Which probiotic has the best effect on preventing Clostridium difficile‐associated diarrhea? A systematic review and network meta‐analysis
Abstract
OBJECTIVE: Clostridium difficile-associated diarrhea (CDAD) accounts for up to 25% of patients with antibiotic-associated diarrhea (AAD). We aimed to determine which probiotic is most effective in preventing CDAD using a network meta-analysis. METHODS: Studies were identified by searching PubMed, EMBASE and the Cochrane Library databases for randomized controlled trials (RCTs) that evaluated the efficacy of probiotic interventions for CDAD. Primary outcomes were the incidence rates of AAD and CDAD, and secondary outcomes were the duration of diarrhea and the time until onset of diarrhea. The PROSPERO registered number of this study is CRD42018106115. RESULTS: Ten RCTs including 11 analyses and including 4 692 patients were identified. Compared with the control group, probiotic intervention reduced the incidence rates of CDAD (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.17-0.61) and AAD (OR 0.39, 95% CI 0.23-0.66). Similar results were observed regarding the duration of diarrhea and the time until onset of diarrhea. Meta-regression analysis showed a correlation between the type of probiotic used and the incidence of CDAD and AAD. All nine kinds of probiotic interventions were statistically more effective than the placebo, with Lactobacillus casei ranking as the best intervention (OR 0.19, 95% credible interval [CrI] 0.06-0.63) for decreasing the incidence rate of CDAD. L. casei also ranked the highest in reducing the incidence rate of AAD (OR 0.32, 95% CrI 0.14-0.74). CONCLUSION: Lactobacilli strains, especially L. casei, have a good effect on the prevention of CDAD and AAD.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Higher doses of probiotics are the most effective in preventing AAD and/or C. difficile diarrhea.
“The researchers in these studies reported that higher doses are the most effective in these conditions.”
From The Potential Impact of Probiotics on Human Health: An Update on Their Health-Promoting Properties (2024) · cites this paper as [113]
S. boulardii and L. rhamnosus GG have been shown to reduce the risk of Antibiotic-Associated Diarrhea (AAD) and are effective in preventing AAD and/or Clostridium difficile diarrhea.
“Also, S. boulardii and L. rhamnosus GG have been shown to reduce the risk of Antibiotic-Associated Diarrhea (AAD). Both probiotic strains have been shown to be effective in preventing AAD [109,110,111] and/or Clostridium difficile diarrhea [112,113].”
From The Potential Impact of Probiotics on Human Health: An Update on Their Health-Promoting Properties (2024) · cites this paper as [113]
Cites
Operating characteristics of a rank correlation test for publication bias
Begg, C. B., & Mazumdar, M. (1994) · Biometrics · doi:10.2307/2533446 · Cited by 16,955 · see citing works
Hutton, B., Salanti, G., Caldwell, D. M., Chaimani, A., Schmid, C. H., Cameron, C., Ioannidis, J. P. A., Straus, S., Thorlund, K., Jansen, J. P., et al. (2015) · Annals of Internal Medicine · doi:10.7326/m14-2385 · Cited by 8,269 · see citing works
Assessing Risk of Bias in Included Studies
Higgins, J. P., & Altman, D. G. (2008) · Cochrane Handbook for Systematic Reviews of Interventions · doi:10.1002/9780470712184.ch8 · Cited by 3,396 · see citing works
Systematic reviews: CRD's guidance for undertaking reviews in health care
Tacconelli, E. (2010) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(10)70065-7 · Cited by 3,237 · see citing works
McDonald, L. C., Gerding, D. N., Johnson, S., Bakken, J. S., Carroll, K. C., Coffin, S. E., Dubberke, E. R., Garey, K. W., Gould, C. V., Kelly, C., et al. (2018) · Clinical Infectious Diseases · doi:10.1093/cid/cix1085 · Cited by 2,690 · cited 1× · see citing works
“CDAD can cause pseudomembranous colitis and toxic megacolon, and even death.(5,6) C.”
BackgroundA modified test for small‐study effects in meta‐analyses of controlled trials with binary endpoints
Harbord, R. M., Egger, M., & Sterne, J. A. C. (2006) · Statistics in Medicine · doi:10.1002/sim.2380 · Cited by 2,267 · see citing works
Control of pathogens and pathobionts by the gut microbiota
Kamada, N., Chen, G. Y., Inohara, N., & Núñez, G. (2013) · Nature Immunology · doi:10.1038/ni.2608 · Cited by 1,625 · see citing works
Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia
Bartlett, J. G., Chang, T. W., Gurwith, M., Gorbach, S. L., & Onderdonk, A. B. (1978) · New England Journal of Medicine · doi:10.1056/nejm197803092981003 · Cited by 1,374 · see citing works
Evaluation of networks of randomized trials
Salanti, G., Higgins, J. P., Ades, A., & Ioannidis, J. P. (2008) · Statistical Methods in Medical Research · doi:10.1177/0962280207080643 · Cited by 1,078 · see citing works
Guyatt, G., Oxman, A. D., Sultan, S., Brozek, J., Glasziou, P., Alonso-Coello, P., Atkins, D., Kunz, R., Montori, V., Jaeschke, R., et al. (2013) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2012.01.006 · Cited by 762 · see citing works
Hickson, M., D'Souza, A. L., Muthu, N., Rogers, T. R., Want, S., Rajkumar, C., & Bulpitt, C. J. (2007) · BMJ · doi:10.1136/bmj.39231.599815.55 · Cited by 599 · see citing works
Clinical Recognition and Diagnosis ofClostridium difficileInfection
Bartlett, J. G., & Gerding, D. N. (2008) · Clinical Infectious Diseases · doi:10.1086/521863 · Cited by 528 · see citing works
Wiström, J. (2001) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/47.1.43 · Cited by 455 · see citing works
Allen, S. J., Wareham, K., Wang, D., Bradley, C., Hutchings, H. A., Harris, W., Dhar, A., Brown, H., Foden, A. P., Gravenor, M. B., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61218-0 · Cited by 385 · see citing works
Johnston, B. C., Ma, S. S. Y., Goldenberg, J. Z., Thorlund, K., Vandvik, P. O., Loeb, M., & Guyatt, G. H. (2012) · Annals of Internal Medicine · doi:10.7326/0003-4819-157-12-201212180-00563 · Cited by 367 · see citing works
Probiotics for Prevention and Treatment of Diarrhea
Guandalini, S. (2011) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e3182257e98 · Cited by 351 · see citing works
Lawley, T. D., Clare, S., Walker, A. W., Goulding, D., Stabler, R. A., Croucher, N., Mastroeni, P., Scott, P., Raisen, C., Mottram, L., et al. (2009) · Infection and Immunity · doi:10.1128/iai.00558-09 · Cited by 349 · see citing works
Gao, X. W., Mubasher, M., Fang, C. Y., Reifer, C., & Miller, L. E. (2010) · American Journal of Gastroenterology · doi:10.1038/ajg.2010.11 · Cited by 318 · see citing works
Kotowska, M., Albrecht, P., & Szajewska, H. (2005) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2005.02356.x · Cited by 288 · see citing works
Probiotics for Prevention and Treatment of Diarrhea
Guarino, A., Guandalini, S., & Vecchio, A. L. (2015) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000000349 · Cited by 217 · see citing works
Turck, D., Bernet, J., Marx, J., Kempf, H., Giard, P., Walbaum, O., Lacombe, A., Rembert, F., Toursel, F., Bernasconi, P., et al. (2003) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-200307000-00004 · Cited by 172 · see citing works
Beausoleil, M., Fortier, N., Guénette, S., L’Ecuyer, A., Savoie, M., Franco, M., Lachaîne, J., & Weiss, K. (2007) · Canadian Journal of Gastroenterology · doi:10.1155/2007/720205 · Cited by 162 · see citing works
Ruszczyński, M., Radzikowski, A., & Szajewska, H. (2008) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2008.03714.x · Cited by 131 · see citing works
A randomized controlled trial of probiotics for Clostridium difficile infection in adults (PICO)
Barker, A., Duster, M. N., Valentine, S., Hess, T., Archbald‐Pannone, L. R., Guerrant, R. L., & Safdar, N. (2017) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkx254 · Cited by 106 · see citing works
Pozzoni, P., Riva, A., Bellatorre, A. G., Amigoni, M., Redaelli, E., Ronchetti, A. B., Stefani, M., Tironi, R., Molteni, E. E., Conte, D., et al. (2012) · The American Journal of Gastroenterology · doi:10.1038/ajg.2012.56 · Cited by 105 · see citing works
Can, M., Beşirbellioglu, B. A., Avcı, İ. Y., Beker, C. M., & Pahsa, A. (2006) · PubMed · Cited by 101 · see citing works
Clostridium difficile infection and pseudomembranous colitis
Wilcox, M. H. (2003) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/s1521-6918(03)00017-9 · Cited by 98 · see citing works
Cai, J., Zhao, C., Du, Y., Zhang, Y., Zhao, M., & Zhao, Q. (2017) · United European Gastroenterology Journal · doi:10.1177/2050640617736987 · Cited by 80 · see citing works
Probiotics in human infections
Sullivan, Å. (2002) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkf194 · Cited by 77 · see citing works
Shan, L.-S., Hou, P., Wang, Z.-J., Liu, F.-R., Chen, N., Shu, L.-H., Zhang, H., Han, X.-H., Han, X.-X., Cai, X., et al. (2013) · Beneficial Microbes · doi:10.3920/bm2013.0008 · Cited by 76 · see citing works
Dylewski, J. S., Psaradellis, E., & Sampalis, J. S. (2010) · Archives of Medical Science · doi:10.5114/aoms.2010.13508 · Cited by 72 · see citing works
McFarland, L. V., Ship, N. J., Auclair, J., & Millette, M. (2018) · Journal of Hospital Infection · doi:10.1016/j.jhin.2018.04.017 · Cited by 63 · see citing works
Chaudhry, R., Joshy, L., Kumar, L., & Dhawan, B. (2008) · PubMed · Cited by 53 · see citing works
Safdar, N., Barigala, R., Said, A., & McKinley, L. L. (2008) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/j.1365-2710.2008.00980.x · Cited by 50 · see citing works
Assessing Quality of Precut Sphincterotomy in Patients With Difficult Biliary Access
Chen, J., Wan, J., Wu, D. Y., et al. (2018) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000001077 · Cited by 27 · see citing works
Zhang, Y., Hui, F., Yang, Y., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.20921 · Cited by 17 · see citing works
(2000) · Time to knit · doi:10.1016/j.yped.2013.05.013 · Cited by 17 · see citing works
Clostridium difficileInfection and Pseudomembranous Colitis
Moss, A. C., & LaMont, J. T. (2010) · doi:10.1002/9781444328417.ch50 · Cited by 1 · see citing works
Clostridium difficileInfection and Pseudomembranous Colitis
Vaughn, B. P., & LaMont, J. T. (2016) · doi:10.1002/9781119127437.ch55 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Potential Impact of Probiotics on Human Health: An Update on Their Health-Promoting Properties
Maftei, N.-M., Raileanu, C. R., Balta, A. A., Ambrose, L., Boev, M., Marin, D. B., & Lisa, E. L. (2024) · Microorganisms · doi:10.3390/microorganisms12020234 · Cited by 381 · see citing works
Chen, W., Pan, X., Ji, J., Wu, Z., & Lin, X. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1699223 · Cited by 3 · see citing works
- Authors
- Ma, Y., Yang, J. Y., Peng, X., Xiao, K. Y., Xu, Q., & Wang, C.
- Affiliations
- Shenyang Normal University (CN)
- The Sixth People's Hospital of Shenyang (CN)
- Liaoning Academy of Agricultural Sciences (CN)
- Corresponding author
- Xu, Qing
- Wang, Chen
- Venue
- Journal of Digestive Diseases
- Publisher
- Wiley
- Published
- 2020-02
- Volume
- 21
- Issue
- 2
- Pages
- 69-80
- ISSN
- 1751-2972 (ISSN-L)
- 1751-2980
- OpenAlex
- W2997390250
- Cited by
- 44
- References
- 39
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 11 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 5
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Digestive Diseases (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- Clostridium difficile-associated diarrhea, probiotics, antibiotic-associated diarrhea, Lactobacillus casei, Lactobacillus, diarrhea prevention, diarrhea duration
- MeSH terms
- Adult, Aged, Anti-Bacterial Agents, Child, Clostridium Infections, Diarrhea, Enterocolitis, Pseudomembranous, Female, Humans, Male, Middle Aged, Odds Ratio, Randomized Controlled Trials as Topic, Clostridioides difficile, Treatment Outcome, Probiotics
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review