{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:49:11Z","timestamp":1791474551115,"version":"4.3.4"},"reference-count":25,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01HL154998"],"award-info":[{"award-number":["P01HL154998"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI158530"],"award-info":[{"award-number":["R01AI158530"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01HL149883"],"award-info":[{"award-number":["R01HL149883"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01LM013337"],"award-info":[{"award-number":["R01LM013337"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI174159"],"award-info":[{"award-number":["R21AI174159"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01TR003528"],"award-info":[{"award-number":["U01TR003528"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI135964"],"award-info":[{"award-number":["U19AI135964"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009210","name":"Food and Drug Administration","doi-asserted-by":"publisher","award":["75F40122C00134"],"award-info":[{"award-number":["75F40122C00134"]}],"id":[{"id":"10.13039\/100009210","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Cefepime is used in critically ill pneumonia patients, but dosing in renal replacement therapy (RRT) is complicated by altered renal function, extracorporeal removal, and variability in pulmonary epithelial lining fluid (ELF) exposure. We sought to develop an integrated model linking systemic, extracorporeal, and pulmonary cefepime pharmacokinetics in RRT. Pharmacokinetic (PK) data from critically ill adults receiving cefepime and requiring RRT were included. In a dedicated continuous RRT (CRRT) cohort (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 8), pre- and post-filter plasma and effluent PK data were collected. Additional patients (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 43) requiring RRT also contributed plasma and ELF samples. A non-parametric population PK model was developed using an 80\/20 subject-level development-validation split. Covariate models assessed the impact of residual renal function, effluent flow rate, body size, and fixed intradialytic hemodialysis (HD) clearance. Monte Carlo simulations evaluated plasma and ELF target attainment across dosing strategies, weight strata, and minimum inhibitory concentrations (MICs). The final model jointly described systemic, extracorporeal, and pulmonary cefepime disposition using piecewise central volume, native clearance, linear effluent-flow-dependent CRRT clearance, fixed HD clearance, and ELF distribution. Simulations showed adequate plasma target attainment, whereas ELF attainment was sensitive to MIC, target, regimen, and body weight. Continuous infusions of 4 g\/day provided adequate ELF attainment at MICs \u22644 mg\/L. Plasma-based cefepime target attainment may overestimate pulmonary exposure during RRT, particularly at higher MICs, body weights, and\n                      <jats:italic toggle=\"yes\">f<\/jats:italic>\n                      T&gt;MIC targets. External validation and prospective studies are needed to refine pulmonary target estimates and determine whether plasma-guided Bayesian dosing can reliably ensure site-of-infection exposure.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00900-26","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:49:12Z","timestamp":1791470952000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Development and validation of a cefepime population pharmacokinetic model to guide treatment for patients with hospital-acquired pneumonia requiring renal replacement"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4192-5229","authenticated-orcid":true,"given":"Adrian","family":"Valadez","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Practice, Midwestern University, College of Pharmacy","place":["Downers Grove, USA"]},{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmacometrics Center of Excellence, Midwestern University","place":["Downers Grove, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Harlan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Practice, Midwestern University, College of Pharmacy","place":["Downers Grove, USA"]},{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmacometrics Center of Excellence, Midwestern University","place":["Downers Grove, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1091-6130","authenticated-orcid":true,"given":"Marc H.","family":"Scheetz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Practice, Midwestern University, College of Pharmacy","place":["Downers Grove, USA"]},{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmacometrics Center of Excellence, Midwestern University","place":["Downers Grove, USA"]},{"id":[{"id":"https:\/\/ror.org\/009543z50","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy, Northwestern Memorial Hospital","place":["Chicago, USA"]},{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacology, College of Graduate Studies, Midwestern University","place":["Downers Grove, USA"]},{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences, College of Graduate Studies, Midwestern University","place":["Downers Grove, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-8276","authenticated-orcid":true,"given":"Michael N.","family":"Neely","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Keck School of Medicine, University of Southern California","place":["Los Angeles, USA"]},{"id":[{"id":"https:\/\/ror.org\/0511k4970","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Applied Pharmacokinetics and Bioinformatics, The Saban Research Institute, Children's Hospital Los Angeles","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8827-8581","authenticated-orcid":true,"given":"Helen K.","family":"Donnelly","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00m6w7z96","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"Wunderink","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00m6w7z96","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-5434","authenticated-orcid":true,"given":"Nathaniel J.","family":"Rhodes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Practice, Midwestern University, College of Pharmacy","place":["Downers Grove, USA"]},{"id":[{"id":"https:\/\/ror.org\/00t30ch44","id-type":"ROR","asserted-by":"publisher"}],"name":"Pharmacometrics Center of Excellence, Midwestern University","place":["Downers Grove, USA"]},{"id":[{"id":"https:\/\/ror.org\/009543z50","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy, Northwestern Memorial Hospital","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01137-y"},{"key":"e_1_3_5_3_2","unstructured":"Anonymous. 2012. MAXIPIME (cefepime hydrochloride USP) for injection [prescribing information]. Hospira Inc. Lake Forest. IL. USA"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0732-8893(95)00053-d"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10101154"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01141-08"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad223"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.11.2424"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.11.3148-3155.2001"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01700172"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01611-21"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2015.05.020"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2332"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00144-21"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00727-23"},{"key":"e_1_3_5_16_2","unstructured":"SCRIPT Investigators. 2026. Successful clinical response in pneumonia therapy (SCRIPT). Northwestern University. Available from: https:\/\/script.northwestern.edu\/database"},{"key":"e_1_3_5_17_2","unstructured":"Baxter Healthcare Corporation. 2015. PRISMAFLEX system HF1000\/HF1400 hemofilter sets [product specification sheet]. Deerfield. IL. USA"},{"key":"e_1_3_5_18_2","unstructured":"Department of Health and Human Services FaDA. 2018. Center for drug evaluation and research (CDER) Center for veterinary medicine (CVM). Bioanalytical method validation guidance for industry"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31825c4ba6"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13010042"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.28.8.977"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01520-08"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000069734.38738.C8"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00682-18"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1987.135.6.1276"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000675"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00900-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00900-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:49:13Z","timestamp":1791470953000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00900-26"}},"subtitle":[],"editor":[{"given":"Vincent H.","family":"Tam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":25,"alternative-id":["10.1128\/aac.00900-26"],"URL":"https:\/\/doi.org\/10.1128\/aac.00900-26","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]},"assertion":[{"value":"2026-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00900-26"}}