Alveolar diffusion and pharmacokinetics of linezolid administered in continuous infusion to critically ill patients with ventilator-associated pneumonia

J Antimicrob Chemother. 2012 May;67(5):1207-10. doi: 10.1093/jac/dks022. Epub 2012 Feb 20.


Objectives: 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).

Patients and 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / administration & dosage
  • Acetamides / pharmacokinetics*
  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Critical Illness
  • Female
  • Humans
  • Infusions, Intravenous
  • Linezolid
  • Male
  • Middle Aged
  • Oxazolidinones / administration & dosage
  • Oxazolidinones / pharmacokinetics*
  • Pneumonia, Staphylococcal / drug therapy
  • Pneumonia, Ventilator-Associated / drug therapy*
  • Prospective Studies
  • Pulmonary Alveoli / chemistry*
  • Serum / chemistry
  • Staphylococcus aureus / drug effects


  • Acetamides
  • Anti-Bacterial Agents
  • Oxazolidinones
  • Linezolid