Oda Kazutaka, Hiyama Yoko, Ueda Takashi, Furusho Hirokazu, Yamada Tomoyuki, Katanoda Tomomi, Yoshikawa Hiroshi, Tomita Takashi, Ide Takeshi, Jingami Sachiko, Kusaka Yusuke, Jono Hirofumi, Saito Hideyuki
Department of Pharmacy, Kumamoto University Hospital, Kumamoto city, Kumamoto, Japan.
Department of Infection Control, Kumamoto University Hospital, Kumamoto city, Kumamoto, Japan.
Br J Clin Pharmacol. 2025 Jul;91(7):1914-1926. doi: 10.1002/bcp.70002. Epub 2025 Feb 17.
Area under the concentration-time curve (AUC)-guided dosing is recommended in vancomycin therapy. This study aims to determine the empirical dosing for achieving an AUC on the first day (AUC) and the optimal number of samplings for Bayesian estimation.
A multicentric prospective study was conducted across five hospitals. Critically ill patients were included, with rich sampling conducted on the first day and/or days 3-5 of therapy. Cumulative dose on the first day for the trapezoidal AUC > 400 μg·h/mL and the predictive performances of AUC and clearance in limited sampling were evaluated. The probability of adherence to AUC within 400-600 μg·h/mL in the guidelines-compliant or non-compliant doses were also evaluated.
The study included 27 patients and 395 samplings were performed. The mean cumulative dose (standard deviation) on the first day was higher in the group with AUC > 400 μg·h/mL at 49.3 (4.5) mg/kg compared to the group with AUC < 400 μg·h/mL at 42.1 (6.8) mg/kg (P = 0.01) for patients with creatinine clearance > 90 mL/min, respectively. The biases and variations of Bayesian posterior AUC by using only a trough concentration were improved by using two-point concentrations at trough and peak. The probability of adherence to AUC was significantly higher in the guidelines-compliant group (66.7%) than in the non-compliant group (11.1%, P < .01).
This study suggested an empirical dosage of about 50 mg/kg on the first day of vancomycin therapy and the use of two-point sampling in Bayesian estimations to enhance accuracy.
Not applicable because this is a non-intervention study.
在万古霉素治疗中推荐采用浓度-时间曲线下面积（AUC）指导给药。本研究旨在确定首日达到目标AUC的经验性给药方案以及贝叶斯估计的最佳采样次数。
在五家医院开展了一项多中心前瞻性研究。纳入危重症患者，在治疗首日和/或第3 - 5天进行密集采样。评估首日梯形AUC＞400μg·h/mL时的累积剂量，以及有限采样情况下AUC和清除率的预测性能。还评估了符合或不符合指南剂量时AUC在400 - 600μg·h/mL范围内的达标概率。
该研究纳入27例患者，共进行了395次采样。肌酐清除率＞90mL/min的患者中，首日AUC＞400μg·h/mL组的平均累积剂量（标准差）为49.3（4.5）mg/kg，高于首日AUC＜400μg·h/mL组的42.1（6.8）mg/kg（P = 0.01）。仅使用谷浓度时贝叶斯后验AUC的偏差和变异，通过同时使用谷浓度和峰浓度的两点浓度得以改善。符合指南组的AUC达标概率（66.7%）显著高于不符合指南组（11.1%，P＜0.01）。
本研究提示万古霉素治疗首日的经验性剂量约为50mg/kg，并在贝叶斯估计中采用两点采样以提高准确性。
本研究为非干预性研究，故不适用。
