{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T03:37:16Z","timestamp":1778125036342,"version":"3.51.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"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":[[2023,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Linezolid-induced myelosuppression limits optimal therapy in cardiosurgical patients with deep-seated infections at current doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult patients who received a cardiac surgery intervention and linezolid for a documented or presumed serious gram-positive infection were evaluated. Therapeutic monitoring data, dosing, concomitant medications, and other pertinent laboratory data were collected retrospectively. A population pharmacokinetic model was constructed to identify covariates and test potential drug\u2013drug interactions that may account for interpatient variability. Simulations from the final model identified doses that achieve a target therapeutic trough concentration of 2\u20138 mg\/L.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study included 150 patients (79.3% male) with sepsis and hospital-acquired pneumonia in 71.7% as the primary indication. The population had a median (minimum\u2013maximum) age, body weight, and estimated glomerular filtration rate (eGFR) of 66 (30\u201385) years, 76 (45\u2013130) kg, and 46.8 (4.9\u2013153.7) mL\/minute, respectively. The standard linezolid dosage regimen achieved the therapeutic range in only 54.7% of patients. Lower-than-standard doses were necessary in the majority of patients (77%). A 2-compartment Michaelis-Menten clearance model with weight, kidney function, and the number of interacting drugs identified as covariates that best fit the concentration-time data was used. Cyclosporine had the greatest effect on lowering the maximum elimination rate (Vmax) of linezolid. Empiric linezolid doses of 300\u2013450 mg every 12 hours based on eGFR and the number of interacting medications are suggested by this analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Lower empiric linezolid doses in cardiosurgical patients may avoid toxicities. Confirmatory studies are necessary to verify these potential drug interactions.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciac917","type":"journal-article","created":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T12:07:51Z","timestamp":1669378071000},"page":"1173-1179","source":"Crossref","is-referenced-by-count":10,"title":["Linezolid Population Pharmacokinetics to Improve Dosing in Cardiosurgical Patients: Factoring a New Drug\u2013Drug Interaction Pathway"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7119-5034","authenticated-orcid":false,"given":"Manjunath P","family":"Pai","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Michigan , Ann Arbor, Michigan , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Giorgio","family":"Cojutti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna , Bologna , Italy"},{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Gerussi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic, Santa Maria della Misericordia University Hospital of Udine , Udine , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Della Siega","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic, Santa Maria della Misericordia University Hospital of Udine , Udine , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Tascini","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic, Santa Maria della Misericordia University Hospital of Udine , Udine , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Pea","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna , Bologna , Italy"},{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"key":"2023040319412895900_","doi-asserted-by":"crossref","first-page":"525","DOI":"10.2165\/00003495-200161040-00008","article-title":"Linezolid: a review of its use in the management of serious gram-positive infections","volume":"61","author":"Perry","year":"2001","journal-title":"Drugs"},{"issue":"Suppl 1","key":"2023040319412895900_","doi-asserted-by":"crossref","first-page":"i47","DOI":"10.1093\/jac\/dku252","article-title":"Clinical experience with linezolid for the treatment of orthopaedic implant infections","volume":"69","author":"Morata","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2023040319412895900_","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.diagmicrobio.2013.02.019","article-title":"Red espanola para la investigacion en patologia I. 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