{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:57:41Z","timestamp":1791392261491,"version":"4.3.3"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Among adults hospitalized with acute infection, a recent randomized trial observed no significant average treatment effect of cefepime versus piperacillin-tazobactam on acute kidney injury or death, but fewer days-alive-and-free-of delirium and coma with cefepime.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine whether patients\u2019 individual characteristics modify the effect of cefepime versus piperacillin-tazobactam on outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this secondary analysis of the Antibiotic Choice On Renal Outcomes (ACORN) trial, an effect model was derived and validated to predict the effect of cefepime versus piperacillin-tazobactam for adults hospitalized with acute infection. The primary outcome was survival without acute kidney injury; the secondary outcome was survival without delirium or coma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The individualized treatment effect predicted in the validation cohort significantly modified the effect of cefepime versus piperacillin-tazobactam on survival without acute kidney injury (Qini 1.68; 95% confidence interval [CI], 0.25-3.18; p-value = 0.01). Among 626 patients predicted to experience \u22655% benefit from cefepime, 81.2% of patients randomized to cefepime survived without acute kidney injury, versus 74.2% randomized to piperacillin-tazobactam (difference, 7.1%; 95%CI, 0.25 to 13.9%). Among 203 patients predicted to experience \u22655% benefit from piperacillin-tazobactam, 56.6% of patients randomized to cefepime survived without acute kidney injury, versus 63.0% randomized to piperacillin-tazobactam (difference, -6.3%; 95%CI, -20.7 to 8.2%). The effect of trial group on survival without delirium or coma was not modified by individual characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients\u2019 individual characteristics modified the effect of cefepime versus piperacillin-tazobactam on survival without acute kidney injury but not on survival without delirium or coma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajrccm\/aamag544","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:52:45Z","timestamp":1791373965000},"source":"Crossref","is-referenced-by-count":0,"title":["Individualized Treatment Effects of Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized with Acute Infection"],"prefix":"10.1093","author":[{"given":"Edward T","family":"Qian","sequence":"first","affiliation":[{"name":"Vanderbilt University Medical Center Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, , Nashville, TN"},{"name":"Vanderbilt University Medical Center Department of Biomedical Informatics, , Nashville, TN"},{"name":"Vanderbilt University Medical Center Department of Anesthesia, , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma J","family":"Graham Linck","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison Division of Pulmonary and Critical Care, Department of Medicine, , Madison, WI"},{"name":"University of Wisconsin-Madison Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, , Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra B","family":"Spicer","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison Division of Pulmonary and Critical Care, Department of Medicine, , Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin G","family":"Buell","sequence":"additional","affiliation":[{"name":"Rush University Medical Center Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, , Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D","family":"Casey","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin P","family":"Seitz","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley H","family":"Self","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Vanderbilt Institute for Clinical and Translational Research, , Nashville, TN"},{"name":"Vanderbilt University Medical Center, Nashville Department of Emergency Medicine, , Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine Department of Biostatistics, , Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Wright","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Department of Biomedical Informatics, , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd W","family":"Rice","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, , Nashville, TN"},{"name":"Vanderbilt University Medical Center Vanderbilt Institute for Clinical and Translational Research, , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew W","family":"Semler","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, , Nashville, TN"},{"name":"Vanderbilt University Medical Center Vanderbilt Institute for Clinical and Translational Research, , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew M","family":"Churpek","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison Division of Pulmonary and Critical Care, Department of Medicine, , Madison, WI"},{"name":"University of Wisconsin-Madison Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, , Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Evidence-based Individualized Treatment Effects (EvITE) Group and the Pragmatic Critical Care Research Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,7]]},"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/advance-article-pdf\/doi\/10.1093\/ajrccm\/aamag544\/71666831\/aamag544.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/advance-article-pdf\/doi\/10.1093\/ajrccm\/aamag544\/71666831\/aamag544.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:34:57Z","timestamp":1791390897000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/advance-article\/doi\/10.1093\/ajrccm\/aamag544\/8875878"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/ajrccm\/aamag544","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"aamag544"}}