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Cited by 275Probiotics and Fermented FoodsGut microbiota and healthGastrointestinal motility and disorders

Probiotics for the prevention of pediatric antibiotic-associated diarrhea

Guo, Qin, Goldenberg, Joshua Z, Humphrey, Claire, El Dib, Regina, Johnston, Bradley C·2019·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd004827.pub5
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Abstract

Background Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of the gut microflora, and other potential mechanisms of action. Objectives The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. Search methods MEDLINE, Embase, CENTRAL, CINAHL, and the Web of Science (inception to 28 May 2018) were searched along with registers including the ISRCTN and Clinicaltrials.gov. We also searched the NICE Evidence Services database as well as reference lists from relevant articles. Selection criteria Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. Data collection and analysis Study selection, data extraction, and risk of bias assessment were conducted independently by two authors. Dichotomous data (incidence of AAD, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea) as mean difference (MD), along with corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For studies reporting on microbiome characteristics using heterogeneous outcomes, we describe the results narratively. The certainty of the evidence was evaluated using GRADE. Main results Thirty-three studies (6352 participants) were included. Probiotics assessed included Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. The risk of bias was determined to be high in 20 studies and low in 13 studies. Complete case (patients who did not complete the studies were not included in the analysis) results from 33 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control. After 5 days to 12 weeks of follow-up, the incidence of AAD in the probiotic group was 8% (259/3232) compared to 19% (598/3120) in the control group (RR 0.45, 95% CI 0.36 to 0.56; I² = 57%, 6352 participants; NNTB 9, 95% CI 7 to 13; moderate certainty evidence). Nineteen studies had loss to follow-up ranging from 1% to 46%. After making assumptions for those lost, the observed benefit was still statistically significant using an extreme plausible intention-to-treat (ITT) analysis, wherein the incidence of AAD in the probiotic group was 12% (436/3551) compared to 19% (664/3468) in the control group (7019 participants; RR 0.61; 95% CI 0.49 to 0.77; P <0.00001; I² = 70%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (≥ 5 billion CFUs per day) is more effective than low probiotic dose (< 5 billion CFUs per day), interaction P value = 0.01. For the high dose studies the incidence of AAD in the probiotic group was 8% (162/2029) compared to 23% (462/2009) in the control group (4038 participants; RR 0.37; 95% CI 0.30 to 0.46; P = 0.06; moderate certainty evidence). For the low dose studies the incidence of AAD in the probiotic group was 8% (97/1155) compared to 13% (133/1059) in the control group (2214 participants; RR 0.68; 95% CI 0.46 to 1.01; P = 0.02). Again, assumptions for loss to follow-up using an extreme plausible ITT analysis was statistically significant. For high dose studies the incidence of AAD in the probiotic group was 13% (278/2218) compared to 23% (503/2207) in control group (4425 participants; RR 0.54; 95% CI 0.42 to 0.70; P <0.00001; I² = 68%; moderate certainty evidence). None of the 24 trials (4415 participants) that reported on adverse events reported any serious adverse events attributable to probiotics. Adverse event rates were low. After 5 days to 4 weeks follow-up, 4% (86/2229) of probiotics participants had an adverse event compared to 6% (121/2186) of control participants (RD 0.00; 95% CI-0.01 to 0.01; P < 0.00001; I² = 75%; low certainty evidence). Common adverse events included rash, nausea, gas, flatulence, abdominal bloating, and constipation. After 10 days to 12 weeks of follow-up, eight studies recorded data on our secondary outcome, the mean duration of diarrhea; with probiotics reducing diarrhea duration by almost one day (MD-0.91; 95% CI-1.38 to-0.44; P <0.00001; low certainty evidence). One study reported on microbiome characteristics, reporting no difference in changes with concurrent antibiotic and probiotic use. Authors’ conclusions The overall evidence suggests a moderate protective effect of probiotics for preventing AAD (NNTB 9, 95% CI 7 to 13). Using five criteria to evaluate the credibility of the subgroup

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Crossref · 10.1002/14651858.cd004827.pub5

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  • Among the general population and in patients who are not immunocompromised or severely debilitated, acute safety issues appear to be minor, especially when considering the large global use of probiotics in foods and nutritional supplements.

    “Among the general population and in patients who are not immunocompromised or severely debilitated, acute safety issues appear to be minor, especially when considering the large global use of probiotics in foods and nutritional supplements.2–5”

    From Emerging issues in probiotic safety: 2023 perspectives (2023) · cites this paper as [4]

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Authors
Guo, Q., Goldenberg, J. Z., Humphrey, C., El Dib, R., & Johnston, B. C.
Affiliations
  • West China Second University Hospital of Sichuan University (CN)
  • National University of Natural Medicine (US)
  • Dalhousie University (CA)
  • Institute of Science and Technology, UNESP - Univ Estadual Paulista; Department of Biosciences and Oral Diagnosis; São José dos Campos SP Brazil
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2019-04-30
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd004827.pub5
OpenAlex
W3045423407
Cited by
275
References
140
Citations by year
2026: 24 · 2025: 27 · 2024: 42 · 2023: 44 · 2022: 43 · 2021: 48 · 2020: 37 · 2019: 10
FWCI
3.10
Type
journal article
Language
en
Open access
closed
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • UNESP Institutional Repository (São Paulo State University) (submittedVersion)
Topics
  • 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
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
probiotics, antibiotic-associated diarrhea, pediatric patients, diarrhea prevention, gut microbiota, Lactobacillus, Bifidobacterium, Bacillus, Saccharomyces, Lactococcus, Clostridium butyricum, adverse events, microbiome, number needed to treat, risk of bias, quality of evidence

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