Abstract：
OBJECTIVE: Central nervous system (CNS) infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) present a major health and economic burden worldwide. This multicentre prospective study aimed to assess the feasibility and usefulness of CSF therapeutic drug monitoring (TDM) after intrathecal/intraventricular administration of polymyxin B in patients with CNS infections.
METHODS: Forty-two patients treated with intrathecal/intraventricular administration of polymyxin B against CR-GNB-induced CNS infections were enrolled. CSF trough level (Cmin) was collected beginning on Day 2 post-polymyxin B initiation and thereafter. The primary outcomes were clinical cure and 28-day all-cause mortality.
RESULTS: All patients started with intrathecal/intraventricular administration of polymyxin B at a dose of 5 g/day, corresponding to a median CSF Cmin of 2.93 mg/L (range, 0.21-25.74 mg/L). Clinical cure was 71.4%, and the median CSF Cmin of this group was higher than that of clinical failure group [3.31 (IQR, 1.73-5.62) mg/L versus 2.25 (IQR, 1.09-4.12) mg/L; P = 0.011]. In addition, with MICs ≤ 0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (P = 0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin.
CONCLUSIONS: After intrathecal/intraventricular administration of polymyxin B, CSF concentrations fluctuated considerably inter- and intra-individual. Polymyxin B CSF Cmin above 2.0 mg/L was associated with clinical cure when MICs were ≤ 0.5 mg/L, and the feasibility of TDM warrants additional clinical studies.
METHODS: Forty-two patients treated with intrathecal/intraventricular administration of polymyxin B against CR-GNB-induced CNS infections were enrolled. CSF trough level (Cmin) was collected beginning on Day 2 post-polymyxin B initiation and thereafter. The primary outcomes were clinical cure and 28-day all-cause mortality.
RESULTS: All patients started with intrathecal/intraventricular administration of polymyxin B at a dose of 5 g/day, corresponding to a median CSF Cmin of 2.93 mg/L (range, 0.21-25.74 mg/L). Clinical cure was 71.4%, and the median CSF Cmin of this group was higher than that of clinical failure group [3.31 (IQR, 1.73-5.62) mg/L versus 2.25 (IQR, 1.09-4.12) mg/L; P = 0.011]. In addition, with MICs ≤ 0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (P = 0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin.
CONCLUSIONS: After intrathecal/intraventricular administration of polymyxin B, CSF concentrations fluctuated considerably inter- and intra-individual. Polymyxin B CSF Cmin above 2.0 mg/L was associated with clinical cure when MICs were ≤ 0.5 mg/L, and the feasibility of TDM warrants additional clinical studies.
摘要：
目的：碳青霉烯类耐药革兰阴性菌（CR-GNB）引起的中枢神经系统（CNS）感染是全球范围内主要的健康和经济负担。这项多中心前瞻性研究旨在评估中枢神经系统感染患者鞘内/脑室内给予多粘菌素B后CSF治疗药物监测（TDM）的可行性和实用性。
方法：纳入42例接受鞘内/脑室内多粘菌素B治疗的患者，以预防CR-GNB诱导的中枢神经系统感染。在多粘菌素B起始后第2天开始和之后收集CSF谷水平(Cmin)。主要结果是临床治愈和28天全因死亡率。
结果：所有患者均开始鞘内/心室内给予多粘菌素B，剂量为5g/天，对应于2.93mg/L的CSFCmin中位数(范围，0.21-25.74mg/L）。临床治愈率为71.4%，并且该组的中位CSFCmin高于临床失败组[3.31（IQR，1.73-5.62）mg/L与2.25（IQR，1.09-4.12)mg/L；P=0.011]。此外,MIC≤0.5mg/L，维持多粘菌素BCSFCmin大于2.0mg/L显示出更高的临床治愈率（P=0.041）。28天全因死亡率为31.0%，与CSFCmin无关。
结论：鞘内/室内注射多粘菌素B后，CSF浓度在个体间和个体内波动很大。当MIC≤0.5mg/L时，多粘菌素BCSFCmin高于2.0mg/L与临床治愈相关，TDM的可行性需要更多的临床研究。
方法：纳入42例接受鞘内/脑室内多粘菌素B治疗的患者，以预防CR-GNB诱导的中枢神经系统感染。在多粘菌素B起始后第2天开始和之后收集CSF谷水平(Cmin)。主要结果是临床治愈和28天全因死亡率。
结果：所有患者均开始鞘内/心室内给予多粘菌素B，剂量为5g/天，对应于2.93mg/L的CSFCmin中位数(范围，0.21-25.74mg/L）。临床治愈率为71.4%，并且该组的中位CSFCmin高于临床失败组[3.31（IQR，1.73-5.62）mg/L与2.25（IQR，1.09-4.12)mg/L；P=0.011]。此外,MIC≤0.5mg/L，维持多粘菌素BCSFCmin大于2.0mg/L显示出更高的临床治愈率（P=0.041）。28天全因死亡率为31.0%，与CSFCmin无关。
结论：鞘内/室内注射多粘菌素B后，CSF浓度在个体间和个体内波动很大。当MIC≤0.5mg/L时，多粘菌素BCSFCmin高于2.0mg/L与临床治愈相关，TDM的可行性需要更多的临床研究。
