1. Academic Validation
  2. Prolonged infusion of linezolid is associated with improved pharmacokinetic/pharmacodynamic (PK/PD) profiles in patients with external ventricular drains

Prolonged infusion of linezolid is associated with improved pharmacokinetic/pharmacodynamic (PK/PD) profiles in patients with external ventricular drains

  • Eur J Clin Pharmacol. 2021 Jan;77(1):79-86. doi: 10.1007/s00228-020-02978-x.
Wenjun Zhao  # 1 2 Lingti Kong  # 3 Chenchen Wu 4 Xiaofei Wu 5
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230000, China.
  • 2 Department of Emergency Internal Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.
  • 3 Departmen of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.
  • 4 Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.
  • 5 Department of Emergency Internal Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China. 13805529866@163.com.
  • # Contributed equally.
Abstract

Objective: We previously investigated the pharmacokinetic and pharmacodynamic (PK/PD) parameters of routine linezolid infusions (1 h) in patients with external ventricular drains (EVD). The aim of the study was to determine whether extended linezolid infusions (200 mg/h for 3 h) were more efficacious than short linezolid infusions (600 mg/h for 1 h).

Methods: We collected cerebrospinal fluid (CSF) and plasma samples from 10 patients who received linezolid infusions after cerebral hemorrhage surgery with EVDs. Linezolid concentrations were measured by high-performance liquid chromatography (HPLC). A Monte Carlo simulation was used to measure the probability of target attainments (PTA) and the PK/PD indexes at four minimum inhibitory concentrations (MIC).

Results: When the same dose (600 mg) was given as an extended infusion (3 h), linezolid reached its maximum concentrations in the plasma and CSF at 3.00 h and 4.40 h, respectively. The mean penetration of linezolid in CSF was 41.31%. Using the parameter of AUC0-24 h/MIC ≥ 100, the plasma PTA provided good coverage at > 90% when MIC was ≤ 1 μg/mL, while the values were 0 in CSF. Using the parameter %T (time) > MIC ≥ 85%, the PTA in both the plasma and CSF provided good coverage when MIC ≤ 2 μg/mL. Compared with routine infusions, prolonged infusion times (3 h) showed increased PTA of linezolid.

Conclusions: Prolonged infusion times increased the concentration of linezolid in the plasma, leading to improved therapeutic outcomes. However, this improvement did not exist in CSF. Lastly, the PK/PD indicator AUC/MIC ≥ 100 may be used to achieve improved outcomes in patients with critical infections.

Keywords

Cerebrospinal fluid; External ventricular drains; Linezolid; Monte Carlo simulation; Pharmacodynamics; Pharmacokinetics; Prolonged infusion.

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