替加环素致低纤维蛋白原血症与血药浓度的相关性

Research on Correlation Between Tigecycline-induced Hypofibrinogenemia and Its BloodConcentration

目的评估替加环素致低纤维蛋白原血症是否与浓度有相关性,并确定造成该不良反应发生的浓度阈值。方法回顾性分析2019年4月—2021年4月使用替加环素的患者,记录其用药后血药浓度监测结果和用药前后纤维蛋白原值及其他临床指标,按设定的标准将患者分为不良反应(ADR)组49例,对照组74例。分析两组患者替加环素的血药浓度值差异,通过受试者工作特征曲线(ROC)获得发生ADR的浓度折点。结果ADR组和对照组年龄、性别、替加环素剂量、疗程等临床特征均差异无统计学意义;替加环素谷浓度(C_(min))、峰浓度(C_(max))和24 h浓度-时间曲线下面积(AUC_(0-24 h))均差异有统计学意义(均P<0.001)。通过ROC曲线得到替加环素导致低纤维蛋白原血症的折点为C_(min)=0.775μg·mL^(-1),AUC_(0-24 h)=28.38μg·h·mL^(-1)。结论替加环素血药浓度与导致低纤维蛋白原血症有关。临床在应用替加环素治疗重症感染时,一方面要考虑疗效,另一方面也不能忽视替加环素可能导致的不良反应,有必要定期进行血药浓度监测。

Objective To determine the existence of correlation between tigecycline-induced hypofibrinogenemia and concentration,and to define thresholds of toxicity.Methods Patients received tigecycline from April 2019 to April 2021 were retrospectively analyzed,and the concentration of tigecycline,fibrinogen(FIB)values and other clinical indicators were recorded before and after treatment,and the patients were classified into adverse drug reaction(ADR)group(n=49)and control group(n=74)according to the criteria.The difference in tigecycline concentration between the two groups was analyzed and the cut-off of ADR was obtained by ROC curve.Results There was no statistical difference in age,gender,dose,course of treatment,and other clinical characteristics between ADR group and control group.There were significant differences in tigecycline trough concentration(C_(min)),peak concentration(C_(max))and 24 h AUC(AUC_(0-24 h)),all P<0.001.According to ROC curve,the cut-off of tigecycline-induced hypofibrinogenemia was C_(min)=0.775μg·mL^(-1)and AUC_(0-24 h)=28.38μg·h·mL^(-1).Conclusion This study revealed the correlation between tigecycline-induced hypofibrinogenemia and concentration.When clinical using of tigecycline in the treatment of severe infection we should not just consider the effect but also should pay attention to the adverse reactions caused by tigecycline.It is necessary to monitor the blood drug concentration regularly.