Abstract：
Omadacycline is an FDA-approved agent for community-acquired bacterial pneumonia (CABP). The purpose of this study is to evaluate the effectiveness of omadacycline for treating CABP patients infected with Staphylococcus aureus, including Methicillin-Resistant Staphylococcus aureus (MRSA) and Methicillin-Susceptible Staphylococcus aureus (MSSA), using pharmacokinetic/pharmacodynamic (PK/PD) analysis. Monte Carlo simulations (MCSs) were performed by utilizing omadacycline pharmacokinetic (PK) parameters, minimum inhibitory concentration (MIC) data, and in vivo PK/PD targets to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) values for different dose regimens against MRSA and MSSA in CABP patients. A dosage regimen with a PTA or CFR expectation value greater than 90% was considered optimal. For all recommended dose regimens, PTA values for MRSA MIC ≤1 and MSSA MIC ≤4 on days 1, 4, and 7 were greater than 90%. Based on the MIC distribution of Staphylococcus aureus, all dose regimens had CFR values greater than 90% for both MRSA and MSSA. CFR values for different bacterial strains were still greater than 90% within the range of PK/PD target values less than 40, although they gradually decreased with increasing PK/PD target values. PK/PD modeling demonstrated that all recommended dose regimens of omadacycline are highly effective against CABP patients infected with MRSA and MSSA. The study provides theoretical support for the efficacy of omadacycline in different dose regimens.
摘要：
Omadacycline是FDA批准的用于社区获得性细菌性肺炎（CABP）的药物。本研究的目的是评估omadacycline治疗感染金黄色葡萄球菌的CABP患者的有效性。包括耐甲氧西林金黄色葡萄球菌（MRSA）和耐甲氧西林金黄色葡萄球菌（MSSA），使用药代动力学/药效学（PK/PD）分析。蒙特卡罗模拟（MCS）通过利用omadacycline药代动力学（PK）参数，最小抑制浓度(MIC)数据，和体内PK/PD目标，以计算CABP患者针对MRSA和MSSA的不同剂量方案的目标达标率（PTA）和累积反应分数（CFR）值。PTA或CFR期望值大于90%的给药方案被认为是最佳的。对于所有推荐的剂量方案，第1、4和7天MRSAMIC≤1和MSSAMIC≤4的PTA值大于90%。基于金黄色葡萄球菌的MIC分布,所有剂量方案的MRSA和MSSA的CFR值均大于90%.在PK/PD目标值小于40的范围内,不同细菌菌株的CFR值仍大于90%,尽管它们随着PK/PD目标值的增加而逐渐降低。PK/PD模型表明，所有推荐剂量的omadacycline方案对感染MRSA和MSSA的CABP患者均高度有效。该研究为奥马环素在不同剂量方案中的疗效提供了理论支持。
