Wang Chuhui, Chen Jiaojiao, Yang Bo, Li Sihan, Zhang Yiran, Chen Lei, Wang Taotao, Dong Yalin
Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
Pharmacotherapy. 2023 Mar;43(3):180-188. doi: 10.1002/phar.2771. Epub 2023 Feb 9.
Few studies have been conducted to quantify the exposure target of vancomycin in intensive care unit (ICU) patients undergoing continuous renal replacement therapy (CRRT) and provide optimized dosage regimens. We aimed to determine vancomycin exposure target and dosing recommendations using data from an open database in critically ill patients undergoing CRRT.
A retrospective observational cohort study.
A large public database.
The adult patients who received intravenous vancomycin and CRRT treatment in the database between 2017 and 2019 were reviewed to determine eligibility. A total of 180 patients with 1186 observations were included in the population pharmacokinetic (PPK) model development. The clinical efficacy of vancomycin was analyzed in 159 eligible patients.
A PPK model was developed to estimate individual pharmacokinetic (PK) parameters. The area under the concentration-time curve (AUC) was estimated by a Bayesian approach based on individual vancomycin concentrations. Multivariate logistic regression analyses were performed to identify the factors of clinical outcomes. Threshold of vancomycin exposure in predicting efficacy was identified via receiver operating characteristic (ROC) curve. Dosing recommendations were designed using Monte Carlo Simulations (MCS) based on the optimized exposure target.
On covariate analysis, CRRT intensity significantly affected vancomycin PK. The AUC above 427 mg*h/L was the only significant predictor of clinical efficacy (adjusted odds ratio (aOR): 1.008, 95% confidence interval (CI): 1.004-1.011, p = 0.000). MCS indicated that vancomycin dosage regimens of 5 mg/kg q12h or 7.5 mg/kg q12h were recommended for patients with CRRT intensities of 20-25 mL/kg/h or 25.1-45 mL/kg/h, respectively.
An AUC threshold of 427 mg*h/L (assuming the minimal inhibitory concentration (MIC) = 1 mg/L) was a recommended efficacy exposure target of vancomycin for critically ill patients undergoing CRRT. Vancomycin 5-7.5 mg/kg q12h is recommended as the initial dosage regimens for ICU patients undergoing CRRT.
很少有研究对接受持续肾脏替代治疗（CRRT）的重症监护病房（ICU）患者的万古霉素暴露目标进行量化并提供优化的给药方案。我们旨在利用来自接受CRRT的危重症患者开放数据库的数据确定万古霉素暴露目标和给药建议。
一项回顾性观察队列研究。
一个大型公共数据库。
对2017年至2019年期间在数据库中接受静脉万古霉素和CRRT治疗的成年患者进行评估以确定入选资格。共有180例患者的1186次观察结果被纳入群体药代动力学（PPK）模型开发。对159例符合条件的患者分析了万古霉素的临床疗效。
建立PPK模型以估计个体药代动力学（PK）参数。基于个体万古霉素浓度通过贝叶斯方法估计浓度-时间曲线下面积（AUC）。进行多变量逻辑回归分析以确定临床结局的影响因素。通过受试者工作特征（ROC）曲线确定预测疗效的万古霉素暴露阈值。基于优化的暴露目标使用蒙特卡洛模拟（MCS）设计给药建议。
在协变量分析中，CRRT强度显著影响万古霉素的PK。AUC高于427mg*h/L是临床疗效的唯一显著预测指标（调整优势比（aOR）：1.008，95%置信区间（CI）：1.004-1.011，p = 0.000）。MCS表明，对于CRRT强度为20-25mL/kg/h或25.1-45mL/kg/h的患者，分别推荐每12小时5mg/kg或每12小时7.5mg/kg的万古霉素给药方案。
427mg*h/L的AUC阈值（假设最低抑菌浓度（MIC）=1mg/L）是接受CRRT的危重症患者万古霉素推荐的疗效暴露目标。对于接受CRRT的ICU患者，推荐每12小时5-7.5mg/kg作为初始给药方案。
