Universität zu Köln

Taubert, Max ORCID: 0000-0001-8925-7782, Zoller, Michael, Maier, Barbara, Frechen, Sebastian, Scharf, Christina, Holdt, Lesca-Miriam, Frey, Lorenz, Vogeser, Michael, Fuhr, Uwe and Zander, Johannes (2016). Predictors of Inadequate Linezolid Concentrations after Standard Dosing in Critically Ill Patients. Antimicrob. Agents Chemother., 60 (9). S. 5254 - 5262. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-6596

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Abstract

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(12)]/MIC ratio of>50; MIC = 2 mg/liter) was calculated for both the study patients and a simulated independent patient group (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 <= 9% between the first and fourth quartiles of the respective parameters). In contrast, the presence of ARDS had the strongest influence, with only <= 6% 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Taubert, Max UNSPECIFIED orcid.org/0000-0001-8925-7782 UNSPECIFIED Zoller, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Maier, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Frechen, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Scharf, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Holdt, Lesca-Miriam UNSPECIFIED UNSPECIFIED UNSPECIFIED Frey, Lorenz UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogeser, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuhr, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-263181
DOI:	10.1128/AAC.00356-16
Journal or Publication Title:	Antimicrob. Agents Chemother.
Volume:	60
Number:	9
Page Range:	S. 5254 - 5262
Date:	2016
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-6596
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POPULATION PHARMACOKINETIC ANALYSIS; COMPASSIONATE-USE PROGRAM; LOWER-BODY WEIGHT; PHARMACOKINETIC/PHARMACODYNAMIC PROFILE; PROSPECTIVE MULTICENTER; ADULT PATIENTS; SEVERE SEPSIS; EPIDEMIOLOGY; OUTCOMES; NONMEM Multiple languages Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26318