抗革兰阳性菌药物的研究进展肖永红教授课件.pptVIP

* Dr.Xiao * 甘酰胺环素——替加环素 增加对核糖体位点亲和力,避免保护性耐药机制(tetM,tetO)作用. 位障作用,避免成为主动外排机制(tetB,tetK)底物 * Dr.Xiao * 超广谱抗菌药物；对30S亚基变异、主动外派耐药菌有抗菌作用； 对革兰阳性、阴性菌、非发酵菌、厌氧菌等均具有抗菌活性，但奇异变形杆菌、铜绿假单胞菌对其耐药； 时间依赖性抗菌药物，有较长PAE, PK/PD参数为AUC/MIC(10以上)。 替加环素(PD) * Dr.Xiao * 替加环素PD ICAAC 2004, Tegacil Posters * Dr.Xiao * 替加环素PK Parameter 50mg iv q12h Cmax (μg/mL) 0.63 Cmin (μg/mL) 0.13 AUC24 (μg/h/mL) 4.70 T1/2 (h) 42.4 CL (L/h/kg) ~0.2 Protein binding(%) 71-89 Vd(L/kg) 7-9 Urine ex(%) 33 Tegcil PI * Dr.Xiao * Vancomycin/aztronam vs tigecycline for the treatment of cSSSI CID 2005,41 (Suppl 5) :S341 * Dr.Xiao * Indications: cSSSI cIAI HAP? ADR 一般反应：胃肠道反应明显 实验室检查：肝功异常较为常见 替加环素—indications/ADR * Dr.Xiao * β—内酰胺类 头孢菌素： Ceftobiprole ceftaroline 碳青霉烯类： PZ-601 CS-023 ME-1036 * Dr.Xiao * Ceftobiprole 抗菌活性 Agents MRSA MRCNS MIC90 MBC90 MIC90 MBC90 Ceftobiprole 0.125-2 0.25-2 0.125-2 0.125-4 Daptomycin 0.125-1 0.25-4 0.125-1 0.125-4 Linezolid 0.25-4 4-128 0.25-2 4-128 Vancomycin 0.5-2 1-8 0.25-2 0.5-8 * Dr.Xiao * 小结 临床革兰阳性菌感染发生率呈上升趋势; 革兰阳性菌耐药性严重； 革兰阳性菌感染需要及时、正确治疗； 抗菌药物开发处于低谷,但孕育着希望； 抗阳性菌药物选择有限，我国可供使用的为糖肽类药物、利奈唑胺； 注意耐药阳性菌感染危险因素，及时开始经验治疗，目标治疗； 万古霉素是治疗耐药革兰阳性菌感染的标准。 * Dr.Xiao * 谢谢 * 24 * 28 * SLIDE 24. To make this new precursor, enterococci have elements with up to seven genes, of which five –vanRSHAX- are essential. These multi-gene systems are carried by plasmids, and the fear is that they will spread from enerococci, which are low-grade pathogens, to MRSA, which are much more potent. * * 28 22 * Mechanism of Action of Linezolid Bacterial protein synthesis involves a series of reactions that are essential for the bacterial protein translation process. These reactions include initiation, elongation, and termination. Linezolid has a unique mechanism of action.1 It is the only antibiotic that targets the formation of the initiation complex Initiation requires formation of a ternary complex consisting of N-formylmethionyl-tRNA, mRNA, and the ribosome.1,2 Linezolid binds to the 50S subunit of the rib