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Pharmacokinetics and intrapulmonary concentrations of linezolid administered to critically ill patients with ventilator-associated pneumonia*

Boselli, Emmanuel MD; Breilh, Dominique PharmD, PhD; Rimmelé, Thomas MD; Djabarouti, Sarah PharmD; Toutain, Jérôme PharmD; Chassard, Dominique MD, PhD; Saux, Marie-Claude PharmD, PhD; Allaouchiche, Bernard MD, PhD

doi: 10.1097/01.CCM.0000168206.59873.80
Clinical Investigations

Objective: To determine the steady-state plasma pharmacokinetic variables and epithelial lining fluid concentrations of linezolid administered to critically ill patients with ventilator-associated pneumonia.

Design: Prospective, open-label study.

Setting: An intensive care unit and research ward in a university hospital.

Patients: Sixteen critically ill adult patients with ventilator-associated pneumonia.

Interventions: All subjects received 1-hr intravenous infusions of linezolid 600 mg twice daily. After 2 days of therapy, the steady-state plasma pharmacokinetic variables and epithelial lining fluid concentrations of linezolid were determined by high-performance liquid chromatography.

Measurements and Main Results: The mean ± sd linezolid peak and trough concentrations were 17.7 ± 4.0 mg/L and 2.4 ± 1.2 mg/L in plasma and 14.4 ± 5.6 mg/L and 2.6 ± 1.7 mg/L in epithelial lining fluid, respectively, showing a mean linezolid percentage penetration in epithelial lining fluid of approximately 100%. The mean ± sd area under concentration-time curve during the observational period (AUC0–12) was 77.3 ± 23.7 mg·hr/L, corresponding to a mean AUC0–24 of 154.6 mg·hr/L.

Conclusions: Our study shows satisfactory results, with linezolid concentrations exceeding the susceptibility breakpoint for Gram-positive bacteria in both plasma and epithelial lining fluid. This suggests that a dosage of 600 mg administered intravenously twice daily to critically ill patients with Gram-positive ventilator-associated pneumonia would achieve success against organisms with minimum inhibitory concentrations as high as 2–4 mg/L in both plasma and epithelial lining fluid.

From the Department of Anesthesiology and Intensive Care, Edouard Herriot hospital, Lyon, France (EB, TR, BA); and Hôtel-Dieu Hospital (DC) and the Clinical Pharmacokinetics Laboratory, Haut-Lévêque hospital, Pessac, France (DB, SD, JT, M-CS).

Support was provided only by institutional sources. The authors have no financial interests to disclose.

Presented, in part, at the 24th ICAAC, Washington, DC, 2004, abstract A1131.

© 2005 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins