Document Detail

Pharmacokinetics and intrapulmonary concentrations of linezolid administered to critically ill patients with ventilator-associated pneumonia.
MedLine Citation:
PMID:  16003058     Owner:  NLM     Status:  MEDLINE    
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.
Emmanuel Boselli; Dominique Breilh; Thomas Rimmelé; Sarah Djabarouti; Jérôme Toutain; Dominique Chassard; Marie-Claude Saux; Bernard Allaouchiche
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  33     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-08     Completed Date:  2005-08-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1529-33     Citation Subset:  AIM; IM    
Department of Anesthesiology and Intensive Care, Edouard Herriot Hospital, Lyon, France.
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MeSH Terms
Acetamides / blood,  pharmacokinetics*
Anti-Bacterial Agents / blood,  pharmacokinetics*
Area Under Curve
Bronchoalveolar Lavage Fluid / chemistry
Cross Infection / drug therapy*,  etiology
Hospitals, University
Intensive Care Units
Lung / metabolism*
Middle Aged
Oxazolidinones / blood,  pharmacokinetics*
Pneumonia, Bacterial / drug therapy*,  etiology
Prospective Studies
Respiration, Artificial / adverse effects*
Respiratory Mucosa / metabolism
Reg. No./Substance:
0/Acetamides; 0/Anti-Bacterial Agents; 0/Oxazolidinones; 165800-03-3/linezolid
Comment In:
Crit Care Med. 2005 Jul;33(7):1654-5   [PMID:  16003083 ]
Crit Care Med. 2006 Jan;34(1):267-8; author reply 268   [PMID:  16374201 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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