优化利奈唑胺、替考拉宁和达托霉素治疗葡萄球菌属血流感染给药方案的蒙特卡洛模拟研究  

Monte Carlo simulation study to optimize administration regimens of linezolid,teicoplanin and daptomycin for Staphylococcal bloodstream infections

作　　者：金丹婷[1] 喻玮[2] 嵇金如 应超群 王培培 刘志盈 茆海丰[1] 肖永红[2] Jin Danting;Yu Wei;Ji Jinru;Ying Chaoqun;Wang Peipei;Liu Zhiying;Mao Haifeng;Xiao Yonghong(Department of Clinical Laboratory,The First People′s Hospital of Lianyungang,Lianyungang 222002,China;State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,National Clinical Research Center for Infectious Diseases,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,Zhejiang University,Hangzhou 310003,China)

机构地区：[1]连云港市第一人民医院检验科,连云港222002 [2]浙江大学医学院附属第一医院传染病诊治国家重点实验室,国家感染性疾病临床研究中心,感染性疾病诊治协同创新中心,杭州310003

出　　处：《中华传染病杂志》2022年第3期137-142,共6页Chinese Journal of Infectious Diseases

基　　金：浙江省重点研发计划(2021C03068);连云港市第一人民医院青年英才基金项目(QN1813)。

摘　　要：目的通过蒙特卡洛模拟预测和评价利奈唑胺、替考拉宁和达托霉素对葡萄球菌属血流感染的抗菌效果,优化临床给药方案。方法借助全国血流感染细菌耐药监测联盟(Blood Bacterial Resistant Investigation Collaborative System,BRICS)平台收集2018年1月至2019年12月从全血标本中分离的1847株葡萄球菌属菌株。利奈唑胺和达托霉素采用肉汤稀释法进行菌株的最低抑菌浓度(minimum inhibitory concentration,MIC)测定,替考拉宁则采用琼脂稀释法测定MIC。利奈唑胺的给药方案为800 mg(1次/d)、500 mg(每12 h 1次)、600 mg(每12 h 1次)、600 mg(每8 h 1次)。替考拉宁的给药方案为400 mg(每12 h 1次)、600 mg(每12 h 1次)、800 mg(每12 h 1次)、1000 mg(每12 h 1次)。达托霉素的给药方案为4 mg·kg^(-1)·d^(-1)、6 mg·kg^(-1)·d^(-1)、8 mg·kg^(-1)·d^(-1)、10 mg·kg^(-1)·d^(-1)和12 mg·kg^(-1)·d^(-1)。通过蒙特卡洛模拟计算3种药物不同给药方案的目标获得概率(probability of target attainment,PTA)和累计反应分数(cumulative fraction of response,CFR)。CFR≥90.0%的给药方案是抗菌药物经验治疗的合理选择。结果当MIC≤0.500 mg/L时,利奈唑胺剂量为800 mg(1次/d)、500 mg(每12 h 1次)、600 mg(每12 h 1次)、600 mg(每8 h 1次)对葡萄球菌属的PTA均>90.0%;当MIC为1.000 mg/L时,利奈唑胺500 mg(每12 h 1次)、600 mg(每12 h 1次)、600 mg(每8 h 1次)对葡萄球菌属的PTA分别为92.2%、96.6%、97.6%。4种利奈唑胺给药方案对应的CFR分别为73.9%、83.7%、90.8%和95.3%。在MIC≤1.000 mg/L时,替考拉宁400 mg(每12 h 1次)、600 mg(每12 h 1次)、800 mg(每12 h 1次)、1000 mg(每12 h 1次)对葡萄球菌属的PTA均为100.0%;当MIC为2.000 mg/L时,替考拉宁800 mg(每12 h 1次)、1000 mg(每12 h 1次)对葡萄球菌属的PTA均为100.0%。4种替考拉宁给药方案对应的CFR分别为90.8%、92.8%、93.5%和94.6%。在MIC≤0.500 mg/L时,达托霉素4 mg·kg^(-1)·d^(-1)、6 mg·kg^(-1)·d^(-1)、8 mg·kg^Objective To predict and evaluate the antibacterial efficacy of linezolid,teicoplanin and daptomycin against Staphylococci bloodstream infections with Monte Carlo simulation,and to optimize the clinical administration program.Methods A total of 1847 Staphylococci strains isolated from blood samples between January 2018 to December 2019 were collected with the help of the Blood Bacterial Resistant Investigation Collaborative System(BRICS).Minimum inhibitory concentrations(MIC)of linezolid and daptomycin were detected by broth dilution method,while MIC of teicoplanin were detected by agar dilution method.The dosage regimens of linezolid were 800 mg once daily,500 mg once every 12 hours,600 mg once every 12 hours and 600 mg once every eight hours.The dosage regimens of teicoplanin were 400 mg once every 12 hours,600 mg once every 12 hours,800 mg once every 12 hours,and 1000 mg once every 12 hours.The dosage regimens of daptomycin were 4 mg·kg^(-1)·d^(-1),6 mg·kg^(-1)·d^(-1),8 mg·kg^(-1)·d^(-1),10 mg·kg^(-1)·d^(-1)and 12 mg·kg^(-1)·d^(-1).The probability of target attainment(PTA)and cumulative fraction of response(CFR)of three different dosage regimens were calculated by Monte Carlo simulation.A dosage regimen with CFR≥90.0%was a reasonable choice for empirical antimicrobial therapy.Results PTA of linezolid against Staphylococci when MIC≤0.500 mg/L at four dosage regimens(800 mg once daily,500 mg once every 12 hours,600 mg once every 12 hours and 600 mg once every eight hours)were all over 90.0%.When MIC was 1.000 mg/L,the PTA of linezolid against Staphylococci under the dosages of 500 mg once every 12 hours,600 mg once every 12 hours and 600 mg once every eight hours were 92.2%,96.6%and 97.6%,respectively.The CFR of the four dosage regimens of linezolid were 73.9%,83.7%,90.8%and 95.3%,respectively.When MIC≤1.000 mg/L,PTA of teicoplanin against Staphylococci were all 100.0%at four dosage regimens(400 mg once every 12 hours,600 mg once every 12 hours,800 mg once every 12 hours and 1000 mg once every 12

关 键 词：葡萄球菌属 替考拉宁 达托霉素 利奈唑胺 血流感染 蒙特卡洛模拟 

分 类 号：R5I5[医药卫生—内科学]