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Cited by 741Clostridium difficile and Clostridium perfringens researchProbiotics and Fermented FoodsGut microbiota and health

The DOI matches its Crossref record; 167 of the 173 references it cites were found in a registry or an index.

Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children

Open access
Goldenberg, Joshua Z, Ma, Stephanie SY, Saxton, Jane D, Martzen, Mark R, Vandvik, Per O, Thorlund, Kristian, Guyatt, Gordon H, Johnston, Bradley C·2013·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd006095.pub3PMC PMC6486212
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Abstract

BACKGROUND: Antibiotics are widely prescribed; however they can cause disturbances in gastrointestinal flora which may lead to reduced resistance to pathogens such as Clostridium difficile (C. difficile). Probiotics are live organisms thought to balance the gastrointestinal flora. OBJECTIVES: The primary objectives were to assess the efficacy and safety of probiotics for preventing Clostridium difficile-associated diarrhea (CDAD) or C. difficile infection in adults and children. SEARCH METHODS: On February 21, 2013 we searched PubMed (1966-2013), EMBASE (1966-2013), Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 1), CINAHL (1982-2013), AMED (1985-2013), and ISI Web of Science. Additionally, we conducted an extensive grey literature search including contact with industry representatives. SELECTION CRITERIA: Randomized controlled (placebo, alternative prophylaxis, or no treatment control) trials investigating probiotics (any strain, any dose) for prevention of CDAD, or C. difficile infection were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently and in duplicate extracted data and assessed risk of bias using pre-constructed, and piloted, data extraction forms. Any disagreements were resolved by a third adjudicator. For articles published in abstract form only, further information was sought by contacting principal authors. The primary outcome was the incidence of CDAD. Secondary outcomes included the incidence of C. difficile infection, adverse events, antibiotic-associated diarrhea (AAD) and length of hospital stay. Dichotomous outcomes (e.g. incidence of CDAD) were pooled using a random-effects model to calculate the relative risk and corresponding 95% confidence interval (95% CI). Continuous outcomes (e.g. length of hospital) were pooled using a random-effects model to calculate the mean difference and corresponding 95% CI. Sensitivity analyses were conducted to explore the impact of missing data on efficacy and safety outcomes. For the sensitivity analyses, we assumed that the event rate for those participants in the control group who had missing data was the same as the event rate for those participants in the control group who were successfully followed. For the probiotic group we calculated effects using the following assumed ratios of event rates in those with missing data in comparison to those successfully followed: 1.5:1, 2:1, 3:1, and 5:1. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic species, dose, adult versus pediatric population, and risk of bias.The overall quality of the evidence supporting each outcome was assessed using the GRADE criteria. MAIN RESULTS: A total of 1871 studies were identified with 31 (4492 participants) meeting eligibility requirements for our review. Overall 11 studies were rated as a high risk of bias due mostly to missing outcome data. A complete case analysis (i.e. participants who completed the study) of those trials investigating CDAD (23 trials, 4213 participants) suggests that probiotics significantly reduce this risk by 64%. The incidence of CDAD was 2.0% in the probiotic group compared to 5.5% in the placebo or no treatment control group (RR 0.36; 95% CI 0.26 to 0.51). Sixteen of 23 trials had missing CDAD data ranging from 5% to 45%. These results proved robust to sensitivity analyses of plausible and worst-plausible assumptions regarding missing outcome data and were similar whether considering trials in adults versus children, lower versus higher doses, different probiotic species, or higher versus lower risk of bias. Our judgment is that the overall evidence warrants moderate confidence in this large relative risk reduction. We downgraded the overall quality of evidence for CDAD to 'moderate' due to imprecision. There were few events (154) and the calculated optimal information size (n = 8218) was more than the total sample size. With respect to the incidence of C. difficile infection, a secondary outcome, pooled complete case results from 13 trials (961 participants) did not show a statistically significant reduction. The incidence of C. difficile infection was 12.6% in the probiotics group compared to 12.7% in the placebo or no treatment control group (RR 0.89; 95% CI 0.64 to 1.24). Adverse events were assessed in 26 studies (3964 participants) and our pooled complete case analysis indicates probiotics reduce the risk of adverse events by 20% (RR 0.80; 95% CI 0.68 to 0.95). In both treatment and control groups the most common adverse events included abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance. For the short-term use of probiotics in patients that are not immunocompromised or severely debilitated, we consider the strength of this evidence to be moderate. AUTHORS' CONCLUSIONS: Based on this systematic review and meta-analysis of 23 randomized controlled trials including 4213 patients, moderate qua

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  1. Benhamou, 1999, Antibiotic-associated diarrhoea in children: A computer monitored double-blind outpatients trial comparing a protective and a probiotic agent, Medecine et Chirurgie Digestives, 28, 163
  2. Plewinska, 2006, Probiotics in the treatment of Helicobacter pylori infection in children, Gastroenterologia Polska, 13, 315
  3. Potts, 1996, Randomised double blind placebo controlled study of the ability of saccharomyces boulardii to prevent antibiotic related diarrhoea, Gut, 38 Suppl 1, A61
  4. Schrezenmeir, 2002, Benefits of oral supplementation with and without synbiotics in young children with acute bacterial infections, American Journal of Clinical Nutrition, 75, 400S
  5. The Nordic Cochrane Centre, The Cochrane Collaboration Review Manager (RevMan). Version 5.2 2012

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Metadata

Authors
Goldenberg, J. Z., Ma, S. S., Saxton, J. D., Martzen, M. R., Vandvik, P. O., Thorlund, K., Guyatt, G. H., & Johnston, B. C.
Affiliations
  • Bastyr University (US)
  • McMaster University; Division of Plastic & Reconstructive Surgery; 1200 Main Street West - HSC 4E9 Hamilton Ontario Canada L8N 3Z5
  • Nasjonalt Kunnskapssenter for Helsetjenesten (NO)
  • McMaster University (CA)
  • University of Toronto (CA)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2013-05-31
Volume
12
Issue
5
Pages
CD006095-CD006095
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd006095.pub3
PMC
PMC6486212
OpenAlex
W1505136191
Cited by
741
References
173
Citations by year
2026: 1 · 2025: 12 · 2024: 42 · 2023: 60 · 2022: 54 · 2021: 74 · 2020: 79 · 2019: 85 · 2018: 80 · 2017: 65 · 2016: 54 · 2015: 59 · 2014: 51 · 2013: 20
FWCI
7.92
Type
journal article
Language
en
Update notices
new_version (2017-12-19)
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UTS ePRESS (University of Technology Sydney) (submittedVersion)
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, Clostridium difficile-associated diarrhea, Clostridium difficile infection, antibiotic-associated diarrhea, antibiotic prophylaxis, gut microbiota, length of hospital stay, adverse events, children, adults, probiotic safety, probiotic efficacy, risk of bias, heterogeneity, subgroup analysis, risk of bias assessment
MeSH terms
Adult, Anti-Bacterial Agents, Child, Diarrhea, Enterocolitis, Pseudomembranous, Humans, Randomized Controlled Trials as Topic, Clostridioides difficile, Probiotics

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