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

  • Pharmacokinetics and Disposition
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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.

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Funding

This work was funded by the Research Innovation Program for College Graduates of Bengbu Medical College (Byycxz1833), Key Special Project of Translational Medicine Research of Bengbu Medical College (BYTM2019015), and Program of Study Abroad for the Excellent Youth Key Scholars of Education Department of Anhui Province of China (gxgwfx2019030).

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Author notes

  1. Wenjun Zhao and Lingti Kong contributed equally to this work.

Authors and Affiliations

  1. Department of Critical Care Medicine, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230000, China

    Wenjun Zhao

  2. Department of Emergency Internal Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China

    Wenjun Zhao & Xiaofei Wu

  3. Departmen of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China

    Lingti Kong

  4. Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China

    Chenchen Wu

Authors
  1. Wenjun Zhao
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  4. Xiaofei Wu
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Contributions

Wenjun Zhao and Lingti Kong contributed equally to this work. Wenjun Zhao, Lingti Kong, and Xiaofei Wu participated in research design, performed the research, and wrote the manuscript. Wenjun Zhao and Chenchen Wu conducted the experiment. All authors contributed towards critically revising the manuscript.

Corresponding author

Correspondence to Xiaofei Wu.

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The authors declare that they have no competing interests.

Ethical approval

This experiment was approved by the Ethics Committee of the First Affiliated Hospital of Bengbu Medical College. This study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki.

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Zhao, W., Kong, L., Wu, C. et al. Prolonged infusion of linezolid is associated with improved pharmacokinetic/pharmacodynamic (PK/PD) profiles in patients with external ventricular drains. Eur J Clin Pharmacol 77, 79–86 (2021). https://doi.org/10.1007/s00228-020-02978-x

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