氣道分泌物培養(yǎng)的臨床意義北京協(xié)和醫(yī)院杜斌ConflictsofInterestAstellasAstraZenecaBayerDainipponSumimotoPharmaEliLillyGlaxoWellcomeMSDPfizer(Wyeth)…臨床病例臨床病例2021/3/13ICUDay12BT39.8°CWCC16.8體格檢查雙肺濕羅音呼吸機(jī)條件升高PEEP816FiO20.40.6PaO2/FiO216580臨床病例考慮VAP準(zhǔn)備應(yīng)用經(jīng)驗(yàn)性抗生素住院醫(yī)師意見(jiàn)一周前曾留取痰培養(yǎng)銅綠假單胞菌有助于確定目前致病菌?VAP發(fā)生前的微生物學(xué)檢查739名可疑VAP患者入選281名(39%)患者入選前1–3日有培養(yǎng)結(jié)果130名(46%)患者培養(yǎng)出致病微生物SandersKM,AdhikariNKJ,FriedrichJO,etal.Previousculturesarenotclinicallyusefulforguidingempiricantibioticsinsuspectedventilator-associatedpneumonia:secondaryanalysisfromarandomizedtrial.JCritCare2021;23:58-63VAP發(fā)生前的微生物學(xué)檢查SandersKM,AdhikariNKJ,FriedrichJO,etal.Previousculturesarenotclinicallyusefulforguidingempiricantibioticsinsuspectedventilator-associatedpneumonia:secondaryanalysisfromarandomizedtrial.JCritCare2021;23:58-63VAP發(fā)生前的微生物學(xué)檢查SandersKM,AdhikariNKJ,FriedrichJO,etal.Previousculturesarenotclinicallyusefulforguidingempiricantibioticsinsuspectedventilator-associatedpneumonia:secondaryanalysisfromarandomizedtrial.JCritCare2021;23:58-63VAP發(fā)生前的微生物學(xué)檢查經(jīng)驗(yàn)性抗生素錯(cuò)誤率根據(jù)革蘭染色結(jié)果 16%(11–33%)根據(jù)別離所有微生物 37%(29–45%)根據(jù)藥敏結(jié)果 39%(31–48%)SandersKM,AdhikariNKJ,FriedrichJO,etal.Previousculturesarenotclinicallyusefulforguidingempiricantibioticsinsuspectedventilator-associatedpneumonia:secondaryanalysisfromarandomizedtrial.JCritCare2021;23:58-63VAP發(fā)生前的微生物學(xué)檢查BouzaE,PérezA,Mu?ozP,etal.Ventilator-associatedpneumoniaafterheartsurgery:Aprospectiveanalysisandthevalueofsurveillance.CritCareMed2003;31:1964–1970.VAP發(fā)生前的微生物學(xué)檢查VAP診斷標(biāo)準(zhǔn)CXR出現(xiàn)新發(fā)浸潤(rùn)影或原有浸潤(rùn)影加重以下標(biāo)準(zhǔn)中2條或2條以上:發(fā)熱(38.5C)或低體溫(<36C)白細(xì)胞升高(12x109/L)膿性氣管分泌物過(guò)去48小時(shí)內(nèi)PaO2/FIO2下降15%或CPIS>6TBX診斷標(biāo)準(zhǔn)膿性氣管分泌物CXR沒(méi)有肺炎導(dǎo)致的浸潤(rùn)影以下標(biāo)準(zhǔn)中2條或2條以上:發(fā)熱(38.5C)或低體溫(<36C)白細(xì)胞升高(12x109/L)呼吸道分泌物細(xì)菌計(jì)數(shù)明顯升高BouzaE,PérezA,Mu?ozP,etal.Ventilator-associatedpneumoniaafterheartsurgery:Aprospectiveanalysisandthevalueofsurveillance.CritCareMed2003;31:1964–1970.VAP發(fā)生前的微生物學(xué)檢查VAP患病率 7.87%(28/356)發(fā)病率 34.5例/1,000機(jī)械通氣日TBX患病率 8.15%(29/356)發(fā)病率 31.13例/1,000機(jī)械通氣日BouzaE,PérezA,Mu?ozP,etal.Ventilator-associatedpneumoniaafterheartsurgery:Aprospectiveanalysisandthevalueofsurveillance.CritCareMed2003;31:1964–1970.VAP發(fā)生前的微生物學(xué)檢查微生物學(xué)監(jiān)測(cè)1626個(gè)標(biāo)本平均每名患者4.562.8個(gè)標(biāo)本[2–30]預(yù)測(cè)準(zhǔn)確性VAP 1/28TBX 1/29BouzaE,PérezA,Mu?ozP,etal.Ventilator-associatedpneumoniaafterheartsurgery:Aprospectiveanalysisandthevalueofsurveillance.CritCareMed2003;31:1964–1970.VAP發(fā)生前微生物培養(yǎng)結(jié)果BouzaE,PérezA,Mu?ozP,etal.Ventilator-associatedpneumoniaafterheartsurgery:Aprospectiveanalysisandthevalueofsurveillance.CritCareMed2003;31:1964–1970.VAP發(fā)生前微生物培養(yǎng)結(jié)果BouzaE,PérezA,Mu?ozP,etal.Ventilator-associatedpneumoniaafterheartsurgery:Aprospectiveanalysisandthevalueofsurveillance.CritCareMed2003;31:1964–1970.VAP發(fā)生前的微生物學(xué)檢查致病菌僅能發(fā)現(xiàn)33%(73/220)的致病菌呼吸道別離細(xì)菌的陽(yáng)性預(yù)期值<72h:56%72h:13%患者對(duì)38%(47/125)的病例完全沒(méi)有幫助僅31%(39/125)的病例致病菌完全吻合BouzaE,PérezA,Mu?ozP,etal.Ventilator-associatedpneumoniaafterheartsurgery:Aprospectiveanalysisandthevalueofsurveillance.CritCareMed2003;31:1964–1970.VAP發(fā)生前的微生物學(xué)檢查結(jié)論VAP發(fā)生前常規(guī)進(jìn)行微生物檢查僅能發(fā)現(xiàn)少量致病菌由于別離的多數(shù)細(xì)菌并不參與其后的VAP發(fā)病,因此培養(yǎng)結(jié)果常常引起誤導(dǎo)耐藥細(xì)菌在引發(fā)感染前能夠別離到敏感性<70%不能作為經(jīng)驗(yàn)性抗生素選擇的唯一依據(jù)經(jīng)驗(yàn)性抗生素治療應(yīng)當(dāng)覆蓋VAP發(fā)生前72小時(shí)內(nèi)呼吸道別離出的細(xì)菌HayonJ,FiglioliniC,CombesA,TrouilletJL,KassisN,DombretMC,GibertC,ChastreJ.RoleofSerialRoutineMicrobiologicCultureResultsintheInitialManagementofVentilator-associatedPneumonia.AmJRespirCritCareMed2002;165:41-46VAP發(fā)生前的微生物學(xué)檢查結(jié) 論既往培養(yǎng)結(jié)果與疑心VAP時(shí)培養(yǎng)結(jié)果一致性很差不應(yīng)根據(jù)既往培養(yǎng)結(jié)果指導(dǎo)經(jīng)驗(yàn)性抗生素治療SandersKM,AdhikariNKJ,FriedrichJO,etal.Previousculturesarenotclinicallyusefulforguidingempiricantibioticsinsuspectedventilator-associatedpneumonia:secondaryanalysisfromarandomizedtrial.JCritCare2021;23:58-63臨床病例決定不考慮既往呼吸道分泌物培養(yǎng)結(jié)果經(jīng)驗(yàn)性抗生素選擇?主治醫(yī)師問(wèn)題是否等待痰涂片結(jié)果?北京協(xié)和醫(yī)院檢驗(yàn)科細(xì)菌室姓名：XXX 性別：男性年齡：75 病房：MICU標(biāo)本：痰 日期：2021/3/12鏡檢結(jié)果上皮細(xì)胞 <10/LPFWCC >25/LPF涂片結(jié)果革蘭陰性桿菌 大量革蘭陽(yáng)性球菌 可見(jiàn)VAP治療

–革蘭染色結(jié)果QuestionsAnswersInthecaseofanegativeGram’sstainofarespiratorysampleofapatientwithasuspicionofVAP,wouldyouwaitforculturestostartantibiotics?NoDependingonthepatient*(10/12)(2/12)RelloJ,PaivaJA,BaraibarJ,etal.Internationalconferenceforthedevelopmentofconsensusonthediagnosisandtreatmentofventilator-associatedpneumonia.Chest2001;120:955-970*YesiftheclinicalsituationclearlysuggestiveofpneumoniaandifpatientathighriskorclinicallydeterioratingVAP治療

–革蘭染色結(jié)果完全符合部分符合不符合Allaouchiche(n=51)26205Duflo(n=67)261922Davis(n=155)715430Raghavendran(n=186)903750Albert(n=705)389108208總計(jì)(n=1164)602(51.7)238(20.4)324(27.8)僅有1/2的VAP病例ETA革蘭染色結(jié)果與培養(yǎng)結(jié)果相符AllaouchicheB,JaumainH,ChassardD,etal.Gramstainofbronchoalveolarlavagefluidintheearlydiagnosisofventilator-associatedpneumonia.BrJAnaesth1999;83:845-849DufloF,AllaouchicheB,DebonR,etal.AnevaluationoftheGramstaininprotectedbronchoalveolarlavagefluidfortheearlydiagnosisofventilator-associatedpneumonia.AnesthAnalg2001;92:442-447DavisKA,EckertMJ,ReedRLII,etal.Ventilator-associatedpneumoniaininjuredpatients:doyoutrustyourGramstain?JTrauma2005;58:462-466RaghavendranK,WangJ,BelberC,etal.PredictivevalueofsputumGramstainforthedeterminationofappropriateantibiotictherapyinventilator-associatedpneumonia.JTrauma2007;62:1377-1383AlbertM,FriedrichJO,AdhikariNKJ,etal.UtilityofGramstainintheclinicalmanagementofsuspectedventilator-associatedpneumonia:secondaryanalysisofamulticenterrandomizedtrial.JCritCare2021;23:74-81VAP治療

–革蘭染色結(jié)果VeinsteinA,Brun-BuissonC,DerrodeN,etal.Validationofanalgorithmbasedondirectexaminationofspecimensinsuspectedventilator-associatedpneumonia.IntensiveCareMed2006;32:676-683SuspectedVAPPTCGramstain-veETAGramstain+veETA&PTC*ETAGramstain-vePTCGramstain+veEmpiricTherapyWithholdTherapySeverityCriteria**YesNo*ETA,endotrachealaspirate;PTC,protectedtelescopingcatheter**extensivelunginvolvementorseverehypoxemia(P/Fratio<200),oroccurrenceofseveresepsisorsepticshockVAP治療

–革蘭染色結(jié)果VeinsteinA,Brun-BuissonC,DerrodeN,etal.Validationofanalgorithmbasedondirectexaminationofspecimensinsuspectedventilator-associatedpneumonia.IntensiveCareMed2006;32:676-683SuspectedVAP(n=76)PTCGramstain-ve(n=40)ETAGramstain–ve(n=21)PTCGramstain+ve(n=36)EmpiricTherapyTherapyWithheldPendingCulturesSeverityCriteriaYes(n=7)No(n=12)ETAGramstain+ve(n=19)ConfirmedVAP(n=30)ConfirmedVAP(n=4)ConfirmedVAP(n=4)ConfirmedVAP(n=3)VAP治療–革蘭染色結(jié)果SeSpPPVNPVSimplifiedCPIS>632665245CPISETA-Gramstain>676406058CPISPTC-Gramstain>666546358Strategystudies83747979VeinsteinA,Brun-BuissonC,DerrodeN,etal.Validationofanalgorithmbasedondirectexaminationofspecimensinsuspectedventilator-associatedpneumonia.IntensiveCareMed2006;32:676-683這一治療策略提示PTC革蘭染色敏感性73%，特異性83%，PPV83%，NPV73%，可能漏診VAPETA革蘭染色敏感性88%，特異性51%，PPV68%，NPV78%，可能誤診VAPWhentostartabx疑心VAP后盡早開(kāi)始12h內(nèi)?不應(yīng)等待痰涂片結(jié)果即使痰涂片陰性，也需使用經(jīng)驗(yàn)性抗生素臨床病例長(zhǎng)期機(jī)械通氣患者下呼吸道的細(xì)菌定植目的：檢查接受長(zhǎng)期機(jī)械通氣患者肺泡內(nèi)細(xì)菌負(fù)荷背景：大學(xué)醫(yī)院及長(zhǎng)期護(hù)理院的呼吸監(jiān)護(hù)病房患者：接受長(zhǎng)期機(jī)械通氣且無(wú)肺炎臨床表現(xiàn)的14名患者指標(biāo)：右中葉及舌葉BALF的定量培養(yǎng)結(jié)果：在進(jìn)行檢查的32個(gè)肺葉中的29個(gè),至少有一種微生物定量培養(yǎng)>104cfu/mL.多數(shù)肺葉有多種微生物生長(zhǎng)BaramD,HulseG,PalmerLB.StablePatientsReceivingProlongedMechanicalVentilationHaveaHighAlveolarBurdenofBacteria.Chest2005;127:1353-1357機(jī)械通氣患者的細(xì)菌定植(n=356)BouzaE,PérezA,Mu?ozP,etal.Ventilator-associatedpneumoniaafterheartsurgery:Aprospectiveanalysisandthevalueofsurveillance.CritCareMed2003;31:1964–1970.下呼吸道別離出念珠菌的意義25名非粒細(xì)胞缺乏的機(jī)械通氣(>72h)患者去世后立即進(jìn)行肺活檢去世后立即進(jìn)行下呼吸道采樣氣道內(nèi)吸取物保護(hù)性毛刷[PSB]肺泡支氣管灌洗[BAL]盲目活檢[平均每例患者14塊組織]雙側(cè)纖維支氣管鏡指導(dǎo)下活檢[每例患者2塊組織]肺組織標(biāo)本的組織學(xué)檢查呼吸道標(biāo)本區(qū)分為念珠菌陽(yáng)性及其他elEbiaryM,TorresA,FabregasN,etal.SignificanceoftheisolationofCandidaspeciesfromrespiratorysamplesincriticallyill,non-neutropenicpatients:animmediatepostmortemhistologicstudy.AmJRespirCritCareMed1997;156:583-590下呼吸道別離出念珠菌的意義25名非粒細(xì)胞缺乏的機(jī)械通氣患者(>72h)去世后立即進(jìn)行尸體解剖,并采取下呼吸道標(biāo)本肺組織病理檢查念珠菌病 8%(2/25)呼吸道標(biāo)本培養(yǎng)念珠菌 40%(10/25)VS.elEbiaryM,TorresA,FabregasN,etal.SignificanceoftheisolationofCandidaspeciesfromrespiratorysamplesincriticallyill,non-neutropenicpatients:animmediatepostmortemhistologicstudy.AmJRespirCritCareMed1997;156:583-590下呼吸道別離出念珠菌的意義XIII.WhatisthesignificanceofCandidaisolatedfromrespiratorysecretions?Recommendation59.GrowthofCandidafromrespiratorysecretionsrarelyindicatesinvasivecandidiasisandshouldnotbetreatedwithantifungaltherapy(A-III)PappasPG,KauffmanCA,AndesD,etal.Clinicalpracticeguidelinesforthemanagementofcandidiasis:2021updatebytheInfectiousDiseasesSocietyofAmerica.ClinInfectDis2021;48:503-535醫(yī)院獲得性肺炎的診斷:痰培養(yǎng)的準(zhǔn)確性敏感性=82%肺炎患者培養(yǎng)陽(yáng)性比例82%肺炎患者培養(yǎng)陰性比例18%特異性=0–33%非肺炎患者培養(yǎng)陰性比例0–33%非肺炎患者培養(yǎng)陽(yáng)性比例67–100%臨床病例如果沒(méi)有痰培養(yǎng)結(jié)果，是否仍然考慮肺炎?臨床表現(xiàn)BT39.8°C

,WCC16.8

呼吸機(jī)條件升高(PEEP8

16,FiO20.4

0.6,PaO2/FiO2165

80)體格檢查雙肺濕羅音氣道分泌物白色，量少腹腔引流轉(zhuǎn)為膿性腹部出現(xiàn)壓痛/反跳痛/肌緊張臨床病例如果沒(méi)有痰培養(yǎng)結(jié)果，是否仍然考慮肺炎?臨床表現(xiàn)高度提示肺以外部位感染腹腔感染明確尚需除外其他部位感染肺炎診斷不明確氣道分泌物性狀CXR對(duì)稱性改變痰培養(yǎng)=定植臨床病例如果沒(méi)有痰培養(yǎng)結(jié)果，是否仍然考慮肺炎?臨床表現(xiàn)BT39.8°C

,WCC16.8

呼吸機(jī)條件升高(PEEP8

16,FiO20.4

0.6,PaO2/FiO2165

80)體格檢查雙肺大量痰鳴音氣道分泌物黃色膿性，大量其他部位無(wú)明顯感染表現(xiàn)腹部，泌尿系，靜脈導(dǎo)管氣管內(nèi)吸取物常規(guī)培養(yǎng)的診斷價(jià)值某些致病菌(如銅綠假單胞菌)培養(yǎng)為陰性時(shí),可以除外其感染致病菌定植菌臨床病例考慮肺部化膿性細(xì)菌感染氣道分泌物培養(yǎng)結(jié)果2021/3/12鮑曼不動(dòng)桿菌2021/3/13MRSA2021/3/13銅綠假單胞菌氣道分泌物培養(yǎng)結(jié)果不一致致病菌=?抗生素選擇?臨床病例考慮肺部化膿性細(xì)菌感染氣道分泌物培養(yǎng)結(jié)果2021/3/12鮑曼不動(dòng)桿菌2021/3/13鮑曼不動(dòng)桿菌2021/3/13鮑曼不動(dòng)桿菌氣道分泌物培養(yǎng)結(jié)果一致提示：不動(dòng)桿菌=致病菌針對(duì)性應(yīng)用抗生素頭孢哌酮/舒巴坦米諾環(huán)素可以考慮停用萬(wàn)古霉素氣管內(nèi)吸取物常規(guī)培養(yǎng)的診斷價(jià)值痰培養(yǎng)陰性致病菌=其他菌?(如MRSA)致病菌=MRSA=1-敏感性 =100%-82%=18%連續(xù)三次未培養(yǎng)出致病菌的概率 =18%x18%x18%=0.6%臨床病例2021/3/31臨床表現(xiàn)BT36.8°C,WCC10.8呼吸機(jī)條件降低PEEP4,FiO20.35,PaO2/FiO2248間斷脫機(jī)體格檢查雙肺呼吸音明顯改善氣道分泌物白色，量少其他部位無(wú)明顯感染表現(xiàn)氣道分泌物培養(yǎng)結(jié)果依然陽(yáng)性VAP停用抗生素的臨床指標(biāo)確認(rèn)引起肺部浸潤(rùn)影的非感染性因素(如肺不張,肺水腫)從而無(wú)需抗生素治療病癥及體征提示感染得到控制體溫38.3C白細(xì)胞計(jì)數(shù)<10,000/L[10x109/L]或較最高值下降>25%胸片表現(xiàn)改善或無(wú)進(jìn)展膿性痰消失PaO2/FiO2>250(停用抗生素時(shí)須滿足所有上述標(biāo)準(zhǔn))MicekST,WardS,FraserVJ,KollefMH.ARandomizedControlledTrialofanAntibioticDiscontinuationPolicyforClinicallySuspectedVentilator-AssociatedPneumonia.Chest2004;125:1791–1799VAP停用抗生素的策略MicekST,WardS,FraserVJ,KollefMH.ARandomizedControlledTrialofanAntibioticDiscontinuationPolicyforClinicallySuspectedVentilator-AssociatedPneumonia.Chest2004;1