{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T11:02:53Z","timestamp":1781002973814,"version":"3.54.1"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Rifaximin is widely used in the management of small intestinal bacterial overgrowth (SIBO), but concerns remain regarding the potential risk of Clostridioides difficile infection (CDI), particularly with repeated antibiotic exposure. Aim: To evaluate the short-term risk of CDI following Rifaximin therapy in patients with SIBO. Materials and Methods: We conducted a retrospective cohort study using the TriNetX Collaborative Research Network. Adult patients with SIBO were identified and categorized based on Rifaximin exposure within 60 days of diagnosis. The primary analysis compared patients with SIBO treated with Rifaximin to those with SIBO who did not receive Rifaximin. Secondary analyses included comparisons between SIBO patients treated with Rifaximin and irritable bowel syndrome (IBS) patients receiving Rifaximin, as well as patients with SIBO receiving a single versus multiple Rifaximin courses. Propensity score matching (1:1) was performed to balance baseline characteristics. The primary outcome was CDI within 60 days of the index event. Secondary outcomes included hospitalization and emergency department (ED) visits. Results: After propensity score matching, 19,597 patients were included in each cohort in the primary comparison of SIBO treated with Rifaximin versus SIBO without Rifaximin. CDI occurred in 0.21% of Rifaximin-treated patients and 0.15% of untreated patients (p = 0.152). In the contextual comparison, CDI incidence was similar between SIBO patients receiving Rifaximin and IBS patients receiving Rifaximin (0.21% vs. 0.15%, p = 0.168). Among patients with SIBO receiving Rifaximin, CDI risk did not differ between single and multiple treatment courses (0.20% vs. 0.21%, p = 0.850). Conclusions: In this large real-world cohort, Rifaximin therapy for SIBO was not associated with a statistically significant increase in short-term CDI risk. However, given the low event rate, wide confidence intervals, and risk of type II error, these findings should be interpreted with caution.<\/jats:p>","DOI":"10.3390\/jcm15124449","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T09:46:54Z","timestamp":1780998414000},"page":"4449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating the Risk of Clostridioides difficile Infection After Rifaximin Treatment for Small Intestinal Bacterial Overgrowth"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7761-8149","authenticated-orcid":false,"given":"Abdelrahman","family":"Yousef","sequence":"first","affiliation":[{"name":"Internal Medicine Department, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niven","family":"Wang","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2550-4837","authenticated-orcid":false,"given":"Mahmoud","family":"Yousef","sequence":"additional","affiliation":[{"name":"General Medicine Department, SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5554-6252","authenticated-orcid":false,"given":"Khaled","family":"Elfert","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, West Virgina University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8391-426X","authenticated-orcid":false,"given":"Ahmed","family":"Telbany","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arman","family":"Vaghefi","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5689-026X","authenticated-orcid":false,"given":"Kevin","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Ripley","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara","family":"Rieth","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Peverini","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadl","family":"Zeineddine","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hareesh K.","family":"Gundlapalli","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaushik","family":"Kondubhatla","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-6961","authenticated-orcid":false,"given":"Abu Baker","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Kaza","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5083-560X","authenticated-orcid":false,"given":"Eliseo F.","family":"Castillo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"},{"name":"Comprehensive Cancer Center, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"},{"name":"Gastroenterology Department, Raymond G. Murphy Veterans Affairs Medical Center, Albuquerque, NM 87108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandr","family":"Birg","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"},{"name":"Gastroenterology Department, Raymond G. Murphy Veterans Affairs Medical Center, Albuquerque, NM 87108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1053\/j.gastro.2009.02.075","article-title":"Patterns and Scales in Gastrointestinal Microbial Ecology","volume":"136","author":"Camp","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1035S","DOI":"10.1093\/ajcn\/69.5.1035s","article-title":"Developmental microbial ecology of the neonatal gastrointestinal tract","volume":"69","author":"Mackie","year":"1999","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.3748\/wjg.v16.i24.2978","article-title":"Small intestinal bacterial overgrowth syndrome","volume":"16","author":"Rstl","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1136\/gutjnl-2012-302167","article-title":"Intestinal microbiota in functional bowel disorders: A Rome foundation report","volume":"62","author":"Barbara","year":"2013","journal-title":"Gut"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3400","DOI":"10.3748\/wjg.v29.i22.3400","article-title":"Epidemiology of small intestinal bacterial overgrowth","volume":"29","author":"Efremova","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_6","first-page":"112","article-title":"Small Intestinal Bacterial Overgrowth","volume":"3","author":"Dukowicz","year":"2007","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.gtc.2017.09.008","article-title":"Small Intestinal Bacterial Overgrowth: Nutritional Implications, Diagnosis, and Management","volume":"47","author":"Adike","year":"2018","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/j.1572-0241.2001.03533.x","article-title":"Small Intestinal Mucosal Immunity and Morphometry in Luminal Overgrowth of Indigenous Gut Flora","volume":"96","author":"Riordan","year":"2001","journal-title":"Off. J. Am. Coll. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/ageing\/20.1.29","article-title":"Duodenal Mucosal Morphometry of Elderly Patients with Small Intestinal Bacterial Overgrowth: Response to Antibiotic Treatment","volume":"20","author":"Haboubi","year":"1991","journal-title":"Age Ageing"},{"key":"ref_10","unstructured":"Sorathia, S.J., Chippa, V., and Rivas, J.M. (2026, May 20). Small Intestinal Bacterial Overgrowth, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK546634\/."},{"key":"ref_11","first-page":"225","article-title":"Small Intestinal Bacterial Overgrowth (SIBO)","volume":"4","author":"Salem","year":"2014","journal-title":"J. Gastrointest. Dig. Syst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.gtc.2016.09.008","article-title":"Small Intestinal Bacterial Overgrowth and Other Intestinal Disorders","volume":"46","author":"Ghoshal","year":"2017","journal-title":"Gastroenterol. Clin."},{"key":"ref_13","first-page":"27","article-title":"Uninvited guests: The impact of small intestinal bacterial overgrowth on nutritional status","volume":"27","author":"Zaidel","year":"2003","journal-title":"Pract. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e00078","DOI":"10.14309\/ctg.0000000000000078","article-title":"Small Intestinal Bacterial Overgrowth: Clinical Features and Therapeutic Management","volume":"10","author":"Rao","year":"2019","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s11894-023-00909-1","article-title":"Getting the BS out of Irritable Bowel Syndrome with Diarrhea (IBS-D): Let\u2019s Make a Diagnosis","volume":"26","author":"Frissora","year":"2024","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1053\/j.gastro.2020.06.090","article-title":"AGA Clinical Practice Update on Small Intestinal Bacterial Overgrowth: Expert Review","volume":"159","author":"Quigley","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"165","DOI":"10.14309\/ajg.0000000000000501","article-title":"ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth","volume":"115","author":"Pimentel","year":"2020","journal-title":"Off. J. Am. Coll. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1159\/000089778","article-title":"Treatment of functional bowel disorders: Is there room for antibiotics?","volume":"73","author":"Corazza","year":"2006","journal-title":"Digestion"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1111\/apt.12531","article-title":"Commentary: Towards an effective and safe treatment of small intestine bacterial overgrowth","volume":"38","author":"Scarpignato","year":"2013","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/apt.13928","article-title":"Systematic review with meta-analysis: Rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth","volume":"45","author":"Gatta","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S1473-3099(01)00066-4","article-title":"Effect of antimicrobial agents on the ecological balance of human microflora","volume":"1","author":"Sullivan","year":"2001","journal-title":"Lancet Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Soliman, N., Kruithoff, C., San Valentin, E.M., Gamal, A., McCormick, T.S., and Ghannoum, M. (2025). Small Intestinal Bacterial and Fungal Overgrowth: Health Implications and Management Perspectives. Nutrients, 17.","DOI":"10.3390\/nu17081365"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1111\/j.1572-0241.2008.02030.x","article-title":"Small Intestinal Bacterial Overgrowth Recurrence After Antibiotic Therapy","volume":"103","author":"Lauritano","year":"2008","journal-title":"Off. J. Am. Coll. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Griffith, D.J., Ardouin, S., Cramp, L., and Cooper, S.C. (2026). Dietary and Medical Management of Small-Intestinal Bacterial Overgrowth: A Narrative Review. Dietetics, 5.","DOI":"10.3390\/dietetics5010010"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ludwig, R.J., Anson, M., Zirpel, H., Thaci, D., Olbrich, H., Bieber, K., Kridin, K., Dempfle, A., Curman, P., and Zhao, S.S. (2025). A comprehensive review of methodologies and application to use the real-world data and analytics platform TriNetX. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1516126"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"ooae077","DOI":"10.1093\/jamiaopen\/ooae077","article-title":"Leveraging a global, federated, real-world data network to optimize investigator-initiated pediatric clinical trials: The TriNetX Pediatric Collaboratory Network","volume":"7","author":"Wilson","year":"2024","journal-title":"JAMIA Open"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1111\/apt.12735","article-title":"Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: A pooled analysis of randomised, double-blind, placebo-controlled trials","volume":"39","author":"Schoenfeld","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1056\/NEJMoa1004409","article-title":"Rifaximin Therapy for Patients with Irritable Bowel Syndrome without Constipation","volume":"364","author":"Pimentel","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1053\/j.gastro.2016.08.003","article-title":"Repeat Treatment with Rifaximin Is Safe and Effective in Patients with Diarrhea-Predominant Irritable Bowel Syndrome","volume":"151","author":"Lembo","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1093\/jac\/dkt477","article-title":"Antibiotics and hospital-acquired Clostridium difficile infection: Update of systematic review and meta-analysis","volume":"69","author":"Slimings","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1093\/jac\/dkt129","article-title":"Community-associated Clostridium difficile infection and antibiotics: A meta-analysis","volume":"68","author":"Deshpande","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16","DOI":"10.7453\/gahmj.2014.019","article-title":"Herbal therapy is equivalent to rifaximin for the treatment of small intestinal bacterial overgrowth","volume":"3","author":"Chedid","year":"2014","journal-title":"Glob. Adv. Health Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/j.1572-0241.2006.00458.x","article-title":"A Randomized Double-Blind Placebo-Controlled Trial of Rifaximin in Patients with Abdominal Bloating and Flatulence","volume":"101","author":"Sharara","year":"2006","journal-title":"Off. J. Am. Coll. Gastroenterol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"557","DOI":"10.7326\/0003-4819-145-8-200610170-00004","article-title":"The Effect of a Nonabsorbed Oral Antibiotic (Rifaximin) on the Symptoms of the Irritable Bowel Syndrome","volume":"145","author":"Pimentel","year":"2006","journal-title":"Ann. Intern. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1365-2036.2005.02516.x","article-title":"Rifaximin dose-finding study for the treatment of small intestinal bacterial overgrowth","volume":"22","author":"Lauritano","year":"2005","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1517\/13543780902780175","article-title":"Review of rifaximin as treatment for SIBO and IBS","volume":"18","author":"Pimentel","year":"2009","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S141","DOI":"10.14309\/00000434-200609001-00293","article-title":"Is Rifaximin Effective Treatment for Small Intestinal Bacterial Overgrowth?","volume":"101","author":"Majewski","year":"2006","journal-title":"Off. J. Am. Coll. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1586\/14787210.4.3.417","article-title":"Current and future developments in travelers\u2019 diarrhea therapy","volume":"4","author":"Koo","year":"2006","journal-title":"Expert. Rev. Anti-Infect. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1159\/000089776","article-title":"Experimental and Clinical Pharmacology of Rifaximin, a Gastrointestinal Selective Antibiotic","volume":"73","author":"Scarpignato","year":"2006","journal-title":"Digestion"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"ofad413","DOI":"10.1093\/ofid\/ofad413","article-title":"Comparison of Different Antibiotics and the Risk for Community-Associated Clostridioides difficile Infection: A Case\u2013Control Study","volume":"10","author":"Miller","year":"2023","journal-title":"Open Forum Infect. 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