Effect of severity of sepsis on tissue concentrations of linezolid.

OBJECTIVES In the present study, we examined whether differences in the severity of sepsis translate to differences in the pharmacokinetic profile of linezolid in plasma and the interstitium of target tissues after a single intravenous dose of 600 mg by means of the microdialysis technique. PATIENTS AND METHODS A total of 24 patients were included in the trial. Sixteen patients suffered from septic shock and eight patients presented with severe sepsis. Sepsis was diagnosed and verified according to the criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. Historic data derived from a previous study determining the pharmacokinetic profiles of linezolid in tissues and plasma in young healthy volunteers served as controls. RESULTS In the present study, the AUC for free linezolid from 0 to 24 h (fAUC(0-24)) ranged from 50 to 71 mg x h/L after single-dose administration in patients presenting with severe sepsis or septic shock. The mathematically extrapolated fAUC(0-24) ranged from 100 to 146 mg x h/L for twice-daily administration and a dosing interval of 12 h. No statistically significant difference in key pharmacokinetic parameters was detected between patients suffering from severe sepsis and septic shock (P > 0.05). CONCLUSIONS These data indicated that the severity of sepsis has no substantial effect on the pharmacokinetic profile of linezolid in plasma and in the interstitium of soft tissues.