三种抗阳性菌药物比较.ppt

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level,*,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,Vancocinpro20091216,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,Vancocinpro20091216,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,Vancocinpro20091216,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,Vancocinpro20091216,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,Vancocinpro20091216,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,Vancocinpro20091216,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,Vancocinpro20091216,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,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,本套幻灯仅供内部学习，团销时按实际情况重组,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,本套幻灯仅供内部学习，团销时按实际情况重组,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,本套幻灯仅供内部学习，团销时按实际情况重组,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,本套幻灯仅供内部学习，团销时按实际情况重组,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,本套幻灯仅供内部学习，团销时按实际情况重组,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,本套幻灯仅供内部学习，团销时按实际情况重组,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,本套幻灯仅供内部学习，团销时按实际情况重组,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,稳可信,VS,替考拉宁及利奈唑胺,（药物的三大特性比较）,稳可信的有效性,作用机制,耐药及敏感率,MIC,：万古,MIC“,飘逸”而非“漂移”,临床疗效,指南推荐,重杀菌机制,3,相对于,人工合成,抗生素的,单一抑菌机制,万古霉素,让葡萄球菌更无从抵抗,1.,影响细菌细胞膜的通透性,2.,抑制细菌细胞壁的合成,3.,抑制细菌浆内,RNA,合成,1,2,3,MDRSP=,多药耐药菌株,MRSH=,溶血性葡萄球菌,实用抗感染治疗学第一版,汪复、张婴元主编，第九章 多肽类抗生素：,pp281,pp284.,稳可信上市 年全球仅出现 株耐药,9,1997,年日本首先,报告了对万古霉素,中度敏感的金黄色,葡萄球菌,(VISA),1,2002,年,07,年在北美地区先后共确定,9,株耐药的金黄色葡萄球菌,(VRSA),2,我国尚无报道,50+,1,Chemother JA,Hiramatsu K,Janaki H.Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility,.1997,40:135-136,2,Finks J,Wells E,Dyke TL,et al.,Vancomycin,Resistant Staphylococcus aureus,Michigan USA,2007.,Emerging Infectiuos Diseases 2009,15(6):943-945.,重杀菌机制赋予万古霉素持久不变的敏感率,3,1.Sanches IS,Mato R,Lencastre HD,et al.Patterns of multidrug resistance among Methicillin,Resistant Hospital Isolates of Coagulase-Positive and Coagulase-Negative Staphylococci Colleted in the International Muticenter Study RESIST in 1997 and 1998.Microbial Drug Resistance 2000,6(3):199-211.,2.,实用抗感染治疗学第一版,汪复、张婴元主编,第九章 多肽类抗生素：,pp281,pp284.,作用于核糖体,单一,抑菌机制的利奈唑胺的耐药,1999,年,1,2000,年,2001,年,2,2005,年,3,三期临床时出现,2,株,LRE,利奈唑胺上市,出现,3,株,LRSA,美国,匹兹堡,大学,医疗中心,ICU,出现,74,株,LRCNS,LRE=,耐利奈唑胺肠球菌,LRSA=,耐利奈唑胺金葡菌,LRCNS=,耐利奈唑胺凝固酶阴性葡萄球菌,1.Venikata G,Gold HS.Antimicrobial resistance to Linezolid.Clinical Infectious Diseases 2004,39:1010-1015.,2.Tsiodras S,Gold HS,Sakoulas G,et al.Linezolid resistance in a clinical isolate of Staphylococcus aureus.Lancet 2001,358:207-208.,3.Poloski BA,Adams J,Clarke L,et al.Epidemiological Pro Linezolid-Resistant Coagulase-Negative Staphylocucci.Clinical Infectious Diseases 2006,43:165-171.,所有金葡菌对万古霉素仍保持,100%,敏感率,2007,年,ZAAPS,细菌耐药性监测结果,Jones RN,Kohno S,Ono Y,et al.ZAAPS International Surveillance Program(2007)for Linezolid resistance:results from 5591 Gram-Positive clinical isolates in 23 countries.Diagnostic Microbiology and Infectious Disease 2009,64:191-201.,敏感率,%,国内葡萄球菌对万古霉素保持 敏感率,100%,2008,年中国,CHINET,细菌耐药性监测结果,(n=3525),(n=2313),耐药金葡菌敏感率,(%),汪复,朱德妹,胡付品,等.,2008,年中国,CHINET,细菌耐药性监测,.,中国感染与化疗杂志 2009,9(5):321-329.,国内葡萄球菌对万古霉素保持 敏感率,100%,全国主要抗生素对葡萄球菌属敏感率监测,(Mohnarin)2008,(n=10409),(n=5981),肖永红，王 进，赵彩云等，,20062007,年,Mohnarin,细菌耐药监测,中华医院感染学杂志,2008,18(8):1051-1056,利奈唑胺目前的,MIC,分布情况图,2200,0,400,800,1200,1600,2000,0.12,0.25,0.5,1,2,4,8,利奈唑胺,MIC(,g/ml),株数,(N),6,株,4,株,2007,年,ZAAPS,细菌耐药性监测结果,1,万古霉素对于,金葡菌的,MIC90,仅为,1mg/L,Jones RN,Kohno S,Ono Y,et al.ZAAPS International Surveillance Program(2007)for Linezolid resistance:results from 5591 Gram-Positive clinical isolates in 23 countries.Diagnostic Microbiology and Infectious Disease 2009,64:191-201.,欧洲,43,家医院监测结果,Bacteria,Year,Strain No,Vancomycin,Teicoplanin,MICr,MIC90,MICr,MIC90,S.aureus,2005,337,0.25-2,1,0.12-8,2,2006,220,0.5-2,1,0.25-4,1,2007,131,0.5-2,1,0.25-4,1,2008,69,0.25-2,1,0.25-4,1,CoNS,2005,93,32,8,2007,81,0.5-2,2,0.25-8,4,2008,91,0.25-2,2,0.12-8,4,S.pyogenes,2005,41,0.25,0.25,Nt,Nt,2006,-,-,-,-,-,2007,146,0.12-0.5,0.25,0.03-4,0.03,2008,54,0.12-0.25,0.25,0.03-1,128,2,025-128,0.25,ECCMID 2009,p1620,ECCMID 2009,1637,13,万古霉素和利奈唑胺治疗院内肺炎疗效相当,在利奈唑胺提交给,FDA,的临床报告中详细描述了治疗医院内肺炎的临床研究,.,该研究用万古霉素和利奈唑胺进行对照显示万古霉素可评价临床疗效为,60%,，利奈唑胺可评价临床疗效,57%,，二者疗效相当，利奈唑胺疗效并未超越万古霉素。,0,10,20,30,40,50,60,利奈唑胺,万古霉素,利奈唑胺,万古霉素,ZYVOX,产品说明书信息,Distributed by Pfizer Pharmacia&Upjohn Company Divison of Pfizer Inc,NY,NY10017 LAB-0319-16.0,%,linezolid versus Vancomycin or Teicoplanin,for Nosocomial Pneumonia:A Meta-Analysis,AC.KALIL,M.H.MURTHY,E.HERMSEN,et al.,Methods:Prospective,randomized trials which tested linezolid vs.vancomycin or teicoplanin for treatment of NP were included.Heterogeneity was analyzed by I2 and Q statistics.Relative Risks(RR)were based on the Mantel-Haenszel method.Outcomes analyzed included clinical cure(CC),microbiologic eradication(ME),and side effects.,Results:8 linezolid trials(6 vancomycin,2 teicoplanin)were included(N=853).The linezolid vs glycopeptide analysis shows:CC RR=1.01(95%CI 0.93,1.10,p=0.80;I2=0%;N=853);ME RR=1.10(CI 0.97,1.23;p=0.11;I2=0%;N=597);and MRSA population RR=1.14(CI 0.82,1.58;p=0.44;I2=47%;N=191).If linezolid is compared to vancomycin only,the CC RR remains 1.01(CI 0.90,1.12),and ME and MRSA RRs are:1.06(CI 0.88,1.28)and 1.04(CI 0.731.47),respectively.The risk of thrombocytopenia(RR=1.92 CI 1.29,2.86;p=0.001)and GI events(RR=1.90 CI 1.04,3.48;p=0.03)were significantly higher with linezolid,but no differences were seen for renal dysfunction(RR=0.82 CI 0.52,1.27;p=0.37),or all-cause deaths(RR=0.95 CI 0.76,1.18;p=0.63).,2008 ICAAC K-533,Conclusions:,Meta-analysis did not detect clinical superiority of linezolid vs.glycopeptides for treatment of NP.Compared to linezolid,vancomycin was not associated with more renal dysfunction.linezolid showed a significant increase in the risk of thrombocytopenia and GI events.Available data does not support the claim that linezolid is superior to vancomycin for the treatment of NP.,万古霉素治疗,MRSA,感染疗效未被超越,包括菌血症、肺炎以及皮肤软组织感染,万古霉素,1g/,次，每天,2,次,7-28,天,(n=220),利奈唑胺,600mg/,次，每天,2,次,7-28,天,(n=240),Stevens DL,Herr D,Lampiris H,et al.Linezolid versus Vancomycin for the Treatment of Methicillin,Resistant Staphylococcus aureus Infections.Clinical Infectious Diseases 2002,34:1481-1490.,万古霉素治疗,MRSA,起效时间未被超越,万古霉素,1g q12h,，,7-21,天,(n=61),利奈唑胺,600mg q12h,，,7-21,天,(n=57),*退热定义为体温完全恢复正常,时间,(,天,),P=0.2057,P=0.1760,P=0.6149,稳可信：众多权威指南推荐,桑福德,抗微生物治疗指南,2009-2010,版,美国胸科协会,(ATS),关于医院获得性、呼吸机相关及医疗相关肺炎治疗指南,美国抗感染协会,(IDSA),关于导管相关感染治疗指南,HAP,亚洲工作组,关于,HAP,组首次共识,欧洲心脏协会,(ESC),关于感染性心内膜炎的预防、诊断及治疗指南,英国抗菌化疗协会,(BSAC),关于,MRSA,感染预防和治疗指南,万古霉素,治疗,MRS,感染的首选,稳可信的安全性,适应症比较,副作用比较,患者，疗效安全看得见！,1,亿,稳可信,：拥有,广泛,的适应症,适应症,万古霉素,1,利奈唑胺,2,替考拉宁,3,肺炎,皮肤软组织感染,导管相关血流感染,FDA,警告,？,感染性心内膜炎,X,？,脑膜炎,X,肺脓肿,X,脓胸,X,腹膜炎,X,骨髓炎,X,关节炎,X,1,.,万古霉素产品说明书,2.,利奈唑胺产品说明书,3.,替考拉宁产品说明书,利奈唑胺受到美国,FDA,的警告,1,利奈唑胺已被,FDA,批准的适应证包括：,用于治疗耐万古霉素的屎肠球菌感染、医源性肺炎、社区获得性肺炎、非复杂性的皮肤及软组织感染、复杂性的皮肤和软组织感染（包括未并发骨髓炎的糖尿病足部感染）,。,2007,年,FDA,提醒医务工作者：,利奈唑胺,未获批准,用于导管相关性血流感染、导管 接触部位感染。,相关报导：,C:/Documents%20and%20Settings/Administrator/Local%20Settings/Temp/Rar$DI06.171/%E5%88%A9%E5%A588%E5%94%91%E8%83%BA%E9%80%82%E5%BA%94%E8%AF%81%E5%A4%96%E7%94%A8%E8%8D%AF%E5%A2%9E%E5%8A%A0%E6%AD%BB%E4%BA%A1%E9%A3%8E%E9%99%A9-%E5%8C%BB%E8%8D%AF%E8%B5%84%E8%AE%AF-%E4%B8%AD%E5%9B%BD%E5%8C%BB%E8%8D%AF%E7%BD%91.mht,利奈唑胺适应证外用药增加死亡风险,C:/Documents%20and%20Settings/Administrator/Local%20Settings/Temp/Rar$DI06.171/%E5%88%A9%E5%A5%88%E5%94%91%E8%83%BA%E5%AE%89%E5%85%A8%E6%80%A7%E5%BC%95%E8%B5%B7%E5%B9%BF%E6%B3%9B%E9%87%8D%E8%A7%86-%E5%8C%BB%E8%8D%AF%E8%B5%84%E8%AE%AF-%E4%B8%AD%E5%9B%BD%E5%8C%BB%E8%8D%AF%E7%BD%91.mht,网站相关报导检索关键词：利奈唑胺,1,Wilcox MH,Tack KJ,Bouza E,et al.Complicated skin and skin,structure infections and Catheter,Related Bloodstream Infections Noninferiority of Linezolid in Phase 3 Sutdy.Clinical Infectious Disease 2009,48:203-212.,2,FDA Alert 3/18/2007.,万古霉素纯度提高，肾毒性发生率大大减少,Rybak M,Lomaest o B,Rotschafer JC,et al.Therapeutic monitory of vancomycin in adult patients:A consensus review of the ASHP,IDSA and the SIDP.Am J Health-Syst Pharm 2009,66:82-98.,林东昉、吴菊芳、张婴元等。利奈唑胺与万古霉素治疗革兰阳性菌感染的随机、双盲、对照、多中心临床试验。中国感染与化疗杂志,2009,9(1):10-17,Stevens D.L.Herr D,Lampiris H,et al.Linezolid versus Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections.Clinical Infectious Diseases 2002,34:148190,Abad F,CalboF,Zapater P,et al.,Comparative pharmacoeconomic study of vancomycin and teicoplanin in intensive care patients.International Journal of Antimicrobial Agents,2000,15:6571,Downs NJ,Robert E.Neihart,MD,Jeanette M.Dolezal,et al.Mild Nephrotoxicity Associated With Vancomycin Use.,Sorrell TC,Collignon PJ.A prospective study of adverse reactions associated with vancomycin therapy.J Antimicrob Chemother.1985 Aug,16(2):235-41.,Farbert BF,Moellering RC,Retrospective Study of the Toxicity of Preparations of Vancomycin from 1974 to 1981,Antimicrobial agents and chemotherapy.1983,23(1):138-141,Levine DP.Vancomycin:A History.Clinical Infectious Diseases 2006,42:S5-12,稳可信稀释后静脉滴注,药物浓度不超过 5毫克/毫升,每次滴注时间应该超过 60分钟,肾功能损害及年长患者应调整剂量,必要时监测血药浓度,经常改变输注部位,稳可信,应用准则,肾功能异常病人剂量调整方法,肌酐值以,mol/L,表示时，,K=0.814,本公式应用于女性值，求得值需乘以,0.85,首次负荷剂量,:15mg/kg,(,),血清肌酐值,年龄,）,肌酐清除率（,-,=,K,kg,ml,140,min/,/,24,剂量调整例子,某男性病人,65,岁，体重为,70kg,血肌酐值为,160,mol/L,该病人每日稳可信的给药总量为,9.3,70=651mg,(,),6,.,0,160,814,.,0,65,140,k,min/,/,=,-,=,）,肌酐清除率（,g,ml,万古霉素与替考拉宁安全性比较,万古霉素,(n=252),替考拉宁,(n=275),肾毒性,意大利,大样本,临床对照试验,1,血小板减少,美国,大样本,临床对照试验,2,发生率,(%),发生率,(%),P=0.68,P=0.003,万古霉素,(n=417),替考拉宁,(n=406),Menichetiti F,Martino B,Bucaneve G,et al.Effects of Teicoplanin and Those of Vancomycin in Initial Emperical Antibiotic Regimen for Febrile Neutropenic Patients with Heamatologic Malignancies.Anitmicrobial agents and chemotherapy,1994,38(9):2041-2046.,Wilson APR,Compative safety of Teicoplanin and Vancomycin.International Journal of Antimicrobial Agents,1998,10:143-152,万古霉素治疗,MRSA,感染副反应发生率与利奈唑胺比较,发生率,(%),P=0.006,P=0.037,P=0.139,无统计学差异,万古霉素,1g/,次，每天,2,次,7-28,天,(n=220),利奈唑胺,600mg/,次，每天,2,次,7-28,天,(n=240),Stevens DL,Herr D,Lampiris H,et al.Linezolid versus Vancomycin for the Treatment of Methicillin,Resistant Staphylococcus aureus Infections.Clinical Infectious Diseases 2002,34:1481-1490.,万古霉素和利奈唑胺安全性的比较,由于万古霉素制剂的纯度显著提高，目前临床大量应用万古霉素，证实其肾毒性很少见,包括调整剂量后用于肾功能受损的病人，同时万古霉素的肾毒性具有可逆性,28,。而有数据表明，利奈唑胺引起的严重不良反应血小板减少的病例高达,35%,在肾功能损伤的病人应用利奈唑胺引起的血小板减少达到,65%,29,。,高纯度的万古霉素具有良好的安全性,28 Wakefield DS,Pfaller M,Massanari RM,Hammons GT.,Variation in methicillin-resistant Staphylococcus aureus occurrence by geographic location and hospital characteristics.Infect Control.1987;8(4):151-7,29 Yen-Hung Lin,Vin-Cent Wu High frequency of linezolid-associated thrombocytopenia Among patients with renal insufficiency.International Journal of Antimicrobial Agent 28(2006)345-351,linezolid versus Vancomycin or Teicoplanin,for Nosocomial Pneumonia:A Meta-Analysis,AC.KALIL,M.H.MURTHY,E.HERMSEN,et al.,Methods:Prospective,randomized trials which tested linezolid vs.vancomycin or teicoplanin for treatment of NP were included.Heterogeneity was analyzed by I2 and Q statistics.Relative Risks(RR)were based on the Mantel-Haenszel method.Outcomes analyzed included clinical cure(CC),microbiologic eradication(ME),and side effects.,Results:8 linezolid trials(6 vancomycin,2 teicoplanin)were included(N=853).The linezolid vs glycopeptide analysi