呼吸机相关性肺炎（VAP）的流行病学及预防（英文PPT）Prevention of Ventilator Associated Pneumonia (VAP）.ppt 70页

TrackingNIhasbecomedifficultShorterinpatientstays(averagepostoperativestay,nowapproximately5days,isusuallyshorterthanthe5-to7-dayincubationperiodforS.aureussurgicalwoundinfections)Surveillancesystemsareoptionaltohospitalswithinfection-controlprograms PreventionofVentilatorAssociatedPneumonia(VAP)AACNVAPPracticeAlert LectureContentEpidemiologyofVAPPreventionstrategiesHOBelevationVentilatorequipmentchangesContinuousremovalofsubglotticsecretionsHandwashingAACNVAPPracticeAlert EpidemiologyofVentilatorAssociatedPneumonia(VAP)AACNVAPPracticeAlert NosocomialPneumoniasAccountfor15%ofallhospitalassociatedinfectionsAccountfor27%ofallMICUacquiredinfectionsPrimaryriskfactorismechanicalventilation(risk6to21timestheratefornonventilatedpatients)CDCGuidelineforPreventionofHealthcareAssociatedPneumonias2003Cooketal,AnnInternMed1998;129:433AACNVAPPracticeAlert CriticalCareInterventionsIncreaseSusceptibilitytoNosocomialPneumoniasTrachealColonizationAlteredHostDefensesIncreasedNosocomialPneumoniasIntubationAACNVAPPracticeAlert VAPEtiologyMostarebacterialpathogens,withGramnegativebacillicommon:PseudomonasaeruginosaProteussppAcinetobactersppStaphlococcusaureusEarlyVAPassociatedwithnon-multi-antibiotic-resistantorganismsLateVAPassociatedwithantibiotic-resistantorganismAACNVAPPracticeAlert SignificanceofNosocomialPneumoniasMortalityrangesfrom20to41%,dependingoninfectingorganism,antecedentantimicrobialtherapy,andunderlyingdisease(s)LeadingcauseofmortalityfromnosocomialinfectionsinhospitalsCDCGuidelineforPreventionofHealthcareAssociatedPneumonias2003Heylandetal,AmJRespirCritCareMed1999;159:1249Bercaultetal,CritCareMed2001;29:2303AACNVAPPracticeAlert SignificanceofNosocomialPneumoniasIncreasesventilatorysupportrequirementsandICUstayby4.3daysIncreaseshospitalLOSby4to9daysIncreasescost-Heylandetal,AmJRespirCritCareMed1999;159:1249CravenD.Chest2000;117:186-187SRelloetal,Chest2002;122:2115AACNVAPPracticeAlert VAPPreventionAACNVAPPracticeAlert ContinuousRemovalofSubglotticSecretionsUseanETtubewithcontinuoussuctionthroughadorsallumenabovethecufftopreventdrainageaccumulationCDCGuidelineforPreventionofHealthcareAssociatedPneumonias2003Kollefetal,Chest1999;116;1339AACNVAPPracticeAlert HOBElevationHOBat30-45oCDCGuidelineforPreventionofHealthcareAssociatedPneumonias2003Drakulovicetal,Lancet1999;354:1851 FrequencyofEquipmentChangesVentilatorTubingInnerCannulasofTrachsAmbuBagsNoRoutineChangesNotEnoughDataBetweenPatientsCDCGuidelineforPreventionofHealthcareAssociatedPneumonias2003AACNVAPPracticeAlert HandwashingWhatroledoeshandwashingplayinnosocomialpneumonias?Albert,NEJM1981;Preston,AJM1981;Tablan,1994AACNVAPPracticeAlert VAPPreventionAllrecommendationsarelevelIACDCGuidelineforPreventionofHealthcareAssociatedPneumonias2003AACNPracticeAlertforVAP,2004Washhandsbeforeandaftersuctioning,touchingventilatorequipment,and/orcomingintocontactwithrespiratorysecretions.AACNVAPPracticeAlert UseacontinuoussubglotticsuctionETtubeforintubationsexpectedtobe>24hoursKeeptheHOBelevatedtoatleast30degreesunlessmedicallycontraindicatedVAPPreventionAllrecommendationsarelevelIICDCGuidelineforPreventionofHealthcareAssociatedPneumonias2003AACNPracticeAlertforVAP,2004AACNVAPPracticeAlert NoDatatoSupportTheseStrategiesUseofsmallboreversuslargeboregastrictubesContinuousversusbolusfeedingGastricversussmallintestinetubesClosedversusopensuctioningmethodsKineticbedsCDCGuidelineforPreventionofHealthcareAssociatedPneumonias2003AACNVAPPracticeAlert PotentialconsequencesofinappropriateantibiotictherapyInappropriateempiricantibiotictherapycanleadtoincreasesin:mortalitymorbiditylengthofhospitalstaycostburdenresistanceselection InappropriateantibiotictherapyInappropriateantibiotictherapycanbedefinedasoneormoreofthefollowing:ineffectiveempirictreatmentofbacterialinfectionatthetimeofitsidentificationthewrongchoice,doseordurationoftherapyuseofanantibiotictowhichthepathogenisresistant EvidenceofimprovedclinicaloutcomeswithappropriateempiricantibiotictherapyAnumberofstudieshavedemonstratedthebenefitsofearlyuseofappropriateempiricantibiotictherapyforpatientswithnosocomialinfectionsSeveralkeyclinicalstudiesarereviewedinthefollowingslides Inappropriateantibiotictherapyisariskfactorformortalityamongpatientsintheintensivecareunit(ICU)Infection-relatedmortalityrateswereassessedinaprospectivecohort,single-centrestudyof2000patientsadmittedtomedical/surgicalICUs655patientshadaclinicallyrecognisedinfection:442(67.5%)hadacommunity-acquiredinfection286(43.7%)developedanosocomialinfection73(11.1%)hadbothcommunity-acquiredandnosocomialinfections169(25.8%)patientsreceivedinappropriateinitialantimicrobialtreatmentKollefetal.Chest1999;115:462–474 InappropriateantibiotictherapyisariskfactorformortalityamongpatientsintheICUKollefetal.Chest1999;115:462–474Hospitalmortality(%)0205060AppropriatetherapyInappropriatetherapy403010AllcausesInfectiousdisease-relatedp<0.001p<0.001Mortalitytype AppropriateantibiotictherapyreducesmortalityandcomplicationsinpatientswithnosocomialpneumoniaThefrequencyofandreasonsforchangingempiricantibioticsduringthetreatmentofhospital-acquiredpneumoniawereassessedinaprospectivemulticentrestudyacross30SpanishhospitalsOfthe16872patientsinitiallyenrolled,530developed565episodesofpneumoniaafterICUadmissionEmpiricantibiotics(administeredin490[86.7%]ofepisodes)weremodifiedin214(43.7%)casesbecauseof:isolationofmicro-organismnotcoveredbytreatment(62.1%)lackofclinicalresponse(36.0%)developmentofresistance(6.6%)Alvarez-Lermaetal.IntensiveCareMed1996;22:387–394 Alvarez-Lermaetal.IntensiveCareMed1996;22:387–394AppropriateantibiotictherapyreducesmortalityandcomplicationsinpatientswithnosocomialpneumoniaAppropriatetherapy(n=284)AttributablemortalityNo.complications/patientShockGastrointestinalbleedingRespiratoryfailureMultipleorganfailureExtrapulmonaryinfectionInappropriatetherapy(n=146)p-value16.2%1.73±1.8217.1%10.7%24.9%12.5%13.2%24.7%2.25±1.9828.8%21.2%32.2%21.2%17.1%0.04<0.001<0.0050.003NSNSNS Appropriateearlyantibiotictherapyreducesmortalityratesinpatientswithsuspectedventilator-associatedpneumonia(VAP)(Study1)AprospectiveobservationandbronchoscopystudyofpatientswithVAPassessedtheimpactofbronchoalveolarlavage(BAL)dataontheselectionofantibioticsandclinicaloutcomesinamedical/surgicalICU132mechanicallyventilatedpatients(hospitalised>72hours)withclinicallyconfirmedVAPunderwentBALwithin24hoursofdiagnosis107patientsreceivedantibioticspriortobronchoscopy25patientsreceivedantibioticsimmediatelyafterbronchoscopyMortalityrateswereassessedinrelationtotheadequacyandtimeofinitiationofantibiotictherapyLunaetal.Chest1997;111:676–685 Lunaetal.Chest1997;111:676–685AppropriateearlyantibiotictherapyreducesmortalityratesinpatientswithsuspectedVAP(Study1)Mortality(%)Pre-BALPost-BALPost-cultureresult060100204080p<0.001AppropriateantibioticNoantibioticInappropriateantibiotic Appropriateearlyantibiotictherapyreducesmortalityratesandlengthofhospitalstayinpatientswithbloodstreaminfection(Study1)AnobservationalprospectivecohortstudyofpatientswithbloodstreaminfectionexaminedwhetherappropriateantibiotictherapyimprovedsurvivalrateOfthe3413evaluablepatients,2158(63%)receivedearlyappropriateantibioticsdefinedasstartingwithin2daysofthefirstpositivebloodculture,andifthecausativepathogenwassusceptibleinvitrototheadministereddrugMortalityratesandmediandurationofhospitalstayforsurvivingpatientsweredeterminedLeibovicietal.JInternMed1998;244:379–386 Appropriateearlyantibiotictherapyreducesmortalityratesandlengthofhospitalstayinpatientswithbloodstreaminfection(Study1)Leibovicietal.JInternMed1998;244:379–386Appropriatetherapy(n=2158)MortalityrateMediandurationofhospitalstayInappropriatetherapy(n=1255)p-value20.2%9days(range0–117)34.4%11days(range0–209)0.00010.0001 SummaryClinicalevidencesuggeststhatearlyuseofappropriateempiricantibiotictherapyimprovespatientoutcomesintermsof:reducedmortalityreducedmorbidityreduceddurationofhospitalstay ResistancetoantibacterialagentsAntibioticresistanceeitherarisesasaresultofinnateconsequencesorisacquiredfromothersourcesBacteriaacquireresistanceby:mutation:spontaneoussingleormultiplechangesinbacterialDNAadditionofnewDNA:usuallyviaplasmids,whichcantransfergenesfromonebacteriumtoanothertransposons:short,specialisedsequencesofDNAthatcaninsertintoplasmidsorbacterialchromosomes Mechanismsofantibacterialresistance(1)Structurallymodifiedantibiotictargetsite,resultingin:reducedantibioticbindingformationofanewmetabolicpathwaypreventingmetabolismoftheantibiotic StructurallymodifiedantibiotictargetsiteInterioroforganismCellwallTargetsiteBindingAntibioticAntibioticsnormallybindtospecificbindingproteinsonthebacterialcellsurface StructurallymodifiedantibiotictargetsiteInterioroforganismCellwallModifiedtargetsiteAntibioticChangedsite:blockedbindingAntibioticsarenolongerabletobindtomodifiedbindingproteinsonthebacterialcellsurface Mechanismsofantibacterialresistance(2)Altereduptakeofantibiotics,resultingin:decreasedpermeabilityincreasedefflux Altereduptakeofantibiotics:decreasedpermeabilityInterioroforganismCellwallPorinchannelintoorganismAntibioticAntibioticsnormallyenterbacterialcellsviaporinchannelsinthecellwall Altereduptakeofantibiotics:decreasedpermeabilityInterioroforganismCellwallNewporinchannelintoorganismAntibioticNewporinchannelsinthebacterialcellwalldonotallowantibioticstoenterthecells Altereduptakeofantibiotics:increasedeffluxInterioroforganismCellwallPorinchannelthroughcellwallAntibioticEnteringEnteringAntibioticsenterbacterialcellsviaporinchannelsinthecellwall Altereduptakeofantibiotics:increasedeffluxInterioroforganismCellwallPorinchannelthroughcellwallAntibioticEnteringExitingActivepumpOnceantibioticsenterbacterialcells,theyareimmediatelyexcludedfromthecellsviaactivepumps Mechanismsofantibacterialresistance(3)AntibioticinactivationbacteriaacquiregenesencodingenzymesthatinactivateantibioticsExamplesinclude:-lactamasesaminoglycoside-modifyingenzymeschloramphenicolacetyltransferase AntibioticinactivationInterioroforganismCellwallAntibioticTargetsiteBindingEnzymeInactivatingenzymestargetantibiotics AntibioticinactivationInterioroforganismCellwallAntibioticTargetsiteBindingEnzymeEnzymebindingEnzymesbindtoantibioticmolecules AntibioticinactivationInterioroforganismCellwallAntibioticTargetsiteEnzymeAntibioticdestroyedAntibioticaltered,bindingpreventedEnzymesdestroyantibioticsorpreventbindingtotargetsites Manypathogenspossessmultiplemechanismsofantibacterialresistance+–Quinolones–++Trimethoprim–++Sulphonamide++Macrolide+–Chloramphenicol+–Tetracycline+++–Aminoglycoside+Glycopeptide++++-lactamModifiedtargetAltereduptakeDruginactivation Focuson-lactamantibioticresistancemechanismsThreemechanismsof-lactamantibioticresistancearerecognised:reducedpermeabilityinactivationwith-lactamaseenzymesalteredpenicillin-bindingproteins(PBPs) Multipleantibioticresistancemechanisms:the-lactams -lactamantibioticresistanceAmpCandextended-spectrum-lactamase(ESBL)productionarethemostimportantmechanismsof-lactamresistanceinnosocomialinfectionsTheantimicrobialandclinicalfeaturesoftheseresistancemechanismsarehighlightedinthefollowingslides -lactamresistance:AmpC-lactamaseproductionWorldwideproblem:incidenceincreasedfrom17−23%between1991and2001inUKVerycommoninGram-negativebacilliAmpCgeneisusuallysitedonchromosomes,butcanbepresentonplasmidsEnzymeproductioniseitherconstitutive(occurringallthetime)orinducible(onlyoccurringinthepresenceoftheantibiotic)Pfalleretal.IntJAntimicrobAgents2002;19:383–388Saderetal.BrazJInfectDis1999;3:97–110;Livermoreetal.IntJAntimicrobAgents2003;22:14−27 -lactamresistance:ESBLproductionAnincreasingglobalproblemFoundinasmall,expandinggroupofGram-negativebacilli,mostcommonlytheEnterobacteriaceaespp.UsuallyassociatedwithlargeplasmidsEnzymesarecommonlymutantsofTEM-andSHV-type-lactamasesJonesetal.IntJAntimicrobAgents2002;20:426–431Saderetal.DiagnMicrobiolInfectDis2002;44:273–280 AntimicrobialfeaturesofESBLsInhibitedby-lactamaseinhibitorsUsuallyconferresistanceto:first-,second-andthird-generationcephalosporins(egceftazidime)monobactams(egaztreonam)carboxypenicillins(egcarbenicillin)Variedsusceptibilitytopiperacillin/tazobactamTypicallysusceptibletocarbapenemsandcephamycinsOftenclinicallyand/ormicrobiologicallynon-susceptibletofourth-generationcephalosporins ClinicalfeaturesofESBLsEvenifsensitivetofourth-generationcephalosporinsinvitro,treatmentfailuresoccurinclinicalpracticeCreateclinicaldifficultiesduetocross-resistancewithotherantibioticclasses(egaminoglycosides)AssociatedwithnosocomialoutbreaksofhighmorbidityandmortalityResultinoveruseofotherbroad-spectrumagents ClinicalfailureinthepresenceofESBLsRecentdatashowhighclinicalfailureratesamongpatientstreatedwithcephalosporinsforseriousinfectionscausedbyESBL-producingpathogenssusceptibletocephalosporinsinvitro4/32patientsreceivedcephalosporinstowhichpathogensshowedintermediatesusceptibilityandallfailedtreatment15/28remainingpatientswithcephalosporin-susceptiblepathogensfailedtreatmentand4died11patientsrequiredachangeinantibiotictherapyPatersonetal.JClinMicrobiol2001;39:2206–2212 PatientswhofailedcephalosporintherapyforseriousinfectionsduetoESBL-producingorganismsPatersonetal.JClinMicrobiol2001;39:2206–2212Clinicalfailurerate(%)0601002014080248CephalosporinMIC(µg/mL) Featuresofmethicillin-resistantStaphylococcusaureus(MRSA)Introductionofmethicillinin1959wasfollowedrapidlybyreportsofMRSAisolatesRecognisedhospitalpathogensincethe1960sMajorcauseofnosocomialinfectionsworldwidecontributesto50%ofinfectiousmorbidityinICUsinEuropesurveillancestudiessuggestprevalencehasincreasedworldwide,reaching25–50%in1997Jones.Chest2001;119:397S–404S SeriousinfectionstestingpositiveforMRSAisolatesamonghospitalisedpatients(1997SENTRYdata)Patients(%)0305010Pneumonia2040UTIWoundBloodstreamInfectiontypeJones.Chest2001;119:397S–404SUTIUTI=urinarytractinfection FeaturesofMRSA:epidemicstrainsProblemescalatedintheearly1980swithemergenceofepidemicstrains(EMRSA)firstrecognisedintheUK17EMRSAsidentifiedtodateImpactonhospitalsisvariablepresenceofEMRSAcanaccountfor>50%ofS.aureusisolatesAuckenetal.JAntimicrobChemother2002;50:171–175 RiskfactorsforcolonisationorinfectionwithMRSAinhospitalsChambers.EmergInfectDis2001;7:178–182AdmissiontoanICUSurgeryPriorantibioticexposureExposuretoanMRSA-colonisedpatient EmergenceofMRSAinthecommunityMRSAinhospitalsleadstoanassociatedriseinincidenceinthecommunityCommunity-acquiredMRSAstrainsmaybedistinctfromthoseinhospitalsInahospital-basedstudy,>40%ofMRSAinfectionswereacquiredpriortoadmissionRiskfactorsforcommunityacquisitionincluded:recenthospitalisationpreviousantibiotictherapyresidenceinalong-termcarefacilityintravenousdruguseColonisationandtransmissionarealsoseeninindividuals(includingchildren)lackingtheseriskfactorsHiramatsuetal.CurrOpinInfectDis2002;15:407–413Laytonetal.InfectControlHospEpidemiol1995;16:12–17;Naimietal.2003;290:2976−2984 AntimicrobialfeaturesofMRSA(1)Mechanisminvolvesalteredtargetsitenewpenicillin-bindingprotein—PBP2"(PBP2a)encodedbychromosomallylocatedmecAgeneConfersresistancetoall-lactamsGenecarriedonamobilegeneticelement—staphylococcalcassettechromosomemec(SCCmec)LaboratorydetectionrequirescareNotallmecA-positiveclonesareresistanttomethicillinHiramatsuetal.TrendsMicrobiol2001;9:486–493Berger-Bachi&Rohrer.ArchMicrobiol2002;178:165–171 AntimicrobialfeaturesofMRSA(2)Cross-resistancecommonwithmanyotherantibioticsCiprofloxacinresistanceisaworldwideprobleminMRSA:involves≥2resistancemutationsusuallyinvolvesparCandgyrAgenesrendersorganismhighlyresistanttociprofloxacin,withcross-resistancetootherquinolonesIntermediateresistancetoglycopeptidesfirstreportedin1997Hiramatsuetal.JAntimicrobChemother1997;40:135–136Hooper.LancetInfectDis2002;2:530–538 ClinicalfeaturesofMRSACommonassociationsinclude:underlyingchronicdisease,especiallyrepeatedhospitalstaysprolonged/repeatedantibiotics,especiallythe-lactamsUsuallysusceptibletoatleastoneotherantibioticNotallMRSAsbehaveasEMRSAsMethicillinresistanceisnotamarkerofvirulence ClinicalfeaturesofMRSA:transmissionOccursprimarilyfromcolonisedorinfectedpatientsviathehandsofhealthcareworkerscontacttransmissiontootherpatientsorstaffverycommonAirbornetransmissionimportantintheacquisitionofnasalcarriageInfectioncontrolmeasuresinclude:screeningandisolationofnewpatientssuspectedofcarryingMRSAorS.aureuswithvancomycinresistanceimplementinginfectioncontrolprogrammesestablishingadequateantibioticpolicytominimisedevelopmentofresistance ManagementofMRSAEducateonrisksandcontrolmeasuresAdheretostrictcontrolmeasurestopreventtransmission,especiallythroughcontactTreatpatientwithappropriateempiricandtargetedtherapyConsiderclearingpatientofMRSAcarriage Glycopeptideresistance:focusonvancomycinresistanceVancomycin-resistantenterococci(VRE)Vancomycin-resistantS.aureus(VRSA) Featuresofquinoloneresistance:Gram-negativeorganismsResistancemostcommoninorganismsassociatedwithnosocomialinfectionsPseudomonasaeruginosaAcinetobacterspp.alsoincreasingamongESBL-producingstrainsMeropenemYearlySusceptibilityTestInformationCollection(MYSTIC)surveillanceprogramme(1997―2000)13.4%ofGram-negativestrainsresistanttociprofloxacinP.aeruginosaandAcinetobacterbaumanniiarethemostprevalentresistantstrainsincreasingprevalenceofresistanceduringsurveillanceperiodMasterton.JAntimicrobChemother2002;49:218–220Thomson.JAntimicrobChemother1999;43(Suppl.A):31–40 Gram-negativeorganismswithresistancetociprofloxacin(1997SENTRYdata)Organisms(%)0305010Stenotrophomonasmaltophilia2040Acinetobacterspp.P.aeruginosaEscherichiacoliAllpatients(USA)LowerRTI(USAandCanada)OrganismtypeJones.Chest2001;119:397S–404S Featuresofquinoloneresistance:Gram-positiveorganismsMRSAS.aureusoccurredin22.9%ofpneumoniasinhospitalisedpatientsinUSAandCanada(1997SENTRYdata)Enterococcusspp.resistancehasdevelopedrapidly,especiallyamongVREStreptococcuspneumoniaeresistanceemerginginmanycountries,includingcommunity-acquiredresistanceHongKong(12.1%),Spain(5.3%)andUSA(<1%)markedcross-resistancewithotherfrequentlyusedantibioticsHooper.LancetInfectDis2002;2:530–538 SummaryAntibioticresistanceinthehospitalsettingisincreasingatanalarmingrateandislikelytohaveanimportantimpactoninfectionmanagementStepsmustbetakennowtocontroltheincreaseinantibioticresistanceCosgroveetal.ArchInternMed2002;162:185–190 SummaryTheAcademyforInfectionManagementsupportstheconceptofusingappropriateantibioticsearlyinnosocomialinfectionsandproposes:selectingthemostappropriateantibioticbasedonthepatient,riskfactors,suspectedinfectionandresistanceadministeringantibioticsattherightdosefortheappropriatedurationchangingantibioticdosageortherapybasedonresistanceandpathogeninformationrecognisingthatpriorantimicrobialadministrationisariskfactorforthepresenceofresistantpathogensknowingtheunit’santimicrobialresistanceprofileandchoosingantibioticsaccordingly