{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:14:56Z","timestamp":1792682096679,"version":"4.5.0"},"reference-count":31,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Clostridioides difficile<\/jats:italic> is a leading cause of health care\u2013associated infections. Understanding the association among C difficile<\/jats:italic> carriage, antibiotic use, and infection hazard is essential for infection prevention.<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate the hazard of C difficile<\/jats:italic> infection (CDI) among asymptomatic carriers vs noncarriers of C difficile<\/jats:italic> and whether it is associated with antibiotic exposure.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This retrospective cohort study conducted between June 18, 2017, and June 21, 2023, analyzed hospitalizations from Sheba Medical Center in Ramat Gan, Israel, which routinely screens for C difficile<\/jats:italic> in high-risk patients admitted to internal medicine. Adult patients (aged &amp;gt;18 years) without active CDI at admission were included.<\/jats:p><\/jats:sec>Exposure<\/jats:title>Antibiotic exposure during hospitalization, including specific classes.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was the development of CDI, as confirmed by laboratory testing for C difficile<\/jats:italic>. Antibiotic exposure was assessed as a time-varying variable.<\/jats:p><\/jats:sec>Results<\/jats:title>The study included 33\u202f756 hospitalizations among 23\u202f001 patients (median [IQR] age, 78 [68-87] years; 52.8% men). C difficile<\/jats:italic> infection occurred in 67 of 1624 hospitalizations (4.1%) with positive screening results and in 47 of 32 132 hospitalizations (0.1%) with negative screening results. A positive C difficile<\/jats:italic> screening result at admission was associated with a high hazard of infection (hazard ratio [HR], 27.5; 95% CI, 18.7-40.3). Antibiotic exposure was associated with an increased hazard for CDI (HR, 1.98; 95% CI, 1.24-3.16). Piperacillin and tazobactam showed the most pronounced hazard for CDI (HR, 2.18; 95% CI, 1.41-3.36). Among asymptomatic carriers, antibiotic exposure was not significantly associated with a further increase in CDI hazard (HR, 1.07; 95% CI, 0.73-1.58).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this cohort study, carriers of C difficile<\/jats:italic> had a substantially higher baseline hazard for hospital-onset CDI. Antibiotic exposure was associated with an increased hazard among noncarriers but was not significantly associated with additional hazard among carriers. These findings suggest that while antibiotic stewardship may reduce CDI risk in noncarriers, additional strategies may be needed for carriers given their elevated baseline risk.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.25252","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T15:30:33Z","timestamp":1754667033000},"page":"e2525252","source":"Crossref","is-referenced-by-count":24,"title":["Antibiotic Use and the Risk of Hospital-Onset Clostridioides Difficile<\/i> Infection"],"prefix":"10.1001","volume":"8","author":[{"given":"Mayan","family":"Gilboa","sequence":"first","affiliation":[{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel"},{"name":"The Sheba Pandemic Preparedness Research Institute, Sheba Medical Center, Ramat-Gan, Israel"},{"name":"Infection Prevention and Control Unit, Sheba Medical Center, Ramat-Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gili","family":"Regev-Yochay","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel"},{"name":"The Sheba Pandemic Preparedness Research Institute, Sheba Medical Center, Ramat-Gan, Israel"},{"name":"Infection Prevention and Control Unit, Sheba Medical Center, Ramat-Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Meltzer","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel"},{"name":"Internal Medicine C, Sheba Medical Center, Ramat-Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ido","family":"Cohen","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel"},{"name":"Internal Medicine E, Sheba Medical Center, Ramat-Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yovel","family":"Peretz","sequence":"additional","affiliation":[{"name":"The Sheba Pandemic Preparedness Research Institute, Sheba Medical Center, Ramat-Gan, Israel"},{"name":"Infection Prevention and Control Unit, Sheba Medical Center, Ramat-Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Zilberman-Daniels","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel"},{"name":"Microbiology Laboratory, Sheba Medical Center, Ramat-Gan, Israel"},{"name":"Infectious Diseases Unit, Sheba Medical Center, Ramat-Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitai","family":"Segev","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel"},{"name":"Cardiovascular Division, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Amit","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel"},{"name":"Microbiology Laboratory, Sheba Medical Center, Ramat-Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafna","family":"Yahav","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Health Sciences, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel"},{"name":"Infectious Diseases Unit, Sheba Medical Center, Ramat-Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam","family":"Barda","sequence":"additional","affiliation":[{"name":"The Sheba Pandemic Preparedness Research Institute, Sheba Medical Center, Ramat-Gan, Israel"},{"name":"ARC Innovation Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel"},{"name":"Software and Information Systems Engineering, Ben-Gurion University of the Negev, Be\u2019er Sheva, Israel"},{"name":"Epidemiology, Biostatistics, and Community Health Sciences, Ben-Gurion University of the Negev, Be\u2019er Sheva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"issue":"12","key":"zoi250715r1","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1093\/cid\/ciy455","article-title":"Clostridium difficile screening for colonization during an outbreak setting.","volume":"67","author":"Linsenmeyer","year":"2018","journal-title":"Clin Infect Dis"},{"issue":"13","key":"zoi250715r2","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1056\/NEJMoa1306801","article-title":"Multistate point-prevalence survey of health care-associated infections.","volume":"370","author":"Magill","year":"2014","journal-title":"N Engl J Med"},{"issue":"6","key":"zoi250715r3","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1086\/660013","article-title":"Epidemiological model for Clostridium difficile transmission in healthcare settings.","volume":"32","author":"Lanzas","year":"2011","journal-title":"Infect Control Hosp Epidemiol"},{"key":"zoi250715r4","doi-asserted-by":"publisher","first-page":"S88","DOI":"10.1093\/cid\/cis335","article-title":"Burden of Clostridium difficile on the healthcare system.","volume":"55","author":"Dubberke","year":"2012","journal-title":"Clin Infect Dis"},{"issue":"9","key":"zoi250715r5","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1056\/NEJMoa1408913","article-title":"Burden of Clostridium difficile infection in the United States.","volume":"372","author":"Lessa","year":"2015","journal-title":"N Engl J Med"},{"issue":"16","key":"zoi250715r6","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1056\/NEJMra1403772","article-title":"Clostridium difficile infection.","volume":"372","author":"Leffler","year":"2015","journal-title":"N Engl J Med"},{"issue":"8","key":"zoi250715r7","doi-asserted-by":"publisher","first-page":"4533","DOI":"10.1128\/AAC.00642-15","article-title":"Risk factors for acquisition and loss of Clostridium difficile colonization in hospitalized patients.","volume":"59","author":"Dubberke","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"issue":"18","key":"zoi250715r8","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1056\/NEJMoa1012413","article-title":"Host and pathogen factors for Clostridium difficile infection and colonization.","volume":"365","author":"Loo","year":"2011","journal-title":"N Engl J Med"},{"issue":"4","key":"zoi250715r9","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02169-19","article-title":"Antibiotic exposure and risk for hospital-associated Clostridioides difficile infection.","volume":"64","author":"Webb","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"issue":"11","key":"zoi250715r10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078445","article-title":"Asymptomatic Clostridium difficile colonisation and onward transmission.","volume":"8","author":"Eyre","year":"2013","journal-title":"PLoS One"},{"issue":"5","key":"zoi250715r11","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1053\/j.gastro.2016.12.035","article-title":"Asymptomatic carriers contribute to nosocomial Clostridium difficile infection: a cohort study of 4508 patients.","volume":"152","author":"Blixt","year":"2017","journal-title":"Gastroenterology"},{"issue":"7","key":"zoi250715r12","doi-asserted-by":"publisher","first-page":"e1727","DOI":"10.1093\/cid\/ciaa894","article-title":"Genomic determination of relative risks for Clostridioides difficile infection from asymptomatic carriage in intensive care unit patients.","volume":"73","author":"Worley","year":"2021","journal-title":"Clin Infect Dis"},{"issue":"2","key":"zoi250715r13","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1017\/ice.2019.309","article-title":"Screening of Clostridioides difficile carriers in an urban academic medical center: Understanding implications of disease.","volume":"41","author":"Baron","year":"2020","journal-title":"Infect Control Hosp Epidemiol"},{"issue":"9","key":"zoi250715r14","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.cmi.2019.02.002","article-title":"Universal screening for Clostridioides difficile in a tertiary hospital: risk factors for carriage and clinical disease.","volume":"25","author":"Meltzer","year":"2019","journal-title":"Clin Microbiol Infect"},{"issue":"9","key":"zoi250715r15","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1007\/s40121-023-00856-4","article-title":"Screening for asymptomatic Clostridioides difficile carriage among hospitalized patients: a narrative review.","volume":"12","author":"Gilboa","year":"2023","journal-title":"Infect Dis Ther"},{"issue":"4","key":"zoi250715r16","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.","volume":"61","author":"von Elm","year":"2008","journal-title":"J Clin Epidemiol"},{"issue":"7","key":"zoi250715r17","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/cid\/cix1085","article-title":"Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA).","volume":"66","author":"McDonald","year":"2018","journal-title":"Clin Infect Dis"},{"issue":"5","key":"zoi250715r18","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.","volume":"40","author":"Charlson","year":"1987","journal-title":"J Chronic Dis"},{"issue":"3","key":"zoi250715r19","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1093\/ije\/dyr213","article-title":"Competing risks in epidemiology: possibilities and pitfalls.","volume":"41","author":"Andersen","year":"2012","journal-title":"Int J Epidemiol"},{"issue":"42","key":"zoi250715r20","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1093\/eurheartj\/ehu131","article-title":"Competing risks analyses: objectives and approaches.","volume":"35","author":"Wolbers","year":"2014","journal-title":"Eur Heart J"},{"issue":"8","key":"zoi250715r21","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.1093\/jac\/dkab151","article-title":"Antibiotic exposure and the risk of hospital-acquired diarrhoea and Clostridioides difficile infection: a cohort study.","volume":"76","author":"Schechner","year":"2021","journal-title":"J Antimicrob Chemother"},{"issue":"1","key":"zoi250715r22","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s13756-021-00986-9","article-title":"Correlation between antibiotic consumption and the incidence of healthcare facility-onset Clostridioides difficile infection: a retrospective chart review and analysis.","volume":"10","author":"Yun","year":"2021","journal-title":"Antimicrob Resist Infect Control"},{"issue":"1","key":"zoi250715r23","doi-asserted-by":"publisher","first-page":"76","DOI":"10.3390\/healthcare12010076","article-title":"Clostridioides difficile infection in hospitalized patients-a retrospective epidemiological study.","volume":"12","author":"Fonseca","year":"2023","journal-title":"Healthcare (Basel)"},{"issue":"9","key":"zoi250715r24","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.3390\/antibiotics11091178","article-title":"Association between antibiotic use and hospital-onset Clostridioides difficile infection in university tertiary hospital in Serbia, 2011-2021: an ecological analysis.","volume":"11","author":"Peric","year":"2022","journal-title":"Antibiotics (Basel)"},{"issue":"2","key":"zoi250715r25","doi-asserted-by":"publisher","first-page":"144","DOI":"10.3390\/antibiotics13020144","article-title":"A real-world study on the clinical characteristics, outcomes, and relationship between antibiotic exposure and Clostridioides difficile infection.","volume":"13","author":"Vintila","year":"2024","journal-title":"Antibiotics (Basel)"},{"issue":"11","key":"zoi250715r26","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1056\/NEJMoa2404991","article-title":"Antibiotic treatment for 7 versus 14 days in patients with bloodstream infections.","volume":"392","author":"Daneman","year":"2025","journal-title":"N Engl J Med"},{"issue":"2","key":"zoi250715r27","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.cmi.2022.04.005","article-title":"The Shorter Is Better movement: past, present, future.","volume":"29","author":"Spellberg","year":"2023","journal-title":"Clin Microbiol Infect"},{"issue":"10","key":"zoi250715r28","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1093\/cid\/ciz626","article-title":"Predictors of Clostridioides difficile infection among asymptomatic, colonized patients: a retrospective cohort study.","volume":"70","author":"Poirier","year":"2020","journal-title":"Clin Infect Dis"},{"key":"zoi250715r29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.anaerobe.2015.03.008","article-title":"Insight into alteration of gut microbiota in Clostridium difficile infection and asymptomatic C. difficile colonization.","volume":"34","author":"Zhang","year":"2015","journal-title":"Anaerobe"},{"issue":"3","key":"zoi250715r30","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1056\/NEJMoa2106516","article-title":"SER-109, an oral microbiome therapy for recurrent Clostridioides difficile Infection.","volume":"386","author":"Feuerstadt","year":"2022","journal-title":"N Engl J Med"},{"issue":"15","key":"zoi250715r31","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1007\/s40265-022-01797-x","article-title":"Efficacy and safety of RBX2660 in PUNCH CD3, a phase III, randomized, double-blind, placebo-controlled trial with a bayesian primary analysis for the prevention of recurrent Clostridioides difficile infection.","volume":"82","author":"Khanna","year":"2022","journal-title":"Drugs"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2837369\/gilboa_2025_oi_250715_1753980330.13797.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T15:30:34Z","timestamp":1754667034000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2837369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,8]]},"references-count":31,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2025.25252","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,8]]}}}