蒙特卡洛模拟评价万古霉素治疗金黄色葡萄球菌和表皮葡萄球菌引起血流感染的给药方案  

Monte Carlo simulation to evaluate vancomycin dosing regimens in the treatment of bloodstream infection caused by Staphylococcus aureus and Staphylococcus epidermidis

作　　者：金丹婷 杨晋 茆海丰 喻玮[2] 嵇金如 应超群 刘志盈 邹秀珍 肖永红[2] Jin Danting;Yang Jin;Mao Haifeng;Yu Wei;Ji Jinru;Ying Chaoqun;Liu Zhiying;Zou Xiuzhen;Xiao Yonghong(The First Affiliated Hospital of Kangda College,Nanjing Medical University The First People's Hospital of Lianyungang,Lianyungang 222002;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)

机构地区：[1]南京医科大学康达学院第一附属医院,连云港市第一人民医院检验科,江苏省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：《中国抗生素杂志》2023年第11期1295-1299,共5页Chinese Journal of Antibiotics

基　　金：浙江省重点研发计划(No.2021C03068);连云港市第一人民医院青年英才基金项目(No.QN1813)。

摘　　要：目的 利用蒙特卡洛模拟评价万古霉素治疗金黄色葡萄球菌和表皮葡萄球菌引起血流感染的合理性。方法 由全国血流感染细菌耐药监测联盟(BRICS)收集全血标本中分离的1438株金黄色葡萄球菌和409株表皮葡萄球菌,采用微量肉汤稀释法对分离的菌株进行最低抑菌浓度(minimum inhibitoryconcentration,MIC)的测定。万古霉素4种给药方案分别为500mg q6 h、1000 mg q12 h、1500 mg q12 h和2000 mg q12 h。通过蒙特卡洛模拟10000例次后,获得4种给药方案的fAUC/MIC达标概率(probability of target attainment,PTA)和累计反应分数(cumulative fraction of response,CFR)。CFR≥90%时的给药方案是经验性用药的最佳选择。结果 当对葡萄球菌MIC≤0.5 mg/L时,万古霉素4种给药方案fAUC/MIC均可达到满意的抗菌活性(PTA=100%),当MIC=1 mg/L时,1500 mg q12 h和2000 mg q12 h两种给药方案可达到目标PTA。万古霉素给药剂量500 mg q6 h、1000 mg q12 h、1500 mg q12 h、2000 mg q12 h对金黄色葡萄球菌的fAUC/MIC CFR分别为83%、83%、87%和98%;对应表皮葡萄球菌的CFR分别为53%、53%、59%和92%。结论 万古霉素用于因金黄色葡萄球菌和表皮葡萄球菌引起的血流感染时,应根据MIC值的不同而选择不同的给药剂量进行治疗,经验性选择万古霉素进行抗感染治疗时,给药剂量需达到2000 mg q12 h方能达到较好的抗菌效果。Objective To evaluate the appropriateness of vancomycin regimens in the treatment of bloodstream infection caused by Staphylococcus aureus and Staphylococcus epidermidis by Monte Carlo simulation(MCS).Method 1,438 strains of S.aureus and 409 strains of S.epidermidis isolated from blood samples were collected in the Blood Bacterial Resistant Investigation Collaborative System(BRICS)were examined for the minimum inhibitory concentration(MIC)of vancomycin with microbroth dilution method.The four regimens of vancomycin(500 mg q6 h,1000 mg q12 h,1500 mg q12 h and 2000 mg q12 h)were evaluated with MCS of 10,000 simulations,the probability of target attainment(PTA)and cumulative fraction of response(CFR)of fAUC/MIC of the regimens were obtained.CFR>90%is the best choice for empiric administration.Results All the four vancomycin regimes could achieve satisfactory antibacterial PK/PD target(PTA=100%)when MIC≤0.5 mg/L,and 1500 mg q12 h and 2000 mg q12 h could achieve satisfactory targets when MIC=1 mg/L.The CFR against S.aureus after 500 mg q6 h,1000 mg q12 h,1500 mg q12 h and 2000 mg q12 h administration were 83%,83%,87%and 98%,respectively;The CFR against S.epidermidis were 53%,53%,59%and 92%,respectively.Conclusion Treatment of bloodstream infections caused by S.aureus and S.epidermidis with vancomycin should be used in regimen referring to different MIC.Empiric therapy with vancomycin should be in the regimen of 2000 mg q12 h.

关 键 词：蒙特卡洛模拟 万古霉素 累计反应分数 

分 类 号：R978.1[医药卫生—药品]