Dataset Information

Lactobacillus probiotics in the prevention of diarrhea associated with Clostridium difficile: a systematic review and Bayesian hierarchical meta-analysis.

ABSTRACT:

Background

Recent meta-analyses of the efficacy of probiotics for preventing diarrhea associated with Clostridium difficile have concluded there is a large effect favouring probiotics. We reexamined this evidence, which contradicts the results of a more recent large randomized controlled trial that found no benefit of Lactobacillus probiotics for preventing C. difficile-associated diarrhea.

Methods

We performed a systematic review of the efficacy of treatment with Lactobacillus probiotics for preventing nosocomial C.?difficile-associated diarrhea in adults and carried out a meta-analysis using a Bayesian hierarchical model. We used credibility analysis and meta-regression to characterize the heterogeneity between studies.

Results

Ten studies met our inclusion criteria. The pooled risk ratio was highly statistically significant, at 0.25 (95% credible interval 0.08-0.47). However, the 95% prediction interval for the risk ratio in a future study, 0.02-1.34, was wider than the credible interval, owing to heterogeneity between studies. Furthermore, a credibility analysis showed that the strength of the evidence was weaker than the observed number of cases of C. difficile-associated diarrhea across studies would suggest. Meta-regression suggested that the beneficial effect of probiotics was more likely to be reported in studies with an increased risk of C. difficile-associated diarrhea in the control group, although this association was not statistically significant.

Interpretation

Accounting for between-study heterogeneity showed that there is considerable uncertainty regarding the apparently large efficacy estimate associated with Lactobacillus probiotic treatment in preventing C. difficile-associated diarrhea. Most studies to date have been carried out in populations with a low risk of C. difficile-associated diarrhea, such that the evidence is inconclusive and inadequate to support a policy concerning routine use of probiotics in to prevent this condition.

SUBMITTER: Sinclair A

PROVIDER: S-EPMC5173486 | biostudies-literature | 2016 Oct-Dec

REPOSITORIES: biostudies-literature

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Publications

Lactobacillus probiotics in the prevention of diarrhea associated with Clostridium difficile: a systematic review and Bayesian hierarchical meta-analysis.

Sinclair Alison A Xie Xuanqian X Saab Lama L Dendukuri Nandini N

CMAJ open 20161001 4

<h4>Background</h4>Recent meta-analyses of the efficacy of probiotics for preventing diarrhea associated with <i>Clostridium difficile</i> have concluded there is a large effect favouring probiotics. We reexamined this evidence, which contradicts the results of a more recent large randomized controlled trial that found no benefit of <i>Lactobacillus</i> probiotics for preventing <i>C. difficile</i>-associated diarrhea.<h4>Methods</h4>We performed a systematic review of the efficacy of treatment ...[more]

PMID: 28018885

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Project description:Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials.

Dataset Information

Lactobacillus probiotics in the prevention of diarrhea associated with Clostridium difficile: a systematic review and Bayesian hierarchical meta-analysis.

Background

Methods

Results

Interpretation

Publications

Lactobacillus probiotics in the prevention of diarrhea associated with Clostridium difficile: a systematic review and Bayesian hierarchical meta-analysis.

Similar Datasets

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