呼吸机相关性肺炎01936.ppt

呼吸机相关性肺炎,2,利益冲突,默沙东辉瑞葛兰素史克西安杨森礼来,惠氏住友安万特安斯泰来拜耳,HAP/VAP:概要,流行病学诊断策略抗生素治疗,HAP/VAP:问题1,呼吸机相关性肺炎指应用机械通气多长时间以后发生的肺炎?24小时48小时72小时96小时48-72小时,HAP/VAP/HCAP:定义,医院获得性肺炎(HAP)住院48小时后发生且住院时不处于潜伏期的肺炎呼吸机相关性肺炎(VAP)气管插管48-72小时以后发生的肺炎因重度HAP需要气管插管者应按照VAP处理医疗相关肺炎(HCAP)发生感染前90天内在急性病医院住院2天在养护院或长期医疗机构住院近期接受静脉抗生素治疗、化疗或发生感染前30天内接受伤口治疗就诊于医院门诊或透析门诊,ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416,HAP/VAP:流行病学,发病率美国医院获得性感染的第二位5-15例/1,000住院病例罹患率和病死率升高预后住院日延长7-9天医疗费用增加$40,000,HAP/VAP:流行病学,HAPICU所有感染的25%ICU抗生素用量的50%以上VAP气管插管患者：9-27%ICU患者HAP的90%,HAP/VAP:流行病学,KumpfG,etal.JClinEpidemiol1998;54:495-502LizioliA,etal.JHospInfect2003;54:141-148RichardsMJ,etal.CritCareMed1999;27:887-892,HAP/VAP:流行病学,机械通气,5,10,累积患病率(%),3%/d,1%/d,2%/d,CookDJ,WalterSD,CookRJ,GriffithLE,GuyattGH,LeasaD,JaeschkeRZ,Brun-BuissonC.Incidenceofandriskfactorsforventilator-associatedpneumoniaincriticallyillpatients.AnnInternMed1998;129:440,迟发性HAP50%,早发性HAP50%,HAP/VAP:流行病学,机械通气,5,10,累积患病率(%),HAP/VAP:病死率,总病死率30-70%归因病死率33-50%,HAP/VAP:危险因素,气管插管和机械通气平卧位缺乏感染控制措施缺乏ICU感染监测经鼻气管插管,紧急插管或再次插管基础肺病肠道营养气管插管套囊压力低,HAP/VAP:危险因素,H2受体拮抗剂进行应激性溃疡预防“自由”输血去白细胞输血血糖控制不佳ARDS深度镇静或肌松,HAP/VAP:病因学,HAP/VAP:病因学,支气管远端标本培养分离出口咽部定植菌（草绿色链球菌，凝固酶阴性葡萄球菌，奈瑟氏菌属，棒状杆菌属）难以解释在免疫抑制甚至免疫正常患者可能引起感染,CabelloH,TorresA,CelissR,El-EbiaryM,delaBellacasaJP,XaubetA,GonzalezJ,AugustiC,SolerN.Bacterialcolonizationofdistalairwaysinhealthysubjectsandcroniclungdiseases:abronchoscopicstudy.EurRespirJ1997;10:11371144,HAP/VAP:病因学,金黄色葡萄球菌糖尿病，头颅创伤，住ICU厌氧菌非插管患者误吸VAP罕见肺炎军团菌免疫抑制患者如器官移植，HIV，糖尿病，基础肺病，终末期肾病,HAP/VAP:病因学,真菌（包括念珠菌和曲霉菌）器官移植，免疫抑制，中性粒细胞缺乏免疫正常患者罕见病毒免疫正常者罕见流感病毒，副流感病毒，腺病毒，麻疹病毒，呼吸道合胞病毒占病毒的70%,HAP/VAP:病因学,多种致病菌ARDS患者老年患者与迟发性HAP/VAP相似未插管患者与插管患者相似?,HAP/VAP:MDR危险因素,既往90天应用抗生素住院5天所在社区或医院病房中抗生素耐药率高HCAP危险因素发生感染前90天内在急性病医院住院2天在养护院或长期医疗机构住院家庭输液治疗（包括抗生素）30天内接受慢性透析家庭伤口护理家人有多重耐药菌感染/定植免疫抑制疾病和（或）治疗,HAP/VAP:分类,0,1,2,3,4,5,6,7,8,Early-onsetHAP,Late-onsetHAP,Timefromhospitalization(days),0,1,2,3,4,5,6,7,8,Early-onsetVAP,Late-onsetVAP,TimefromIntubation(days),ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416,HAP/VAP:病因学,ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416,HAP/VAP:病因学,ParkDR.Themicrobiologyofventilator-assistedpneumonia.RespirCare2005;50:742-765,HAP/VAP:问题2,以下哪个不是呼吸机相关性肺炎确切的发病机制误吸直接吸入血行性播散胃肠道细菌移位以上答案均不对,HAP/VAP:发病机制,改变胃排空及胃液pH值的药物,有生物膜的装置(气管插管,鼻胃管),既往应用抗生素,宿主因素(免疫抑制,烧伤),消化道细菌定植,细菌误吸,细菌吸入,医院获得性肺炎,水,药物溶液及呼吸治疗装置污染,感染控制措施不够(洗手,隔离衣,手套),医务人员不足,经胸种植原发性菌血症胃肠道细菌移位,HAP/VAP:发病机制,HAP/VAP:影像学诊断,对于可疑肺炎患者，如果根据其他临床表现不能确诊，影像学判断也不能提高诊断的正确性若胸片显示明显浸润影，则鉴别心源性肺水肿、非心源性肺水肿、肺挫伤和肺不张将非常困难各种影像学表现的敏感性和特异性差异很大，诊断准确性均不超过70%支气管气像诊断肺炎的准确性最高(64%),HAP/VAP:影像学诊断,CXRvs.CT手术后肺实变：敏感性0.331.00，特异性0.79不同医生判读的一致性放射科医生：kappa0.27ICU医生：1239%,WunderinkRG,WoldenbergLS,ZeissJ,etal.Theradiologicdiagnosisofautopsy-provenventilator-associatedpneumonia.Chest1992;101:458-63.FagonJ,ChastreJ,HanceA.Evaluationofclinicaljudgmentintheidentificationandtreatmentofnosocomialpneumoniainventilatedpatients.Chest1993;103:547-53.BeydonL,SaadaM,LiuN,etal.Canportablechestx-rayexaminationaccuratelydiagnoselungconsolidationaftermajorabdominalsurgery?:acomparisonwithcomputedtomographyscan.Chest1992;102:1698-703.,HAP/VAP:临床诊断,胸片新出现浸润影或原有浸润性加重以下临床表现中两条：T38C白细胞增多或白细胞缺乏脓性气道分泌物,敏感性69%，特异性75%,HAP/VAP:细菌学诊断,下呼吸道标本的半定量培养特异性低：培养结果阳性可能仅提示定植敏感性高：培养结果阴性有助于除外感染除非刚刚应用或更换抗生素常导致过度应用抗生素革兰染色结果结合培养结果有助于指导抗生素治疗,HAP/VAP:细菌学诊断,采样部位越远特异性越高敏感性越低诊断阈值越低,HAP/VAP:细菌学诊断,试验设计:多中心随机临床试验入选标准:免疫功能正常的成年患者住ICU超过4天后怀疑呼吸机相关性肺炎排除标准:假单胞菌属或MRSA定植或感染分组:诊断:BALF定量培养vs.ETA的非定量培养治疗:美罗培南+环丙沙星vs.美罗培南,TheCanadianCriticalCareTrialsGroup.Arandomizedtrialofdiagnostictechniquesforventilator-associatedpneumonia.NEnglJMed2006;355:2619-2630,HAP/VAP:细菌学诊断,高度可疑VAP=临床诊断+BALF104cfu/ml;可能VAP=临床诊断,TheCanadianCriticalCareTrialsGroup.Arandomizedtrialofdiagnostictechniquesforventilator-associatedpneumonia.NEnglJMed2006;355:2619-2630,HAP/VAP:细菌学诊断,TheCanadianCriticalCareTrialsGroup.Arandomizedtrialofdiagnostictechniquesforventilator-associatedpneumonia.NEnglJMed2006;355:2619-2630,HAP/VAP:细菌学诊断,呼吸道分泌物分离出念珠菌很少提示深部念珠菌感染，不应进行抗真菌治疗(A-III),PappasPG,KauffmanCA,AndesD,etal.Clinicalpracticeguidelinesforthemanagementofcandidiasis:2009updatebytheInfectiousDiseasesSocietyofAmerica.2009;48:503-535,HAP/VAP:综合诊断,PuginJ,AuckenthalerR,MiliN,JanssensJP,LewPD,SuterPM.Diagnosisofventilator-associatedpneumoniabybacteriologicanalysisofbronchoscopicandnon-bronchoscopicblindbronchoalveolarlavagefluid.AmRevRespirDis1991;143:1121-1129,HAP/VAP:鉴别诊断,肿瘤结缔组织疾病血管炎综合征肺泡出血药物诱发肺泡炎,肺不张血栓栓塞性疾病胃内容物误吸未治愈社区获得性肺炎充血性心力衰竭,HAP/VAP:治疗,LunaCM,VujacichP,NiedermanMS,etal.ImpactofBALdataonthetherapyandoutcomeofventilator-associatedpneumonia.Chest1997;111:676-685,HAP/VAP:治疗,HeylandDK,CookDJ,GriffithL,etal.Theattributablemorbidityandmortalityofventilator-associatedpneumoniainthecriticallyillpatient.TheCanadianCriticalCareTrialsGroup.AmJRespirCritCareMed1999;159:1249-1256,不充分的抗生素治疗,2000名连续收治的MICU/SICU患者655(25.8%)罹患感染169(8.5%)抗生素治疗不充分,KollefMH,ShermanG,WardS,etal.Inadequateantimicrobialtreatmentofinfections.Ariskfactorforhospitalmortalityamongcriticallyillpatients.Chest1999;115:462-474,不充分的抗生素治疗,KollefMH,ShermanG,WardS,etal.Inadequateantimicrobialtreatmentofinfections.Ariskfactorforhospitalmortalityamongcriticallyillpatients.Chest1999;115:462-474,HAP/VAP:经验性抗生素,ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416,HAP/VAP:经验性抗生素,ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416,HAP/VAP:抗生素剂量,ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416,HAP/VAP:治疗,怀疑HAP/VAP,迟发性HAP/VAP或MDR危险因素,否,是,使用窄谱抗生素治疗,使用广谱抗生素治疗,ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416,HAP/VAP:治疗,怀疑HAP/VAP/HCAP,采取下呼吸道(LRT)进行培养(定量或半定量)和显微镜检,除非肺炎的临床概率低且LRT镜检阴性，否则应根据当地细菌流行病资料应用经验性抗生素,第2/3天：培养结果并评价临床疗效(体温,WCC,CXR,氧合,脓痰,循环改变及器官功能),ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416,HAP/VAP:治疗,ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416,48-72小时临床改善,寻找其他致病菌,并发症,其他诊断或其他感染灶,调整抗生素,寻找其他致病菌,并发症,其他诊断或其他感染灶,考虑停用抗生素,如可能抗生素降阶梯,治疗7-8天后再次评估,培养阴性,培养阳性,培养阴性,培养阳性,否,是,HAP/VAP:局部抗生素,局部注射氨基糖甙局部用药提高细菌学清除率，但不改变临床预后雾化吸入氨基糖甙或多粘菌素B治疗MDR致病菌副作用耐药率?诱发支气管痉挛,HamerDH.Treatmentofnosocomialpneumoniaandtracheobronchitiscausedbymultidrug-resistantPseudomonasaeruginosawithaerosolizedcolistin.AmJRespirCritCareMed2000;162:328-330.BrownRB,KruseJA,CountsGW,RussellJA,ChristouNV,SandsML,EndotrachealTobramycinStudyGroup.Double-blindstudyofendotrachealtobramycininthetreatmentofgram-negativebacterialpneumonia.AntimicrobAgentsChemother1990;34:269-272KlickJM,duMoulinGC,Hedley-WhyteJ,TeresD,BushnellLS,FeingoldDS.Preventionofgram-negativebacillarypneumoniausingpolymyxinaerosolasprophylaxis.II.Effectontheincidenceofpneumoniainseriouslyillpatients.JClinInvest1975;55:514-519,HAP/VAP:联合用药,抗生素的协同效应体外试验证实有效中性粒细胞缺乏或血行性感染患者预防耐药发生增加抗菌谱-内酰胺+氨基糖甙-内酰胺+喹诺酮?,HAP/VAP:联合用药,美罗培南+环丙沙星(n=369)vs.美罗培南(n=371)RR1.05,95%CI0.781.42MDR革兰阴性杆菌感染(n=56)28天细菌学清除：64.1%vs.29.4%机械通气时间：10.7(3.3)vs.15.0(9.3)ICU住院日：14.2(8.1)vs.21.2(14.1)ICU病死率：23.1%vs.29.4%住院病死率：33.3%vs.41.2%,HeylandD,DodekP,MuscedereJ,etal.Randomizedtrialofcombinationversusmonotherapyfortheempirictreatmentofsuspectedventilator-associatedpneumonia.CritCareMed2008;36(3):737-744,HAP/VAP:联合用药,PaulM,Benuri-SilbigerI,Soares-WeiserK,etal.-lactammonotherapyversus-lactam-aminoglycosidecombinationtherapyforsepsisinimmunocompetentpatients:systematicreviewandmeta-analysisofrandomisedtrials.BMJ2004;328:668,HAP/VAP:联合用药,PaulM,Benuri-SilbigerI,Soares-WeiserK,etal.-lactammonotherapyversus-lactam-aminoglycosidecombinationtherapyforsepsisinimmunocompetentpatients:systematicreviewandmeta-analysisofrandomisedtrials.BMJ2004;328:668,HAP/VAP:联合用药,PaulM,Benuri-SilbigerI,Soares-WeiserK,etal.-lactammonotherapyversus-lactam-aminoglycosidecombinationtherapyforsepsisinimmunocompetentpatients:systematicreviewandmeta-analysisofrandomisedtrials.BMJ2004;328:668,肾脏毒性RR0.3695%CI0.270.47,敏感性分析无显著差异,HAP/VAP:问题3,呼吸机相关性肺炎的抗生素疗程应为8天15天CPIS评分6:按照肺炎治疗,CPIS6:停用环丙沙星,SinghN,RogersP,AtwoodCW,etal.Short-courseempiricantibiotictherapyforpatientswithpulmonaryinfiltratesintheintensivecareunit.AmJRespirCritCareMed2000;162(2):505-511,HAP/VAP:抗生素疗程,SinghN,RogersP,AtwoodCW,etal.Short-courseempiricantibiotictherapyforpatientswithpulmonaryinfiltratesintheintensivecareunit.AmJRespirCritCareMed2000;162(2):505-511,HAP/VAP:抗生素疗程,NobreV,HarbarthS,GrafJD,etal.Useofprocalcitonintoshortenantibiotictreatmentdurationinsepticpatients:arandomizedtrial.AmJRespirCritCareMed2008;177:498-505,HAP/VAP:抗生素疗程,PCT指导抗生素治疗社区获得性下呼吸道感染不良预后相似(15.4%vs.18,9%)，抗生素疗程缩短(5.7dvs.8.7d)AECOPD减少抗生素使用(40%vs.72%)，减少6个月内抗生素使用(RR0.76;95%CI0.640.92)社区获得性肺炎减少抗生素使用(RR0.52,95%CI0.480.58),SchuetzP,Christ-CrainM,ThomannR,etal.Effectofprocalcitonin-basedguidelinesvsstandardguidelinesonantibioticuseinlowerrespiratorytractinfections:TheProHOSPrandomizedcontrolledtrial.JAMA2009;302(10):1059-1066StolzD,Christ-CrainM,BingisserR,etal.AntibiotictreatmentofexacerbationsofCOPD.Chest2007;131:9-19Christ-CrainM,StolzD,BingisserR,etal.Procalcitoninguidanceofantibiotictherapyincom