Department of Pharmacy, University Hospital of Heidelberg, Im Neuenheimer Feld 670, Heidelberg, Germany.
Department of Molecular and Clinical Pharmacology, University of Liverpool, Sherington Building, Liverpool, UK.
J Antimicrob Chemother. 2019 Apr 1;74(4):991-996. doi: 10.1093/jac/dky543.
Vancomycin is recommended for ventriculitis. However, penetration into the CNS is relatively poor.
To investigate the population pharmacokinetics of vancomycin in serum and CSF in critical care patients with proven or suspected CNS infections from neurosurgical procedures.
This was an observational pharmacokinetic study in critical care patients with proven or suspected CNS infections receiving intravenous vancomycin. Multiple blood and intraventricular CSF samples were collected. Population pharmacokinetic analysis and simulation were undertaken with ADAPT5 and Pmetrics.
A total of 187 blood and CSF samples were collected from 21 patients. The median (range) Cmax and Cmin concentrations in serum were 25.67 (10.60-50.78) and 9.60 (4.46-23.56) mg/L, respectively, with a median daily dose of 2500 (500-4000) mg. The corresponding median concentrations in CSF were 0.65 (<0.24-3.83) mg/L and 0.58 (<0.24-3.95) mg/L, respectively. The median AUC0-24 in serum and CSF was 455.09 and 14.10 mg·h/L, respectively. A three-compartment linear population pharmacokinetic model best fitted the observed data. Vancomycin demonstrated poor penetration into CSF, with a median CSF/serum ratio of 3% and high intersubject pharmacokinetic variability of its penetration.
Therapeutic drug monitoring in both serum and CSF and higher daily doses may be an option to ensure adequate trough levels and to optimize patient therapy. Novel dosing strategies designed to reduce renal toxicity, such as administration by continuous infusion, should be investigated in further clinical studies to avoid antibiotic underexposure in CSF.
万古霉素被推荐用于脑室炎。然而，其向中枢神经系统的穿透性相对较差。
研究经神经外科手术证实或疑似中枢神经系统感染的重症监护患者血清和脑脊液中万古霉素的群体药代动力学。
这是一项在接受静脉万古霉素治疗的经神经外科手术证实或疑似中枢神经系统感染的重症监护患者中进行的观察性药代动力学研究。采集了多个血样和脑室内脑脊液样本。采用 ADAPT5 和 Pmetrics 进行群体药代动力学分析和模拟。
从 21 名患者中采集了 187 份血样和脑脊液样本。血清中 Cmax 和 Cmin 浓度的中位数（范围）分别为 25.67（10.60-50.78）和 9.60（4.46-23.56）mg/L，中位日剂量为 2500（500-4000）mg。相应的脑脊液中浓度中位数分别为 0.65（<0.24-3.83）和 0.58（<0.24-3.95）mg/L。血清和脑脊液中的 AUC0-24 中位数分别为 455.09 和 14.10mg·h/L。观察数据最佳拟合为三室线性群体药代动力学模型。万古霉素向脑脊液中的穿透性较差，脑脊液/血清比值中位数为 3%，其穿透性的个体间药代动力学变异性较高。
在血清和脑脊液中进行治疗药物监测以及增加每日剂量可能是确保足够的谷浓度并优化患者治疗的一种选择。为了降低肾毒性，应在进一步的临床研究中探索新的给药策略，如连续输注给药，以避免脑脊液中抗生素暴露不足。
