Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.
Yonsei Med J. 2011 Jul;52(4):616-23. doi: 10.3349/ymj.2011.52.4.616.
The present study was conducted to determine and compare the target attainment rate (TAR) between microorganism-nonspecific (C(trough)) and microorganism- specific (AUC24/MIC) targets over two weeks of teicoplanin administration according to several dose regimens for the treatment of Staphylococcus aureus in Korean patients with neutropenic fever.
One thousand virtual concentrations were obtained for each dose using the population pharmacokinetic parameters of teicoplanin adopted from a published study. Simulation of 1,000 virtual MICs was performed using the MICs of 78 clinical isolates of S. aureus collected from a hospital in Korea. Thereafter, these simulated MICs were randomly allocated to 1,000 virtual patients in whom the TARs for AUC24/MIC>125 [or 345] and C(trough)>10 [or 20] mg/L were determined. The relationship of the maintenance dose with the steady-state TAR was predicted with respect to the AUC24/MIC>125 [or 345] using logistic analysis.
The standard dose regimen of teicoplanin showed TARs of about 70% [or 33%] and 70% [or 20%] at steady-state in cases with AUC24/MIC>125 [or 345] and C(trough)>10 [or 20] mg/L, respectively.
The current standard dose regimen was predicted to be insufficient to adequately treat S. aureus in Korean patients with neutropenic fever. To assure at least an 80% TAR in this population, dose adjustment of teicoplanin should be considered.
本研究旨在确定并比较不同剂量方案下替考拉宁治疗中性粒细胞减少性发热韩国患者金黄色葡萄球菌时,两周内微生物非特异性(C(谷))和微生物特异性(AUC24/MIC)目标的达标率(TAR)。
使用从已发表研究中采用的替考拉宁群体药代动力学参数,为每个剂量获得 1000 个虚拟浓度。使用从韩国一家医院收集的 78 株金黄色葡萄球菌临床分离株的 MIC 模拟 1000 个虚拟 MIC。此后,这些模拟的 MIC 被随机分配给 1000 个虚拟患者,确定 AUC24/MIC>125 [或 345] 和 C(谷)>10 [或 20] mg/L 的 TAR。使用逻辑分析预测维持剂量与 AUC24/MIC>125 [或 345] 稳态 TAR 的关系。
替考拉宁的标准剂量方案在 AUC24/MIC>125 [或 345] 和 C(谷)>10 [或 20] mg/L 时,稳态时的 TAR 分别约为 70%[或 33%]和 70%[或 20%]。
目前的标准剂量方案预计不足以充分治疗韩国中性粒细胞减少性发热患者的金黄色葡萄球菌。为了确保该人群中至少 80%的 TAR,应考虑调整替考拉宁的剂量。