{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:08:32Z","timestamp":1788793712182,"version":"build-2803163510"},"reference-count":23,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Introduction: Antibiotic-associated diarrhea (AAD) is a common complication of antibiotic therapy, while evidence supporting Saccharomyces boulardii for its prevention among hospitalized adults in resource-constrained settings remains limited. We evaluated the efficacy of Bularen\u00ae in preventing AAD among hospitalized adults receiving systemic antibiotics. Methods: This single-center, randomized, double-blind, placebo-controlled trial was conducted at a tertiary care hospital in Bosnia and Herzegovina. Participants were randomly assigned to Bularen\u00ae (S. boulardii) 250 mg twice daily or a matching placebo for 28 days. The primary outcome was at least one episode of AAD, defined as two or more loose or liquid stools within 24 h, during the 28-day follow-up. Results: Of 435 patients screened, 100 were randomized to Bularen\u00ae (n = 51) or placebo (n = 49), and all completed follow-up. AAD occurred in 4\/51 participants (7.8%) receiving Bularen\u00ae and 35\/49 (71.4%) receiving placebo (risk ratio, 0.11; 95% confidence interval, 0.04\u20130.29; p &lt; 0.001), corresponding to an absolute risk reduction of 63.6 percentage points. During intravenous antibiotic therapy, AAD occurred in 0% versus 26.5% of participants, respectively (p &lt; 0.001), and during oral therapy in 7.8% versus 51.0% (risk ratio, 0.15; 95% confidence interval, 0.06\u20130.41; p &lt; 0.001). No toxin-positive Clostridioides difficile infections were identified. Conclusions: Bularen\u00ae substantially reduced AAD incidence in this study population. Given the high placebo event rate and single-center design, confirmation in larger multicenter trials using standardized AAD definitions is warranted.<\/jats:p>","DOI":"10.3390\/antibiotics15090868","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Saccharomyces boulardii for the Prevention of Antibiotic-Associated Diarrhea in Hospitalized Patients Receiving Antibiotics: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Trial"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-5351","authenticated-orcid":false,"given":"Pedja","family":"Kovacevic","sequence":"first","affiliation":[{"name":"Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, Dvanaest beba bb, 78000 Banja Luka, Bosnia and Herzegovina"},{"name":"Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Mrdja","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Critical Care, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tijana","family":"Kovacevic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Mrdja","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4893-1683","authenticated-orcid":false,"given":"Ivan","family":"Soldatovic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvezdana","family":"Rajkovaca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1136\/bmj.324.7350.1345","article-title":"Managing antibiotic associated diarrhoea","volume":"324","author":"Barbut","year":"2002","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"563","DOI":"10.2217\/17460913.3.5.563","article-title":"Antibiotic-associated diarrhea: Epidemiology, trends and treatment","volume":"3","author":"McFarland","year":"2008","journal-title":"Future Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1365-2036.2005.02624.x","article-title":"Meta-analysis: Non-pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea","volume":"22","author":"Szajewska","year":"2005","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2217\/ahe.13.37","article-title":"Clostridium difficile infection in older adults","volume":"9","author":"Jump","year":"2013","journal-title":"Aging Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.3748\/wjg.v22.i11.3078","article-title":"Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections","volume":"22","author":"McFarland","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhang, S., Palazuelos-Munoz, S., Balsells, E.M., Nair, H., Chit, A., and Kyaw, M.H. (2016). Cost of hospital management of Clostridium difficile infection in United States\u2014A meta-analysis and modelling study. BMC Infect. Dis., 16.","DOI":"10.1186\/s12879-016-1786-6"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kopacz, K., and Phadtare, S. (2022). Probiotics for the Prevention of Antibiotic-Associated Diarrhea. Healthcare, 10.","DOI":"10.3390\/healthcare10081450"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Chandrasekaran, P., Weiskirchen, S., and Weiskirchen, R. (2024). Effects of probiotics on gut microbiota: An overview. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116022"},{"key":"ref_9","unstructured":"Food and Agriculture Organization of the United Nations (FAO), and World Health Organization (WHO) (2001). Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria: Report of a Joint FAO\/WHO Expert Consultation, WHO. Available online: https:\/\/openknowledge.fao.org\/server\/api\/core\/bitstreams\/8b1233c6-f928-4ff0-85e1-78b2e27c6e4e\/content."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nrgastro.2014.66","article-title":"Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic","volume":"11","author":"Hill","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1177\/1756283X11428502","article-title":"Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders","volume":"5","author":"Kelesidis","year":"2012","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s00134-002-1267-9","article-title":"Seven cases of fungemia with Saccharomyces boulardii in critically ill patients","volume":"28","author":"Lherm","year":"2002","journal-title":"Intensive Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1111\/apt.13344","article-title":"Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea","volume":"42","author":"Szajewska","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"ofw011","DOI":"10.1093\/ofid\/ofw011","article-title":"Saccharomyces boulardii to prevent antibiotic-associated diarrhea: A randomized, double-masked, placebo-controlled trial","volume":"3","author":"Ehrhardt","year":"2016","journal-title":"Open Forum Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1007\/s00134-023-07203-8","article-title":"Can the terms \u201clow resource setting\u201d and \u201clow-income country\u201d be used interchangeably in the context of intensive care medicine?","volume":"49","author":"Kovacevic","year":"2023","journal-title":"Intensive Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1038\/ajg.2012.56","article-title":"Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: A single-center, randomized, double-blind, placebo-controlled trial","volume":"107","author":"Pozzoni","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.3748\/wjg.v16.i18.2202","article-title":"Systematic review and meta-analysis of Saccharomyces boulardii in adult patients","volume":"16","author":"McFarland","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1155\/2009\/915847","article-title":"Prevention of Clostridium difficile infection with Saccharomyces boulardii: A systematic review","volume":"23","author":"Tung","year":"2009","journal-title":"Can. J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3390\/antibiotics4020160","article-title":"Probiotics for the primary and secondary prevention of C. difficile infections: A meta-analysis and systematic review","volume":"4","author":"McFarland","year":"2015","journal-title":"Antibiotics"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Liu, L.H., Han, B., Tao, J., Zhang, K., Wang, X.K., and Wang, W.Y. (2023). The effect of Saccharomyces boulardii supplementation on Helicobacter pylori eradication in children: A systematic review and meta-analysis of randomized controlled trials. BMC Infect. Dis., 23.","DOI":"10.1186\/s12879-023-08896-4"},{"key":"ref_21","first-page":"208","article-title":"Saccharomyces boulardii CNCM I-745 for prevention of antibiotic-associated diarrhea and Clostridioides difficile in China: Systematic review and meta-analysis","volume":"9","author":"McFarland","year":"2024","journal-title":"J. Dig. Dis. Hepatol."},{"key":"ref_22","first-page":"PI19","article-title":"Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: A prospective study","volume":"12","author":"Can","year":"2006","journal-title":"Med. Sci. Monit."},{"key":"ref_23","first-page":"981","article-title":"Effect of probiotic Saccharomyces boulardii on prevention of antibiotic-associated diarrhea in adult outpatients with amoxicillin treatment","volume":"136","author":"Bravo","year":"2008","journal-title":"Rev. M\u00e9dica Chile"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/9\/868\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:15:20Z","timestamp":1788790520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/9\/868"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,6]]},"references-count":23,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["antibiotics15090868"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15090868","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,6]]}}}