• Emmanuel Boselli, Dominique Breilh, Aurore Caillault-Sergent, Sarah Djabarouti, Christian Guillaume, Fabien Xuereb, Lionel Bouvet, Thomas Rimmelé, Marie-Claude Saux, and Bernard Allaouchiche.
• Department of Anaesthesiology and Intensive Care, Édouard Herriot Hospital, HCL, University of Lyon, Lyon, France. emmanuel.boselli@chu-lyon.fr
• J. Antimicrob. Chemother. 2012 May 1;67(5):1207-10.

ObjectivesThis 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 MethodsThis 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.ResultsThe 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%).ConclusionsOur 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.

30 keywords...

hide…