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

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). 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. The median (IQR) serum and epithelial lining fluid (ELF) linezolid concentrations at steady state (C-ss) were 7.1 (6.19.8) and 6.9 (5.88.6) mg/L, respectively, and the median (IQR) AUC (AUC(024)) values were 169 (146235) and 164 (139202) mgh/L, respectively, corresponding to a median (IQR) linezolid alveolar diffusion of 97 (80108). 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.