Department of Pharmacy, King Hussein Cancer Center, Amman, Jordan.
Infectious Disease Pharmacokinetics Laboratory, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Pharmacol Res Perspect. 2022 Feb;10(1):e00912. doi: 10.1002/prp2.912.
The updated vancomycin guideline and recent studies suggested that trough concentrations may result in underestimation of the actual area under the curve (AUC), leading to excessive dosing and nephrotoxicity. With limited data available on critically ill cancer patients, this study aimed to compare the two methods in this patient population. This was a 5-year retrospective study on patients treated with vancomycin in the intensive care unit (ICU) of a comprehensive cancer center. The measured trough concentration was compared to Bayesian-derived AUC/minimum-inhibitory-concentration (MIC), considering MIC as 1. Trough concentrations of 15-20 mg/L and AUC of 400-600 mg h/L were considered the targeted goal. Multivariate analysis was performed to identify factors associated with an AUC below the targeted goal. During the study period, 316 patients were included. The mean age was 54 years ±16 (SD); most patients had solid tumors (75%), and 11% had neutropenia. A targeted goal AUC and trough were recorded in 128 (41%) patients and in 64 (20%) patients, respectively. Of the 128 patients with targeted goal AUC, 31 (24%) had targeted goal trough concentrations and 91 (71%) had trough concentrations below 15 mg/L. Furthermore, among the patients with targeted goal trough concentration (n = 64), 33 (52%) had higher than targeted goal AUC. Augmented renal clearance (ARC), defined as a calculated creatinine-clearance ≥130 ml/min, was associated with an AUC below the targeted goal. In a cohort of critically ill patients with cancer, over two-thirds of the patients with a targeted goal Bayesian AUC/MIC had trough concentrations below the targeted goal. ARC was associated with AUC below the targeted goal.
更新的万古霉素指南和最近的研究表明,谷浓度可能导致对实际曲线下面积(AUC)的低估,从而导致过度给药和肾毒性。由于危重症癌症患者的可用数据有限,本研究旨在比较这两种方法在该患者人群中的应用。这是一项对综合癌症中心重症监护病房(ICU)中接受万古霉素治疗的患者进行的为期 5 年的回顾性研究。比较了测量的谷浓度与贝叶斯衍生的 AUC/最小抑菌浓度(MIC),将 MIC 设为 1。将 15-20mg/L 的谷浓度和 400-600mg·h/L 的 AUC 作为目标浓度。进行了多变量分析以确定与目标 AUC 以下相关的因素。在研究期间,纳入了 316 名患者。平均年龄为 54 岁±16(标准差);大多数患者为实体瘤(75%),11%为中性粒细胞减少症。128 名(41%)患者记录了目标 AUC 和谷浓度,64 名(20%)患者记录了目标谷浓度。在 128 名具有目标 AUC 的患者中,31 名(24%)具有目标谷浓度,91 名(71%)的谷浓度低于 15mg/L。此外,在具有目标谷浓度的患者中(n=64),33 名(52%)的 AUC 高于目标值。定义为计算肌酐清除率≥130ml/min 的增强肾清除(ARC)与 AUC 低于目标值相关。在癌症危重症患者队列中,超过三分之二的具有目标 AUC 的贝叶斯 AUC/MIC 患者的谷浓度低于目标值。ARC 与 AUC 低于目标值相关。