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Critical Care
Published in: Critical Care 4/2014

Open Access 01-08-2014 | Research

Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study

Authors: Michael Zoller, Barbara Maier, Cyrill Hornuss, Christina Neugebauer, Gundula Döbbeler, Dorothea Nagel, Lesca Miriam Holdt, Mathias Bruegel, Thomas Weig, Béatrice Grabein, Lorenz Frey, Daniel Teupser, Michael Vogeser, Johannes Zander

Published in: Critical Care | Issue 4/2014

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Abstract

Introduction

Severe infections in intensive care patients show high morbidity and mortality rates. Linezolid is an antimicrobial drug frequently used in critically ill patients. Recent data indicates that there might be high variability of linezolid serum concentrations in intensive care patients receiving standard doses. This study was aimed to evaluate whether standard dosing of linezolid leads to therapeutic serum concentrations in critically ill patients.

Methods

In this prospective observational study, 30 critically ill adult patients with suspected infections received standard dosing of 600 mg linezolid intravenously twice a day. Over 4 days, multiple serum samples were obtained from each patient, in order to determine the linezolid concentrations by liquid chromatography tandem mass spectrometry.

Results

A high variability of serum linezolid concentrations was observed (range of area under the linezolid concentration time curve over 24 hours (AUC24) 50.1 to 453.9 mg/L, median 143.3 mg*h/L; range of trough concentrations (Cmin) < 0.13 to 14.49 mg/L, median 2.06 mg/L). Furthermore, potentially subtherapeutic linezolid concentrations over 24 hours and at single time points (defined according to the literature as AUC24 < 200 mg*h/L and Cmin < 2 mg/L) were observed for 63% and 50% of the patients, respectively. Finally, potentially toxic levels (defined as AUC24 > 400 mg*h/L and Cmin > 10 mg/L) were observed for 7 of the patients.

Conclusions

A high variability of linezolid serum concentrations with a substantial percentage of potentially subtherapeutic levels was observed in intensive care patients. The findings suggest that therapeutic drug monitoring of linezolid might be helpful for adequate dosing of linezolid in critically ill patients.

Trial registration

Clinicaltrials.gov NCT01793012. Registered 24 January 2013.
Appendix
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Metadata
Title
Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study
Authors
Michael Zoller
Barbara Maier
Cyrill Hornuss
Christina Neugebauer
Gundula Döbbeler
Dorothea Nagel
Lesca Miriam Holdt
Mathias Bruegel
Thomas Weig
Béatrice Grabein
Lorenz Frey
Daniel Teupser
Michael Vogeser
Johannes Zander
Publication date
01-08-2014
Publisher
BioMed Central
Published in
Critical Care / Issue 4/2014
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc13984

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