呼吸機(jī)相關(guān)性肺炎(已看,有必要再看)課件

呼吸機(jī)相關(guān)性肺炎HAP/VAP:概要流行病學(xué)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(shí)后發(fā)生且住院時(shí)不處于潛伏期的肺炎呼吸機(jī)相關(guān)性肺炎(VAP)氣管插管48小時(shí)以后發(fā)生的肺炎因重度HAP需要?dú)夤懿骞苷邞?yīng)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(hù)院或長(zhǎng)期醫(yī)療機(jī)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(xué)KumpfG,etal.JClinEpidemiol1998;54:495-502LizioliA,etal.JHospInfect2003;54:141-148RichardsMJ,etal.CritCareMed1999;27:887-892HAP/VAP:流行病學(xué)機(jī)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(xué)機(jī)械通氣510累積患病率(%)d敏感菌引起,預(yù)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(dòng)桿菌屬)感染、不恰當(dāng)?shù)目股刂委煹纫蛩叵嚓P(guān)。HAP/VAP:危險(xiǎn)因素H2受體拮抗劑進(jìn)行應(yīng)激性潰瘍預(yù)防“自由”輸血去白細(xì)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(dòng)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(yáng)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(yuǎn)端標(biāo)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(tuán)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(xì)胞缺乏免疫正?；颊吆币姴《久庖哒Ｕ吆币娏鞲胁《?，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: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(xì)菌學(xué)肺炎鏈球菌銅綠假單胞菌流感嗜血桿菌不動(dòng)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(tuán)菌粘質(zhì)沙雷氏菌洋蔥伯克霍爾德菌曲霉菌屬預(yù)后病情較輕，對(duì)預(yù)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(wèn)題2以下哪個(gè)不是呼吸機(jī)相關(guān)性肺炎確切的發(fā)病機(jī)制誤吸直接吸入血行性播散胃腸道細(xì)菌移位以上答案均不對(duì)HAP/VAP:發(fā)病機(jī)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(yīng)用抗生素宿主因素(免疫抑制,燒傷)消化道細(xì)菌定植細(xì)菌誤吸細(xì)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(wù)人員不足經(jīng)胸種植原發(fā)性菌血癥胃腸道細(xì)菌移位HAP/VAP:影像學(xué)診斷對(duì)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(xué)判斷也不能提高診斷的正確性若胸片顯示明顯浸潤(rùn)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(xué)表現(xiàn)的敏感性和特異性差異很大，診斷準(zhǔn)確性均不超過(guò)70%支氣管氣像診斷肺炎的準(zhǔn)確性最高(64%)HAP/VAP:影像學(xué)診斷CXRvs.CT手術(shù)后肺實(shí)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(xì)菌學(xué)診斷下呼吸道標(biāo)本的半定量培養(yǎng)特異性低：培養(yǎng)結(jié)果陽(yáng)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(yīng)用或更換抗生素常導(dǎo)致過(guò)度應(yīng)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(dǎo)抗生素治療HAP/VAP:細(xì)菌學(xué)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(zhǔn)確采樣部位越遠(yuǎn)特異性越高敏感性越低診斷閾值越低HAP/VAP:細(xì)菌學(xué)診斷ETA(n=374)BAL(n=365)合計(jì)(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(wú)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(xì)菌學(xué)診斷ETABALP值28天病死率18.4%18.9%0.946天時(shí)針對(duì)性治療74.6%74.2%0.90無(wú)抗生素存活天數(shù)10.6±7.910.4±7.50.86最高M(jìn)ODS評(píng)分8.6±4.08.3±3.60.26TheCanadianCriticalCareTrialsGroup.Arandomizedtrialofdiagnostictechniquesforventilator-associatedpneumonia.NEnglJMed2006;355:2619-2630HAP/VAP:綜合診斷CPIS評(píng)分012氣管吸取物無(wú)無(wú)膿性分泌物膿性分泌物CXR浸潤(rùn)影無(wú)浸潤(rùn)影彌漫性浸潤(rùn)影局灶性浸潤(rùn)影肺部浸潤(rùn)影進(jìn)展無(wú)進(jìn)展有進(jìn)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(wú)ARDS的證據(jù)微生物學(xué)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(píng)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(shí)，立即開始正確的經(jīng)驗(yàn)性抗生素治療至關(guān)重要HAP/VAP:經(jīng)驗(yàn)性抗生素?zé)oMDR致病菌危險(xiǎn)因素、任何嚴(yán)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(yàn)性抗生素有MDR致病菌危險(xiǎn)因素、任何嚴(yán)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(dòng)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(wàn)古霉素嗜肺軍團(tuán)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(wàn)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(xiǎn)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(jìn)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(yīng)根據(jù)當(dāng)?shù)丶?xì)菌流行病資料應(yīng)用經(jīng)驗(yàn)性抗生素第2/3天：培養(yǎng)結(jié)果并評(píng)價(jià)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(shí)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(píng)估培養(yǎng)陰性培養(yǎng)陽(yáng)性培養(yǎng)陰性培養(yǎng)陽(yáng)性否是培養(yǎng)陰性培養(yǎng)陽(yáng)性培養(yǎng)陰性培養(yǎng)陰性培養(yǎng)陽(yáng)性培養(yǎng)陽(yáng)性培養(yǎng)陰性培養(yǎng)陰性培養(yǎng)陽(yáng)性HAP/VAP:局部抗生素局部注射氨基糖甙局部用藥提高細(xì)菌學(xué)清除率，但不改變臨床預(yù)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(yīng)體外試驗(yàn)證實(shí)有效中性粒細(xì)胞缺乏或血行性感染患者預(yù)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(xì)菌學(xué)清除：64.1%vs.29.4%機(jī)械通氣時(shí)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(xì)菌學(xué)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(duì)VAP經(jīng)驗(yàn)性治療時(shí)，應(yīng)根據(jù)當(dāng)?shù)丶?xì)菌耐藥情況，選擇適當(dāng)?shù)目股剡M(jìn)行單藥治療HAP/VAP:問(wèn)題3呼吸機(jī)相關(guān)性肺炎的抗生素療程應(yīng)為8天15天肺部感染評(píng)分

CPIS評(píng)分<6血清降鈣素原

PCT<0.1以上答案都不對(duì)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(jī)械通氣時(shí)間無(wú)顯著差別減少了抗生素使用避免了細(xì)菌耐藥的發(fā)生

8天：亞組發(fā)現(xiàn)非發(fā)酵G-桿菌復(fù)發(fā)（銅綠、不動(dòng)）HAP/VAP:抗生素療程HAP/VAP:抗生素療程對(duì)于接受適當(dāng)?shù)某跏冀?jīng)驗(yàn)性治療的呼吸機(jī)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(yàn)性抗生素治療不正確，需要對(duì)抗生素進(jìn)行調(diào)整時(shí)，沒(méi)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(píng)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(dǎo)抗生素治療社區(qū)獲得性下呼吸道感染不良預(yù)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(gè)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