《ICU獲得性感染》課件

DeptofCriticalCareMedicinePekingUnionMedicalCollegeHospitalICU-acquiredInfectionandStrategyofAntibioticTherapy1整理pptCostofHospitalStayAssociatedwithResistance2整理pptNosocomialInfectioninICUanoverallriskof18%ofacquiringaninfectionduringICUstayoneofthemostcommoncausesofdeathinICUs3整理pptNosocomialInfectioninICUEuropeanPrevalenceofInfectioninIntensiveCareStudy(EPIC)HeldonApril29,1992anoverallof9567patientsfrom1417ICUs4整理pptEPICDataatotalof45%ofpatientshadaninfectionICU-acquiredinfection 21%community-acquiredinfection 14%hospital-acquiredinfectionotherthanICU 10%5整理pptNosocomialInfection

Vincentetal.JAMA1995;374:639-644(EPIC)6整理pptNosocomialInfectioninICUPredisposingriskfactorsprolonglengthofICUstayantibioticusagemechanicalventilationurinarycatheterizationpulmonaryarterycatheterizationcentralvenousaccessstressulcerprophylaxisuseofsteroidnutritionalstatus7整理pptNosocomialInfectioninICU8整理pptNosocomialInfectioninICUUseofAntibiotics--EPICdataof10,038patients,62%receivedantibioticsforeitherprophylaxisortreatment9整理pptNosocomialInfectioninICUPreviousexposuretoantibioticsmodifyintestinalflora,leadingtocolonizationwithresistantbacteria3rdgenerationcephalosporinsfluoroquinolonesvancomycinfavortheselectionofinduciblebeta-lactamaseproducingGNB,suchasPseudomonoasaeruginosa,Enterobacterclocae,Serratiaspp.,andCitrobacterfreundii10整理pptNosocomialInfectioninICUCommonpathogenscommunity-acquiredinfectionandearly(<4d)hospital-acquiredinfectionsStreptococcuspneumoniaeHaemophilusinfluenzaeEnterobacteriaceae(Escherichiacoli,Proteusspp.,Klebsiellapneumoniae)MSSAStreptococcianaerobes11整理pptNosocomialInfectioninICUCommonpathogenslate(>4d)hospital-acquiredinfectionsEnterobacterspp.Serratiaspp.ESBL-producingmicroorganismsPseudomonasaeruginosaAcinetobacterspp.MRSAenterococcifungi12整理pptEPICDatamostcommonpathogensS.aureus 30%P.aeruginosa 29%Coagulase-negativestaphylococci 19%E.coli 13%Enterococcusspp. 12%13整理ppt14整理ppt15整理pptEmergingPathogensDatafromICU,PUMCH199916整理pptEmergingPathogens17整理pptMechanismofResistancetoBeta-lactamAntibioticsDepartmentofCriticalCareMedicinePekingUnionMedicalCollegeHospital18整理pptPrincipleofbeta-lactamactionarigidbacterialcellwallprotectsbacteriafrommechanicalandosmoticinsultbeta-lactaminhibitsPBPspreventingformationofthepeptidebridgesproducingweakenedwallactivatingcellwalldegradingenzymes--autolysinbeta-lactaminterfereswithnormalcellwallbiosynthesis,causingimpairedcellularfunction,alteredcellmorphologyorlysis19整理pptMechanismofAntibioticResistance20整理pptDoesbeta-lactamaseconferresistance?Theamountofenzymeproductsitsabilitytohydrolysetheantibioticinquestionitsinterplaywiththecellularpermeabilitybarriers21整理pptInducibleBeta-lactamasealsocalledclassIbeta-lactamaseorconstitutivebeta-lactamaseorAmpCbeta-lactamasemostarechromosome-mediatedmajorproducersPseudomonasaeruginosaEnterobactersp.Citrobactersp.Serratiasp.Morganellamorgannii22整理pptInducibleBeta-lactamasetransientelevationinbeta-lactamasesynthesiswhenabeta-lactamispresentenzymeproductionreturnstoalowlevelwhentheinducerisremovedlowlevelinsufficienttoprotectbacteriaevenagainstdrugsrapidlyhydrolysedbytheenzymesenzymehyperproducer=mutantsthatproduceClassIenzymescontinuouslyatahighlevel23整理pptInducibleBeta-lactamaseInductionislostwithin4to6hrsoncethestronginducerisremoved.Littleneedforconcerniftherapywithastronginducerisdiscontinuedandthedrugreplacedbyaweakinducer.24整理pptActivityofDrugsAgainstOrganismswithElevatedBeta-LactamaseLevelsDecreasedActivityMonobactamsSecond-,Third-generationcephalosporinsBroad-spectrumpenicillinsMaintainActivityImipenem,MeropenemFourth-generationcephalosporinsCiprofloxacin,ofloxacin,etcSMZ/TMPco(exceptP.Aeruginosa)Aminoglycosides25整理pptAntibiogramofEnterobacter26整理pptEnterobacterBacteremia:ClinicalFeaturesandEmergenceofAntibioticResistanceduringTherapyChowJW,etalAnnIntMed1991;115:585-9027整理pptMultiresistantEnterobacter*Antibioticsreceivedinthe2weeksbeforetheinitialpositivebloodcultureAssociationofPreviouslyAdministeredAntibioticswithMultiresistantEnterobacterintheInitialBloodCulture28整理pptMultiresistantEnterobacterEmergenceofResistancetoCephalosporin,Aminoglycoside,andOtherBeta-LactamTherapy*Cefotaxime,ceftazidime,ceftriaxone,ceftizoxime**Gentamicin,tobramicin,amikacin,netilmicin***Imipenem,piperacillin,ticarcillin,aztreonam,mezlocillin,ticarcillin-clavulanate29整理pptMultiresistantEnterobacterFactorsAssociatedwithMortalityinPatientswithEnterobacterBacteremia30整理pptExtendedspectrumbeta-lactamaseMostareplasmidmediated1to4aminoacidchangesfrombroad-spectrumbeta-lactamases,thereforegreatlyextendingsubstraterangeMajorproducersE.Coli(TEM)Klebsiellasp.(SHV)inhibitedbybeta-lactamaseinhibitors31整理pptReliable(relatively)agentsforESBL-producingpathogensCarbapenemsAmikacinCephamycins(exceptMIR-1type;30%ofstrains)Beta-lactamaseinhibitors pip/tazo 30%RinChicago1996 26%RinICU,PUMCH199932整理pptAntibiogramofE.coli33整理pptAntibiogramofKlebsiella34整理pptPrevalenceofCAZ-RKlebsiellaFromItokazuG,etal.NationwideStudyofMultiresistanceAmongGram-NegativeBacillifromICUpatientsClinicalInfectiousDiseases1996;23:779-8535整理pptCross-Resistancein

CAZ-RKlebsiellaFromItokazuG,etal.NationwideStudyofMultiresistanceAmongGram-NegativeBacillifromICUpatientsClinicalInfectiousDiseases1996;23:779-8536整理pptPrevalenceofESBLDatafromIntensiveCareUnit,PekingUnionMedicalCollegeHospital,199937整理pptCross-Resistancein

CAZ-RKlebsiellaDatafromIntensiveCareUnit,PekingUnionMedicalCollegeHospital,1995-199938整理pptEffectofESBLonMortalityAnalysisofmortalityin216bacteremicpatientscausedbyKlebsiellapneumoniaePattersonetal.37thICAAC,1997,AbstrJ-21039整理pptEffectofESBLonMortalityPattersonetal.37thICAAC,1997,AbstrJ-210Empiricantibiotictherapyin32bacteremicpatientscausedbyESBL-positiveKlebsiellapneumoniae40整理pptMolecularEpidemiologyofCAZ-RE.ColiandK.PneumoniaeBloodIsolatesSchiappaD,etalRushUniversityandUniversityofIllinois,ChicagoILJournalofinfectiousDiseases1996;174:529-3741整理pptRiskFactorsforCAZ-R

KlebsiellaBacteremia42整理pptCAZ-RKlebsiellaBacteremia*p=0.02OutcomeofPatientswithCAZ-RBacteremiaWhoReceivedAppropriatevs.InappropriateTherapyWithin72HoursofBacteremicEvent43整理pptCeftazidime

--emergenceofresistanceEmergenceofAntibiotic-ResistantPseudomonasaeruginosa:ComparisonofRisksAssociatedwithDifferentAntipseudomonalAgentsbyCarmeliY,etal.AntimicrobialAgentsandChemotherapy1999;43(6):1379-8244整理pptCeftazidime

--emergenceofresistancea320-bedurbantertiary-careteachinghospitalinBoston,Mass.11,000admissionsperyear4studyagentswithantipseudomonalactivityceftazidime,ciprofloxacin,imipenem,piperacillinatotalof271patients(followedfor3,810days)withinfectionsduetoP.Aeruginosaweretreatedwiththestudyagentsresistanceemergencein28patients(10.2%),withanincidenceof7.4per1,000patient-days45整理pptCeftazidime

--emergenceofresistanceTable.MultivariableCoxhazardmodelsfortheemergenceofresistancetoanyofthefourstudydrugs46整理pptClassificationofAntibioticTherapyProphylacticUseTherapeuticUseEmpirictherapyDefinitivetherapy47整理pptEmpiricAntibioticTherapyDepartmentofCriticalCareMedicinePekingUnionMedicalCollegeHospital48整理pptEmpiricAntibioticTherapyWhentreatingseriouslyillpatientswhoareatriskofdevelopingsepticshockwhenpathogensareunknownornotconfirmedantibioticselectionaccordingtoepidemiologyofNIinthewardresistanceprofileofmostcommonpathogens49整理pptEmpiricAntibioticTherapySearchingforinfectionfocuscollectingsamplesforculturestartingempiricantibiotictherapyassoonaspossiblereferringtodefinitiveantibiotictherapyassoonaspossible50整理pptAntibioticTherapyandPrognosisObjective:ToevaluatetherelationshipbetweentheadequacyofantibiotictreatmentforBSIandclinicaloutcomesamongICUptsDesign:ProspectivecohortstudySetting:AmedicalICU(19beds)andasurgicalICU(18beds)fromauniversity-affiliatedurbanteachinghospitalPatients:492ptsfromJuly1997toJuly1999Intervention:None51整理pptAntibioticTherapyandPrognosis147(29.9%)ptsreceivedinadequateantimicrobialtreatmentfortheirBSIThemostcommonlyidentifiedbloodstreampathogensandtheirassociatedratesofinadequateantimicrobialtreatmentincludedvancomycin-resistantenterococci(n=17;100%)Candidaspecies(n=41;95.1%)MRSA(n=46;32.6%)SCoN(n=96;21.9%)Pseudomonasaeruginosa(n=22;10.0%)

52整理pptAntibioticTherapyandPrognosisHospitalmortalityrateptswithaBSIreceivinginadequateantimicrobialtx(61.9%)ptswithaBSIreceivingadequateantimicrobialtx(28.4%)(RR,2.18;95%CI,1.77to2.69;p<0.001)Independentdeterminantofhospitalmortalitybymultiplelogisticregressionanalysisadministrationofinadequateantimicrobialtx(OR,6.86;95%CI,5.09to9.24;p<0.001)53整理pptAntibioticTherapyandPrognosisIndependentpredictoroftheadministrationofinadequateantimicrobialtxbymultiplelogisticregressionanalysisBSIattributedtoCandidaspecies(OR,51.86;95%CI,24.57to109.49;p<0.001)prioradministrationofantibioticsduringthesamehospitalization(OR,2.08;95%CI,1.58to2.74;p=0.008)decreasingserumalbuminconcentrations(1-g/dLdecrements)(OR,1.37;95%CI,1.21to1.56;p=0.014)increasingcentralcatheterduration(1-dayincrements)(OR,1.03;95%CI,1.02to1.04;p=0.008)54整理pptInappropriateempiricantibiotictherapyObjective:toassesstheincidence,risk,andprognosisfactorsofNPacquiredduringmechanicalventilation(MV)Settingsa1,000-bedteachinghospitalApril1987throughMay

1988Patients78(24%)episodesofNPin322consecutivemechanicallyventilatedpatients55整理pptInappropriateempiricantibiotictherapyFrom:Torresetal.Incidence,risk,andprognosisfactorsofnosocomialpneumoniainmechanicallyventilatedpatients.AmRevRespirDis1990Sep;142(3):523-856整理pptDifficultyinempiricantibiotictherapyObjective:ToassessthefrequencyofandthereasonsforchangingempiricantibioticsduringthetreatmentofpneumoniaacquiredinICUDesign:Aprospectivemulticenterstudyof1year'sdurationSetting:MedicalandsurgicalICUsin30hospitalsalloverSpain.Patients:Ofatotalof16,872patientsinitiallyenrolledintothestudy,530patientsdeveloped565episodesofpneumoniaafteradmissiontotheICU.57整理pptDifficultyinempiricantibiotictherapyEmpiricantibioticsin490(86.7%)ofthe565episodesofpneumoniaThemostfrequentlyusedantibioticsamikacin 120casestobramycin 110ceftazidime 96cefotaxime 96Monotherapyin135(27.6%)ofthe490episodesCombinationof2antibioticsin306episodes(62.4%)Combinationof3antibioticsin49episodes(10%)58整理pptDifficultyinempiricantibiotictherapyTheempirictxmodifiedin214(43.7%)casesisolationofamicroorganismnotcoveredbytreatment 133(62.1%)caseslackofclinicalresponse 77(36%)developmentofresistance 14(6.6%)Individualfactorsassociatedwithmodificationofempirictreatmentidentifiedinthemultivariateanalysismicroorganismnotcovered(RR22.02;95%CI11.54to42.60;p<0.0001)administrationofmorethanoneantibiotic(RR1.29;95%CI1.02to1.65;p=0.021)previoususeofantibiotics(RR1.22;95%CI1.08to1.39;p=0.0018)59整理pptDifficultyinempiricantibiotictherapyComparedwithappropriateempirictherapy,inappropriatetherapywasassociatedwithhighermortality(p=0.0385)morecomplications(p<0.001)higherincidenceofshock(p<0.005)moreGIB(p=0.003)From:Alvarez-LermaF.Modificationofempiricantibiotictreatmentinpatientswithpneumoniaacquiredintheintensivecareunit.ICU-AcquiredPneumoniaStudyGroup.IntensiveCareMed1996May;22(5):387-9460整理pptDifficultyinempiricantibiotictherapyObjectiveTodefinetheimpactofBALdataontheselectionofantibioticsandtheoutcomesofpatientswithVAPDesign:ProspectiveobservationandbronchoscopywithBAL,performedwithin24hofdxofanewepisodeofhospital-acquiredVAPorprogressionofapriorepisodeofNPSetting:A15-bedmedicalandsurgicalICU61整理pptDifficultyinempiricantibiotictherapyPatients:132ptshospitalizedformorethan72hmechanicallyventilatedaneworprogressivelunginfiltrateplusatleasttwoofthefollowingthreeclinicalcriteriaforVAPabnormaltemperature(>38Cor<35C)abnormalWCC(>10,000or<3,000)purulentbronchialsecretionsInterventions:BronchoscopywithBALwithin24hofclinicaldxofVAPorprogressionofaninfiltrateduetopriorVAPorNPAllpatientsreceivedantibiotics,107priortobronchoscopyand25immediatelyafterbronchoscopy.62整理pptDifficultyinempiricantibiotictherapyFrom:LunaCM,VujacichP,NiedermanMS,VayC,GherardiC,MateraJ,JollyEC.ImpactofBALdataonthetherapyandoutcomeofventilator-associatedpneumonia.Chest1997Mar;111(3):676-8563整理pptDifficultyinempiricantibiotictherapyFrom:KollefMH,WardSTheinfluenceofmini-BALculturesonpatientoutcomes:implicationsfortheantibioticmanagementofventilator-associatedpneumonia.Chest1998Feb;113(2):412-2064整理pptHospitalInfectionControlDepartmentofCriticalCareMedicinePekingUnionMedicalCollegeHospital65整理pptScheduledChangesofEmpiricAntibioticTherapyObjective:Todeterminetheimpactofascheduledchangeofabxclasses,usedfortheempirictxofsuspectedgram-negativebacterialinfections,ontheincidenceofVAPandnosocomialbacteremiaPatients:680patientsundergoingcardiacsurgerywereevaluatedIntervention:Duringa6-moperiod(i.e.,thebefore-period),ourtraditionalpracticeofprescribinga3rdgenerationcephalosporin(ceftazidime)fortheempirictxofsuspectedgram-negativebacterialinfectionswascontinuedThiswasfollowedbya6-moperiod(i.e.,theafter-period)duringwhichaquinolone(ciprofloxacin)wasusedinplaceofthethird-generationcephalosporin.66整理pptScheduledChangesofEmpiricAntibioticTherapyFrom:KollefMH,VlasnikJ,SharplessL,PasqueC,MurphyD,FraserVScheduledchangeofantibioticclasses:astrategytodecreasetheincidenceofventilator-associatedpneumonia.AmJRespirCritCareMed1997Oct;156(4Pt1):1040-867整理pptNosocomialInfectionControlScheduledchangesofantibioticclassesforempirictreatmentofsuspectedordocumentedGNBinfectionsTimeperiod1(n=1323) ceftazidime Timeperiod2(n=1243) ciprofloxacin Timeperiod3(n=1102) cefepime68整理pptNosocomialInfectionControlScheduledchangesofantibioticclassestargetedattheempirictreatmentofgram-negativebacterialinfectionscanreducetheoccurrenceofinadequateantimicrobialtreatmentofnosocomialinfectionsreducingtheadministrationofinadequateantimicrobialtreatmentfor