中国成人万古霉素稳态谷浓度与疗效和安全性相关性的前瞻性队列研究

doi:10.5246/jcps.2020.05.032

摘要/Abstract

摘要：

本研究旨在通过大样本前瞻性队列研究, 评价万古霉素稳态谷浓度与临床疗效和安全性之间的相关性, 从而验证指南将万古霉素稳态谷浓度从5–10 mg/L提高至10–20 mg/L是否适合中国人群特征。为修订我国万古霉素临床应用指南及专家共识提供循证依据, 共纳入2017年3月至2018年11月期间符合标准的331例患者, 根据初次达到稳态谷浓度分为低浓度组(SVTC<10 mg/L), 目标浓度组(10 mg/L≤SVTC≤20 mg/L) 及高浓度组(SVTC>20 mg/L)。考察的主要结局是患者14天的临床治疗失败率和不良反应发生率, 次要结局包括28天感染复发率、细菌清除率、肾毒性等。利用SPSS25.0软件统计分析万古霉素稳态谷浓度与疗效和安全性之间的相关性。通过构建Logistic回归模型对低浓度组和目标浓度组283例患者的基线特征参数进行倾向性得分匹配(propensity score matching, PSM)发现: SVTC<10 mg/L和10 mg/L≤SVTC≤20 mg/L患者14天的临床失败率差异无统计学意义(P = 0.535)。采用Kaplan-Meier生存曲线分析表明: SVTC<10 mg/L和10mg/L≤ SVTC≤20 mg/L患者28天累积感染复发率差异无统计学意义(Log-rank P=0.514)。高浓度组患者不良反应发生率远高于低浓度组和目标浓度组(P<0.001)。与万古霉素肾毒性相关稳态谷浓度的临界值为14.55 mg/L, 其预测肾毒性发生敏感性为70%, 特异性为78%, 准确度77% (OR=0.82, 95%CI=0.72–0.83)。万古霉素稳态谷浓度不是预测临床疗效和细菌清除率的良好指标, 万古霉素稳态谷浓度是预测肾毒性发生的良好指标。

关键词: 万古霉素, 治疗药物监测, 肾毒性, 倾向性得分匹配

Abstract:

Clinical guidelines recommend a steady-state vancomycin(VCM) trough concentration (SVTC) of 10–15 mg/L for regular infections and 15–20 mg/L for severe infections. However, clinical trials have shown that increasing SVTC is not beneficial for efficacy, and instead it leads to nephrotoxicity. To verify whether increasing the SVTC results in improved clinical outcomes with sustainable adverse effects, we prospectively determined its correlation with clinical efficacy and safety. The participants included patients hospitalized with Gram-positive bacterial infections from March 2017 through October 2018. The patients were classified into group I (SVTC<10 mg/L), II (10≤SVTC≤20 mg/L), or III (SVTC>20 mg/L). Clinical, microbiological, and laboratory data were collected. Clinical outcomes between group I and IIwere matched after propensity score matching (PSM). A total of 331 patients were included in this study. Clinical failure occurred in 59 (29%) of 204 patients on day 14, with no significant differencebetween groups I and II (P = 0.535). Infection recurred at 28 d in 62 (30%) of 204 patients, and no significant difference ininfection recurrence was observed between both the groups (log-rank, P = 0.674). Except for a significant increase in the incidence of acute kidney injury in group II, no significant difference was observed between two groups for any clinical results. The incidence of adverse events in groups I and II was significantly lower than that in group III (P<0.001). SVTC had an applicable cut-off point at 14.55 mg/L. SVTC was not correlated with VCMclinical efficacy, while it was a good indicator of nephrotoxicity.

Key words: Vancomycin, Therapeutic drug monitoring, Nephrotoxicity, Propensity score matching

中图分类号:

Supporting:

吴朝晖, 林慧芬, 林玮玮, 刘亦伟, 游翔, 林翠鸿, 林荣芳, 曾大勇, 黄品芳. 中国成人万古霉素稳态谷浓度与疗效和安全性相关性的前瞻性队列研究[J]. 中国药学(英文版), 2020, 29(5): 341-354.

Chaohui Wu, Huifen Lin, Weiwei Lin, Yiwei Liu, Xiang You, Cuihong Lin, Rongfang Lin, Dayong Zeng, Pinfang Huang. A prospective cohort study on the relationship between vancomycin steady-state trough concentration and efficacy and safety in Chinese adults[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(5): 341-354.

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