Fan Ming-Chao, Sun Jia-Lin, Sun Jian, Ma Jun-Wei, Wang Nian, Fang Wei
Department of Neurosurgery, the Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Neurosurgical Intensive Care Unit, the Affiliated Hospital of Qingdao University, Qingdao, China.
Front Neurol. 2022 May 13;13:893089. doi: 10.3389/fneur.2022.893089. eCollection 2022.
The pharmacokinetics of vancomycin in cerebrospinal fluid (CSF) is an important basis for evaluating the bactericidal effect. The accuracy of using serum vancomycin concentrations only to estimate the CSF concentrations remains controversial, may lead to underdosing.
The aims of this study were to evaluate the vancomycin exposure in CSF, investigate the factors affecting the vancomycin blood-brain barrier (BBB) penetration, and to establish the prediction model of vancomycin concentration in CSF.
Eligible patients were included and given a standard dose of vancomycin. At the fifth dose, the blood and CSF samples were collected 0.5 h before the start of infusion of vancomycin, and 1, 2, 3, and 8 h from the start of infusion, and were measured by the enzyme-multiplied immunoassay technique using the Siemens Viva-E Drug Testing System.
The AUC of patients with intracranial infection was higher than that of patients without ( = 0.001). The CSF concentration was relatively stable between dosing periods ( = 0.095). The area under the concentration-time curve (AUC) ratio of CSF to serum (AUC) in patients with intracranial infection ranged from 15.1 to 80.1% (33.23 ± 19.31%; median, 26.25%). The CSF vancomycin AUC levels were affected by the serum trough concentration (: 5.23 ± 2.36, = 2.22, = 0.039), and were mainly affected by the CSF white blood cells (WBCs)/total cells (: 113.96 ± 35.10, = 3.25, = 0.004) (Y = -17.86 + 5.23 × serum trough concentration + 113.96 × CSF [WBCs/total cells]; = 0.473, = 8.542, = 0.002).
After intravenous administration of vancomycin, the CSF concentration curve was fluctuated gently. The CSF vancomycin concentration in patients with postoperative intracranial infection can be predicted by the WBCs to total cells ratio and the serum trough concentration, and help to adjust the administration of vancomycin.
万古霉素在脑脊液（CSF）中的药代动力学是评估其杀菌效果的重要依据。仅使用血清万古霉素浓度来估算脑脊液浓度的准确性仍存在争议，可能导致给药不足。
本研究旨在评估脑脊液中万古霉素的暴露情况，研究影响万古霉素血脑屏障（BBB）穿透的因素，并建立脑脊液中万古霉素浓度的预测模型。
纳入符合条件的患者并给予标准剂量的万古霉素。在第5次给药时，于万古霉素输注开始前0.5小时以及输注开始后1、2、3和8小时采集血液和脑脊液样本，并使用西门子Viva-E药物检测系统通过酶联免疫分析技术进行测量。
颅内感染患者的AUC高于未感染患者（=0.001）。给药期间脑脊液浓度相对稳定（=0.095）。颅内感染患者脑脊液与血清浓度-时间曲线下面积（AUC）之比（AUC）范围为15.1%至80.1%（33.23±19.31%；中位数为26.25%）。脑脊液万古霉素AUC水平受血清谷浓度影响（：5.23±2.36，=2.22，=0.039），且主要受脑脊液白细胞（WBC）/总细胞数影响（：113.96±35.10，=3.25，=0.004）（Y=-17.86+5.23×血清谷浓度+113.96×脑脊液[WBC/总细胞数]；=0.473，=8.542，=0.002）。
静脉注射万古霉素后，脑脊液浓度曲线波动平缓。术后颅内感染患者的脑脊液万古霉素浓度可通过白细胞与总细胞数之比和血清谷浓度进行预测，有助于调整万古霉素的给药方案。
