Prolonged Infusion Of Linezolid Is Associated With Pharmacokinetic/pharmacodynamic(PK/PD)profiles In Patients With External Ventricular Drains

Objective:In a previous report,we investigated the pharmacokinetic and pharmacodynamic?PK/PD?parameters of routine infusions?1 h?of linezolid in patients with external ventricular drains?EVD?.The aim of the current study was to determine whether extended infusions?3 h?of linezolid results in higher anti-infective activity than shorter?1 h?routine infusions.Methods:We collected cerebrospinal fluid?CSF?and plasma samples from 10 patients who underwent intravenous linezolid therapy?600 mg/3h?after cerebral hemorrhage surgery using EVDs.High-performance liquid chromatography?HPLC?was used to analyze the samples.A Monte Carlo simulation was used to measure the probability of target attainments?PTA?for linezolid and to attain the PK/PD index at four specific minimal inhibitory concentrations?MIC?.Results:When given as an extended infusion?3h?,linezolid reached its maximum concentrations in the plasma and CSF at 3.00 h and 4.40 h,respectively.The average penetration of linezolid in the CSF was 41.31%.Using the parameter of AUC_0-24-24 h/MIC?100,the PTA of linezolid in the plasma provided good coverage at>90%when MIC was?1?g/mL,which was 0 in the CSF.Using the parameter%T>MIC?85%,the PTA of linezolid in both the plasma and CSF provided good coverage when MIC?2?g/mL.Compared with routine infusion?1 h?,prolonging the infusion time to 3 h could increase the anti-infective activity of linezolid.Conclusions:If the patient is only infected with MRSA in the blood,it is recommended to use the 3-hour infusion plan;if the patient has intracranial infection with MRSA,the current conventional dose?600mg q12h?is difficult to reach the standard no matter the 1-hour infusion method or the 3-hour infusion method is used.It may be necessary to increase the dosage or intrathecal administration in order to achieve better results.