基于蒙特卡洛模拟优化万古霉素与替考拉宁治疗耐甲氧西林葡萄球菌血流感染的给药方案  

Optimization of Dosing Regimens of Vancomycin and Teicoplanin in Treatment of Methicillin-resistant Staphylococcal Blood stream Infection Based on Monte Carlo Simulation

作　　者：周义正[1,2] 黄晨 嵇金如 应超群 王培培 刘志盈 肖永红 ZHOU Yizheng;HUANG Chen;JI Jinru;YING Chaoqun;WANG Peipei;LIU Zhiying;XIAO Yonghong(Department of Clincal Laboratory, Jingzhou Central Hospital,Hubei Province, Jingzhou 434020,China;The Second Clinical Medical College,Yangtze University,Jingzhou 434020,China;Department of Respiratory Medicine,Ningbo Medical Center Lihuili Hospital,Ningbo 315000,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,College of Medicine,Zhejiang University,Hangzhou 310003,China)

机构地区：[1]湖北省荆州市中心医院检验医学部,荆州434020 [2]长江大学第二临床医学院,荆州434020 [3]宁波市医疗中心李惠利医院呼吸内科,宁波315000 [4]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医学研究中心、感染性疾病诊治协同创新中心,杭州310003

出　　处：《医药导报》2022年第7期1026-1032,共7页Herald of Medicine

基　　金：浙江省重点研发计划资助项目(2021C03068);湖北省卫生计生委联合基金项目(WJ2018H186)。

摘　　要：目的基于蒙特卡洛模拟优化万古霉素与替考拉宁治疗耐甲氧西林葡萄球菌血流感染的给药方案。方法由全国血流感染耐药监测联盟筛选来源于全国56家医院的1235株血流感染相关的耐甲氧西林葡萄球菌,所有菌株采用质谱鉴定。采用头孢西丁纸片检测耐甲氧西林葡萄球菌,采用微量肉汤稀释法检测万古霉素与替考拉宁最低抑菌浓度,具体操作和判定标准遵照临床实验室标准化协会文件。结合不同肾功能情况下万古霉素与替考拉宁在成人体内的药动学参数,应用水晶球软件进行蒙特卡洛模拟得到相应目标获得概率(PTA)与累计反应分数(CFR)。结果4种万古霉素给药方案研究显示,3种肾功能情况下,MIC≥0.5μg·mL^(-1)时,PTA达标概率较低;MIC=0.25μg·mL^(-1)时,PTA均达到100%。4种替考拉宁给药方案研究显示,3种肾功能情况下,MIC≤0.5μg·mL^(-1)时,PTA值均达到100%;MIC≥4μg·mL^(-1)时,PTA值均<90%;MIC值1~2μg·mL^(-1)时,PTA值随MIC值波动。正常肾功能状态下,4种万古霉素给药方案对菌群CFR均<90%;中度或重度肾功能不全时,给药方案1000 mg、q12h和1000 mg、q8h的CFR可能达到90%。在3种肾功能下,4种替考拉宁给药方案对金黄色葡萄球菌与溶血葡萄球菌的CRF值均<90%;部分给药方案可能对人葡萄球菌、表皮葡萄球菌和头状葡萄球菌的CRF值>90%。结论当经验性治疗耐甲氧西林葡萄球菌所致菌血症时,万古霉素1000 mg、q8h和替考拉宁600 mg、q12h是最可能达到疗效的给药方案,但需要考虑患者肾功能状态。MIC值有利于提前评估万古霉素与替考拉宁疗效,并决策联合其他抗菌药物治疗的必要性。Objective To optimize the dosage regimes of vancomycin and teicoplanin in treating methicillin-resistant st aphylococcal bloodstream infection based on Monte Carlo simulation.Methods One thousand two hundred and thirty-five strains of Staphylococci were collected from fifty-six Chinese hospitals which belong to BRICs.All strains were identified by microbial mass spectrometry.The cefoxitin discs detected Methicillin-resistant Staphylococci.The broth dilution method determined the minimal inhibitory concentrations of vancomycin and teicoplanin.The specific operation and judgment criteria followed the Clinical and Laboratory Standards Institute documents.In the pharmacokinetics of vancomycin and teicoplanin in adults with different renal functions.The CFR and PTA were simulated by Crystal Ball software.Results None of the four vancomycin dosing regimens achieved CFR for the flora in normal renal function.The CFR of 1000 mg,q12h and 1000 mg,q8h may reach 90%in moderate or severe renal insufficiency.Under all three renal functions,all four teicoplanin dosing regimens had CRF values less than 90%for Staphylococcus aureus and Staphylococcus haemolyticus;some dosing regimens may have CRF values greater than 90%for Staphylococcus hominis,Staphylococcus epidermidis,and Staphylococcus capitis.Conclusion When empiric treatment of bacteremia caused by methicillin-resistant Staphylococcus,vancomycin 1000 mg q8h and teicoplanin 600 mg q12h are the most likely dosing regimens to achieve the treatment effect,and the patient's renal function status still needs to be considered.The MIC value is helpful in evaluating the effectiveness of vancomycin and teicoplanin in advance and make a decision on the necessity of combined treatment with other antimicrobials.

关 键 词：万古霉素 替考拉宁 葡萄球菌 血流感染 肾功能不全 蒙特卡洛模拟 

分 类 号：R978.1[医药卫生—药品] R969[医药卫生—药学]