Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Department of Clinical Pharmacotherapy, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
J Glob Antimicrob Resist. 2021 Mar;24:83-87. doi: 10.1016/j.jgar.2020.11.014. Epub 2020 Dec 5.
Pharmacokinetic/pharmacodynamic (PK/PD) analysis using murine infection models is a well-established methodology for optimising antimicrobial therapy. Therefore, we investigated the PK/PD indices of teicoplanin againstStaphylococcus aureus using a murine thigh infection model.
Mice were rendered neutropenic by administration of a two-step dosing of cyclophosphamide. Then, isolates of methicillin-susceptibleS. aureus (MSSA) or methicillin-resistant S. aureus (MRSA) were inoculated into the thighs of neutropenic mice. PK/PD analyses were performed by non-linear least-squared regression using the MULTI program.
Target values offC/MIC (r = 0.94) of teicoplanin for static effect and 1 log kill against MSSA were 4.44 and 15.44, respectively. Target values of fAUC/MIC (r = 0.92) of teicoplanin for static effect and 1 log kill against MSSA were 30.4 and 70.56, respectively. Target values of fC/MIC (r = 0.91) of teicoplanin for static effect and 1 log kill against MRSA were 8.92 and 14.16, respectively. Target values of fAUC/MIC (r = 0.92) of teicoplanin for static effect and 1 log kill against MRSA were 54.8 and 76.4, respectively.
These results suggest thatfC/MIC and fAUC/MIC are useful PK/PD indices of teicoplanin against MSSA and MRSA.
使用小鼠感染模型进行药代动力学/药效学（PK/PD）分析是优化抗菌治疗的一种成熟方法。因此，我们使用小鼠大腿感染模型研究了替考拉宁对金黄色葡萄球菌的 PK/PD 指标。
通过两步给予环磷酰胺使小鼠中性粒细胞减少。然后，将耐甲氧西林金黄色葡萄球菌（MSSA）或耐甲氧西林金黄色葡萄球菌（MRSA）分离株接种到中性粒细胞减少小鼠的大腿中。使用 MULTI 程序通过非线性最小二乘回归进行 PK/PD 分析。
替考拉宁针对 MSSA 的静态效果和 1 对数杀灭的 fC/MIC 目标值分别为 4.44 和 15.44。替考拉宁针对 MSSA 的静态效果和 1 对数杀灭的 fAUC/MIC 目标值分别为 30.4 和 70.56。替考拉宁针对 MRSA 的静态效果和 1 对数杀灭的 fC/MIC 目标值分别为 8.92 和 14.16。替考拉宁针对 MRSA 的静态效果和 1 对数杀灭的 fAUC/MIC 目标值分别为 54.8 和 76.4。
这些结果表明，fC/MIC 和 fAUC/MIC 是替考拉宁针对 MSSA 和 MRSA 的有用 PK/PD 指标。
