{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:52:54Z","timestamp":1791550374276,"version":"4.3.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Infections caused by multidrug-resistant organisms (MDROs) are a growing concern in patients with advanced chronic liver disease and acute-on-chronic liver failure, worsening clinical outcomes. Although prior antibiotic exposure is associated with resistance, prospectively defined, clinically actionable exposure thresholds in this population are lacking. We aimed to quantify cumulative-exposure thresholds for de novo MDRO acquisition and assess the prognostic impact of MDRO emergence on survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We prospectively enrolled 256 consecutive adults with advanced chronic liver disease at the University Hospital Frankfurt (2020\u20132023). Antibiotic exposure was quantified using defined daily doses (DDD) and antibiotic use density (AUD); MDRO colonisation and infection were captured by systematic microbiological surveillance. Time-to-death was analysed in a competing-risk framework with liver transplantation as competing event.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 246 patients without MDRO at the first admission swab, de novo acquisition of vancomycin-resistant enterococci (VRE) or Gram-negative MDR was strongly associated with cumulative antibiotic exposure (p&amp;lt;0.001). The 20% probability threshold for VRE was reached at 9.6 cumulative DDDs of any antibiotic, with substantially lower thresholds for \u03b2-lactam\/\u03b2-lactamase inhibitor combinations, carbapenems, and glycopeptides. De novo MDRO detection during follow-up, but not at baseline, was independently associated with increased 180-day mortality (HR 2.15, 95% CI 1.27\u20133.64; p=0.004).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In advanced cirrhosis, MDRO emergence is associated with cumulative antibiotic exposure beyond distinct, class-specific thresholds and carries excess mortality. These prospective findings identify cumulative antibiotic burden as a modifiable risk factor and support an exposure-aware approach to antimicrobial stewardship in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciag610","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:36:43Z","timestamp":1791027403000},"source":"Crossref","is-referenced-by-count":0,"title":["Antibiotic exposure and the emergence of multidrug resistant bacteria in patients with liver cirrhosis: A prospective cohort study"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0948-2777","authenticated-orcid":false,"given":"Myriam W","family":"Heilani","sequence":"first","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Medical Clinic I ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toska","family":"Wiedemann","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Medical Clinic I ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9985-725X","authenticated-orcid":false,"given":"Christopher","family":"Best","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Infection Control, Goethe University Frankfurt ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip G","family":"Ferstl","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Medical Clinic I ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria T","family":"M\u00fccke","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Medical Clinic I ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina M","family":"Schwarzkopf","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Medical Clinic I ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Erasmus","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Medical Clinic I ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Henrik","family":"Peiffer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine B, University Hospital M\u00fcnster , M\u00fcnster ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Burbach","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Infection Control, Goethe University Frankfurt ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hogardt","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Infection Control, Goethe University Frankfurt ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Mohr","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Medical Clinic II ,","place":["Germany"]},{"name":"University Center of Competence for Infection Control , State of Hesse ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Kessel","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Medical Clinic II ,","place":["Germany"]},{"name":"University Center of Competence for Infection Control , State of Hesse ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J G T","family":"Vehreschild","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Medical Clinic II ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zeuzem","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Medical Clinic I ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-3881","authenticated-orcid":false,"given":"Jonel","family":"Trebicka","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine B, University Hospital M\u00fcnster , M\u00fcnster ,","place":["Germany"]},{"name":"European Foundation for the Study of Chronic Liver Failure , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Welsch","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Medical Clinic I ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Institute of Biostatistics and Mathematical Modeling, Goethe University Frankfurt , Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3321-7551","authenticated-orcid":false,"given":"Volkhard A J","family":"Kempf","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Infection Control, Goethe University Frankfurt ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8475-8369","authenticated-orcid":false,"given":"Marcus M","family":"M\u00fccke","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Medical Clinic I ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,9]]},"container-title":["Clinical Infectious 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