Department of Clinical Pharmaceutics, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8602, Japan.
Department of Pharmacy, Nagoya City University Hospital, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8602, Japan.
J Antimicrob Chemother. 2024 Oct 1;79(10):2518-2527. doi: 10.1093/jac/dkae249.
Area under the concentration-time curve (AUC)-guided dosing of vancomycin was introduced in a clinical setting; however, the target range of non-steady-state AUCs, such as Day 1 AUC and Day 2 AUC, remains controversial. Therefore, we sought to determine pharmacokinetic parameter thresholds and identify independent risk factors associated with acute kidney injury (AKI) to establish a safe initial dosing design for vancomycin administration.
A single-centre, retrospective, cohort study of hospitalized patients treated with vancomycin was conducted to determine the threshold of both non-steady-state AUCs (Day 1 and 2 AUCs) and trough levels at the first blood sampling point (therapeutic drug monitoring, TDM). In addition, independent risk factors associated with AKI were evaluated using univariate and multivariate logistic regression analyses.
The thresholds for predicting AKI were estimated as 456.6 mg·h/L for AUC0-24h, 554.8 mg·h/L for AUC24-48h, 1080.8 mg·h/L for AUC0-48h and 14.0 μg/mL for measured trough levels, respectively. In a multivariate analysis, Day 2 AUC ≥ 554.8 mg·h/L [adjusted odds ratio (OR), 57.16; 95% confidence interval (CI), 11.95-504.05], piperacillin/tazobactam (adjusted OR, 15.84; 95% CI, 2.73-127.70) and diuretics (adjusted OR, 4.72; 95% CI, 1.13-21.01) were identified as risk factors for AKI.
We identified thresholds for both AUCs in the non-steady-state and trough levels at the first TDM. Our results highlight the importance of monitoring not only the AUC but also trough levels during vancomycin treatment to reduce the likelihood of AKI.
万古霉素的浓度-时间曲线下面积（AUC）指导给药已在临床环境中引入；然而，非稳态 AUC（如第 1 天 AUC 和第 2 天 AUC）的目标范围仍存在争议。因此，我们旨在确定药代动力学参数阈值，并确定与急性肾损伤（AKI）相关的独立危险因素，以建立万古霉素给药的安全初始剂量设计。
对接受万古霉素治疗的住院患者进行了一项单中心、回顾性队列研究，以确定非稳态 AUC（第 1 天和第 2 天 AUC）和首次采血点（治疗药物监测，TDM）时的谷浓度的阈值。此外，使用单变量和多变量逻辑回归分析评估与 AKI 相关的独立危险因素。
预测 AKI 的阈值估计为 AUC0-24h 为 456.6 mg·h/L，AUC24-48h 为 554.8 mg·h/L，AUC0-48h 为 1080.8 mg·h/L，实测谷浓度为 14.0 μg/mL。在多变量分析中，第 2 天 AUC≥554.8 mg·h/L[调整后的优势比（OR），57.16；95%置信区间（CI），11.95-504.05]、哌拉西林/他唑巴坦（调整后的 OR，15.84；95% CI，2.73-127.70）和利尿剂（调整后的 OR，4.72；95% CI，1.13-21.01）被确定为 AKI 的危险因素。
我们确定了非稳态时 AUC 和首次 TDM 时谷浓度的阈值。我们的结果强调了在万古霉素治疗期间不仅要监测 AUC，还要监测谷浓度以降低 AKI 发生的可能性。
