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Cited by 163Probiotics and Fermented FoodsGut microbiota and healthGastrointestinal motility and disorders

Probiotics for the prevention of antibiotic-associated diarrhoea: A systematic review and meta-analysis

Open access
Goodman, Clare, Keating, Georgia, Georgousopoulou, Ekavi, Hespe, Charlotte, Levett, Kate·2021·BMJ Open
DOI 10.1136/bmjopen-2020-043054PMC PMC8362734
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Abstract

Objective: To evaluate existing evidence for the use of probiotics in preventing antibiotic-associated diarrhoea (AAD) in adults. Design: Systematic review and meta-analysis of randomised controlled trials (RCTs). Data sources: We performed a literature search of the electronic databases CINAHL Plus, EMBASE, MEDLINE (Ovid) and Web of Science from database inception to May 2021 as well as hand searching of trial registries and reference lists of related reviews. Study selection: Two reviewers identified whether RCTs met the following inclusion criteria: adult population to whom antibiotics were administered; a probiotic intervention; a placebo, alternative dose, alternative probiotic strain or no treatment control; and incidence of AAD as the outcome. Data extraction and synthesis: Two reviewers independently collected data and assessed risk of bias using preconstructed data extraction forms. We used a random effects model for all analyses. Subgroup analyses were performed to evaluate species-specific and dose-specific response. Results: Forty-two studies (11,305 participants) were included in this review. The pooled analysis suggests that co-administration of probiotics with antibiotics reduces the risk of AAD in adults by 37% (risk ratio (RR)=0.63 (95% CI 0.54 to 0.73), p<0.00001). The overall quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria was found to be moderate. In subgroup analyses, high dose compared with low dose of the same probiotic demonstrated a positive protective effect (RR 0.54 (95% CI 0.38 to 0.76), p<0.01), and only certain species, mainly of the lactobacillus and bifidobacteria genera, were found to be effective. Studies with a low baseline AAD risk did not show any difference in risk but studies with moderate or high baseline AAD risk demonstrated a significant risk reduction. Conclusions: Probiotics are effective for preventing AAD. Secondary analyses of higher dosages and certain species have shown increased effectiveness. Our results may not be applicable in clinical scenarios of lower baseline AAD risk.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis of 42 RCTs (11,305 adults) found that co-administering probiotics with antibiotics reduced the risk of antibiotic-associated diarrhoea (AAD) by 37% (RR=0.63, 95% CI 0.54 to 0.73). Higher doses and certain Lactobacillus/Bifidobacterium species were more effective, but the evidence was rated moderate and low-baseline-risk settings showed no significant benefit.

Key findings

  • Probiotics versus any control significantly reduced AAD incidence: RR=0.63 (95% CI 0.54 to 0.73), p<0.00001; number needed to treat (NNT) to prevent one case was 20 patients.
  • In four studies directly comparing high versus low dose of the same probiotic, higher dose reduced AAD risk: RR=0.54 (95% CI 0.38 to 0.76), p=0.0004.
  • Species with significant effects included L. acidophilus (RR=0.66, 95% CI 0.54 to 0.80), L. casei (RR=0.59, 95% CI 0.42 to 0.83), S. boulardii (RR=0.63, 95% CI 0.46 to 0.86), B. longum (RR=0.46, 95% CI 0.28 to 0.73), B. subtilis (RR=0.35, 95% CI 0.19 to 0.62), B. licheniformis (RR=0.39, 95% CI 0.19 to 0.79), and B. clausii (RR=0.61, 95% CI 0.41 to 0.89); L. helveticus, L. plantarum, L. reuteri, B. bifidum, S. thermophilus, and C. butyricum were not significant.
  • Baseline AAD risk modified effect: low risk (0%–10%) showed no difference, while moderate risk (11%–30%) showed RR=0.61 (95% CI 0.48 to 0.78) and high risk (>31%) showed RR=0.55 (95% CI 0.46 to 0.66); adjunct probiotics with H. pylori treatment reduced diarrhoeal side effects by 45% (RR=0.55, 95% CI 0.41 to 0.73).

Methods

  • Systematic review and meta-analysis of randomised controlled trials in adults receiving antibiotics, comparing any probiotic strain, dose, or formulation with placebo, alternative dose, alternative probiotic strain, or no treatment; primary outcome was incidence of AAD.
  • Searched CINAHL Plus, EMBASE, MEDLINE (Ovid), Web of Science, and Google Scholar from inception to May 2021, plus trial registries and reference lists; included English-language studies only.
  • Two reviewers independently selected studies, extracted data, and assessed risk of bias; random-effects models were used for all analyses, with risk ratios (RR), 95% CIs, I², NNT, and subgroup analyses by dose, species, H. pylori treatment, and baseline AAD risk; GRADE was used to rate overall evidence.

Limitations

  • The paper states that only incidence of AAD was measured; duration, severity, hospitalisation need, and quality of life were not analysed, and antibiotic-specific subgroup analysis was not possible because many studies did not report antibiotic name, class, route, dose, or course length.
  • The paper also states that inclusion was limited to English-language studies and the initial search was a title search, which may explain fewer identified studies than a recent Cochrane review; substantial heterogeneity existed between study methodologies and outcome measures.
  • Evident from the text: 36 of 42 studies had high or unclear risk of bias, and when only low-risk-of-bias studies were pooled, the protective effect was no longer statistically significant (RR=0.78, 95% CI 0.57 to 1.07, p=0.13); many species analyses relied on single studies or multi-species blends, limiting independent species associations.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1136/bmjopen-2020-043054

Cites

78 of 78 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 22 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    When probiotics were compared with no treatment, there was a significant reduction in relative risk of diarrhoea (RR=0.35, 95% CI 0.27 to 0.47, p<0.00001).

    “When subgroup analyses were performed, where probiotics were compared with placebo (RR=0.69 (95% CI 0.60 to 0.80), p<0.00001), and where probiotics were compared with no treatment (RR=0.35 (95% CI 0.27 to 0.47), p<0.00001), a significant reduction in relative risk of diarrhoea was noted”
    Quote in the paperSubstantial claim
  • Findingown data

    On sensitivity analysis, low risk of bias studies demonstrated no protective effect of probiotics (RR=0.78, 95% CI 0.57 to 1.07, p=0.13).

    “On sensitivity analysis, the low risk of bias studies demonstrated no protective effect of probiotics (RR=0.78 (95% CI 0.57 to 1.07), p=0.13) as opposed to the high or unknown risk of bias studies (RR=0.59 (95% CI 0.50 to 0.70), p<0.00001).”
    Quote in the paperSubstantial claim
  • Findingown data

    Trials enrolling participants with a high baseline AAD risk demonstrated a 45% risk reduction (RR=0.55, 95% CI 0.46 to 0.66, p<0.00001).

    “trials enrolling participants with a moderate or high baseline risk for developing AAD demonstrated 39% (RR=0.61 (95% CI 0.48 to 0.78), p<0.0001) and 45% (RR=0.55 (95% CI 0.46 to 0.66), p<0.00001) risk reduction, respectively”
    Quote in the paperSubstantial claim
  • Findingown data

    Studies with a low baseline AAD risk did not show any difference in risk.

    “Studies with a low baseline AAD risk did not show any difference in risk”
    • Also stated in: § Sensitivity analysis: baseline risk of AAD · plain
      “The pooled studies with a low baseline risk of AAD did not show any difference in risk”
    Quote in the paperSubstantial claim
  • Findingown data

    When probiotics were compared with placebo, there was a significant reduction in relative risk of diarrhoea (RR=0.69, 95% CI 0.60 to 0.80, p<0.00001).

    “When subgroup analyses were performed, where probiotics were compared with placebo (RR=0.69 (95% CI 0.60 to 0.80), p<0.00001), and where probiotics were compared with no treatment (RR=0.35 (95% CI 0.27 to 0.47), p<0.00001), a significant reduction in relative risk of diarrhoea was noted”
    Quote in the paperSubstantial claim
  • May combine two claims. 14
  • Classified as probably not a substantial claim. 18

  • May combine two claims.

    Findingown data

    L. helveticus, L. plantarum, L. reuteri, B. bifidum, S. thermophilus and C. butyricum provided no improvement in AAD compared with control.

    “However, L. helveticus, L. plantarum, L. reuteri, B. bifidum, S. thermophilus and C. butyricum provided no improvement in AAD compared with control.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The review included 42 studies with 11,305 participants.

    “Forty-two studies (11,305 participants) were included in this review.”
    • Also stated in: § Study selection and characteristics · plain
      “A total of 356 articles were identified in the initial search, of which 60 were eligible for full-text review, and 42 of those articles (11 305 participants) were eligible for inclusion in the study.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The following probiotic strains demonstrated significant reduction in AAD when compared with a control: L. acidophilus, L. bulgaricus, L. casei, L. paracasei, L. rhamnosus, Lactobacillus spp, S. boulardii, B. animalis ssp Lactis, B. longum, B. licheniformis, B. subtilis and Bacillus clausii.

    “The following probiotic strains demonstrated significant reduction in AAD when compared with a control: L. acidophilus, L. bulgaricus, L. casei, L. paracasei, L. rhamnosus, Lactobacillus spp, S. boulardii, B. animalis ssp Lactis, B. longum, B. licheniformis, B. subtilis and Bacillus clausii.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Of the 42 included studies, 32 reported on adverse events.

    “Of the 42 included studies, 32 reported on adverse events.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Another included study commented that their probiotic milk was less well tolerated than their placebo milk.

    “and another commented that their probiotic milk was less well tolerated than their placebo milk.27”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Velasco, 2019, Probiotic yogurt for the prevention of antibiotic-associated diarrhea in adults: a randomized double-blind placebo-controlled trial, J Clin Gastroenterol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Of the 42 included studies, 33 were placebo-controlled and eight provided 'no treatment' as the comparison.

    “Of the 42 studies included (table 1), 33 were placebo-controlled and eight provided ‘no treatment’ as the comparison.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was substantial variation in the AAD definition employed in the included studies: 13 studies defined AAD as ≥3 loose stools (5-7 Bristol Stool Scale) in 24 hours, 12 defined AAD as ≥3 loose stools (5-7 Bristol Stool Scale) in 2 days or more, 11 studies used various other definitions of AAD and 5 studies made no mention of their definition.

    “There was substantial variation in the AAD definition employed in the included studies (table 1). Although 13 studies defined AAD as ≥3 loose stools (5–7 Bristol Stool Scale) in 24 hours, 12 defined AAD as ≥3 loose stools (5–7 Bristol Stool Scale) in 2 days or more, 11 studies used various other definitions of AAD and 5 studies made no mention of their definition.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    The most commonly identified indication for antibiotics was treatment of H. pylori.

    “The most commonly identified indication for antibiotics was treatment of H. pylori.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In subgroup analyses, the individual probiotic species that demonstrated the greatest effect sizes were B. licheniformis (one study, RR=0.39), B. longum (four studies, RR=0.46) and B. subtilis (one study, RR=0.35).

    “In our subgroup analyses, the individual probiotic species that demonstrated the greatest effect sizes were B. licheniformis (one study, RR=0.39), B. longum (four studies, RR=0.46) and B. subtilis (one study, RR=0.35).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    L. acidophilus was used in the greatest number of studies, demonstrating a moderate effect with a relatively small confidence interval.

    “The individual species L. acidophilus was used in the greatest number of studies, demonstrating a moderate effect with a relatively small CI.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Overall, the Lactobacillus genus showed a good effect with a small confidence interval.

    “Overall, the lactobacillus genus showed a good effect with a small CI.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    L. acidophilus (18 studies, RR=0.66), L. casei (11 studies, RR=0.59) and S. boulardii (nine studies, RR=0.63) were used in many more studies.

    “Although demonstrating a more moderate effect size, L. acidophilus (18 studies, RR=0.66), L. casei (11 studies, RR=0.59) and S. boulardii (nine studies, RR=0.63) were used in many more studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Six of the 42 included studies were rated as having a low risk of bias, while 36 were rated as having a high or unclear risk of bias.

    “Six of the 42 studies were rated as having a low risk of bias, while 36 were rated as having a high or unclear risk of bias.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    While probiotics significantly reduce incidence of CDAD, they do not appear to reduce C. difficile infection.

    “Furthermore, while probiotics significantly reduce incidence of CDAD they do not appear to reduce C. difficile infection.21”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Goldenberg JZ , Yap C , Lytvyn L , et al . Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 2017;382.doi:10.1002/14651858.CD006095.pub4 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Many included studies demonstrated design limitations, mainly reflecting the reporting of sequence generation and allocation concealment in older studies, which suggests some risk of bias.

    “Although all included studies were RCTs, many demonstrated design limitations, mainly reflecting the reporting of sequence generation and allocation concealment in older studies, which suggests some risk of bias.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    A Cochrane review found moderate quality evidence for a large protective effect of probiotics against C. difficile-associated diarrhoea (RR 0.40, 95% CI 0.30 to 0.52).

    “In a Cochrane review21 authors found moderate quality evidence for a large protective effect of probiotics against C. difficile-associated diarrhoea (CDAD) (RR 0.40, 95% CI 0.30 to 0.52).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Goldenberg JZ , Yap C , Lytvyn L , et al . Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 2017;382.doi:10.1002/14651858.CD006095.pub4 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Data were extracted from each article by two of three authors using a standardised data extraction form.

    “Data were extracted from each article by two of three of the authors (CG, GK, KL), using a standardised data extraction form following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.24”
    • Also stated in: § Data extraction and synthesis · plain
      “Two reviewers independently collected data and assessed risk of bias using preconstructed data extraction forms.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The overall quality of the evidence was rated using the GRADE approach independently by two authors.

    “The overall quality of the evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach26 independently by two authors (CG, KL) and consensus reached through discussion.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Faecal analysis indicates incidence of C. difficile in AAD to be 20% or less.

    “Faecal analysis indicates incidence of C. difficile in AAD to be 20%,22 or less.23”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Hurley, 2002, The spectrum of pseudomembranous enterocolitis and antibiotic-associated diarrhea, Arch Intern Med source

      Not checked in the free run.

    • cites [23] Horosheva T , Sorokulova I , Vodyanoy V . Efficacy of Bacillus probiotics in prevention of antibiotic‐associated diarrhoea: a randomized, double‐blind, placebo‐controlled clinical trial. JMM Case Reports;1:1–6.doi:10.1099/jmmcr.0.004036 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Risk of bias was assessed using the Cochrane Risk of Bias tool.

    “The risk of bias was assessed using the Cochrane Risk of Bias25 tool within the Covidence online software.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Two reviewers independently assessed each study for inclusion in the review.

    “Two of three of the authors (CG, GK and KL) independently assessed each study for inclusion in the review.”
    • Also stated in: § Study selection · plain
      “Two reviewers identified whether RCTs met the following inclusion criteria”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The subgroup analyses were in agreement with the American Gastroenterological Association Clinical Practice Guidelines, which suggest the use of S. boulardii or the two-strain combination of L. acidophilus CL1285 and L. casei LBC80R among other probiotic species for prevention of antibiotic-associated diarrhoea.

    “Our subgroup analyses were also in agreement with The American Gastroenterological Association Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders39 which suggest the use of S. boulardii; or the two-strain combination of L. acidophilus CL1285 and L. casei LBC80R among other probiotic species for prevention of AAD.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Su, 2020, AGA clinical practice guidelines on the role of probiotics in the management of gastrointestinal disorders, Gastroenterology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A more recent meta-analysis found that many Lactobacillus and Bifidobacteria species and S. boulardii were effective.

    “A more recent meta-analysis38 found, also concordantly, that many Lactobacillus and Bifidobacteria species and S. boulardii were effective.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Goldenberg found that probiotics led to a significant reduction in incidence of antibiotic-associated diarrhoea from 18% to 12% of participants (RR=0.58, 95% CI 0.48 to 0.70).

    “Goldenberg found that probiotics led to a significant reduction in incidence of AAD from 18% to 12% of participants (RR=0.58, 95% CI 0.48 to 0.70).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Goldenberg JZ , Yap C , Lytvyn L , et al . Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 2017;382.doi:10.1002/14651858.CD006095.pub4 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    The initial search was a title search as opposed to a keyword search, which may explain the lower number of studies initially identified compared with the recent Cochrane review.

    “Additionally, the initial search was a title search as opposed to keyword search, which may explain the lower number of studies initially identified, compared with the recent Cochrane review.21”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Goldenberg JZ , Yap C , Lytvyn L , et al . Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 2017;382.doi:10.1002/14651858.CD006095.pub4 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    One meta-analysis reported that probiotics may not be effective in reducing the incidence of antibiotic-associated diarrhoea.

    “Contrary to the findings of our review, one meta-analysis40 reported that probiotics may not be effective in reducing the incidence of AAD.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Xie, 2015, Probiotics for the prevention of antibiotic-associated diarrhoea in older patients: a systematic review, Travel Med Infect Dis source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationown data

    These results should be applied with caution in clinical scenarios with inherent lower baseline risk of antibiotic-associated diarrhoea.

    “These results should be applied with caution in clinical scenarios with inherent lower baseline risk of AAD.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    This study is concordant with findings from the Cochrane systematic review.

    “This study is concordant with findings from the aforementioned Cochrane systematic review.21”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Goldenberg JZ , Yap C , Lytvyn L , et al . Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 2017;382.doi:10.1002/14651858.CD006095.pub4 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    That meta-analysis analysed only 13 studies, including adults over 65 only.

    “However, only 13 studies were analysed, including adults over 65 only.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Xie, 2015, Probiotics for the prevention of antibiotic-associated diarrhoea in older patients: a systematic review, Travel Med Infect Dis source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A limitation of this study is that the only outcome measured was incidence of diarrhoea.

    “A limitation of this study is that the only outcome measured was incidence of diarrhoea.”
    Quote in the paperNot a substantial claim
30 of 30

  • The paper relies on this without support.

    The various definitions of AAD used across included studies are sufficiently comparable to be combined in a single meta-analysis.

    “There was substantial variation in the AAD definition employed in the included studies (table 1). Although 13 studies defined AAD as ≥3 loose stools (5–7 Bristol Stool Scale) in 24 hours, 12 defined AAD as ≥3 loose stools (5–7 Bristol Stool Scale) in 2 days or more, 11 studies used various other definitions of AAD and 5 studies made no mention of their definition.”

  • The paper relies on this without support.

    The different control conditions (placebo, no treatment, alternative dose, alternative strain) are sufficiently comparable to be combined as 'any control' in the overall pooled analysis.

    “Of the 42 studies included (table 1), 33 were placebo-controlled and eight provided ‘no treatment’ as the comparison. One study compared its treatment group to both a placebo group and a no treatment control.27”

  • The paper relies on this without support.

    The included studies are sufficiently homogeneous in population, antibiotic type, and probiotic intervention to be pooled in a single meta-analysis.

    “There was also substantial clinical and methodological heterogeneity, therefore we used a random effects model for all analyses.”

  • The paper relies on this without support.

    The effect of probiotics on AAD is consistent across different antibiotic types and clinical settings.

    “Studies of adults, receiving any antibiotic therapy for a course of any length, or for any reason, were included.”

  • The paper relies on this without support.

    The NNT of 20 is applicable to the population studied.

    “These data suggest that the NNT, to prevent one case of AAD would be 20 patients.”

  • The paper relies on this without support.

    Previous meta-analyses have not reported on dose–response.

    “Previous meta-analyses have not reported on dose–response.”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Plummer trial total does not match its group counts

    Minor

    The table lists 20 total participants, but its two groups contain 69 participants each, for a total of 138.

    Reported 20 · recomputed 138

  • de Vrese control is described as both no treatment and placebo

    Minor

    The synthesis describes study 33 as having a no-treatment control, but Table 1 identifies both of its controls as placebos.

  • Initial search count differs between the text and figure caption

    Minor

    The results state that the initial search identified 356 articles, while the Figure 1 caption states 352.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Higgins J , Altman D . Chapter 8: Assessing risk of bias in included studies Table 8.5 a. In: Higgins JPT , Green S , eds. Cochrane Handbook for systematic reviews of interventions version 5.0. 1. London: The Cochrane Collaboration, 2008: 1–50.doi:10.1001/jama.2013.109501.Conflict · DOI
  2. Helps, 2015, Prospective randomized double-blind study of efficacy of probiotic milk drink in reducing the incidence of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea, Int J Probiotics Prebiotics, 11, 145

Cited by

Sorted by citations

Related

Authors
Goodman, C., Keating, G., Georgousopoulou, E., Hespe, C., & Levett, K.
Affiliations
  • The University of Notre Dame Australia (AU)
  • Alice Springs Hospital (AU)
Corresponding author
  • Goodman, Clare
  • Levett, Kate
ORCID
Venue
BMJ Open
Publisher
BMJ
Published
2021-08
Volume
11
Issue
8
Pages
e043054
ISSN
2044-6055 (ISSN-L)
DOI
10.1136/bmjopen-2020-043054
PMC
PMC8362734
OpenAlex
W3189497760
Semantic Scholar
f7cb184e4fcbccbdf1af68083b958af55a93b1d6
Cited by
163
References
78
Citations by year
2026: 37 · 2025: 29 · 2024: 53 · 2023: 30 · 2022: 13 · 2021: 1
FWCI
2.20
Type
journal article
Language
en
Open access
Licence
Locations
  • BMJ Open (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • ResearchOnline@ND (The University of Notre Dame) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Notre Dame
  • University of Notre Dame Australia
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, probiotic dosage, Lactobacillus, Bifidobacterium, adults
MeSH terms
Adult, Anti-Bacterial Agents, Diarrhea, Humans, Lactobacillus, Incidence, Probiotics

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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