目的 应用蒙特卡洛模拟评价奥马环素等6种给药方案对肺炎链球菌、金黄色葡萄球菌和大肠埃希菌感染的疗效.方法 结合药动学参数和药效学参数,以AUC/MIC为PK/PD模型进行蒙特卡洛模拟,得到6种给药方案对上述3种病原菌的达标概率(PTA)及累积反应分数(CFR).结果 奥马环素等6种给药方案对肺炎链球菌、金黄色葡萄球菌(抑菌靶值下模拟),都能达到CFR＞90％;对于金黄色葡萄球菌(杀菌靶值下模拟),仅600 mg po q24h和多剂量C组(负荷剂量450 mg poq12h,维持剂量450 mg poq24h)达到CFR＞90％;但对大肠埃希菌,所有给药方案的CFR均不达标.结论 奥马环素的说明书推荐给药方案(负荷剂量200 mg iv,维持剂量300 mg po q24h)对肺炎链球菌、金黄色葡萄球菌有较好的治疗效果;但对大肠埃希菌,6种给药方案均达不到预期疗效.
Evaluation of omadacycline dosage regimens in the treatment of three bacterial infections by PK/PD
Objective This study estimated 6 dosage regimens of omadacycline for Streptococcus pneumoniae,Staphylococcus aureus,and Escherichia coli with the utilization of Monte Carlo simulation.Methods AUC/MIC as PK/PD model was implied with,pharmacokinetic parameters and pharmacodynamic parameters,and 6 dosage regimens against Streptococcus pneumoniae,Staphylococcus aureus,and Escherichia coli were analyzed.The probabilities of target attainment(PTA)and cumulative fractions of response(CFR)of different dosage regimens against these three different pathogenic bacteria were calculated.Results All of the omadacycline dosage regimens achieved CFR values of＞90％against Streptococcus pneumoniae and Staphylococcus aureus(based on stasis target).Both 600 mg PO q24 h and multidose group C(loading dose:450 mg PO q12 h,maintenance dose:450 mg PO q24 h)achieved CFR values of＞90％against Staphylococcus aureus(based on a 1-log kill target).None of the regimens of omadacycline obtained an expected CFR value of＞90％against Escherichia coli.Conclusion The recommended regimen for omycyclin in the instructio manual(loading dose:200 mg IV;maintenance dose:300 mg PO q24 h)has good efficacy against Streptococcus pneumoniae and Staphylococcus aureus.However,none of the simulated dosage regimens were effective against Escherichia coli.
OmadacyclineMonte Carlo simulationPK/PDCumulative fractions of response
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