Universität zu Köln

Taubert, Max ORCID: 0000-0001-8925-7782, Zander, Johannes, Frechen, Sebastian, Scharf, Christina, Frey, Lorenz, Vogeser, Michael, Fuhr, Uwe and Zoller, Michael (2017). Optimization of linezolid therapy in the critically ill: the effect of adjusted infusion regimens. J. Antimicrob. Chemother., 72 (8). S. 2304 - 2311. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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Abstract

Objectives: Insufficient linezolid levels, which are associated with a poorer outcome, are often observed in ICU patients who receive standard dosing. Although strategies to overcome these insufficient levels have been discussed, appropriate alternative dosing regimens remain to be identified. Methods: Various infusion regimens (1200-3600 mg/day; q6h, q8h, q12h and continuous) were simulated in 67000 ICU patients. The probability of attaining pharmacodynamic targets (T > MIC >= 85%, AUC/MIC >= 100, cumulative fraction of response for Staphylococcus aureus and Enterococcus spp., PTA for an MIC of 0.5-4 mg/L) as well as the avoidance of toxic concentrations and concentrations constantly below the MIC (lack of antibiotic effect) or inside amutant selection window (resistance development) were evaluated. Results: Best target attainment according to T > MIC was observed for continuous infusions, followed by q6h, q8h and q12h. A substantially reduced target attainment was observed in patients with acute respiratory distress syndrome (ARDS). In patients without ARDS, 1200 mg/day was insufficient irrespective of the regimen, while a dose of 1400 mg/day administered q6h or by continuous infusions provided an acceptable target attainment (e.g. cumulative fraction of response with regards to T > MIC >= 93%). Higher rates of potentially toxic trough concentrations (28% versus 12%) and concentrations constantly inside the mutant selection window (15% versus, 0.1%) were observed with continuous infusions compared with q6h infusions (1400 mg/day, patients without ARDS). Conclusions: Irrespective of the regimen, 1200 mg/day linezolid might be insufficient for the treatment of ICU patients. Patients without ARDS might particularly benefit from q6h infusions with increased daily doses (e.g. 1400mg/day).

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Taubert, Max UNSPECIFIED orcid.org/0000-0001-8925-7782 UNSPECIFIED Zander, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Frechen, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Scharf, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Frey, Lorenz UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogeser, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuhr, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Zoller, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-223452
DOI:	10.1093/jac/dkx149
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	72
Number:	8
Page Range:	S. 2304 - 2311
Date:	2017
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GRAM-POSITIVE INFECTIONS; MUTANT SELECTION WINDOW; RESISTANT STAPHYLOCOCCUS; MODEL; PHARMACOKINETICS; INTERMITTENT; PROGRAM; PROFILE; AUREUS Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22345