Population Pharmacokinetics and Dosing Regimen Optimization of Linezolid in Cerebrospinal Fluid and Plasma of Post-operative Neurosurgical Patients

Linezolid is valuable for treating central nervous system infections caused by drug-resistant Gram-positive pathogens, but its penetration into cerebrospinal fluid (CSF) shows wide variability in post-operative neurosurgical patients. This prospective study collected parallel plasma and CSF samples from neurosurgical patients receiving intravenous linezolid, building a population pharmacokinetic model and using Monte Carlo simulation for dose optimization via Phoenix NLME. Creatinine clearance and serum procalcitonin were significant covariates, and linezolid showed highly variable CSF penetration (mean CSF/plasma ratio of 0.53), though plasma trough levels correlated strongly with CSF exposure. The resulting model-based dosing strategies, stratified by renal function and inflammatory status, aim to improve linezolid efficacy and safety in post-operative neurosurgical patients.