{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:34:38Z","timestamp":1770741278481,"version":"3.49.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Linezolid is an essential antimicrobial for treating multidrug-resistant gram-positive infections in critically ill patients. However, its pharmacokinetics (PK) are highly variable, potentially leading to subtherapeutic exposure or toxicity. Therapeutic drug monitoring (TDM) plays a critical role in guiding individualized dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>We describe a 66-year-old intensive care unit (ICU) patient treated with linezolid for vancomycin-resistant Enterococcus faecium (VRE) peritonitis and empyema. Despite standard dosing (600\u2005mg IV every 12\u2005hours), linezolid concentrations remained below the limit of quantification for 6 days, coinciding with persistent VRE isolation. A switch to continuous infusion (CI) at 2,400\u2005mg\/day achieved therapeutic levels (mean concentration [Cmean], 6.17\u2005mg\/L), but subsequent supratherapeutic exposure (Cmean, 12.12\u2005mg\/L; 24-hour area under the curve, 290.9\u2005mg \u00b7 h\/L) led to adrenergic toxicity. Linezolid clearance declined from 14.6 to 6.2 L\/h, unrelated to renal function, suggesting the influence of nonlinear elimination and alternate metabolic pathways. Following empyema drainage and ketamine withdrawal, PK parameters stabilized. This case highlights the extreme intraindividual PK variability of linezolid in critical illness. Contributing mechanisms may include ROS-driven CYP2J2 upregulation in acute lung injury, autoinhibition of metabolite formation, and drug interactions. CI enabled PK and pharmacodynamic target attainment when intermittent dosing failed but required TDM to avoid overexposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Routine TDM is essential to optimize the safely and effectively manage linezolid therapy in ICU patients. This case underscores the importance of integrating TDM with PK modeling to guide personalized dosing strategies in complex and dynamic clinical scenarios.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajhp\/zxaf235","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T11:48:43Z","timestamp":1756381723000},"page":"151-156","source":"Crossref","is-referenced-by-count":0,"title":["Extreme variability in linezolid concentrations in the ICU: A case for routine therapeutic drug monitoring"],"prefix":"10.1093","volume":"83","author":[{"given":"Daniel","family":"Mu\u00f1oz-Pichuante","sequence":"first","affiliation":[{"name":"Escuela de Qu\u00edmica y Farmacia, Facultad de Ciencias, Universidad San Sebasti\u00e1n , Valdivia, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Ignacia","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Escuela de Qu\u00edmica y Farmacia, Facultad de Ciencias, Universidad San Sebasti\u00e1n , Valdivia, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Reyes Hales","sequence":"additional","affiliation":[{"name":"Escuela de Qu\u00edmica y Farmacia, Facultad de Ciencias, Universidad San Sebasti\u00e1n , Valdivia, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Villa Zapata","sequence":"additional","affiliation":[{"name":"Department of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia , Athens, GA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"issue":"7","key":"2026020918532329100_zxaf235-B1","doi-asserted-by":"publisher","first-page":"439","DOI":"10.2165\/11319960-000000000-00000","article-title":"Pharmacological issues of linezolid: an updated critical review","volume":"49","author":"Di Paolo","journal-title":"Clin Pharmacokinet"},{"issue":"12","key":"2026020918532329100_zxaf235-B2","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1111\/j.1469-0691.2006.01577.x","article-title":"EUCAST technical note on linezolid","volume":"12","author":"European Committee on Antimicrobial Susceptibility Testing Steering Committee","year":"2006","journal-title":"Clin Microbiol Infect"},{"key":"2026020918532329100_zxaf235-B3","doi-asserted-by":"publisher","first-page":"135","DOI":"10.7326\/0003-4819-138-2-200301210-00015","article-title":"Linezolid: the first oxazolidinone antimicrobial","volume":"138","author":"Moellering","year":"2003","journal-title":"Ann Intern Med"},{"key":"2026020918532329100_zxaf235-B4","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.2147\/DDDT.S164515","article-title":"Linezolid: a review of its properties, function, and use in critical care","volume":"12","author":"Hashemian","year":"2018","journal-title":"Drug Des Devel Ther"},{"issue":"2","key":"2026020918532329100_zxaf235-B5","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1093\/jac\/dkl219","article-title":"Linezolid for the treatment of patients with endocarditis: a systematic review of the published evidence","volume":"58","author":"Falagas","year":"2006","journal-title":"J Antimicrob Chemother"},{"issue":"11","key":"2026020918532329100_zxaf235-B6","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1080\/23744235.2020.1789212","article-title":"Linezolid for therapy of Staphylococcus aureus meningitis: a cohort study of 26 patients","volume":"52","author":"Pintado","year":"2020","journal-title":"Infect Dis (Lond)"},{"key":"2026020918532329100_zxaf235-B7","doi-asserted-by":"publisher","first-page":"R148","DOI":"10.1186\/cc13984","article-title":"Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study","volume":"18","author":"Zoller","year":"2014","journal-title":"Crit Care"},{"key":"2026020918532329100_zxaf235-B8","doi-asserted-by":"publisher","first-page":"493","DOI":"10.21037\/atm.2020.03.207","article-title":"Does the conventional dosage of linezolid necessitate therapeutic drug monitoring? 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