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. 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 (AUC(0-12)) was 77.3 +/- 23.7 mg center dot hr/L, corresponding to a mean AUC(0-24) of 154.6 mg center dot 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.