Microbial Preparations (Probiotics) for the Prevention of Clostridium difficile Infection in Adults and Children: An Individual Patient Data Meta-analysis of 6,851 Participants
Open accessAbstract
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
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References 47 · Cited by 50
Research works printed but not linked: 2
- [11]11. Hill C, Guarner F, Reid G, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014;11:506-514.
- [21]21. Lytvyn L, Mertz D, Thabane L, et al. Probiotics for the prevention of Clostridium difficile infection in adults and children: an indivi- dual patient data meta-analysis. PROSPERO: International pro- spective register of systematic reviews. Master's thesis, McMaster University. 2015. doi: 10.15124/CRD42015015701. · DOI
- Authors
- 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., Klarin, B., Goldenberg, J. Z., Wang, L., Mbuagbaw, L., Foster, G., Maw, A., Sadeghirad, B., Thabane, L., & Mertz, D.
- Affiliations
- Dalhousie University (CA)
- McMaster University (CA)
- Liverpool School of Tropical Medicine (GB)
- Medical University of Warsaw (PL)
- McGill University (CA)
- Johns Hopkins University (US)
- Marmara University (TR)
- Alessandro Manzoni Hospital (IT)
- University of Gothenburg (SE)
- St James's University Hospital (GB)
- Stoke Mandeville Hospital (GB)
- Cultech (United Kingdom) (GB)
- University of Plymouth (GB)
- University of Chile (CL)
- Lund University (SE)
- Bastyr University (US)
- St. Joseph’s Healthcare Hamilton (CA)
- University of Colorado Denver (US)
- Corresponding author
- Johnston, Bradley C.
- ORCID
- Johnston, Bradley C.
- Lytvyn, Lyubov
- Lo, Calvin Ka-Fung
- Allen, Stephen J.
- Wang, Duolao
- Szajewska, Hania
- Miller, Mark
- Ehrhardt, Stephan
- Sampalis, John
- Duman, Deniz G.
- Colli, Agostino
- Selinger, Christian P.
- Wong, Samford
- Hickson, Mary
- Hirsch, Sandra
- Klarin, Bengt
- Goldenberg, Joshua Z
- Wang, Li
- Foster, Gary
- Maw, Anna
- Sadeghirad, Behnam
- Thabane, Lehana
- Mertz, Dominik
- Venue
- Infection Control & Hospital Epidemiology
- Publisher
- Cambridge University Press (CUP)
- Published
- 2018-04-26
- Volume
- 39
- Issue
- 7
- Pages
- 771-781
- ISSN
- 0899-823X (ISSN-L)
- 1559-6834
- OpenAlex
- W2801532073
- Cited by
- 50
- References
- 47
- Citations by year
- 2026: 3 · 2024: 5 · 2023: 7 · 2022: 3 · 2021: 11 · 2020: 7 · 2019: 8 · 2018: 6
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Infection Control and Hospital Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
- Dspace Repository (Marmara Üniversitesi) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Dspace Repository (Marmara Üniversitesi) (submittedVersion)
- PEARL (University of Plymouth) (submittedVersion)
- Universidad de Chile (submittedVersion)
- Funders
- Danone
- National Institute for Health and Care Research (06/39/02)
- Astellas Pharma
- Topics
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- probiotics, Clostridium difficile infection, probiotic prophylaxis, antibiotic-associated diarrhea, antibiotic exposure, multispecies probiotics, adverse events, children, adults, risk factors, subgroup analysis, missing outcome data, risk of bias, heterogeneity, publication bias, selective reporting, risk of bias assessment, risk of bias adjustment
- MeSH terms
- Adolescent, Adult, Aged, Anti-Bacterial Agents, Child, Child, Preschool, Clostridium Infections, Cross Infection, Female, Humans, Infant, Male, Middle Aged, Risk Factors, Randomized Controlled Trials as Topic, Probiotics, Young Adult
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