Are Probiotics Effective for Treating Clostridium Difficile Disease and Antibiotic-Associated Diarrhea?

Mario Guslandi

Disclosures

Nat Clin Pract Gastroenterol Hepatol. 2006;3(11):606-607. 

In This Article

Synopsis

Background

Antibiotic-associated diarrhea (AAD) and Clostridium difficile disease (CDD) are common conditions linked to the use of antibiotics. Studies evaluating the efficacy of probiotics for the treatment of these two conditions have produced contradictory results.

Objectives

To determine the efficacy and safety of probiotics for the prevention of AAD and CDD.

Design and Intervention

The databases of PubMed, MEDLINE, Google Scholar, metaRegister, the NIH registry of clinical trials, and the Cochrane Central Register of Controlled Trials were searched to identify studies suitable for inclusion in the meta-analysis. In addition, reference lists, commentaries, books, and meeting abstracts were examined. Keywords, including "probiotics", "Clostridium difficile", "antibiotics", "diarrhea", "Saccharomyces", and "Lactobacilli" were used to carry out the search. Studies were eligible for inclusion if they were published between 1977 and 2005 in peer-reviewed publications, used human subjects, and were randomized controlled trials (RCTs) that examined efficacy. Exclusion criteria included case reports, Phase I safety studies, and trials that used unspecified probiotics. Diarrhea was defined ≥3 loose stools within 24 h for ≥2 days, or ≥5 loose stools within 48 h. AAD was defined as diarrhea within 2 months of exposure to antibiotics. CDD was defined as diarrhea associated with a positive Clostridium difficile culture or toxin within a month of exposure to antibiotics. The quality of suitable studies was assessed according to a number of factors, including study design, sample size, and outcome measures. A quality grade was given to each study: 1 = poor, 2 = fair, 3 = good.

Outcome Measure

The main outcome measure was identification of studies suitable for inclusion in the meta-analysis.

Results

In total, 31 RCTs were included in the meta-analysis, and all were rated fair or good quality. Of these, 25 featured patients with AAD, and collectively contained the data of 2,810 patients, and 6 featured patients with CDD, and collectively contained data on 354 patients. Meta-analysis revealed that probiotics had a significant protective effect for the development of AAD (relative risk [RR] 0.43, 95% CI 0.31-0.58, P <0.001). In a further meta-analysis by probiotic strain, Saccharomyces boulardii (S. boulardii), Lactobacillus rhamnosus GG (L. rhamnosus GG), and a mixture of two strains of Lactobacilli showed significant efficacy for treating AAD (RR 0.34, 95% CI 0.26-0.52; P <0.0001; RR 0.31, 95% CI 0.13-0.72; P = 0.006; and RR 0.51, 95% CI 0.38-0.68; P <0.0001, respectively). Meta-analysis also revealed that probiotics had a significant protective effect for the development of CDD (RR =0.59, 95% CI 0.41-0.85; P = 0.005). S.boulardii was the only probiotic that showed a significant reduction in the recurrence of CDD. Overall, 24 trials reported no adverse events, and those that did reported minor adverse events, including thirst and constipation.

Conclusion

S. boulardii, L. rhamnosus GG, and probiotic mixtures significantly reduced the development of AAD. S. boulardii significantly reduced the development of CDD.

Comments

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