e5吸科耐藥革蘭陰性桿菌與治療策略 課件

2023/7/12Dr.HUBijie1呼吸科耐藥革蘭陰性桿菌

與治療策略

株洲市二醫(yī)院劉和平副主任醫(yī)師2023/7/12Dr.HUBijie2CAP:OutpatientPreviouslyHealthyNorecentantibiotictherapy:AmacrolideaordoxycyclineRecentantibiotictherapy:Arespiratoryfluoroquinolone(RFQ)alone,anadvancedmacrolide(AM)plushigh-doseamoxicillinorAMplushigh-doseamoxicillin-clavulanateComorbidities

(COPD,Diabetes,RenalorCongestiveHeartFailure,orMalignancy)Norecentantibiotictherapy:AMorRFQRecentantibiotictherapy:RFQaloneorAMplusaB-lactamSuspectedaspirationwithinfection:Amoxicillin-clavulanateorclindamycinInfluenzawithbacterialsuperinfection:B-lactamoraRFQ2023/7/12Dr.HUBijie3CAP:InpatientMedicalWardNorecentantibiotictherapy:RFQaloneorAMplusB-lactamRecentantibiotictherapy:AMplusB-lactamorRFalone(regimenselectedwilldependonnatureofrecentantibiotictherapy)IntensiveCareUnit(ICU)Pseudomonasinfectionisnotanissue:B-lactampluseitherAMorRFQPseudomonasinfectionisnotanissuebutpatienthasB-lactamallergy:RFQ,withorwithoutclindamycinPseudomonasinfectionisanissue:Either(1)anantipseudomonalagentplusciprofluoxacin,or(2)anantipseudomonalagentplusanaminoglycosideplusRFQoramacrolidePseudomonasinfectionisanissuebutpatienthasa-lactamallergy:theEither(1)aztreonampluslevofluoxacinor(2)aztreonamplusmoxifluoxacinorgatifluoxacin,withorwithoutanaminoglycosideNursingHomeReceivingtreatmentinnursinghome:RFQaloneoramoxicillin-clavulanateplusAMHospitalized:SameasformedicalwardandICU2023/7/12Dr.HUBijie4NNIS報告的醫(yī)院內(nèi)肺炎病原體檢出率％排位80～82(15331)90～96(13433)80～8290～96枸櫞酸菌111111腸桿菌91143大腸桿菌8456肺炎桿菌10834其他克雷伯41811奇異變形桿菌5268其他變形桿菌001413粘質(zhì)沙雷菌4377其他沙雷菌101213腸桿菌科合計4230綠膿桿菌131722金葡菌131911CoNS12138腸球菌22108念珠菌3595其他26252023/7/12Dr.HUBijie5銅綠假單胞菌、肺炎克雷伯菌和鮑曼不動桿菌

是HAP常見的革蘭陰性桿菌AntimicrobAgentsChemother.2003Nov;47(11):3442-72023/7/12Dr.HUBijie6NosocomialtracheobronchitisinMVpatients:

incidence,aetiologyandoutcomeSurgicalMedicalPatientsn36165Gram-negativemicroorganisms34(77.2)162(78.7)Pseudomonasaeruginosa14(31.8)58(28)Acinetobacterbaumannii6(13.6)55(26.5)Klebsiellaspp.4(9.0)6(2.8)Enterobacteraerogenes3(6.8)4(1.9)Serratiaspp.2(4.5)11(5.3)Stenotrophomonasmaltophilia2(4.5)7(3.3)Escherichiacoli1(2.2)8(3.8)Haemophilusinfluenzae04(1.9)Other2(4.5)9(4.3)Gram-positivemicroorganisms10(22.7)45(21.7)MRSA7(15.9)31(14.9)MSSA2(4.5)6(2.8)Streptococcuspneumoniae1(2.2)8(3.8)EurRespirJ2002;20:1483–1489.2023/7/12Dr.HUBijie7醫(yī)院內(nèi)肺炎病原菌

〔Meta分析，全國1990～1998年，6062株菌〕病原體菌株構(gòu)成％綠膿桿菌124120.6克雷伯菌60810.1大腸桿菌3565.9腸桿菌屬2784.6不動桿菌2754.6嗜麥芽窄食單胞1001.7流感嗜血桿菌500.8金黃色葡萄球菌3585.9腸球菌831.4肺炎鏈球菌611.02023/7/12Dr.HUBijie8病原菌發(fā)生類型株數(shù)%早發(fā)性晚發(fā)性鮑曼不動桿菌1121318.6銅綠假單胞菌1101115.7金黃色葡萄球菌36912.9大腸埃希菌0557.1陰溝腸桿菌1457.1肺炎克雷伯菌1345.7粘質(zhì)沙雷菌0445.7念珠菌1345.7嗜麥芽窄食單胞0334.3變形桿菌0334.3表皮葡萄球菌1122.9腸球菌1122.9產(chǎn)堿桿菌0222.9肺炎鏈球菌1011.4洛菲不動桿菌0111.4黃桿菌0111.4合計115970100.0

52

例

VAP

病

原

分

布

(99~01)

2023/7/12Dr.HUBijie9NLRTI前五位病原菌在6個常見科室的比較謝紅梅，胡必杰，何禮賢，等.2819例醫(yī)院下呼吸道感染病原和預后分析.上海醫(yī)學2003；26：880-8852023/7/12Dr.HUBijie10醫(yī)院內(nèi)肺炎病原早期中期晚期135101520鏈球菌流感桿菌金葡菌MRSA腸桿菌肺克，大腸綠膿桿菌不動桿菌嗜麥芽窄食單胞菌入院天數(shù)2023/7/12Dr.HUBijie11呼吸科常見耐藥革蘭陰性桿菌肺炎克雷伯桿菌，大腸埃希菌腸桿菌屬，沙雷菌，枸櫞酸菌，變形桿菌銅綠假單胞菌，其他假單胞菌鮑曼不動桿菌，其他不動桿菌嗜麥芽窄食單胞菌屬伯克霍爾德菌屬產(chǎn)堿桿菌屬，黃桿菌屬

NPRS結(jié)果顯示，銅綠和鮑曼作為MDR問題正在凸現(xiàn)2023/7/12Dr.HUBijie12細菌耐藥是否會影響病死率?治療肺炎桿菌ESBL菌株血液感染(n=31)適宜治療(n=19)病死率5%不恰當治療(n=12)病死率42%P=0.02Source:SchiappaetalJID1996;74:529-362023/7/12Dr.HUBijie132023/7/12Dr.HUBijie14在ICU中肺部感染耐藥菌問題尤為突出2023/7/12Dr.HUBijie15MDR引起肺炎的防治策略預防醫(yī)院內(nèi)肺炎〔HAP、VAP、HCAP〕早期、準確的病原學診斷，不要治療定植菌和污染菌停止無效、耐藥的抗生素，防止更嚴重的后果加大劑量：從藥敏單中尋找中介〔低敏〕的藥物聯(lián)合使用，在平安范圍內(nèi)的最大劑量，時間依賴性的藥在允許范圍縮短用藥間隔，甚至24h連續(xù)點滴舊藥新用：多粘菌素E，舒巴坦對不動桿菌等聯(lián)合用藥：MIC為16ug/ml的頭孢他啶和16ug/ml的阿米卡星合用可能有效；特門汀與氨曲南聯(lián)合治不發(fā)酵糖菌效果有時很好；氨曲南可耐受金屬酶2023/7/12Dr.HUBijie16ManagingInfectionInTheCriticalCareUnit:HowCanInfectionControlMakeTheICUSafe?CritCareClin.2005Jan;21(1):111-28ShulmanL,OstDDivisionofPulmonaryandCriticalCareMedicine,NorthShoreUniversityHospital,Manhasset,NY11030,USA2023/7/12Dr.HUBijie17VAP預防方法的有效性評價RouteofintubationSearchforsinusitisCircuitchangesHumidifierHumidifierchangesEndotrachealsuctioningSubglotticsecretiondrainageChestphysiotherapyTracheostomyKineticbedsSemi-recumbentpositionPronepositionStressulcerprophylaxisProphylacticantibiotics2023/7/12Dr.HUBijie182023/7/12Dr.HUBijie19Antisepticimpregnatedendotrachealtubesforthepreventionofbacterialcolonization在實驗室氣道模型中建立不同對MRSA,PA,AB和產(chǎn)氣腸桿菌有抗菌作用的氣管插管(ETTs)，包裹有洗必泰和碳酸銀抗菌ETT和對照ETT(未包裹〕用濃度108cfu/ml的菌液污染，5天孵育，管腔的遠端和近端分別采樣細菌培養(yǎng)抗菌ETT細菌定植量為1-100cfu/管，而對照ETT達106cfu/管(P<0.001).結(jié)論：抗菌導管可有效預防VAP相關(guān)細菌在ETT上的生長JHospInfect.2004Jun;57(2):170-42023/7/12Dr.HUBijie20EfficacyofheatandmoistureexchangersinpreventingVAP:meta-analysisofRCTOBJECTIVE:SeveralRCThaveexaminedtheeffectofantibacterialhumidificationstrategies,particularlythereplacementofheatedhumidifiers(HH)byheatandmoistureexchangers(HME),inpreventingVAP.Thepresentmeta-analysisreviewstheseRCTs.METHODS:RCTswereidentifiedbysearchingtheMedlineandCochraneCentralRegisterofControlledTrialsdatabasesfrom1990to2003.WeincludedRCTsusingHMEsinthetreatmentgroupandHHsinthecontrolgroupandreportingtheincidenceofpneumoniaasastudyoutcome.Twoinvestigatorsindependentlyabstractedkeydataondesign,population,interventionandoutcomeofthestudies.RESULTS:Between1990and2003eightRCTsmettheinclusioncriteriaofthisanalysis.PoolingtheresultsfromthesestudiesrevealedareductionintherelativeriskofVAPintheHMEgroup(0.7),particularlyinMVwithadurationofatleast7days(fiveRCTs,relativerisk0.57).CONCLUSIONS:Thismeta-analysisfoundasignificantreductionintheincidenceofVAPinptshumidifiedwithHMEsduringMV,particularlyinptsventilatedfor7daysorlonger.Thisfindingislimitedbytheexclusionofptsathighriskforairwayocclusionfromsomeofthestudies.Contraindications(tenacioussecretions,airwayobstructivedisease,hypothermia)andtechnicalissuesofHMEsmustbeconsidered.FurtherRCTsarenecessarytoexaminethewiderapplicabilityofHMEsandtheirextendeduse.IntensiveCareMed.2005Jan;31(1):5-112023/7/12Dr.HUBijie21Ventilator-associatedpneumoniausingaclosedversusanopentrachealsuctionsystemOBJECTIVE:TheaimofthisstudywastoanalyzetheprevalenceofVAPusingaclosed-trachealsuctionsystem(CS)vs.anopensystem(OS).SETTING:A24-bedmedical-surgicalICUina650-bedtertiaryhospital.PATIENTS:PatientsrequiringMVfor>24hrs.INTERVENTIONS:Patientswererandomizedintotwogroups;onegroupwassuctionedwithCSandanothergroupwiththeOS.MEASUREMENTS:Throatswabsweretakenatadmissionandtwiceaweekuntildischargetoclassifypneumoniainendogenousandexogenous.MAINRESULTS:Atotalof443pts(210withCS,233withOS)wereincluded.Therewerenosignificantdifferencesbetweengroupsofpatientsinage,sex,diagnosisgroups,mortality,numberofaspirationsperday,andAPCHEIIscore.Nosignificantdifferences:inpercentageofptswhodevelopedVAP(20.47%vs.18.02%);inthenumberofVAPcasesper1000MVDs(17.59vs.15.84);intheVAPincidencebyMVduration;intheincidenceofexogenousVAP;inthemicroorganismsresponsibleforpneumonia.PatientcostperdayfortheCSwasmoreexpensivethantheOS(11.11USdollars+/-2.25USdollarsvs.2.50USdollars+/-1.12USdollars,p<.001).結(jié)論:閉合痰液吸引系統(tǒng)不能降低VAP發(fā)病率，包括外源性肺炎CritCareMed.2005Jan;33(1):115-92023/7/12Dr.HUBijie22EarlyantibiotictreatmentforBAL-confirmedventilator-associatedpneumonia:aroleforroutineendotrachealaspiratecultures方法：299需要機械通氣至少48h的病例，每周兩次采集氣管內(nèi)吸引物〔EA〕定量培養(yǎng)。發(fā)生VAP后用BAL培養(yǎng)確定病原體，并與EA結(jié)果進行比較。最后有75例診斷VAP，41例BAL培養(yǎng)陽性，先前常規(guī)EA培養(yǎng)中有34例(83%)陽性，1例早發(fā)肺炎發(fā)生VAP時還沒有采集EA；4例結(jié)果不一致但抗菌藥物選用適宜，2例選用藥物有延遲結(jié)論：每周兩次常規(guī)EA培養(yǎng)對早期正確選用VAP治療抗菌藥物是適宜的Chest.2005Feb;127(2):589-972023/7/12Dr.HUBijie23BlindandbronchoscopicsamplingmethodsinsuspectedVAP-Amulticentreprospectivestudy.OBJECTIVE:Tocompare4samplingmethods:blindtrachealaspirate(blindTA),blindprotectedtelescopingcatheter(blindPTC),bronchoscopicPTCandbronchoscopicBAL,fordiagnosisofVAP.DESIGN&SETTING:Prospectivemulticentrestudy.FiveICUinFrance.PATIENTS:63ptswithMVformorethan48h,norecentantibioticchange(<72h)andsuspectednosocomialpneumonia.INTERVENTIONS:Allpatientsunderwentthefoursamplingmethods.Directexaminationandquantitativeculturesofthefourspecimenswereperformed.MEASUREMENTSANDRESULTS:Visiblesecretionsexpelledfromthecatheterwerepresent40times(63%)forblindPTCand45times(71%)forbronchoscopicPTC.Afterexclusionof11uncertaincases,34VAPwerediagnosed.DirectexaminationofPTC(eitherblindorbronchoscopic)didnotdifferfromdirectexaminationofbronchoscopicBALinpredictingVAPdiagnosisandinguidinginitialantibiotictreatmentcorrectly.ComparedtothatofbronchoscopicBAL(0.98),theareaunderreceiveroperatingcharacteristics(ROC)curvewassmallerforblindTA(0.78,p=0.002),blindPTC(0.83,p=0.009)andbronchoscopicPTC(0.85,p=0.01).Whensampleswithvisiblesecretionsexpelledfromthecatheterwereconsidered,blindandbronchoscopicPTChadareasunderROCcurveclosetothatofbronchoscopicBAL(0.90,p=0.22and0.91,p=0.27,respectively).CONCLUSIONS:BlindPTCappearstobeagoodalternativetobronchoscopicsamplingforVAPdiagnosis,providedthatthesamplecontainsvisiblesecretionsexpelledfromthecatheter.IntensiveCareMed.2004Jul;30(7):1319-262023/7/12Dr.HUBijie24CombinationtherapywithpolymyxinBforthetreatmentofmultidrug-resistantGram-negativerespiratorytractinfectionsBACKGROUND:Thetreatmentofinfectionscausedbymultidrug-resistant(MDR)Gram-negativeorganismsposesatherapeuticchallenge.TheuseofpolymyxinBhasbeenresurrectedspecificallyforthispurpose.PATIENTSANDMETHODS:Weretrospectivelyreviewedtheclinicalandmicrobiologicalefficacy,andsafetyprofileofpolymyxinBinthetreatmentofMDRGram-negativebacterialinfectionsoftherespiratorytract.Twenty-fivecriticallyillpatientsreceivedatotalof29coursesofpolymyxinBadministeredincombinationwithanotherantimicrobialagent.RESULTS:Patientsweretreatedwithintravenous,and/oraerosolizedpolymyxinB.MeandurationofpolymyxinBtherapywas19days(range2-57days).Endoftreatmentmortalitywas21%,andoverallmortalityatdischargewas48%.Nephrotoxicitywasobservedinthreepatients(10%)anddidnotresultindiscontinuationoftherapy.CONCLUSIONS:PolymyxinBincombinationwithotherantimicrobialscanbeconsideredareasonableandsafetreatmentoptionforMDRGram-negativerespiratorytractinfectionsinthesettingoflimitedtherapeuticoptions.JAntimicrobChemother.2004Aug;54(2):566-92023/7/12Dr.HUBijie25銅綠假單胞菌Pseudomonasaeruginosa2023/7/12Dr.HUBijie26A7-yearstudyofseverehospital-acquiredpneumoniarequiringICUadmission在16張和20張內(nèi)科-外科ICU中，連續(xù)觀察需要入住ICU的重癥HAP，共7年。96次重癥HAP中，GNB占51％，PA最常見〔24％〕。51例〔53％〕死亡，曲菌和PA引起的肺炎病死率最高。感染性休克(OR:14.27)和COPD(OR:6.11)是影響預后的獨立危險因素。IntensiveCareMed.2003Nov;29(11):1981-82023/7/12Dr.HUBijie27鮑曼不動桿菌Acinetobacterbaumannii2023/7/12Dr.HUBijie28Effectfrommultipleepisodesofinadequateempiricantibiotictherapyforventilator-associatedpneumoniaonmorbidityandmortalityamongcriticallyilltraumapatientsBACKGROUND:Thepurposeofthisretrospectivestudywastodeterminetheeffectofinadequateempiricantibiotictherapy(IEAT)ontheoutcomeforadulttraumapatientswithVAP.METHODS:Thisstudyenrolled82patientswithmultipleVAPepisodes(200VAPepisodes;mean2.4;range2-5).AnepisodeofIEATwasaVAPepisodewithempirictherapyhavingnoinvitroactivityagainstcausativebacteria.Therewere78(39%)IEATepisodesinvolving54patients.Mostoften,IEATwasattributabletothepresenceofAcinetobacterspp,Stenotrophomonasmaltophilia,orAlcaligenesxylosoxidans.Allthepatientsreceivedappropriatedefinitivetherapyaccordingtothefinalculture.ThepatientswereclassifiedbynumberofIEATepisodes:0(n=28),1(n=34),andmorethan1(n=20).RESULTS:Demographicsandinjuryseverityweresimilaramongthegroups.Themortalityratewas3.6%fornoepisodes,8.8%foroneepisode,and45%formorethanoneepisode(p<0.001).Onthebasisofmultiplelogisticregression,experiencingmultipleIEATepisodeswa