{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:43:36Z","timestamp":1776854616224,"version":"3.51.2"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Research Foundation \u2013 Flanders"},{"name":"FWO","award":["12X9420N"],"award-info":[{"award-number":["12X9420N"]}]},{"name":"Clinical Research Fund of the University Hospitals Leuven"},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"crossref","award":["C24\/16\/039"],"award-info":[{"award-number":["C24\/16\/039"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>PTA of protein-unbound ceftriaxone may be compromised in critically ill patients with community-acquired pneumonia (CAP) with augmented renal clearance (ARC). We aimed to determine an optimized ceftriaxone dosage regimen based on the probability of developing ARC on the next day (PARC,d+1; www.arcpredictor.com).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and methods<\/jats:title>\n                  <jats:p>Thirty-three patients enrolled in a prospective cohort study were admitted to the ICU with severe CAP and treated with ceftriaxone 2\u2005g once daily. Patients contributed 259 total ceftriaxone concentrations, collected during 1 or 2\u2005days (\u00b17 samples\/day). Unbound fractions of ceftriaxone were determined in all peak and trough samples (n\u200a=\u200a76). Population pharmacokinetic modelling and simulation were performed using NONMEM7.4. Target attainment was defined as an unbound ceftriaxone concentration &amp;gt;4\u2005mg\/L throughout the dosing interval.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A two-compartment population pharmacokinetic model described the data well. The maximal protein-bound ceftriaxone concentration decreased with lower serum albumin. Ceftriaxone clearance increased with body weight and PARC,d+1 determined on the previous day. A high PARC,d+1 was identified as a clinically relevant predictor for underexposure on the next day (area under the receiver operating characteristics curve 0.77). Body weight had a weak predictive value and was therefore considered clinically irrelevant. Serum albumin had no predictive value. An optimal PARC,d+1 threshold of 5.7% was identified (sensitivity 73%, specificity 69%). Stratified once- or twice-daily 2\u2005g dosing when below or above the 5.7% PARC,d+1 cut-off, respectively, was predicted to result in 81% PTA compared with 47% PTA under population-level once-daily 2\u2005g dosing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Critically ill patients with CAP with a high PARC,d+1 may benefit from twice-daily 2\u2005g ceftriaxone dosing for achieving adequate exposure on the next day.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac209","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T09:40:12Z","timestamp":1657532412000},"page":"2479-2488","source":"Crossref","is-referenced-by-count":14,"title":["Ceftriaxone dosing based on the predicted probability of augmented renal clearance in critically ill patients with pneumonia"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0785-2930","authenticated-orcid":false,"given":"Erwin","family":"Dreesen","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacotherapy Unit, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven , Leuven , Belgium"},{"name":"Uppsala Pharmacometrics Research Group, Department of Pharmacy, Uppsala University , Uppsala , Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1378-3772","authenticated-orcid":false,"given":"Matthias","family":"Gijsen","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacotherapy Unit, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven , Leuven , Belgium"},{"name":"Pharmacy Department, University Hospitals Leuven , Leuven , Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5708-9497","authenticated-orcid":false,"given":"Omar","family":"Elkayal","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacotherapy Unit, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven , Leuven , Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter","family":"Annaert","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven , Leuven , Belgium"},{"name":"BioNotus , Niel , Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yves","family":"Debaveye","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, University Hospitals Leuven , Leuven , Belgium"},{"name":"Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven , Leuven , 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