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Crit Care Med. 2005 Jul;33(7):1529-33.

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

Author information

1
Department of Anesthesiology and Intensive Care, Edouard Herriot Hospital, Lyon, France.

Abstract

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 x hr/L, corresponding to a mean AUC0-24 of 154.6 mg x 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.

[Indexed for MEDLINE]

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