治疗革兰氏阳性菌感染重症患者替考拉宁安全浓度范围的探讨  

Safe concentration range of teicoplanin for patients with severe gram-positive bacterial infection

作　　者：郑灵招 林小青 温悦[1] 黄本润 欧阳华[1,2] ZHENG Ling-zhao;LIN Xiao-qing;WEN Yue;HUANG Ben-run;OU-YANG Hua(Department of Pharmacy,Zhongshan Hospital Affiliated to Xiamen University,Xiamen Fujian 361004;School of Pharmacy,Fujian Medical University,Fuzhou 350000)

机构地区：[1]厦门大学附属中山医院药学部,福建厦门361004 [2]福建医科大学药学院,福州350000

出　　处：《中南药学》2023年第10期2766-2772,共7页Central South Pharmacy

摘　　要：目的研究革兰氏阳性菌感染的重症患者使用替考拉宁的血药谷浓度(Cmin)与疗效和安全性的关系,摸索替考拉宁治疗的最佳安全有效血药浓度范围。方法回顾性收集2019年1月—2020年12月使用替考拉宁治疗革兰氏阳性菌感染的重症患者的相关临床数据,通过Medcalc 18.2.1和SPSS 26.0软件绘制受试者工作特征(ROC)曲线、Kaplan-Meier曲线及分组分析比较探讨最佳安全有效浓度范围。结果收集的247例样本中,临床有效率及细菌学有效率均为65.18%,替考拉宁Cmin与临床疗效、细菌学疗效、肝毒性及肾毒性相关性显著;替考拉宁Cmin≥15 mg·L^(-1)患者有效率(临床有效率与细菌学有效率)均显著高于Cmin<15 mg·L^(-1)的患者(χ^(2)=14.69,P<0.001;χ^(2)=9.84,P=0.002),并且Cmin≥15 mg·L^(-1)的临床有效率与Cmin≥10 mg·L^(-1)比较差异有统计学意义(χ^(2)=4.71,P=0.030);当替考拉宁Cmin≥27.70 mg·L^(-1)时,患者更易发生肝毒性(AUC=0.852,P<0.001),当替考拉宁Cmin≥30.53 mg·L^(-1)时,患者更易发生肾毒性(AUC=0.749,P=0.001);<25 mg·L^(-1)组发生肝、肾毒性的风险显著低于≥25 mg·L^(-1)组(肝:χ^(2)=59.95,P<0.001;肾:χ^(2)=47.05,P<0.001),肝毒性中位发生时间为第9日,肾毒性中位发生时间为第7日。结论替考拉宁血药浓度维持在15~25 mg·L^(-1)时临床疗效好,肝肾毒性发生风险低,对使用替考拉宁革兰氏阳性菌感染重症患者临床精准用药调整具有重要参考价值。Objective To determine the relationship between the serum trough concentration(Cmin)and efficacy and safety of teicoplanin in critically ill patients with gram-positive bacterial infection,and to explore the safe and effective blood concentration range for teicoplanin treatment.Methods We retrospectively collected the clinical data related to critically ill patients with gram-positive infections treated with teicoplanin from January 2019 to December 2020.The safe and effective concentration range was determined with the subject operating characteristic(ROC)curves,Kaplan-Meier curves and group analysis by Medcalc 18.2.1 and SPSS 26.0 software.Results The clinical efficiency and bacteriological efficiency were 65.18%in the 247 samples collected,and teicoplanin Cmin was much associated with the clinical efficacy,bacteriological efficacy,hepatotoxicity and nephrotoxicity.Patients with Cmin≥15 mg·L^(-1) had significantly higher clinical efficiency and bacteriological efficiency than those with Cmin<15 mg·L^(-1)(χ^(2)=14.69,P<0.001;χ^(2)=9.84,P=0.002).The clinical effective rate of Cmin≥15 mg·L^(-1) was statistically different from Cmin≥10 mg·L^(-1)(χ^(2)=4.71,P=0.030).Patients were more likely to suffer hepatotoxicity when Cmin≥27.70 mg·L^(-1)(AUC=0.852,P<0.001)and nephrotoxicity when Cmin≥30.53 mg·L^(-1)(AUC=0.749,P=0.001).The risk of hepatotoxicity and nephrotoxicity was significantly lower in group<25 mg·L^(-1) than that in group≥25 mg·L^(-1)(liver:χ^(2)=59.95,P<0.001;kidney:χ^(2)=47.05,P<0.001),with a median time of showing hepatotoxicity on day 9 and a median time of nephrotoxicity on day 7.Conclusion Good clinical efficacy and low risk of hepatic and renal toxicity are expected Cmin levels are maintained at 15~25 mg·L^(-1),which has important reference value for the clinical precision drug adjustment of in patients with severe gram-positive bacterial infections receiving teicoplanine treatment.

关 键 词：替考拉宁 革兰氏阳性菌感染 疗效 不良反应 安全浓度范围 

分 类 号：R978.1[医药卫生—药品] R969.3[医药卫生—药学]