三种抗阳性菌药物比较ppt课件

三种抗阳性菌药物比较,稳可信VS替考拉宁及利奈唑胺（药物的三大特性比较）,三种抗阳性菌药物比较,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,三种抗阳性菌药物比较,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.,三种抗阳性菌药物比较,稳可信上市年全球仅出现株耐药,9,50+,1,ChemotherJA,HiramatsuK,JanakiH.Methicillin-resistantStaphylococcusaureusclinicalstrainwithreducedvancomycinsusceptibility.1997,40:135-1362,FinksJ,WellsE,DykeTL,etal.VancomycinResistantStaphylococcusaureus,MichiganUSA,2007.EmergingInfectiuosDiseases2009,15(6):943-945.,三种抗阳性菌药物比较,重杀菌机制赋予万古霉素持久不变的敏感率,3,1.SanchesIS,MatoR,LencastreHD,etal.PatternsofmultidrugresistanceamongMethicillinResistantHospitalIsolatesofCoagulase-PositiveandCoagulase-NegativeStaphylococciColletedintheInternationalMuticenterStudyRESISTin1997and1998.MicrobialDrugResistance2000,6(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.,三种抗阳性菌药物比较,作用于核糖体单一抑菌机制的利奈唑胺的耐药,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.VenikataG,GoldHS.AntimicrobialresistancetoLinezolid.ClinicalInfectiousDiseases2004,39:1010-1015.2.TsiodrasS,GoldHS,SakoulasG,etal.LinezolidresistanceinaclinicalisolateofStaphylococcusaureus.Lancet2001,358:207-208.3.PoloskiBA,AdamsJ,ClarkeL,etal.EpidemiologicalProLinezolid-ResistantCoagulase-NegativeStaphylocucci.ClinicalInfectiousDiseases2006,43:165-171.,三种抗阳性菌药物比较,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,JonesRN,KohnoS,OnoY,etal.ZAAPSInternationalSurveillanceProgram(2007)forLinezolidresistance:resultsfrom5591Gram-Positiveclinicalisolatesin23countries.DiagnosticMicrobiologyandInfectiousDisease2009,64:191-201.,敏感率%,三种抗阳性菌药物比较,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,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.,三种抗阳性菌药物比较,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):1051-1056,三种抗阳性菌药物比较,利奈唑胺目前的MIC分布情况图,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,JonesRN,KohnoS,OnoY,etal.ZAAPSInternationalSurveillanceProgram(2007)forLinezolidresistance:resultsfrom5591Gram-Positiveclinicalisolatesin23countries.DiagnosticMicrobiologyandInfectiousDisease2009,64:191-201.,三种抗阳性菌药物比较,欧洲43家医院监测结果,ECCMID2009,p1620,三种抗阳性菌药物比较,ECCMID2009,1637,三种抗阳性菌药物比较,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,ZYVOX产品说明书信息DistributedbyPfizerPharmaciaI2=0%;N=853);MERR=1.10(CI0.97,1.23;p=0.11;I2=0%;N=597);andMRSApopulationRR=1.14(CI0.82,1.58;p=0.44;I2=47%;N=191).Iflinezolidiscomparedtovancomycinonly,theCCRRremains1.01(CI0.90,1.12),andMEandMRSARRsare:1.06(CI0.88,1.28)and1.04(CI0.73,1.47),respectively.Theriskofthrombocytopenia(RR=1.92CI1.29,2.86;p=0.001)andGIevents(RR=1.90CI1.04,3.48;p=0.03)weresignificantlyhigherwithlinezolid,butnodifferenceswereseenforrenaldysfunction(RR=0.82CI0.52,1.27;p=0.37),orall-causedeaths(RR=0.95CI0.76,1.18;p=0.63).,2008ICAACK-533,Conclusions:Meta-analysisdidnotdetectclinicalsuperiorityoflinezolidvs.glycopeptidesfortreatmentofNP.Comparedtolinezolid,vancomycinwasnotassociatedwithmorerenaldysfunction.linezolidshowedasignificantincreaseintheriskofthrombocytopeniaandGIevents.AvailabledatadoesnotsupporttheclaimthatlinezolidissuperiortovancomycinforthetreatmentofNP.,三种抗阳性菌药物比较,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),StevensDL,HerrD,LampirisH,etal.LinezolidversusVancomycinfortheTreatmentofMethicillinResistantStaphylococcusaureusInfections.ClinicalInfectiousDiseases2002,34:1481-1490.,三种抗阳性菌药物比较,万古霉素治疗MRSA起效时间未被超越,万古霉素1gq12h，7-21天(n=61),利奈唑胺600mgq12h，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=0.6149,三种抗阳性菌药物比较,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,三种抗阳性菌药物比较,稳可信的安全性,适应症比较副作用比较,三种抗阳性菌药物比较,患者，疗效安全看得见！,1亿,稳可信：拥有广泛的适应症,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,三种抗阳性菌药物比较,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$DI06.171/%E5%88%A9%E5%A5%88%E5%94%91%E8%83%BA%E9%80%82%E5%BA%94%E8%AF%81%E5%A4%96%E7%94%A8%E8%8D%AF%E5%A2%9E%E5%8A%A0%E6%AD%BB%E4%BA%A1%E9%A3%8E%E9%99%A9-%E5%8C%BB%E8%8D%AF%E8%B5%84%E8%AE%AF-%E4%B8%AD%E5%9B%BD%E5%8C%BB%E8%8D%AF%E7%BD%91.mht利奈唑胺适应证外用药增加死亡风险C:/Documents%20and%20Settings/Administrator/Local%20Settings/Temp/Rar$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,WilcoxMH,TackKJ,BouzaE,etal.ComplicatedskinandskinstructureinfectionsandCatheterRelatedBloodstreamInfectionsNoninferiorityofLinezolidinPhase3Sutdy.ClinicalInfectiousDisease2009,48:203-212.2,FDAAlert3/18/2007.,三种抗阳性菌药物比较,万古霉素纯度提高，肾毒性发生率大大减少,RybakM,LomaestoB,RotschaferJC,etal.Therapeuticmonitoryofvancomycininadultpatients:AconsensusreviewoftheASHP,IDSAandtheSIDP.AmJHealth-SystPharm2009,66:82-98.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):10-17StevensD.L.HerrD,LampirisH,etal.LinezolidversusVancomycinfortheTreatmentofMethicillin-ResistantStaphylococcusaureusInfections.ClinicalInfectiousDiseases2002,34:148190AbadF,CalboF,ZapaterP,etal.Comparativepharmacoeconomicstudyofvancomycinandteicoplanininintensivecarepatients.InternationalJournalofAntimicrobialAgents,2000,15:6571DownsNJ,RobertE.Neihart,MD,JeanetteM.Dolezal,etal.MildNephrotoxicityAssociatedWithVancomycinUse.SorrellTC,CollignonPJ.Aprospectivestudyofadversereactionsassociatedwithvancomycintherapy.JAntimicrobChemother.1985Aug,16(2):235-41.FarbertBF,MoelleringRC,RetrospectiveStudyoftheToxicityofPreparationsofVancomycinfrom1974to1981,Antimicrobialagentsandchemotherapy.1983,23(1):138-141LevineDP.Vancomycin:AHistory.ClinicalInfectiousDiseases2006,42:S5-12,三种抗阳性菌药物比较,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,三种抗阳性菌药物比较,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,三种抗阳性菌药物比较,剂量调整例子,某男性病人65岁，体重为70kg,血肌酐值为160mol/L,该病人每日稳可信的给药总量为9.370=651mg,三种抗阳性菌药物比较,万古霉素与替考拉宁安全性比较,MenichetitiF,MartinoB,BucaneveG,etal.EffectsofTeicoplaninandThoseofVancomycininInitialEmpericalAntibioticRegimenforFebrileNeutropenicPatientswithHeamatologicMalignancies.Anitmicrobialagentsandchemotherapy,1994,38(9):2041-2046.WilsonAPR,CompativesafetyofTeicoplaninandVancomycin.InternationalJournalofAntimicrobialAgents,1998,10:143-152,三种抗阳性菌药物比较,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),StevensDL,HerrD,LampirisH,etal.LinezolidversusVancomycinfortheTreatmentofMethicillinResistantStaphylococcusaureusInfections.ClinicalInfectiousDiseases2002,34:1481-1490.,三种抗阳性菌药物比较,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,28WakefieldDS,PfallerM,MassanariRM,HammonsGT.Variationinmethicillin-resistantStaphylococcusaureusoccurrencebygeographiclocationandhospitalcharacteristics.InfectControl.1987;8(4):151-729Yen-HungLin,Vin-CentWuHighfrequencyoflinezolid-associatedthrombocytopeniaAmongpatientswithrenalinsufficiency.InternationalJournalofAntimicrobialAgent28(2006)345-351,三种抗阳性菌药物比较,linezolidversusVancomycinorTeicoplaninforNosocomialPneumonia:AMeta-AnalysisAC.KALIL,M.H.MURTHY,E.HERMSEN,etal.Methods:Prospective,randomizedtrialswhichtestedlinezolidvs.vancomycinorteicoplaninfortreatmentofNPwereincluded.HeterogeneitywasanalyzedbyI2andQstatistics.RelativeRisks(RR)werebasedontheMantel-Haenszelmethod.Outcomesanalyzedincludedclinicalcure(CC),microbiologiceradication(ME),andsideeffects.Results:8linezolidtrials(6vancomycin,2teicoplanin)wereincluded(N=853).Thelinezolidvsglycopeptideanalysisshows:CCRR=1.01(95%CI0.93,1.10,p=0.80;I2=0%;N=853);MERR=1.10(CI0.97,1.23;p=0.11;I2=0%;N=597);andMRSApopulationRR=1.14(CI0.82,1.58;p=0.44;I2=47%;N=191).Iflinezolidiscomparedtovancomycinonly,theCCRRremains1.01(CI0.90,1.12),andMEandMR