{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T12:18:31Z","timestamp":1793449111273,"version":"4.5.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Merieux Research Grant"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Adequate linezolid blood concentrations have been shown to be associated with an improved clinical outcome. Our goal was to assess new predictors of inadequate linezolid concentrations often observed in critically ill patients. Fifty-two critically ill patients with severe infections receiving standard dosing of linezolid participated in this prospective observational study. Serum samples (median, 32 per patient) were taken on four consecutive days, and total linezolid concentrations were quantified. Covariates influencing linezolid pharmacokinetics were identified by multivariate analysis and a population pharmacokinetic model. Target attainment (area under the concentration-time curve over 12 h [AUC\n            <jats:sub>12<\/jats:sub>\n            ]\/MIC ratio of &gt;50; MIC = 2 mg\/liter) was calculated for both the study patients and a simulated independent patient group (\n            <jats:italic>n<\/jats:italic>\n            = 67,000). Target attainment was observed for only 36% of the population on both days 1 and 4. Independent covariates related to significant decreases of linezolid concentrations included higher weight, creatinine clearance rates, and fibrinogen and antithrombin concentrations, lower concentrations of lactate, and the presence of acute respiratory distress syndrome (ARDS). Linezolid clearance was increased in ARDS patients (by 82%) and in patients with elevated fibrinogen or decreased lactate concentrations. In simulated patients, most covariates, including fibrinogen and lactate concentrations and weight, showed quantitatively minor effects on target attainment (difference of \u22649% between the first and fourth quartiles of the respective parameters). In contrast, the presence of ARDS had the strongest influence, with only \u22646% of simulated patients reaching this target. In conclusion, the presence of ARDS was identified as a new and strong predictor of insufficient linezolid concentrations, which might cause treatment failure. Insufficient concentrations might also be a major problem in patients with combined alterations of other covariate parameters. (This study has been registered at ClinicalTrials.gov under registration number NCT01793012.)\n          <\/jats:p>","DOI":"10.1128\/aac.00356-16","type":"journal-article","created":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T03:08:33Z","timestamp":1466564913000},"page":"5254-5261","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":54,"title":["Predictors of Inadequate Linezolid Concentrations after Standard Dosing in Critically Ill Patients"],"prefix":"10.1128","volume":"60","author":[{"given":"Max","family":"Taubert","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Clinical Pharmacology Unit, Hospital of the University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Zoller","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Hospital of the Ludwig Maximilians University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Maier","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Hospital of the Ludwig Maximilians University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Frechen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Clinical Pharmacology Unit, Hospital of the University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Scharf","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Hospital of the Ludwig Maximilians University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesca-Miriam","family":"Holdt","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Hospital of the Ludwig Maximilians University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenz","family":"Frey","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Hospital of the Ludwig Maximilians University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Vogeser","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Hospital of the Ludwig Maximilians University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Fuhr","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Clinical Pharmacology Unit, Hospital of the University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Zander","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Hospital of the Ludwig Maximilians University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000256726.80998.BF"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-006-0517-7"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-006-0504-z"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31819285f0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc12598"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200342150-00007"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks153"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.2165\/11319960-000000000-00000"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2006.01577.x"},{"key":"e_1_3_3_11_2","first-page":"1136","article-title":"Pharmacokinetics, metabolism, and excretion of linezolid following an oral dose of [(14)C]linezolid to healthy human subjects","volume":"29","author":"Slatter JG","year":"2001","unstructured":"Slatter JG, Stalker DJ, Feenstra KL, Welshman IR, Bruss JB, Sams JP, Johnson MG, Sanders PE, Hauer MJ, Fagerness PE, Stryd RP, Peng GW, Shobe EM. 2001. 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