Pharmacodynamics of SMP-601 (PTZ601) against Vancomycin-Resistant Enterococcus faecium and Methicillin-Resistant Staphylococcus aureus in Neutropenic Murine Thigh Infection Models
Pharmacodynamics of SMP-601 (PTZ601) against Vancomycin-Resistant Enterococcus faecium and Methicillin-Resistant Staphylococcus aureus in Neutropenic Murine Thigh Infection Models
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DOI：
10.1128/aac.00972-08
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发表时间：
2009-08-01
影响因子：
4.9
通讯作者：
Ueda, Yutaka
中科院分区：
文献类型：
--
作者：
Eguchi, Ken;Kanazawa, Katsunori;Ueda, Yutaka
SMP601(又称PTZ601、PZ-601或SM-216601)是一种新型的肠外碳青霉烯类抗生素，对多重耐药的革兰氏阳性病原菌具有很强的抗菌活性，包括耐万古霉素的屎肠球菌和耐甲氧西林的金黄色葡萄球菌。在中性粒细胞减少的小鼠大腿感染模型上，研究了SMP-601对Vref和MRSA的药效学。SMP-601游离浓度超过MIC的给药间隔百分比(f%T&gT；MIC)是与药效关系最密切的药代动力学-药效学参数，两株Vref的R2值为0.81~0.84，两株MRSA的R2值为0.92~0.93，0~24 h浓度-时间曲线下面积的R2值除以MIC为0.12~0.89，峰值值除以MIC的R2值为0~0.22。对两株Vref的静止性或杀伤力所需的f%T>；MIC(9%至19%)明显低于对两株MRSA(23%至37%)。这些结果表明，SMP-601对Vref和MRSA的体内疗效具有时间依赖性，与MRSA感染相比，SMP-601在较低暴露条件下对Vref感染有足够的治疗效果。
SMP-601 (also known as PTZ601, PZ-601, or SM-216601) is a novel parenteral carbapenem with potent activity against multidrug-resistant gram-positive pathogens, including vancomycin-resistant Enterococcus faecium (VREF) and methicillin-resistant Staphylococcus aureus (MRSA). The pharmacodynamics of SMP-601 against VREF and MRSA were investigated in neutropenic murine thigh infection models. The percentage of the dosing interval that the unbound SMP-601 concentration exceeded the MIC (f%T>MIC) was the pharmacokinetic-pharmacodynamic parameter that correlated most closely with efficacy with R-2 values of 0.81 to 0.84 for two strains of VREF and 0.92 to 0.93 for two strains of MRSA, whereas the R-2 values for the area under the concentration-time curve from 0 to 24 h divided by the MIC were 0.12 to 0.89, and the R-2 values for the peak level divided by the MIC were 0 to 0.22. The f%T>MIC levels required for static or killing efficacy against two strains of VREF ( 9 to 19%) apparently were lower than those against two strains of MRSA (23 to 37%). These results suggested that SMP-601 showed time-dependent in vivo efficacy against VREF and MRSA, and SMP-601 had a sufficient therapeutic effect against VREF infections at lower exposure conditions compared to those for with MRSA infections.