使用体外模型比较头孢比普与万古霉素对耐甲氧西林金黄色葡萄球菌（MRSA）、万古霉素中介金黄色葡萄球菌（VISA）和耐万古霉素金黄色葡萄球菌（VRSA）的药效学活性。
Pharmacodynamic activity of ceftobiprole compared with vancomycin versus methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA) using an in vitro model.
作者信息
Zhanel George G, Voth Dylan, Nichol Kim, Karlowsky James A, Noreddin Ayman M, Hoban Daryl J
机构信息
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
出版信息
J Antimicrob Chemother. 2009 Aug;64(2):364-9. doi: 10.1093/jac/dkp176. Epub 2009 May 19.
BACKGROUND
This study compared the pharmacodynamics of ceftobiprole and vancomycin against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA) using an in vitro model.
METHODS
Two methicillin-susceptible S. aureus (MSSA), two community-associated (CA)-MRSA, one healthcare-associated (HA)-MRSA, three VISA and two VRSA were studied. The pharmacodynamic model was inoculated with a concentration of 1 x 10(6) cfu/mL and ceftobiprole dosed every 8 h (at 0, 8 and 16 h) to simulate the fC(max) and t(1/2) obtained after 500 mg intravenous (iv) every 8 h dosing (fC(max,) 30 mg/L; t(1/2,) 3.5 h). Vancomycin was dosed every 12 h (at 0 and 12 h) to simulate fC(max) and t(1/2) obtained after 1 g iv every 12 h dosing (fC(max), 20 mg/L; t(1/2), 8 h). Samples were collected over 24 h to assess viable growth.
RESULTS
Ceftobiprole T > MIC of > or =100% (ceftobiprole MICs, < or =2 mg/L) was bactericidal (> or =3 log(10) killing) against MSSA, CA-MRSA, HA-MRSA, VISA and VRSA at 16 and 24 h. Vancomycin fAUC(24)/MIC of 340 (vancomycin MIC, 1 mg/L for MSSA and MRSA) resulted in a 1.8-2.6 log(10) reduction in colony count at 24 h. Vancomycin fAUC(24)/MIC of 85-170 (vancomycin MIC, 2-4 mg/L for VISA) resulted in a 0.4-0.7 log(10) reduction at 24 h. Vancomycin fAUC(24)/MIC of 5.3 (vancomycin MIC, 64 mg/L for VRSA) resulted in a limited effect.
CONCLUSIONS
Ceftobiprole T > MIC of > or =100% (ceftobiprole MICs, < or =2 mg/L) was bactericidal (> or =3 log(10) killing) against MSSA, CA-MRSA, HA-MRSA, VISA and VRSA at 16 and 24 h. Vancomycin was bacteriostatic against MSSA, MRSA and VISA, while demonstrating no activity against VRSA.
背景
本研究使用体外模型比较了头孢比普和万古霉素对耐甲氧西林金黄色葡萄球菌（MRSA）、万古霉素中介金黄色葡萄球菌（VISA）和万古霉素耐药金黄色葡萄球菌（VRSA）的药效学。
方法
研究了两株甲氧西林敏感金黄色葡萄球菌（MSSA）、两株社区获得性（CA）-MRSA、一株医院获得性（HA）-MRSA、三株VISA和两株VRSA。将药效学模型接种浓度为1×10⁶ cfu/mL的菌液，每8小时（0、8和16小时）给予头孢比普，以模拟每8小时静脉注射（iv）500 mg后获得的fC(max)和t(1/2)（fC(max)，30 mg/L；t(1/2)，3.5小时）。万古霉素每12小时（0和12小时）给药一次，以模拟每12小时静脉注射1 g后获得的fC(max)和t(1/2)（fC(max)，20 mg/L；t(1/2)，8小时）。在24小时内收集样本以评估活菌生长情况。
结果
头孢比普T>MIC≥100%（头孢比普MIC≤2 mg/L）在16和24小时对MSSA、CA-MRSA、HA-MRSA、VISA和VRSA具有杀菌作用（杀菌率≥3 log₁₀）。万古霉素fAUC(24)/MIC为340（万古霉素对MSSA和MRSA的MIC为1 mg/L）时，在24小时菌落计数减少1.8 - 2.6 log₁₀。万古霉素fAUC(24)/MIC为85 - 170（万古霉素对VISA的MIC为2 - 4 mg/L）时，在24小时菌落计数减少0.4 - 0.7 log₁₀。万古霉素fAUC(24)/MIC为5.3（万古霉素对VRSA的MIC为64 mg/L）时，效果有限。
结论
头孢比普T>MIC≥100%（头孢比普MIC≤2 mg/L）在16和24小时对MSSA、CA-MRSA、HA-MRSA、VISA和VRSA具有杀菌作用（杀菌率≥3 log₁₀）。万古霉素对MSSA、MRSA和VISA具有抑菌作用，而对VRSA无活性。
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