达托霉素药理特性.pptx

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,革兰阳性球菌感染与达托霉素,的临床实践,上海交通大学医学院,附属瑞金医院,院感科 临床微生物科,倪语星,一、达托霉素（,Daptomycin,）的杀菌特性,3,环脂肽类抗生素,Cyclic lipopeptide,Streptomyces roseosporus,的天然發酵物,分子式,C,72,H,101,N,17,O,26,分子量,1620.67,無菌、無熱原,淡黃色,淺棕色,塊狀凍晶,賦形劑為,NaOH(,調整,pH,值,),Clinical Infectious Diseases,2004;38:994-1000,4,Anti MRSA,比,较,分,类,Brand Name,Cubicin,Tygacil,Zyvox,Vancocin,Targocid,Daptomycin,Tigecycline,Linezolid,Vancomycin,Teicoplanin,US Launch,2003,2005,2000,1964,none,Class,cyclic lipopeptide,glycylcycline,oxazolidinone,glycopeptide,glycopeptide,cidal/static,rapidly cidal,static,static,slowly cidal,slowly cidal,Location of activity,Cell Membrane,Ribosomal subunit,Ribosomal RNA subunit,Cell Wall,Cell Wall,Daptomycin,达托霉素作用机制为插入革兰阳性菌细胞膜内，由于细菌膜结构的不同，对革兰阴性菌无作用,。,达托霉素具有杀菌性，相比其他抗菌药物，达托霉素对于静止期细菌的杀菌率有显著性升高。,达托霉素对附着于医疗装置表面及生物被,膜,的细菌有显著有效性。,Pharmacology 2008;81:7991,.,达托霉素的快速杀菌活性,-,in vitro,对于金葡菌，,2-4,倍,MIC,的达托霉素达到杀菌作用（降低,3log),只需要,1,小时左右；,对于,VRE,，则需要,2-6,小时,Clinical Microbiology Newsletter:Vol.24,No.5;March 1,2002,7,0,2,4,6,8,10,12,14,0,12,24,36,48,60,72,Time(hours),CFU/g(log,10,),对静止生长期金黄色葡萄球菌有快速杀菌活性,Pharmacodynamic model utilizing simulated endocardial vegetations(Tedesco and Rybak,ICAAC 2003),对照,达托霉素,利奈唑胺,奈夫西林,万古霉素,Rapid Bactericidal Activity of Daptomycin Against MRSA,Peritonitis in,Healthy,Mice,Mortin LI,LI T,Van Praagh ADG,Zhang S,Zhang X-X,Alder JD.Rapid bactericidal activity of daptomycin against methicillin-resistant and methicillin-susceptible,Staphylococcus aureus,peritonitis in mice as measured with bioluminescent bacteria.,Antimicrob Agents Chemother,.2007;51:1787-1794.,Rapid Bactericidal Activity of Daptomycin Against MRSA,Peritonitis in,Neutropenic,Mice,Mortin LI,LI T,Van Praagh ADG,Zhang S,Zhang X-X,Alder JD.Rapid bactericidal activity of daptomycin against methicillin-resistant and methicillin-susceptible,Staphylococcus aureus,peritonitis in mice as measured with bioluminescent bacteria.,Antimicrob Agents Chemother,.2007;51:1787-1794.,体外超微结构电镜显示,:,达托霉素不会使,MSSA/MRSA,的死亡后崩解,A),没有抗生素,(B),达托霉素,8 mg/L,，,1 h,C),达托霉素,8 mg/L,，,24 h,.,Wale LJ,et al.,J Med Microbiol.,1989;30(1):45-49.,10,A),没有抗生素,(B),达托霉素,8 mg/L,，,4 h,C),达托霉素,8 mg/L,，,24 h,MSSA,MRSA,Biofilms,细菌生物膜常见于植入导管，假体等的表面,ASM Microbe Library,www.microbe/library.org,达托霉素对于形成生物被膜的导管葡萄球菌感染具有很强的的穿透力,ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,May 2007,p.16561660,达托霉素的杀菌速度很快,Raad,et al.Antimicrobial Agents and Chemotherapy,2007,51:16561660,二、指南推荐,GUIDELINES,美国,IDSA,MRSA,感染治疗指南,Liu et al.Clin Infect Dis 2011 Jan 4,关于达托霉素的推荐要点,达托霉素作为,MRSA,血流感染和自身瓣膜感染性心内膜炎的治疗方案,证据等级及推荐度,(,AI,),高于万古霉素,(,AII,),达托霉素在成人复杂性,SSTI,治疗推荐中与万古霉素、利奈唑胺等药物为同等级,(,AI,),骨髓炎和化脓性关节炎治疗中与万古霉素、利奈唑胺等药物同等级,(,BII,),IDSA MRSA,指南,:,患有菌血症或自体瓣膜感染性心内膜炎的成人,1,推荐的治疗持续时间,非复杂性菌血症,至少,2,周,复杂性菌血症,4-6,周,自体瓣膜感染性心内膜炎,6,周,患有,菌血症或自体瓣膜感染性心内膜炎的成人的抗菌治疗选择汇总,治疗,成人用量,等级*,评论,万古霉素,15-20 mg/kg/,剂,IV q8-12h,A-II,不建议在万古霉素中加入庆大霉素,(A-II),或利福平,(A-I),达托霉素,6 mg/kg/,剂,IV,QD,A-I,一些专家建议使用更高剂量，,8-10 mg/kg/,天,IV QD(B-III),*,推荐度和证据等级分类,1.,Liu C,Bayer A,Cosgrove SE et al.Clinical practice guidelines by the Infectious Diseases Society of America for the,药剂,of methicillin-resistant,Staphylococcus aureus,infections in,成人,s and children.,Clin Infect Dis,.2011 Jan 4,Epub ahead of print,万古霉素是此类治疗的主流治疗药物,达托霉素是万古霉素的替代治疗药物,三、临床实践,REVIEWS,（一）金葡菌感染经验性用药,19,-,do not use,+,use only as alternative,+,good drug for this indication,+,very good drug for this indication,Minerva Anestesiol 2011,；,77,：,821-827,（二）自体瓣膜心内膜炎的治疗,Donald P.Levine1,，,Kenneth C.Lamp DAPTOMYCIN FOR NATIVE VALVE ENDOCARDITIS:EXPERIENCE FROM A REGISTRY 10th International Symposium on Modern Concepts in Endocarditis and Cardiovascular Infections Naples,Italy,April 26-28,2009,结果,疗效,不同病原菌感染的治疗成功率相似,自体瓣膜心内膜炎的达托霉素治疗成功率为,84%,（三）,VANCOMYCIN MIC 1,Evaluation of a Clinical Pathway for the Treatment of Methicillin-Resistant,Staphylococcus aureus,Bacteremia(MRSAB)with an MIC of 1 mg/L to Vancomycin,*,Ravina Kullar,1,Susan L.Davis,1,Jason M.Pogue,2,Jing J.Zhao,2,;Donald P.Levine,2,3,Keith K.Kaye,2,3,;Michael J.Rybak,1,2,3,PHARMACOTHERAPY Volume 33,Number 1,2013,p0.001,Clinical Outcomes,（四）肿瘤及粒细胞缺乏患者,达托霉素在血液肿瘤患者中导管相关血流感染的疗效,P=0.04,P 1 mg/L,，耐药革兰阳性球菌（,VISA,，,VRSA,，,VRE,）全身感染治疗的首选,。,Thank You!,