最新ICU獲得性感染課件

ICU獲得性感染NosocomialInfectioninICUanoverallriskof18%ofacquiringaninfectionduringICUstayoneofthemostcommoncausesofdeathinICUsNosocomialInfectioninICUEuropeanPrevalenceofInfectioninIntensiveCareStudy(EPIC)HeldonApril29,1992anoverallof9567patientsfrom1417ICUsEPICDataatotalof45%ofpatientshadaninfectionICU-acquiredinfection 21%community-acquiredinfection 14%hospital-acquiredinfectionotherthanICU 10%NosocomialInfection

Vincentetal.JAMA1995;374:639-644(EPIC)NosocomialInfectioninICUPredisposingriskfactorsprolonglengthofICUstayantibioticusagemechanicalventilationurinarycatheterizationpulmonaryarterycatheterizationcentralvenousaccessstressulcerprophylaxisuseofsteroidnutritionalstatusNosocomialInfectioninICUNosocomialInfectioninICUUseofAntibiotics--EPICdataof10,038patients,62%receivedantibioticsforeitherprophylaxisortreatmentNosocomialInfectioninICUPreviousexposuretoantibioticsmodifyintestinalflora,leadingtocolonizationwithresistantbacteria3rdgenerationcephalosporinsfluoroquinolonesvancomycinfavortheselectionofinduciblebeta-lactamaseproducingGNB,suchasPseudomonoasaeruginosa,Enterobacterclocae,Serratiaspp.,andCitrobacterfreundiiNosocomialInfectioninICUCommonpathogenscommunity-acquiredinfectionandearly(<4d)hospital-acquiredinfectionsStreptococcuspneumoniaeHaemophilusinfluenzaeEnterobacteriaceae(Escherichiacoli,Proteusspp.,Klebsiellapneumoniae)MSSAStreptococcianaerobesNosocomialInfectioninICUCommonpathogenslate(>4d)hospital-acquiredinfectionsEnterobacterspp.Serratiaspp.ESBL-producingmicroorganismsPseudomonasaeruginosaAcinetobacterspp.MRSAenterococcifungiEPICDatamostcommonpathogensS.aureus 30%P.aeruginosa 29%Coagulase-negativestaphylococci 19%E.coli 13%Enterococcusspp. 12%EmergingPathogensDatafromICU,PUMCH1999EmergingPathogensMechanismofResistancetoBeta-lactamAntibioticsDepartmentofCriticalCareMedicinePekingUnionMedicalCollegeHospitalPrincipleofbeta-lactamactionarigidbacterialcellwallprotectsbacteriafrommechanicalandosmoticinsultbeta-lactaminhibitsPBPspreventingformationofthepeptidebridgesproducingweakenedwallactivatingcellwalldegradingenzymes--autolysinbeta-lactaminterfereswithnormalcellwallbiosynthesis,causingimpairedcellularfunction,alteredcellmorphologyorlysisMechanismofAntibioticResistanceDoesbeta-lactamaseconferresistance?TheamountofenzymeproductsitsabilitytohydrolysetheantibioticinquestionitsinterplaywiththecellularpermeabilitybarriersInducibleBeta-lactamasealsocalledclassIbeta-lactamaseorconstitutivebeta-lactamaseorAmpCbeta-lactamasemostarechromosome-mediatedmajorproducersPseudomonasaeruginosaEnterobactersp.Citrobactersp.Serratiasp.MorganellamorganniiInducibleBeta-lactamasetransientelevationinbeta-lactamasesynthesiswhenabeta-lactamispresentenzymeproductionreturnstoalowlevelwhentheinducerisremovedlowlevelinsufficienttoprotectbacteriaevenagainstdrugsrapidlyhydrolysedbytheenzymesenzymehyperproducer=mutantsthatproduceClassIenzymescontinuouslyatahighlevelInducibleBeta-lactamaseInductionislostwithin4to6hrsoncethestronginducerisremoved.Littleneedforconcerniftherapywithastronginducerisdiscontinuedandthedrugreplacedbyaweakinducer.ActivityofDrugsAgainstOrganismswithElevatedBeta-LactamaseLevelsDecreasedActivityMonobactamsSecond-,Third-generationcephalosporinsBroad-spectrumpenicillinsMaintainActivityImipenem,MeropenemFourth-generationcephalosporinsCiprofloxacin,ofloxacin,etcSMZ/TMPco(exceptP.Aeruginosa)AminoglycosidesAntibiogramofEnterobacterEnterobacterBacteremia:ClinicalFeaturesandEmergenceofAntibioticResistanceduringTherapyChowJW,etalAnnIntMed1991;115:585-90MultiresistantEnterobacter*Antibioticsreceivedinthe2weeksbeforetheinitialpositivebloodcultureAssociationofPreviouslyAdministeredAntibioticswithMultiresistantEnterobacterintheInitialBloodCultureMultiresistantEnterobacterEmergenceofResistancetoCephalosporin,Aminoglycoside,andOtherBeta-LactamTherapy*Cefotaxime,ceftazidime,ceftriaxone,ceftizoxime**Gentamicin,tobramicin,amikacin,netilmicin***Imipenem,piperacillin,ticarcillin,aztreonam,mezlocillin,ticarcillin-clavulanateMultiresistantEnterobacterFactorsAssociatedwithMortalityinPatientswithEnterobacterBacteremiaExtendedspectrumbeta-lactamaseMostareplasmidmediated1to4aminoacidchangesfrombroad-spectrumbeta-lactamases,thereforegreatlyextendingsubstraterangeMajorproducersE.Coli(TEM)Klebsiellasp.(SHV)inhibitedbybeta-lactamaseinhibitorsReliable(relatively)agentsforESBL-producingpathogensCarbapenemsAmikacinCephamycins(exceptMIR-1type;30%ofstrains)Beta-lactamaseinhibitors pip/tazo 30%RinChicago1996 26%RinICU,PUMCH1999AntibiogramofE.coliAntibiogramofKlebsiellaPrevalenceofCAZ-RKlebsiellaFromItokazuG,etal.NationwideStudyofMultiresistanceAmongGram-NegativeBacillifromICUpatientsClinicalInfectiousDiseases1996;23:779-85Cross-Resistancein

CAZ-RKlebsiellaFromItokazuG,etal.NationwideStudyofMultiresistanceAmongGram-NegativeBacillifromICUpatientsClinicalInfectiousDiseases1996;23:779-85PrevalenceofESBLDatafromIntensiveCareUnit,PekingUnionMedicalCollegeHospital,1999Cross-Resistancein

CAZ-RKlebsiellaDatafromIntensiveCareUnit,PekingUnionMedicalCollegeHospital,1995-1999EffectofESBLonMortalityAnalysisofmortalityin216bacteremicpatientscausedbyKlebsiellapneumoniaePattersonetal.37thICAAC,1997,AbstrJ-210EffectofESBLonMortalityPattersonetal.37thICAAC,1997,AbstrJ-210Empiricantibiotictherapyin32bacteremicpatientscausedbyESBL-positiveKlebsiellapneumoniaeMolecularEpidemiologyofCAZ-RE.ColiandK.PneumoniaeBloodIsolatesSchiappaD,etalRushUniversityandUniversityofIllinois,ChicagoILJournalofinfectiousDiseases1996;174:529-37RiskFactorsforCAZ-R

KlebsiellaBacteremiaCAZ-RKlebsiellaBacteremia*p=0.02OutcomeofPatientswithCAZ-RBacteremiaWhoReceivedAppropriatevs.InappropriateTherapyWithin72HoursofBacteremicEventCeftazidime

--emergenceofresistanceEmergenceofAntibiotic-ResistantPseudomonasaeruginosa:ComparisonofRisksAssociatedwithDifferentAntipseudomonalAgentsbyCarmeliY,etal.AntimicrobialAgentsandChemotherapy1999;43(6):1379-82Ceftazidime

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

--emergenceofresistanceTable.MultivariableCoxhazardmodelsfortheemergenceofresistancetoanyofthefourstudydrugsClassificationofAntibioticTherapyProphylacticUseTherapeuticUseEmpirictherapyDefinitivetherapyEmpiricAntibioticTherapyDepartmentofCriticalCareMedicinePekingUnionMedicalCollegeHospitalEmpiricAntibioticTherapyWhentreatingseriouslyillpatientswhoareatriskofdevelopingsepticshockwhenpathogensareunknownornotconfirmedantibioticselectionaccordingtoepidemiologyofNIinthewardresistanceprofileofmostcommonpathogensEmpiricAntibioticTherapySearchingforinfectionfocuscollectingsamplesforculturestartingempiricantibiotictherapyassoonaspossiblereferringtodefinitiveantibiotictherapyassoonaspossibleAntibioticTherapyandPrognosisObjective:ToevaluatetherelationshipbetweentheadequacyofantibiotictreatmentforBSIandclinicaloutcomesamongICUptsDesign:ProspectivecohortstudySetting:AmedicalICU(19beds)andasurgicalICU(18beds)fromauniversity-affiliatedurbanteachinghospitalPatients:492ptsfromJuly1997toJuly1999Intervention:NoneAntibioticTherapyandPrognosis147(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%)

AntibioticTherapyandPrognosisHospitalmortalityrateptswithaBSIreceivinginadequateantimicrobialtx(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)AntibioticTherapyandPrognosisIndependentpredictoroftheadministrationofinadequateantimicrobialtxbymultiplelogisticregressionanalysisBSIattributedtoCandidaspecies(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)InappropriateempiricantibiotictherapyObjective:toassesstheincidence,risk,andprognosisfactorsofNPacquiredduringmechanicalventilation(MV)Settingsa1,000-bedteachinghospitalApril1987throughMay

1988Patients78(24%)episodesofNPin322consecutivemechanicallyventilatedpatientsInappropriateempiricantibiotictherapyFrom:Torresetal.Incidence,risk,andprognosisfactorsofnosocomialpneumoniainmechanicallyventilatedpatients.AmRevRespirDis1990Sep;142(3):523-8DifficultyinempiricantibiotictherapyObjective:ToassessthefrequencyofandthereasonsforchangingempiricantibioticsduringthetreatmentofpneumoniaacquiredinICUDesign:Aprospectivemulticenterstudyof1year'sdurationSetting:MedicalandsurgicalICUsin30hospitalsalloverSpain.Patients:Ofatotalof16,872patientsinitiallyenrolledintothestudy,530patientsdeveloped565episodesofpneumoniaafteradmissiontotheICU.DifficultyinempiricantibiotictherapyEmpiricantibioticsin490(86.7%)ofthe565episodesofpneumoniaThemostfrequentlyusedantibioticsamikacin 120casestobramycin 110ceftazidime 96cefotaxime 96Monotherapyin135(27.6%)ofthe490episodesCombinationof2antibioticsin306episodes(62.4%)Combinationof3antibioticsin49episodes(10%)DifficultyinempiricantibiotictherapyTheempirictxmodifiedin214(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)DifficultyinempiricantibiotictherapyComparedwithappropriateempirictherapy,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):387-94DifficultyinempiricantibiotictherapyObjectiveTodefinetheimpactofBALdataontheselectionofantibioticsandtheoutcomesofpatientswithVAPDesign:ProspectiveobservationandbronchoscopywithBAL,performedwithin24hofdxofanewepisodeofhospital-acquiredVAPorprogressionofapriorepisodeofNPSetting:A15-bedmedicalandsurgicalICUDifficultyinempiricantibiotictherapyPatients:132ptshospitalizedformorethan72hmechanicallyventilatedaneworprogressivelunginfiltrateplusatleasttwoofthefollowingthreeclinicalcriteriaforVAPabnormaltemperature(>38Cor<35C)abnormalWCC(>10,000or<3,000)purulentbronchialsecretionsInterventions:BronchoscopywithBALwithin24hofclinicaldxofVAPorprogressionofaninfiltrateduetopriorVAPorNPAllpatientsreceivedantibiotics,107priortobronchoscopyand25immediatelyafterbronchoscopy.DifficultyinempiricantibiotictherapyFrom:LunaCM,VujacichP,NiedermanMS,VayC,GherardiC,MateraJ,JollyEC.ImpactofBALdataonthetherapyandoutcomeofventilator-associatedpneumonia.Chest1997Mar;111(3):676-85DifficultyinempiricantibiotictherapyFrom:KollefMH,WardSTheinfluenceofmini-BALculturesonpatientoutcomes:implicationsfortheantibioticmanagementofventilator-associatedpneumonia.Chest1998Feb;113(2):412-20HospitalInfectionControlDepartmentofCriticalCareMedicinePekingUnionMedicalCollegeHospitalScheduledChangesofEmpiricAntibioticTherapyObjective:Todeterminetheimpactofascheduledchangeofabxclasses,usedfortheempirictxofsuspectedgram-negativebacterialinfections,ontheincidenceofVAPandnosocomialbacteremiaPatients:680patientsundergoingcardiacsurgerywereevaluatedIntervention:Duringa6-moperiod(i.e.,thebefore-period),ourtraditionalpracticeofprescribinga3rdgenerationcephalosporin(ceftazidime)fortheempirictxofsuspectedgram-negativebacterialinfectionswascontinuedThiswasfollowedbya6-moperiod(i.e.,theafter-period)duringwhichaquinolone(ciprofloxacin)wasusedinplaceofthethird-generationcephalosporin.ScheduledChangesofEmpiricAntibioticTherapyFrom:KollefMH,VlasnikJ,SharplessL,PasqueC,MurphyD,FraserVScheduledchangeofantibioticclasses:astrategytodecreasetheincidenceofventilator-associatedpneumonia.AmJRespirCritCareMed1997Oct;156(4Pt1):1040-8NosocomialInfectionControlScheduledchangesofantibioticclassesforempirictreatmentofsuspectedordocumentedGNBinfectionsTimeperiod1(n=1323) ceftazidime Timeperiod2(n=1243) ciprofloxacin Timeperiod3(n=1102) cefepimeNosocomialInfectionControlScheduledchangesofantibioticclassestargetedattheempirictreatmentofgram-negativebacterialinfectionscanreducetheoccurrenceofinadequateantimicrobialtreatmentofnosocomialinfectionsreducingtheadministrationofinadequateantimicrobialtreatmentforpatientswithanAPAC