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

Published online by Cambridge University Press:  26 April 2018

Bradley C. Johnston ,
Lyubov Lytvyn ,
Calvin Ka-Fung Lo ,
Stephen J. Allen ,
Duolao Wang ,
Hania Szajewska ,
Mark Miller ,
Stephan Ehrhardt ,
John Sampalis  and
Deniz G. Duman
...Show all authors
Bradley C. Johnston*
Affiliation:
Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Lyubov Lytvyn
Affiliation:
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
Calvin Ka-Fung Lo
Affiliation:
McMaster University, Hamilton, Ontario, Canada
Stephen J. Allen
Affiliation:
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Duolao Wang
Affiliation:
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Hania Szajewska
Affiliation:
Department of Pediatrics, The Medical University of Warsaw, Warsaw, Poland
Mark Miller
Affiliation:
McGill University, Montreal, Québec, Canada
Stephan Ehrhardt
Affiliation:
Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
John Sampalis
Affiliation:
McGill University, Montreal, Québec, Canada
Deniz G. Duman
Affiliation:
Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey
Pietro Pozzoni
Affiliation:
Department of Internal Medicine, A Manzoni Hospital AO Provincia di Lecco, Lecco, Italy
Agostino Colli
Affiliation:
Department of Internal Medicine, A Manzoni Hospital AO Provincia di Lecco, Lecco, Italy
Elisabet Lönnermark
Affiliation:
Department of Infectious Diseases, Gothenburg University, Göteborg, Sweden
Christian P. Selinger
Affiliation:
Department of Gastroenterology, St James University Hospital, Leeds, United Kingdom
Samford Wong
Affiliation:
National Spinal Injuries Center, Stoke Mandeville Hospital, Aylesbury, United Kingdom
Susan Plummer
Affiliation:
Research and Development Department, Cultech Ltd, Port Talbot, United Kingdom
Mary Hickson
Affiliation:
Nutrition and Dietetic Research Group, Plymouth University, United Kingdom
Ruzha Pancheva
Affiliation:
Department of Hygiene, Medical University, Varna, Bulgaria
Sandra Hirsch
Affiliation:
Instituto de Nutrición y Tecnología de los Alimentos, University of Chile, Santiago, Chile
Bengt Klarin
Affiliation:
Department of Anesthesiology and Intensive Care, Lund University Hospital, Lund, Sweden
Joshua Z Goldenberg
Affiliation:
Bastyr University Research Institute, Kenmore, Washington, United States
Li Wang
Affiliation:
Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
Lawrence Mbuagbaw
Affiliation:
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
Gary Foster
Affiliation:
St Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada
Anna Maw
Affiliation:
Division of Hospital Medicine, Department of Medicine, University of Colorado, Denver, Colorado, United States
Behnam Sadeghirad
Affiliation:
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
Lehana Thabane
Affiliation:
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
Dominik Mertz
Affiliation:
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada Department of Medicine, McMaster University, Hamilton, Ontario, Canada
*
Address correspondence to Bradley C. Johnston, PhD, Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Centre for Clinical Research, Room 404, 5790 University Avenue, Halifax, Nova Scotia, Canada, B3H 1V7 (bjohnston@dal.ca).
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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

Type
Original Article
Information
Infection Control & Hospital Epidemiology , Volume 39 , Issue 7 , July 2018 , pp. 771 - 781
Copyright
© 2018 by The Society for Healthcare Epidemiology of America. All rights reserved. 

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