Department of Critical Care Medicine, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230000, China.
Department of Emergency Internal Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.
Eur J Clin Pharmacol. 2021 Jan;77(1):79-86. doi: 10.1007/s00228-020-02978-x. Epub 2020 Aug 18.
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).
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).
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 AUC/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.
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.
我们之前研究了带外部引流管（EVD）脑出血术后患者常规输注（1 小时）利奈唑胺的药代动力学和药效学（PK/PD）参数。本研究旨在确定延长输注（200mg/h 持续 3 小时）是否比短时间输注（600mg/h 持续 1 小时）更有效。
我们收集了 10 例接受 EVD 脑出血手术后利奈唑胺输注的患者的脑脊液（CSF）和血浆样本。采用高效液相色谱法（HPLC）测定利奈唑胺浓度。采用蒙特卡罗模拟法测定四个最低抑菌浓度（MIC）下的目标达标率（PTA）和 PK/PD 指标。
当以相同剂量（600mg）进行延长输注（3 小时）时，利奈唑胺在血浆和 CSF 中的最大浓度分别出现在 3.00 小时和 4.40 小时。利奈唑胺在 CSF 中的平均穿透率为 41.31%。当 MIC 为≤1μg/mL 时，AUC/MIC≥100 的参数可提供 90%以上的血浆 PTA 覆盖率，而 CSF 中的值为 0。当 MIC≤2μg/mL 时，%T（时间）>MIC≥85%的参数在血浆和 CSF 中均可提供良好的 PTA 覆盖率。与常规输注相比，延长输注时间（3 小时）可提高利奈唑胺的 PTA。
延长输注时间可增加利奈唑胺在血浆中的浓度，从而改善治疗效果。然而，这一改善在 CSF 中并不存在。最后，AUC/MIC≥100 的 PK/PD 指标可能用于实现重症感染患者的治疗效果改善。
