{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:33:21Z","timestamp":1790948001492,"version":"4.1.0"},"reference-count":36,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Systemic antibiotic use for patients with a non\u2013Clostridioides difficile<\/jats:italic> infection (CDI) is a major risk factor for recurrent CDI. Increasing use of oral vancomycin for secondary prophylaxis against recurrent CDI in this context has uncertain efficacy.<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate whether oral vancomycin prophylaxis compared with placebo is effective against recurrent CDI during and 8 weeks after the end of study treatment.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This phase 2, placebo-controlled, double-blind randomized clinical trial was conducted in 4 large health systems across the upper Midwest US. Adults who had completed treatment for CDI within the past 180 days and were taking a systemic antibiotic for a non-CDI indication were enrolled between May 21, 2018, and March 30, 2023, and followed up for 8 weeks after the end of study treatment.<\/jats:p><\/jats:sec>Intervention<\/jats:title>Participants were randomized 1:1 to 125 mg of oral vancomycin or placebo once daily during antibiotic use for a non-CDI plus 5 days following cessation of those antibiotics.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was recurrent CDI incidence during treatment and the 8-week follow-up period. The secondary outcome was vancomycin-resistant Enterococcus<\/jats:italic> carriage in stool.<\/jats:p><\/jats:sec>Results<\/jats:title>Among 81 randomized participants (median age, 59 years [IQR, 50-67 years]), all were included in the primary as-randomized analysis (39 in the vancomycin group; 42 in the placebo group). Sixty patients (74.1%) completed 8-week follow-up and were included in the secondary as\u2013completed treatment analysis (31 in the vancomycin group; 29 in the placebo group). Recurrent CDI occurred in 17 of 39 participants in the oral vancomycin group (43.6%) and 24 of 42 in the placebo group (57.1%; absolute difference in percentage, \u221213.5% [95% CI, \u221235.1% to 8.0%]). Adverse events occurred in 27 of 39 participants in the oral vancomycin group (69.2%) and 27 of 42 in the placebo group (64.3%). Vancomycin-resistant Enterococcus<\/jats:italic> carriage was found in 15 of 30 patients in the oral vancomycin group (50.0%) and 6 of 25 in the placebo group (24.0%) (P<\/jats:italic>\u2009=\u2009.048) 8 weeks after treatment.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this randomized clinical trial, the incidence of recurrent CDI was lower (though did not reach significance) in participants taking oral vancomycin compared with those taking placebo. Because the study was underpowered, it was unable to reveal firm conclusions about the efficacy (or lack thereof) of vancomycin prophylaxis with respect to recurrent CDI.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT03462459<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.17834","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T15:00:33Z","timestamp":1751468433000},"page":"e2517834","source":"Crossref","is-referenced-by-count":16,"title":["Oral Vancomycin for Prevention of Recurrent Clostridioides difficile<\/i> Infection"],"prefix":"10.1001","volume":"8","author":[{"given":"Julie A.","family":"Keating","sequence":"first","affiliation":[{"name":"Department of Medicine, School of Medicine and Public Health, University of Wisconsin\u2013Madison"},{"name":"William S. 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