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.
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.
Authors: Els van Nood; Anne Vrieze; Max Nieuwdorp; Susana Fuentes; Erwin G Zoetendal; Willem M de Vos; Caroline E Visser; Ed J Kuijper; Joep F W M Bartelsman; Jan G P Tijssen; Peter Speelman; Marcel G W Dijkgraaf; Josbert J Keller Journal: N Engl J Med Date: 2013-01-16 Impact factor: 91.245
Authors: Joshua Z Goldenberg; Stephanie S Y Ma; Jane D Saxton; Mark R Martzen; Per O Vandvik; Kristian Thorlund; Gordon H Guyatt; Bradley C Johnston Journal: Cochrane Database Syst Rev Date: 2013-05-31
Authors: Jennifer K Spinler; Jennifer Auchtung; Aaron Brown; Prapaporn Boonma; Numan Oezguen; Caná L Ross; Ruth Ann Luna; Jessica Runge; James Versalovic; Alex Peniche; Sara M Dann; Robert A Britton; Anthony Haag; Tor C Savidge Journal: Infect Immun Date: 2017-09-20 Impact factor: 3.441
Authors: A P S Hungin; C R Mitchell; P Whorwell; C Mulligan; O Cole; L Agréus; P Fracasso; C Lionis; J Mendive; J-M Philippart de Foy; B Seifert; K-A Wensaas; C Winchester; N de Wit Journal: Aliment Pharmacol Ther Date: 2018-02-20 Impact factor: 8.171