Abstract
Background: Linezolid is effective against methicillin-resistant Staphylococcus aureus, which may cause central nervous system (CNS) infections, but drug concentrations in plasma are characterized by a large inter-patient variability. Therefore, the present study was aimed at evaluating linezolid pharmacokinetics in plasma and cerebrospinal fluid (CSF) in 7 patients with external ventricular drainage, who received linezolid 600 mg twice daily as 1-h intravenous infusion to prevent CNS infections. Methods: Plasma and CSF linezolid concentrations were measured by high-performance liquid chromatography (HPLC) after the 1st and 5th dose, and pharmacokinetics were evaluated by non-compartmental analysis. Results: Values of the CSF area under the time/concentration curve (AUC) (range 18.2–85.5 and 19.6–160.5 h × mg/l at the 1st and 5th dose, respectively) were lower than those calculated in plasma (range 27.6–224.0 and 27.5–166.1 h × mg/l, respectively). For minimum inhibitory concentration (MIC) = 1 mg/l, CSF AUC/MIC values were nearly equal to or greater than 100 only in 2 subjects after the 1st and 5th dose, whereas mean time above the MIC (T > MIC) values were higher than 75% in only 3 patients. Similar results were obtained when pharmacokinetic/pharmacodynamic parameters were evaluated in plasma. Conclusion: The present results suggest that changes in linezolid doses and measurement of drug concentrations should be considered as useful strategies to optimize treatment in some patients.
Acknowledgements
The authors wish to thank the nursing staff for their valuable help in performing the study.
Declaration of Interest: No financial support was received to perform the present study, and the authors have no potential conflict of interest to declare.