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1 847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)、1 000 mg(每12 h 1次)。达托霉素的给药方案为4 mg·kgn －1·dn －1、6 mg·kgn －1·dn －1、8 mg·kgn －1·dn －1、10 mg·kgn －1·dn －1和12 mg·kgn －1·dn －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。n 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)、1 000 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)、1 000 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·kgn －1·dn －1、6 mg·kgn －1·dn －1、8 mg·kgn －1·dn －1、10 mg·kgn －1·dn －1、12 mg·kgn －1·dn －1对葡萄球菌属的PTA均>90.0%；当MIC为1.000 mg/L时，达托霉素8 mg·kgn －1·dn －1、10 mg·kgn －1·dn －1、12 mg·kgn －1·dn －1对葡萄球菌属的PTA分别为96.9%、100.0%和100.0%。5种达托霉素给药方案对葡萄球菌属的CFR分别为97.4%、99.2%、99.9%、100.0%和100.0%。n 结论:针对葡萄球菌属引起的血流感染，利奈唑胺600 mg(每12 h 1次)、替考拉宁400 mg(每12 h 1次)、达托霉素4 mg·kgn －1·dn －1的给药方案可达到有效的抗菌效果。n “,”Objective:To predict and evaluate the antibacterial efficacy of linezolid, teicoplanin and daptomycin against n Staphylococci bloodstream infections with Monte Carlo simulation, and to optimize the clinical administration program.n Methods:A total of 1 847 n 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 1 000 mg once every 12 hours. The dosage regimens of daptomycin were 4 mg·kgn -1·dn -1, 6 mg·kgn -1·dn -1, 8 mg·kgn -1·dn -1, 10 mg·kgn -1·dn -1and 12 mg·kgn -1·dn -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.n Results:PTA of linezolid against n 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 n 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 n 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 1 000 mg once every 12 hours). When MIC was 2.000 mg/L, the PTA of teicoplanin (800 mg once every 12 hours and 1 000 mg once every 12 hours) against n Staphylococci were both 100.0%. The CFR of the four dosage regimens of teicoplanin were 90.8%, 92.8%, 93.5% and 94.6%, respectively. When MIC≤0.500 mg/L, PTA of daptomycin against n Staphylococci under the five dosages of 4 mg·kgn -1·dn -1, 6 mg·kgn -1·dn -1, 8 mg·kgn -1·dn -1, 10 mg·kgn -1·dn -1 and 12 mg·kgn -1·dn -1 were all over 90.0%. When MIC was 1.000 mg/L, the PTA of daptomycin against n Staphylococci under the three dosages of 8 mg·kgn -1·dn -1, 10 mg·kgn -1·dn -1 and 12 mg·kgn -1·dn -1were 96.9%, 100.0% and 100.0%, respectively. The CFR of the five dosage regimens of daptomycin against n Staphylococci were 97.4%, 99.2%, 99.9%, 100.0% and 100.0%, respectively.n Conclusions:Linezolid (600 mg once every 12 hours), teicoplanin (400 mg once every 12 hours) and daptomycin (4 mg·kgn -1·dn -1) can achieve satisfactory antibacterial activity for n Staphylococci bloodstream infections.n