呼吸機相關(guān)性肺炎(已看,有必要再看)課件

呼吸機相關(guān)性肺炎HAP/VAP:概要流行病學診斷策略抗生素治療HAP/VAP/HCAP:定義醫(yī)院獲得性肺炎(HAP)住院48小時后發(fā)生且住院時不處于潛伏期的肺炎呼吸機相關(guān)性肺炎(VAP)氣管插管48小時以后發(fā)生的肺炎因重度HAP需要氣管插管者應按照VAP處理醫(yī)療相關(guān)肺炎(HCAP)發(fā)生感染前90天內(nèi)在急性病醫(yī)院住院≥2天在養(yǎng)護院或長期醫(yī)療機構(gòu)住院近期接受靜脈抗生素治療、化療或發(fā)生感染前30天內(nèi)接受傷口治療就診于醫(yī)院門診或透析門診ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:流行病學KumpfG,etal.JClinEpidemiol1998;54:495-502LizioliA,etal.JHospInfect2003;54:141-148RichardsMJ,etal.CritCareMed1999;27:887-892HAP/VAP:流行病學機械通氣510累積患病率(%)3%/d1%/d2%/dCookDJ,WalterSD,CookRJ,GriffithLE,GuyattGH,LeasaD,JaeschkeRZ,Brun-BuissonC.Incidenceofandriskfactorsforventilator-associatedpneumoniaincriticallyillpatients.AnnInternMed1998;129:440d遲發(fā)性HAP～50%早發(fā)性HAP～50%HAP/VAP:流行病學機械通氣510累積患病率(%)d敏感菌引起,預后好致病菌常是多藥耐藥菌(MDR),病死率高HAP/VAP:病死率總病死率30-70%:

大多數(shù)HAP患者死于基礎(chǔ)病

歸因病死率33-50%

VAP的歸因病死率升高與菌血癥、耐藥菌(如銅綠假單胞菌、不動桿菌屬)感染、不恰當?shù)目股刂委煹纫蛩叵嚓P(guān)。HAP/VAP:危險因素H2受體拮抗劑進行應激性潰瘍預防“自由”輸血去白細胞輸血血糖控制不佳ARDS深度鎮(zhèn)靜或肌松HAP/VAP:病因?qū)WFagonKollefPapazianRelloTimsitTorres革蘭陰性桿菌

55~85%銅綠假單胞菌192927501628不動桿菌屬104501224嗜麥芽窄食單胞菌073000腸桿菌屬168004流感嗜血桿菌61810130其他革蘭陰性桿菌24102841032革蘭陽性球菌20~30%金黃色葡萄球菌20302192620肺炎鏈球菌410744HAP/VAP:病因?qū)W支氣管遠端標本培養(yǎng)分離出口咽部定植菌（草綠色鏈球菌，凝固酶陰性葡萄球菌，奈瑟氏菌屬，棒狀桿菌屬）難以解釋在免疫抑制甚至免疫正?；颊呖赡芤鸶腥綜abelloH,TorresA,CelissR,El-EbiaryM,delaBellacasaJP,XaubetA,GonzalezJ,AugustiC,SolerN.Bacterialcolonizationofdistalairwaysinhealthysubjectsandcroniclungdiseases:abronchoscopicstudy.EurRespirJ1997;10:1137–1144HAP/VAP:病因?qū)W金黃色葡萄球菌糖尿病，頭顱創(chuàng)傷，住ICU厭氧菌：在VAP中的重要性尚不明確非插管患者誤吸VAP罕見肺炎軍團菌：發(fā)生率缺乏數(shù)據(jù)，但重要性受關(guān)注免疫抑制患者如器官移植，HIV，糖尿病，基礎(chǔ)肺病，終末期腎病HAP/VAP:病因?qū)W真菌（包括念珠菌和曲霉菌）器官移植，免疫抑制，中性粒細胞缺乏免疫正?；颊吆币姴《久庖哒Ｕ吆币娏鞲胁《荆绷鞲胁《?，腺病毒，麻疹病毒，呼吸道合胞病毒占病毒的70%HAP/VAP:分類012345678Early-onsetHAPLate-onsetHAPTimefromhospitalization(days)012345678Early-onsetVAPLate-onsetVAPTimefromIntubation(days)ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:病因?qū)W早發(fā)性HAP/VAP遲發(fā)性HAP/VAP細菌學肺炎鏈球菌銅綠假單胞菌流感嗜血桿菌不動桿菌MSSAMRSA敏感GNB耐藥腸桿菌科大腸桿菌腸桿菌屬肺炎克氏菌ESBL+ve菌變形桿菌屬克雷伯菌屬腸桿菌屬嗜肺軍團菌粘質(zhì)沙雷氏菌洋蔥伯克霍爾德菌曲霉菌屬預后病情較輕，對預后影響小歸因病死率高病死率低罹患率高ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:問題2以下哪個不是呼吸機相關(guān)性肺炎確切的發(fā)病機制誤吸直接吸入血行性播散胃腸道細菌移位以上答案均不對HAP/VAP:發(fā)病機制改變胃排空及胃液pH值的藥物有生物膜的裝置(氣管插管,鼻胃管)既往應用抗生素宿主因素(免疫抑制,燒傷)消化道細菌定植細菌誤吸細菌吸入醫(yī)院獲得性肺炎水,藥物溶液及呼吸治療裝置污染感染控制措施不夠(洗手,隔離衣,手套)醫(yī)務人員不足經(jīng)胸種植原發(fā)性菌血癥胃腸道細菌移位HAP/VAP:影像學診斷對于可疑肺炎患者，如果根據(jù)其他臨床表現(xiàn)不能確診，影像學判斷也不能提高診斷的正確性若胸片顯示明顯浸潤影，則鑒別心源性肺水腫、非心源性肺水腫、肺挫傷和肺不張將非常困難各種影像學表現(xiàn)的敏感性和特異性差異很大，診斷準確性均不超過70%支氣管氣像診斷肺炎的準確性最高(64%)HAP/VAP:影像學診斷CXRvs.CT手術(shù)后肺實變：敏感性0.33–1.00，特異性>0.79不同醫(yī)生判讀的一致性放射科醫(yī)生：kappa0.27ICU醫(yī)生：12–39%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:細菌學診斷下呼吸道標本的半定量培養(yǎng)特異性低：培養(yǎng)結(jié)果陽性可能僅提示定植敏感性高：培養(yǎng)結(jié)果陰性有助于除外感染除非剛剛應用或更換抗生素常導致過度應用抗生素革蘭染色結(jié)果結(jié)合培養(yǎng)結(jié)果有助于指導抗生素治療HAP/VAP:細菌學診斷PSBETABAL診斷閾值103cfu/mL105–106cfu/mL104–105cfu/mL敏感性667673特異性907582特異敏感準確采樣部位越遠特異性越高敏感性越低診斷閾值越低HAP/VAP:細菌學診斷ETA(n=374)BAL(n=365)合計(n=739)明確VAP01(0.3)1(0.1)高度可疑VAP0180(49.3)180(24.4)可能VAP310(82.9)134(36.7)444(60.1)無VAP64(17.1)50(13.7)114(15.4)高度可疑VAP=臨床診斷+BALF>104cfu/ml;可能VAP=臨床診斷TheCanadianCriticalCareTrialsGroup.Arandomizedtrialofdiagnostictechniquesforventilator-associatedpneumonia.NEnglJMed2006;355:2619-2630HAP/VAP:細菌學診斷ETABALP值28天病死率18.4%18.9%0.946天時針對性治療74.6%74.2%0.90無抗生素存活天數(shù)10.6±7.910.4±7.50.86最高MODS評分8.6±4.08.3±3.60.26TheCanadianCriticalCareTrialsGroup.Arandomizedtrialofdiagnostictechniquesforventilator-associatedpneumonia.NEnglJMed2006;355:2619-2630HAP/VAP:綜合診斷CPIS評分012氣管吸取物無無膿性分泌物膿性分泌物CXR浸潤影無浸潤影彌漫性浸潤影局灶性浸潤影肺部浸潤影進展無進展有進展體溫,°C≥36.5且≤38.4≥38.5且≤38.9≥39或≤36WCC,x109/L≥4.0且≤11.0<4.0或>11.0<4.0或>11.0+桿狀核≥0.5PaO2/FiO2,mmHg>240或ARDS≤240且無ARDS的證據(jù)微生物學陰性或少量中等量或大量+革蘭染色發(fā)現(xiàn)同樣微生物PuginJ,AuckenthalerR,MiliN,JanssensJP,LewPD,SuterPM.Diagnosisofventilator-associatedpneumoniabybacteriologicanalysisofbronchoscopicandnon-bronchoscopic"blind"bronchoalveolarlavagefluid.AmRevRespirDis1991;143:1121-1129肺部感染評分HAP/VAP:鑒別診斷腫瘤結(jié)締組織疾病血管炎綜合征肺泡出血藥物誘發(fā)肺泡炎肺不張血栓栓塞性疾病胃內(nèi)容物誤吸未治愈社區(qū)獲得性肺炎充血性心力衰竭HAP/VAP:治療LunaCM,VujacichP,NiedermanMS,etal.ImpactofBALdataonthetherapyandoutcomeofventilator-associatedpneumonia.Chest1997;111:676-685不充分的抗生素治療2000名連續(xù)收治的MICU/SICU患者655(25.8%)罹患感染169(8.5%)抗生素治療不充分KollefMH,ShermanG,WardS,etal.Inadequateantimicrobialtreatmentofinfections.Ariskfactorforhospitalmortalityamongcriticallyillpatients.Chest1999;115:462-474因此，臨床高度懷疑VAP時，立即開始正確的經(jīng)驗性抗生素治療至關(guān)重要HAP/VAP:經(jīng)驗性抗生素無MDR致病菌危險因素、任何嚴重程度、早發(fā)性HAP/VAP的初始抗生素可能致病菌推薦抗生素肺炎鏈球菌頭孢曲松流感嗜血桿菌或MSSA左旋氧氟沙星，莫西沙星或環(huán)丙沙星敏感的腸道革蘭陰性桿菌或大腸桿菌氨芐青霉素/舒巴坦肺炎克雷伯菌或腸桿菌屬厄他培南變形桿菌屬粘質(zhì)沙雷氏菌ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:經(jīng)驗性抗生素有MDR致病菌危險因素、任何嚴重程度、遲發(fā)性HAP/VAP的初始抗生素可能致病菌推薦抗生素上表中致病菌及抗假單胞菌頭孢菌素（頭孢吡肟，頭孢他啶）MDR致病菌或銅綠假單胞菌抗假單胞菌碳青霉烯（亞胺培南或美羅培南）肺炎克雷伯菌(ESBL+)或不動桿菌屬β-內(nèi)酰胺/β-內(nèi)酰胺酶抑制劑（哌拉西林/他唑巴坦）加抗假單胞菌喹諾酮（環(huán)丙沙星或左旋氧氟沙星）或氨基糖甙（阿米卡星，慶大霉素或妥布霉素）加MRSA利奈唑烷或萬古霉素嗜肺軍團菌ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:抗生素劑量抗生素劑量抗假單胞菌頭孢菌素頭孢吡肟1–2g,q8–12h頭孢他啶2gq8h抗假單胞菌碳青霉烯亞胺培南500mgq6h,1gq8h或美羅培南1gq8hβ-內(nèi)酰胺/β-內(nèi)酰胺酶抑制劑哌拉西林/他唑巴坦4.5q6h氨基糖甙阿米卡星20mg/kg/d，慶大霉素7mg/kg/d妥布霉素7mg/kg/d抗假單胞菌喹諾酮左旋氧氟沙星750mgqd環(huán)丙沙星400mgq8h萬古霉素15mg/kgq12h利奈唑烷600mgq12hATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:治療懷疑HAP/VAP遲發(fā)性HAP/VAP或MDR危險因素否是使用窄譜抗生素治療使用廣譜抗生素治療ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:治療懷疑HAP/VAP/HCAP采取下呼吸道(LRT)進行培養(yǎng)(定量或半定量)和顯微鏡檢除非肺炎的臨床概率低且LRT鏡檢陰性，否則應根據(jù)當?shù)丶毦餍胁≠Y料應用經(jīng)驗性抗生素第2/3天：培養(yǎng)結(jié)果并評價臨床療效(體溫,WCC,CXR,氧合,膿痰,循環(huán)改變及器官功能)ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-416HAP/VAP:治療ATS/IDSA.Guidelinesforthemanagementofadultswithhospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCritCareMed2005;171:388-41648-72小時臨床改善尋找其他致病菌,并發(fā)癥,其他診斷或其他感染灶調(diào)整抗生素,尋找其他致病菌,并發(fā)癥,其他診斷或其他感染灶考慮停用抗生素如可能抗生素降階梯,治療7-8天后再次評估培養(yǎng)陰性培養(yǎng)陽性培養(yǎng)陰性培養(yǎng)陽性否是培養(yǎng)陰性培養(yǎng)陽性培養(yǎng)陰性培養(yǎng)陰性培養(yǎng)陽性培養(yǎng)陽性培養(yǎng)陰性培養(yǎng)陰性培養(yǎng)陽性HAP/VAP:局部抗生素局部注射氨基糖甙局部用藥提高細菌學清除率，但不改變臨床預后霧化吸入氨基糖甙或多粘菌素B治療MDR致病菌副作用耐藥率?誘發(fā)支氣管痙攣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;55:514-519HAP/VAP:聯(lián)合用藥抗生素的協(xié)同效應體外試驗證實有效中性粒細胞缺乏或血行性感染患者預防耐藥發(fā)生增加抗菌譜β-內(nèi)酰胺+氨基糖甙>β-內(nèi)酰胺+喹諾酮?HAP/VAP:聯(lián)合用藥美羅培南+環(huán)丙沙星(n=369)vs.美羅培南(n=371)RR1.05,95%CI0.78–1.42MDR革蘭陰性桿菌感染(n=56)28天細菌學清除：64.1%vs.29.4%機械通氣時間：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):737-744HAP/VAP:聯(lián)合用藥PaulM,Benuri-SilbigerI,Soares-WeiserK,etal.β-lactammonotherapyversusβ-lactam-aminoglycosidecombinationtherapyforsepsisinimmunocompetentpatients:systematicreviewandmeta-analysisofrandomisedtrials.BMJ2004;328:668總病死率RR0.9095%CI0.77–1.06臨床失敗率RR0.8795%CI0.78–0.97細菌學失敗率RR0.8695%CI0.72–1.02HAP/VAP:聯(lián)合用藥PaulM,Benuri-SilbigerI,Soares-WeiserK,etal.β-lactammonotherapyversusβ-lactam-aminoglycosidecombinationtherapyforsepsisinimmunocompetentpatients:systematicreviewandmeta-analysisofrandomisedtrials.BMJ2004;328:668針對VAP經(jīng)驗性治療時，應根據(jù)當?shù)丶毦退幥闆r，選擇適當?shù)目股剡M行單藥治療HAP/VAP:問題3呼吸機相關(guān)性肺炎的抗生素療程應為8天15天肺部感染評分

CPIS評分<6血清降鈣素原

PCT<0.1以上答案都不對HAP/VAP:抗生素療程ProbabilityofSurvival0102030405060DaysafterBronchoscopy0.00.20.40.60.81.015-day8-dayChastreJ,WolffM,FagonJY,etal.Comparisonof8vs15daysofantibiotictherapyforventilator-associatedpneumoniainadults:arandomizedtrial.JAMA2003;290(19):2588-2598結(jié)果：8天與15天抗生素療程相比:

病死率、住院日和機械通氣時間無顯著差別減少了抗生素使用避免了細菌耐藥的發(fā)生

8天：亞組發(fā)現(xiàn)非發(fā)酵G-桿菌復發(fā)（銅綠、不動）HAP/VAP:抗生素療程HAP/VAP:抗生素療程對于接受適當?shù)某跏冀?jīng)驗性治療的呼吸機相關(guān)性肺炎患者，推薦抗生素療程為8天如果患者初始的經(jīng)驗性抗生素治療不正確，需要對抗生素進行調(diào)整時，沒有足夠的資料推薦適宜的抗生素療程。HAP/VAP:抗生素療程環(huán)丙沙星x3天抗生素10–21天抗生素10–21天CPIS>6CPIS≤6可疑HAP/VAP3天后重新評估CPISCPIS>6:按照肺炎治療CPIS≤6:停用環(huán)丙沙星SinghN,RogersP,AtwoodCW,etal.Short-courseempiricantibiotictherapyforpatientswithpulmonaryinfiltratesintheintensivecareunit.AmJRespirCritCareMed2000;162(2):505-511HAP/VAP:抗生素療程PCT指導抗生素治療社區(qū)獲得性下呼吸道感染不良預后相似(15.4%vs.18,9%)，抗生素療程縮短(5.7dvs.8.7d)AECOPD減少抗生素使用(40%vs.72%)，減少6個月內(nèi)抗生素使用(RR0.76;95%CI0.64–0.92)社區(qū)獲得性肺炎減少抗生素使用(RR0.52,95%CI0.48–0.58)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.Procalcitoningu