title: Alveolar diffusion and pharmacokinetics of linezolid administered in continuous infusion to critically ill patients with ventilator-associated pneumonia.
abstract: OBJECTIVE
  This study aimed to determine the steady-state serum and alveolar concentrations of linezolid administered by continuous infusion to critically ill patients with ventilator-associated pneumonia (VAP).
  
  
  METHODS
  This was a prospective, open-label study performed in an intensive care unit and research ward in a university hospital. Twelve critically ill adult patients with VAP received 600 mg of linezolid as a loading dose followed by 1200 mg/day by continuous infusion. After 2 days of therapy, the steady-state serum and alveolar (collected by a mini-bronchoalveolar procedure) concentrations of linezolid were determined by HPLC.
  
  
  RESULTS
  The median (IQR) serum and epithelial lining fluid (ELF) linezolid concentrations at steady state (C(ss)) were 7.1 (6.1-9.8) and 6.9 (5.8-8.6) mg/L, respectively, and the median (IQR) AUC (AUC(0-24)) values were 169 (146-235) and 164 (139-202) mg · h/L, respectively, corresponding to a median (IQR) linezolid alveolar diffusion of 97% (80%-108%).
  
  
  CONCLUSIONS
  Our study shows that the continuous infusion of 1200 mg of linezolid daily in critically ill patients with VAP provides satisfactory pharmacokinetic results, with a linezolid alveolar diffusion of 100% and concentrations exceeding almost twice the susceptibility breakpoint for Staphylococcus aureus (4 mg/L) in both serum and ELF for 100% of the time. However, the clinical benefit of continuous infusion in comparison with standard intermittent infusion is still to be determined.
authors.affiliation: Department of Anaesthesiology and Intensive Care, Édouard Herriot Hospital, HCL, University of Lyon, Lyon, France. emmanuel.boselli@chu-lyon.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Boselli
authors.forename: Dominique
authors.initials: D
authors.lastname: Breilh
authors.forename: Aurore
authors.initials: A
authors.lastname: Caillault-Sergent
authors.forename: Sarah
authors.initials: S
authors.lastname: Djabarouti
authors.forename: Christian
authors.initials: C
authors.lastname: Guillaume
authors.forename: Fabien
authors.initials: F
authors.lastname: Xuereb
authors.forename: Lionel
authors.initials: L
authors.lastname: Bouvet
authors.forename: Thomas
authors.initials: T
authors.lastname: Rimmelé
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Saux
authors.forename: Bernard
authors.initials: B
authors.lastname: Allaouchiche
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016638:Critical Illness; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy*; D011446:Prospective Studies; D011650:Pulmonary Alveoli / Q000737:chemistry*; D044967:Serum / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid