Microbial Preparations (Probiotics) for the Prevention of Clostridium difficile Infection in Adults and Children: An Individual Patient Data Meta-analysis of 6,851 Participants

Bradley C. Johnston, Lyubov Lytvyn, Calvin Ka Fung Lo, Stephen J. Allen, Duolao Wang, Hania Szajewska, Mark Miller, Stephan Ehrhardt, John Sampalis, Deniz G. Duman, Pietro Pozzoni, Agostino Colli, Elisabet Lönnermark, Christian P. Selinger, Samford Wong, Susan Plummer, Mary Hickson, Ruzha Pancheva, Sandra Hirsch, Bengt KlarinJoshua Z. Goldenberg, Li Wang, Lawrence Mbuagbauw, Gary Foster, Anna Maw, Behnam Sadeghirad, Lehana Thabane, Dominik Mertz

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Abstract

OBJECTIVE To determine whether probiotic prophylaxes reduce the odds of Clostridium difficile infection (CDI) in adults and children.DESIGN Individual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.METHODS We searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.RESULTS Probiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25-0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23-0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11-4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89-1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89-1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.CONCLUSIONS Moderate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.TRIAL REGISTRATION PROSPERO 2015 identifier: CRD42015015701 Infect Control Hosp Epidemiol 2018;771-781.

Original languageEnglish (US)
Pages (from-to)771-781
Number of pages11
JournalInfection control and hospital epidemiology
Volume39
Issue number7
DOIs
StatePublished - Jul 1 2018

ASJC Scopus subject areas

  • Epidemiology
  • Microbiology (medical)
  • Infectious Diseases

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    Johnston, B. C., Lytvyn, L., Lo, C. K. F., Allen, S. J., Wang, D., Szajewska, H., Miller, M., Ehrhardt, S., Sampalis, J., Duman, D. G., Pozzoni, P., Colli, A., Lönnermark, E., Selinger, C. P., Wong, S., Plummer, S., Hickson, M., Pancheva, R., Hirsch, S., ... Mertz, D. (2018). Microbial Preparations (Probiotics) for the Prevention of Clostridium difficile Infection in Adults and Children: An Individual Patient Data Meta-analysis of 6,851 Participants. Infection control and hospital epidemiology, 39(7), 771-781. https://doi.org/10.1017/ice.2018.84