中性粒细胞缺乏伴发热患者应用替考拉宁抗感染的剂量监测及优化

The drug monitoring and dosage optimization of teicoplanin in treatment of fever neutropenia

目的探讨替考拉宁在中性粒细胞缺乏(粒缺)伴发热的血液肿瘤患者中的应用现状、血浆谷浓度(Cmin)达标情况及影响浓度达标的因素,并从药代动力学/药效学(PK/PD)的角度评估当前替考拉宁剂量方案。方法监测111例经验性使用替考拉宁抗革兰阳性菌感染的血液肿瘤患者197份血浆谷浓度,根据前3 d的平均给药剂量分为2组,组1(MID=533.33 mg/d组,n=60)与组2(MID<533.33 mg/d组,n=51),比较2组患者用药3 d内及3 d后的Cmin和达标率,以二元Logistic回归分析影响Cmin的因素,蒙特卡洛模拟常用剂量替考拉宁的目标获得概率。结果前3 d内,组1的Cmin高于组2[(10.46±5.27)mg/L vs.(6.23±3.57)mg/L,P=0.019],组1的达标率也高于组2(48.0%vs.10.0%,P=0.002),组1的Cmin在10~15 mg/L的范围内占比高于组2(28.0%vs.6.7%,P=0.033);用药3 d后,2组Cmin均低于10 mg/L,Cmin及达标率差异均无统计学意义(P>0.05)。年龄(P=0.005)和肌酐清除率(P=0.022)是影响患者Cmin达标的危险因素。当MIC>1 mg/L时,需要给予至少600 mg 1次/d,的剂量方案。结论需提高负荷剂量的使用率,也应结合病原菌的MIC值优化用药剂量,同时积极进行药物浓度监测以提高浓度达标率。

Objective To investigate the application current status of teicoplanin in treatment of hematological malignancy with fever,target probability of plasma trough concentration(Cmin)and the factors affecting Cmin,and to assess the current dose regimen of teicoplanin from the point of view of pharmacokinetics/pharmacodynamics(PK/PD).Methods A total of 197 plasma specimens from 111 patients with hematological neoplasms who were infected by Gram-positive bacteria were enrolled in the study.The levels of Cmin were monitored,which were divided into two groups according to the mean initial dose over the first 3 days(MID):group 1(MID=533.33mg/d,n=60)and group 2(MID<533.33mg/d,n=51).The levels of Cmin and compliance rate within three days and at three days after treatment were observed and compared between the two groups.Moreover the factors affecting Cmin were analyzed by binary logistic regression analysis.Monte Carlo simulating the probability of target attainment for the usual dosage of teicoplanin.Results In the first three days,the Cmin of group 1 was significantly higher than that in group 2[(10.46±5.27)mg/L vs(6.23±3.57)mg/L,P<0.01],and the compliance rate in group 1 was significantly higher than that in group 2(48.0%vs 10.0%,P<0.01).The proportion of Cmin in the range of 10~15mg/L in group 1 was significantly higher than that in group 2(28.0%vs 6.7%,P<0.05).After 3-day treatment,the Cmin was lower than 10mg/L in both groups,and there were no significant differences in Cmin and compliance rates between the two groups(P>0.05).The patient’s age and creatinine clearance rate were the risk factors affecting compliance rate.A dosage regimen of at least 600 mg qd was required when the MIC>1mg/L.Conclusion It is necessary to increase the use rate of the loading dose,and the medication dosage should be optimized by combining the MIC value of the pathogen,at the same time,to actively monitor the teicoplanin concentration so as to improve the concentration compliance rate.