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.


METHODS
Prospective, open-label study.


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


METHODS
Sixteen critically ill adult patients with ventilator-associated pneumonia.


METHODS
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.


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.
Department of Anesthesiology and Intensive Care, Edouard Herriot Hospital, Lyon, France.
Emmanuel
E
Boselli
Dominique
D
Breilh
Thomas
T
Rimmelé
Sarah
S
Djabarouti
Jérôme
J
Toutain
Dominique
D
Chassard
Marie-Claude
MC
Saux
Bernard
B
Allaouchiche
D000081:Acetamides / Q000097:blood / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003428:Cross Infection / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D000069349:Linezolid; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000097:blood / Q000493:pharmacokinetics*; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000209:etiology; D011446:Prospective Studies; D012121:Respiration, Artificial / Q000009:adverse effects*; D020545:Respiratory Mucosa / Q000378:metabolism
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid