Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA.
Antimicrob Agents Chemother. 2017 Dec 21;62(1). doi: 10.1128/AAC.01684-17. Print 2018 Jan.
Evidence supports vancomycin therapeutic-drug monitoring by area under the concentration-time curve (AUC), but data to establish an AUC upper limit are limited and published nephrotoxicity thresholds range widely. The objective of this analysis was to examine the association between initial vancomycin AUC and nephrotoxicity. This was a multicenter, retrospective cohort study of adult patients receiving intravenous vancomycin from 2014 to 2015. Nephrotoxicity was defined as a serum creatinine increase of 0.5 mg/liter and 50% from baseline on consecutive measurements. Vancomycin exposure profile during the initial 48 h of therapy was estimated using maximum probability Bayesian estimation. Vancomycin AUC and minimum-concentration () thresholds most strongly associated with nephrotoxicity were identified via classification and regression tree (CART) analysis. Predictive performances of CART-derived and other candidate AUC thresholds was assessed through positive and negative predictive value and receiver operating characteristic curves. Poisson regression was used to quantify the association between exposure thresholds and nephrotoxicity while adjusting for confounders. Among 323 patients included, nephrotoxicity was significantly higher in patients with AUCs from 0 to 48 h (AUC) of ≥1,218 mg · h/liter, AUC of ≥677 mg · h/liter, AUC of ≥683 mg · h/liter, and day 1 () of ≥18.8 mg/liter. Vancomycin exposure in excess of these thresholds was associated with a 3- to 4-fold-increased risk of nephrotoxicity in Poisson regression. The predictive performance of AUC for nephrotoxicity was maximized at daily AUC values between 600 and 800 mg · h/liter. Although these data support an AUC range for vancomycin-associated nephrotoxity rather than a single threshold, available evidence suggests that a daily AUC limit of 700 mg · h/liter is reasonable.
证据支持通过浓度-时间曲线下面积 (AUC) 来监测万古霉素的治疗药物监测，但建立 AUC 上限的数据有限，并且已发表的肾毒性阈值范围很广。本分析的目的是研究初始万古霉素 AUC 与肾毒性之间的关系。这是一项多中心、回顾性队列研究，纳入了 2014 年至 2015 年期间接受静脉万古霉素治疗的成年患者。肾毒性定义为血清肌酐升高 0.5mg/dL，且与基线相比连续测量时升高 50%。使用最大似然贝叶斯估计法来估计治疗开始后 48 小时内的万古霉素暴露情况。通过分类和回归树 (CART) 分析确定与肾毒性最相关的 AUC 和最小浓度 () 阈值。通过阳性和阴性预测值和接收者操作特征曲线评估 CART 衍生和其他候选 AUC 阈值的预测性能。使用泊松回归在调整混杂因素的情况下量化暴露阈值与肾毒性之间的关联。在纳入的 323 例患者中，AUC 0 至 48 小时（AUC）≥1218mg·h/L、AUC≥677mg·h/L、AUC≥683mg·h/L 和第 1 天 ()≥18.8mg/L 的患者肾毒性显著更高。泊松回归显示，万古霉素暴露超过这些阈值与肾毒性的风险增加 3 至 4 倍相关。AUC 对肾毒性的预测性能在每日 AUC 值为 600 至 800mg·h/L 之间达到最佳。尽管这些数据支持万古霉素相关肾毒性的 AUC 范围而不是单一阈值，但现有证据表明，每日 AUC 限值 700mg·h/L 是合理的。
