Wolfe Amanda, Bowling Jonathan, Short Marintha R, Mateyoke Greg, Berger Steven C
Saint Joseph East, Lexington, KY, USA.
Hosp Pharm. 2022 Aug;57(4):532-539. doi: 10.1177/00185787211055791. Epub 2021 Dec 14.
Vancomycin requires therapeutic drug monitoring (TDM) based on its pharmacokinetic properties, and guidelines have shifted to analyzing area under the curve over 24 hours (AUC24) rather than trough concentrations due to nephrotoxicity concerns and correlation to efficacy. Obesity is an established risk factor for vancomycin-induced nephrotoxicity due to increased drug exposure based on dosing calculations and volume of distribution estimation. The aim of this study is to assess the relationship between AUC-based versus trough-based dosing and nephrotoxicity among obese patients receiving vancomycin. This research project was conducted as a retrospective, observational, single-centered study which included obese adults who received at least 48 hours of vancomycin. The electronic medical record provided data for patients with vancomycin pharmacokinetic consults either evaluated with trough-only or AUC-based dosing. The primary objective was to compare the development of nephrotoxicity after vancomycin initiation, while secondary objectives included vancomycin loading dose exposure, total daily dose of vancomycin, and whether target TDM was attained. Nominal data were evaluated utilizing the chi-square test and continuous data using the independent samples -test or Mann-Whitney test. The a priori level of significance was .05. Data analysis was performed using Microsoft Excel and SAS statistical software. Two hundred fifty-four patients were included in the primary analysis. Four patients in the AUC cohort (6.3%) developed nephrotoxicity compared to 32 (17.4%) in the trough cohort ( = .035). Both cohorts received a median of 4 days of therapy; however, the median loading dose per actual body weight in the AUC cohort was 20 mg/kg as compared to 16 mg/kg in the trough cohort. Of the 130 patients with available TDM in the trough cohort, 97 (74.6%) did not meet target attainment as compared to 15 of the 57 in the AUC cohort (26.3%) ( < .001). AUC dosing was associated with a statistically significant reduction in AKI occurrence despite overall higher loading dose exposure as compared to the trough cohort. Though maintenance dose exposure was similar between both cohorts, patients in the AUC cohort maintained therapeutic concentrations at a higher percentage than the trough cohort.
基于其药代动力学特性，万古霉素需要进行治疗药物监测（TDM），并且由于对肾毒性的担忧以及与疗效的相关性，指南已转向分析24小时曲线下面积（AUC24）而非谷浓度。肥胖是万古霉素诱导肾毒性的既定危险因素，因为基于剂量计算和分布容积估计，药物暴露增加。本研究的目的是评估在接受万古霉素治疗的肥胖患者中，基于AUC的给药与基于谷浓度的给药之间的关系以及肾毒性情况。 本研究项目作为一项回顾性、观察性、单中心研究开展，纳入了接受至少48小时万古霉素治疗的肥胖成年人。电子病历为接受万古霉素药代动力学咨询的患者提供了数据，这些患者要么采用仅基于谷浓度的给药方式，要么采用基于AUC的给药方式进行评估。主要目标是比较万古霉素开始使用后肾毒性的发生情况，次要目标包括万古霉素负荷剂量暴露、万古霉素每日总剂量以及是否达到目标TDM。名义数据采用卡方检验进行评估，连续数据采用独立样本t检验或曼-惠特尼检验。先验显著性水平为0.05。使用Microsoft Excel和SAS统计软件进行数据分析。 254名患者纳入了初步分析。AUC队列中有4名患者（6.3%）发生了肾毒性，而谷浓度队列中有32名患者（17.4%）发生了肾毒性（P = 0.035）。两个队列的治疗中位天数均为4天；然而，AUC队列中按实际体重计算的中位负荷剂量为20mg/kg，而谷浓度队列中为16mg/kg。在谷浓度队列中130名有可用TDM数据的患者中，97名（74.6%）未达到目标，而AUC队列中57名患者中有15名（26.3%）未达到目标（P < 0.001）。 尽管与谷浓度队列相比，AUC给药的总体负荷剂量暴露较高，但AUC给药与急性肾损伤发生率的统计学显著降低相关。尽管两个队列的维持剂量暴露相似，但AUC队列中的患者维持治疗浓度的百分比高于谷浓度队列。
