controlled trials (RCTs) published as full articles in peer-reviewed journals that assessed the efficacy of specific probiotics for prevention of AAD or treatment or prevention of CDD in patients of any age. 25 RCTs (n= 2810) for AAD (16 in adults and 9 in children) and 6 RCTs (n= 354) for CDD (all in adults, 5 treatment and 1 prevention) met the selection criteria. Methodological quality assessment of trials included randomization, study design, sample size, generalizability, study biases, and outcome assessment.

Outcomes: For AAD: diarrhea within 2 months of antibiotic exposure. For CDD: new episode of C. difficile–positive diarrhea within 1 month of antibiotic exposure or a previous CDD episode.

Main results

Probiotics, Saccharomyces boulardii and Lactobacillus rhamnosus GG in particular, reduced risk for AAD (Table). Probiotics reduced risk for recurrence or development of CDD (Table).

Conclusion

Selected probiotics can be effective for preventing antibiotic-associated diarrhea and treating Clostridium difficile disease.

Source of funding: Not stated.

For correspondence: Dr. L. McFarland, VA Puget Sound Health Care System, Seattle, WA, USA. E-mail lvmcfarl@u.washington.edu.


Table. Probiotics for prevention of antibiotic-associated diarrhea (AAD) and treatment or prevention of Clostridium difficile disease (CDD) at 1 to 12 weeks*

Outcomes Type of probiotic Number of trials (n) Weighted event rates RRR (95% CI) NNT (CI)
Probiotics Control
AAD Overall 25 (2810) 12% 27% 57% (42 to 69)† 7 (6 to 9)
SB 6 (1119) 7% 18% 63% (48 to 74) 9 (8 to 12)
LRGG 6 (817) 8% 27% 69% (28 to 87)† 6 (5 to 14)
Other single probiotics 6 (502) 15% 33% 54% (−3 to 79)† Not significant
Mixture of 2 probiotics 7 (372) 23% 45% 49% (32 to 62) 5 (4 to 7)
CDD Overall 6 (354) 18% 31% 41% (15 to 59) 8 (6 to 22)

*SB = Saccharomyces boulardii; LRGG = Lactobacillus rhamnosus GG. Other abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article using a fixed-effects model.
†A random-effects model was used.


Commentary

During recent years, outbreaks of CDD of surprising severity, as well as cases of CDD that respond poorly to metronidazole, have been reported (1, 2). These reports have led to a search for new approaches to the treatment and prevention of AAD and CDD. Probiotic therapy, the use of nonpathogenic microorganisms to restore a normal intestinal flora, is an attractive alternative. The meta-analysis by McFarland indicates that probiotic treatment can be effective in the management of both CDD and AAD, although the effectiveness varies notably with different probiotic regimens.

So, how should probiotics be prescribed? Unfortunately, this is difficult to determine because major unanswered questions remain about the pathogenesis of AAD and CDD. Recent analysis of human intestinal microflora using molecular techniques has shown that the diversity of bacterial strains present is far greater than previously recognized, with a large percentage of species not yet cultivated (3). At this time, we understand neither how these microflora are affected by antibiotics nor how alterations in the flora contribute to AAD and CDD. Moreover, we do not understand how probiotic agents affect human intestinal flora to allow a rational approach to their use. This knowledge deficit is not a reason to avoid probiotics, but is a reason to restrict their use to specific indications and defined protocols for which there is objective evidence of efficacy, as noted in this review.

Richard T. Ellison III, MD
University of Massachusetts Medical School
Worcester, Massachusetts, USA


References

1. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005;353:2433-41. [PubMed ID: 16322603]

2. Musher DM, Aslam S, Logan N, et al. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis. 2005;40:1586-90. [PubMed ID: 15889354]

3. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005;308:1635-8. [PubMed ID: 15831718]