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

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 (AUC012) was 77.3 23.7 mghr/L, corresponding to a mean AUC024 of 154.6 mghr/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 24 mg/L in both plasma and epithelial lining fluid. [ABSTRACT FROM AUTHOR]