Zhao Jinjin, Fan Yaxin, Yang Minjie, Liang Xiaoyu, Wu Jufang, Chen Yuancheng, Guo Beining, Zhang Huifang, Wang Ruilan, Zhang Fengying, Hang Jingqing, Li Huayin, Zhang Jing
Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China.
Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of People's China, Shanghai 200040, China.
Antibiotics (Basel). 2022 Jun 22;11(7):837. doi: 10.3390/antibiotics11070837.
This study aimed to examine the risk factors of augmented renal clearance (ARC) and the association between ARC and vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices in Chinese adult patients. A prospective, observational, multicenter study was conducted, and 414 adult patients undergoing vancomycin therapeutic drug monitoring (TDM) were enrolled. Clinical and PK/PD data were compared between ARC and non-ARC groups. Independent risk factors were examined using a multivariate logistic regression analysis. The ARC and augmented renal clearance in trauma intensive care (ARCTIC) scoring systems were evaluated. Eighty-eight of the enrolled patients (88/414, 21.3%) had ARC before vancomycin therapy. Patients with ARC were more likely to have subtherapeutic vancomycin PK/PD indices, including trough concentration (p = 0.003) and 24 h area under the concentration−time curve (AUC24) to minimal inhibitory concentration (MIC) ratio (p < 0.001). Male sex (OR = 2.588), age < 50 years (OR = 2.713), overweight (OR = 2.072), receiving mechanical ventilation (OR = 1.785), enteral nutrition (OR = 2.317), neutrophil percentage (OR = 0.975), and cardiovascular diseases (OR = 0.281) were significantly associated with ARC. In conclusion, ARC is associated with subtherapeutic vancomycin trough concentration and AUC24/MIC; therefore, higher than routine doses may be needed. Risk factors and ARC risk scoring systems are valuable for early identification.
本研究旨在探讨中国成年患者中肾清除率增加(ARC)的危险因素以及ARC与万古霉素药代动力学/药效学(PK/PD)指标之间的关联。开展了一项前瞻性、观察性、多中心研究,纳入了414例接受万古霉素治疗药物监测(TDM)的成年患者。比较了ARC组和非ARC组的临床及PK/PD数据。采用多因素逻辑回归分析检查独立危险因素。对ARC和创伤重症监护中的肾清除率增加(ARCTIC)评分系统进行了评估。88例纳入患者(88/414,21.3%)在万古霉素治疗前存在ARC。ARC患者更有可能出现万古霉素PK/PD指标低于治疗水平,包括谷浓度(p = 0.003)以及24小时浓度-时间曲线下面积(AUC24)与最低抑菌浓度(MIC)之比(p < 0.001)。男性(OR = 2.588)、年龄<50岁(OR = 2.713)、超重(OR = 2.072)、接受机械通气(OR = 1.785)、肠内营养(OR = 2.317)、中性粒细胞百分比(OR = 0.975)和心血管疾病(OR = 0.281)与ARC显著相关。总之,ARC与万古霉素谷浓度及AUC24/MIC低于治疗水平相关;因此,可能需要高于常规剂量的药物。危险因素及ARC风险评分系统对早期识别很有价值。