吸科耐药革兰阴性杆菌与治疗策略课件

2023/7/27Dr.HUBijie1CAP:OutpatientPreviouslyHealthyNorecentantibiotictherapy:AmacrolideaordoxycyclineRecentantibiotictherapy:Arespiratoryfluoroquinolone(RFQ)alone,anadvancedmacrolide(AM)plushigh-doseamoxicillinorAMplushigh-doseamoxicillin-clavulanateComorbidities

(COPD,Diabetes,RenalorCongestiveHeartFailure,orMalignancy)Norecentantibiotictherapy:AMorRFQRecentantibiotictherapy:RFQaloneorAMplusaB-lactamSuspectedaspirationwithinfection:Amoxicillin-clavulanateorclindamycinInfluenzawithbacterialsuperinfection:B-lactamoraRFQ2023/7/27Dr.HUBijie1CAP:Outp2023/7/27Dr.HUBijie2CAP: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:SameasformedicalwardandICU2023/7/27Dr.HUBijie2CAP:Inpa2023/7/27Dr.HUBijie3NNIS报告的医院内肺炎病原体检出率％排位80～82(15331)90～96(13433)80～8290～96枸橼酸菌111111肠杆菌91143大肠杆菌8456肺炎杆菌10834其他克雷伯41811奇异变形杆菌5268其他变形杆菌001413粘质沙雷菌4377其他沙雷菌101213肠杆菌科合计4230绿脓杆菌131722金葡菌131911CoNS12138肠球菌22108念珠菌3595其他26252023/7/27Dr.HUBijie3NNIS报告的医院2023/7/27Dr.HUBijie4铜绿假单胞菌、肺炎克雷伯菌和鲍曼不动杆菌

是HAP常见的革兰阴性杆菌AntimicrobAgentsChemother.2003Nov;47(11):3442-72023/7/27Dr.HUBijie4铜绿假单胞菌、肺炎2023/7/27Dr.HUBijie5NosocomialtracheobronchitisinMVpatients:

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;20:1483–1489.2023/7/27Dr.HUBijie5Nosocomia2023/7/27Dr.HUBijie6

医院内肺炎病原菌

（Meta分析，全国1990～1998年，6062株菌）

病原体菌株构成％绿脓杆菌124120.6克雷伯菌60810.1大肠杆菌3565.9肠杆菌属2784.6不动杆菌2754.6嗜麦芽窄食单胞1001.7流感嗜血杆菌500.8金黄色葡萄球菌3585.9肠球菌831.4肺炎链球菌611.02023/7/27Dr.HUBijie6医院内肺炎病原菌2023/7/27Dr.HUBijie7病原菌发生类型株数%早发性晚发性鲍曼不动杆菌1121318.6铜绿假单胞菌1101115.7金黄色葡萄球菌36912.9大肠埃希菌0557.1阴沟肠杆菌1457.1肺炎克雷伯菌1345.7粘质沙雷菌0445.7念珠菌1345.7嗜麦芽窄食单胞0334.3变形杆菌0334.3表皮葡萄球菌1122.9肠球菌1122.9产碱杆菌0222.9肺炎链球菌1011.4洛菲不动杆菌0111.4黄杆菌0111.4合计115970100.0

52

例

VAP

病

原

分

布

(99~01)

2023/7/27Dr.HUBijie7病原菌发生类型株数2023/7/27Dr.HUBijie8NLRTI前五位病原菌在6个常见科室的比较

谢红梅，胡必杰，何礼贤，等.2819例医院下呼吸道感染病原和预后分析.上海医学2003；26：880-8852023/7/27Dr.HUBijie8NLRTI前五位病2023/7/27Dr.HUBijie9医院内肺炎病原早期中期晚期135101520链球菌流感杆菌金葡菌MRSA肠杆菌肺克，大肠绿脓杆菌不动杆菌嗜麦芽窄食单胞菌入院天数2023/7/27Dr.HUBijie9医院内肺炎病原早期2023/7/27Dr.HUBijie10呼吸科常见耐药革兰阴性杆菌肺炎克雷伯杆菌，大肠埃希菌肠杆菌属，沙雷菌，枸橼酸菌，变形杆菌铜绿假单胞菌，其他假单胞菌鲍曼不动杆菌，其他不动杆菌嗜麦芽窄食单胞菌属伯克霍尔德菌属产碱杆菌属，黄杆菌属

NPRS结果显示，铜绿和鲍曼作为MDR问题正在凸现2023/7/27Dr.HUBijie10呼吸科常见耐药革2023/7/27Dr.HUBijie11细菌耐药是否会影响病死率?治疗肺炎杆菌ESBL菌株血液感染(n=31)合适治疗(n=19)病死率5%不恰当治疗(n=12)病死率42%P=0.02Source:SchiappaetalJID1996;74:529-362023/7/27Dr.HUBijie11细菌耐药是否会影2023/7/27Dr.HUBijie122023/7/27Dr.HUBijie122023/7/27Dr.HUBijie13在ICU中肺部感染耐药菌问题尤为突出2023/7/27Dr.HUBijie13在ICU中肺部感2023/7/27Dr.HUBijie14MDR引起肺炎的防治策略预防医院内肺炎（HAP、VAP、HCAP）早期、准确的病原学诊断，不要治疗定植菌和污染菌停止无效、耐药的抗生素，避免更严重的后果加大剂量：从药敏单中寻找中介（低敏）的药物联合使用，在安全范围内的最大剂量，时间依赖性的药在允许范围缩短用药间隔，甚至24h连续点滴旧药新用：多粘菌素E，舒巴坦对不动杆菌等联合用药：MIC为16ug/ml的头孢他啶和16ug/ml的阿米卡星合用可能有效；特门汀与氨曲南联合治不发酵糖菌效果有时很好；氨曲南可耐受金属酶2023/7/27Dr.HUBijie14MDR引起肺炎的2023/7/27Dr.HUBijie15ManagingInfectionInTheCriticalCareUnit:HowCanInfectionControlMakeTheICUSafe?CritCareClin.2005Jan;21(1):111-28ShulmanL,OstDDivisionofPulmonaryandCriticalCareMedicine,NorthShoreUniversityHospital,Manhasset,NY11030,USA2023/7/27Dr.HUBijie15Managing2023/7/27Dr.HUBijie16VAP预防方法的有效性评价RouteofintubationSearchforsinusitisCircuitchangesHumidifierHumidifierchangesEndotrachealsuctioningSubglotticsecretiondrainageChestphysiotherapyTracheostomyKineticbedsSemi-recumbentpositionPronepositionStressulcerprophylaxisProphylacticantibiotics2023/7/27Dr.HUBijie16VAP预防方法的2023/7/27Dr.HUBijie172023/7/27Dr.HUBijie172023/7/27Dr.HUBijie18Antisepticimpregnatedendotrachealtubesforthepreventionofbacterialcolonization在实验室气道模型中建立不同对MRSA,PA,AB和产气肠杆菌有抗菌作用的气管插管(ETTs)，包裹有洗必泰和碳酸银抗菌ETT和对照ETT(未包裹）用浓度108cfu/ml的菌液污染，5天孵育，管腔的远端和近端分别采样细菌培养抗菌ETT细菌定植量为1-100cfu/管，而对照ETT达106cfu/管(P<0.001).结论：抗菌导管可有效预防VAP相关细菌在ETT上的生长JHospInfect.2004Jun;57(2):170-42023/7/27Dr.HUBijie18Antisept2023/7/27Dr.HUBijie19EfficacyofheatandmoistureexchangersinpreventingVAP: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):5-112023/7/27Dr.HUBijie19Efficacy2023/7/27Dr.HUBijie20Ventilator-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).结论:闭合痰液吸引系统不能降低VAP发病率，包括外源性肺炎CritCareMed.2005Jan;33(1):115-92023/7/27Dr.HUBijie20Ventilat2023/7/27Dr.HUBijie21EarlyantibiotictreatmentforBAL-confirmedventilator-associatedpneumonia:aroleforroutineendotrachealaspiratecultures方法：299需要机械通气至少48h的病例，每周两次采集气管内吸引物（EA）定量培养。发生VAP后用BAL培养确定病原体，并与EA结果进行比较。最后有75例诊断VAP，41例BAL培养阳性，先前常规EA培养中有34例(83%)阳性，1例早发肺炎发生VAP时还没有采集EA；4例结果不一致但抗菌药物选用合适，2例选用药物有延迟结论：每周两次常规EA培养对早期正确选用VAP治疗抗菌药物是合适的Chest.2005Feb;127(2):589-972023/7/27Dr.HUBijie21Earlyan2023/7/27Dr.HUBijie22BlindandbronchoscopicsamplingmethodsinsuspectedVAP-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):1319-262023/7/27Dr.HUBijie22Blindan2023/7/27Dr.HUBijie23CombinationtherapywithpolymyxinBforthetreatmentofmultidrug-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):566-92023/7/27Dr.HUBijie23Combinat2023/7/27Dr.HUBijie24铜绿假单胞菌Pseudomonasaeruginosa2023/7/27Dr.HUBijie24铜绿假单胞菌2023/7/27Dr.HUBijie25A7-yearstudyofseverehospital-acquiredpneumoniarequiringICUadmission在16张和20张内科-外科ICU中，连续观察需要入住ICU的重症HAP，共7年。96次重症HAP中，GNB占51％，PA最常见（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)是影响预后的独立危险因素。IntensiveCareMed.2003Nov;29(11):1981-82023/7/27Dr.HUBijie25A7-year2023/7/27Dr.HUBijie26鲍曼不动杆菌Acinetobacterbaumannii2023/7/27Dr.HUBijie26鲍曼不动杆菌2023/7/27Dr.HUBijie27Effectfrommultipleepisodesofinadequateempiricantibiotictherapyforventilator-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,experiencingmultipleIEATepisodeswasindependentlyassociatedwiththeriskofdeath(oddsratio,4.28;95%confidence