-抗生素课件(英文)ANTIBIOTIC-RESISTANT-PATHOGENS-IMPACT-AND-CONTROL(104p)

ANTIBIOTICRESISTANTPATHOGENS:IMPACTANDCONTROLDavidJayWeber,M.D.,M.P.H.ProfessorofMedicine,Pediatrics&EpidemiologyUniversityofNorthCarolinaatChapelHill,USASOURCESOFSLIDESThanksaregiventothefollowingpersonswhoprovidedslidesforthislectureWilliamJarvis,CDCMarinKollef,WashingtonUniversitiy,St.LouisChristopherOhl,WakeForestUniversityJanPatterson,UniversityofTexas,SanAntonioMichaelPfaller,UniversityofIowaLouisRice,VAMedicalCenter,ClevelandIMPACTOF

NOSOCOMIALINFECTIONSIMPACTOFNOSOCOMIALINFECTIONSIncidence=5-10%Incidencerisingwithtime~2,000,000patientsdevelopahealthcare-associatedinfectioneachyearHealthcare-associatedinfectionsresultin~90,000deathCostestimatedat$4.5to$5.7billiondollarsperyearNOSOCOMIALINFECTIONS

INTHEUNITEDSTATESVariable19751995Admissions37,700,00035,900,000Patient-days299,000,000190,000,000Averagelengthofstay7.95.3Inpatientsurgicalprocedures18,300,00013,300,000Nosocomialinfections2,100,0001,900,000Incidenceofnosocomialinfections(Numberper1000patient-days)7.29.8BurkeJP.NEJM2003;348:651PREVALENCE:ICU(EUROPE)Studydesign:Pointprevalencerate17countries,1447ICUs,10,038patientsFrequencyofinfections:4,501(44.8%)Community-acquired:1,876(13.7%)Hospital-acquired:975(9.7%)ICU-acquired:2,064(20.6%)Pneumonia:967(46.9%)Otherlowerrespiratorytract:368(17.8%)Urinarytract:363(17.6%)Bloodstream:247(12.0%)VincentJ-L,etal.JAMA1995;274:639CHALLENGESINTHEPREVENTIONANDMANAGEMENTOFHEALTHCARE-ASSOCIATEDINFECTIONSChangingpopulationofhospitalpatientsIncreasedseverityofillnessIncreasednumbersofimmunocompromisedpatientsShorterdurationofhospitalizationMoreandlargerintensivecareunitsGrowingfrequencyofantimicrobial-resistantpathogensImportationofantimicrobial-resistantpathogensfromthecommunityintothehospitalLackofcompliancewithhandhygieneReducedinfectioncontrolresourcesnationwideFuture:Priondiseases,bioterrorismagents,genetherapy,xenotransplantationHEALTHCARESYSTEMOFTHEPASTTranquilGardensNursingHomeHomeCareAcuteCareFacilityOutpatient/AmbulatoryFacilityLongTermCareFacilityCURRENTHEALTHCARESYSTEMTranquilGardensNursingHomeHomeCareAcuteCareFacilityOutpatient/AmbulatoryFacilityLongTermCareFacilityCURRENTSTATEOFHEALTHCAREEPIDEMIOLOGYINACUTECAREHOSPITALSFewerhospitalsSmallerhospitalsMoreandlargerintensivecareunitsGreaterpatientseverityofillnessMoreimmunocompromisedpatientsShorterstaysFewernurses?Fewerinfectioncontrolpersonnel?MECHANISMSOF

ANTIBIOTICRESISTANCEIntrinsicresistanceAcquiredresistanceAntibioticmodifyingenzymes(e.g.,penicillinresistanceinS.aureus)Targetsitealteration(e.g.,methicillinresistanceinS.aureus)Permeabilitybarriers(e.g.,vancomycintoleranceinVISA)Effluxpumps(e.g.,erythromycinresistanceinS.pneumoniae)MechanismsofResistanceEliopoulos.InfectiousDiseases.1992.IMPACTOFDRUGRESISTANTPATHOGENSInappropriatetherapywithworseoutcomeProlongedhospitalizationIncreaseddifficultywithplacementinanextendedcarefacilityNeedofisolationprecautions(maynegativelyimpactonqualityofpatientcare)IncreasedcostHighermortalityEMERGINGDRUGRESISTANCEINCOMMUNITYPATHOGENSEMERGINGRESISTANTPATHOGENS:

COMMUNITYHIV:MultipleagentsPneumococcus:Penicillin/cephalosporins,erythromycinGroupAstreptococcus:ErythromycinMycobacteriumtuberculosis:INH,rifampinNeisseria

gonorrhoeae:Penicillin,quinolonesStaphyloccus

aureus:OxacillinPlasmodiumfalciparum:Chloroquine,mefloquine,othersVAFeedlotsForeignDaycareCommunityHospitalsTertiaryHospitalsNursingHomesCommunityHomecareEnvironmentsWhereAntibioticResistanceDevelopsandTheirRelationshipsAdaptedfromB.MurrayS.PNEUMONIAE:INCIDENCE,USMeningitis:3,000casesBacteremia:50,000casesPneumonia:500,000casesOtitismedia:7millioncasesDeaths:20,000Source:CentersforDiseaseControl.MMWR1997;46(RR-8)%ofIsolatesResistant

toPenicillinYearBreimanRF,etal.JAMA.1994;271:1831-1835.DoernGV,etal.AAC.1996;40:1208-1213.ThornsberryC,etal.DMID.1997;29:249-257.

ThornsberryC,etal.JAC.1999;44:749-759.ThornsberryC,etal.CID2002;34(S1):S4-S16.Karlowsky,etal.CID.2003;36:963-970.Sahm,etal.IDSA2003,abstract201.Dataonfile,Ortho-McNeilPharmaceutical,Inc.Invitroactivitydoesnotnecessarilycorrelatewithclinicalresults.TrendforPenicillin-Resistant(MIC2mg/ml)

S.pneumoniaeintheUS(1988-2002)PENICILLINSUSCEPTIBILITYCLINICALSYNDROMES:

STAPHYLOCOCCUSAUREUSSkinPrimarypyodermas:Impetigo,folliculitis,furuncles,carbuncles,paronychia,cellulitisToxinmediatedsyndromes:Toxicshocksyndrome(TSS),scaldedskinsyndrome(SSS)Systemic:Sepsis,bacteremia,endocarditisOrgansystem:Meningitis,osteomyelitis,septicarthritis,paratitis,myositisEvolutionofAntimicrobialResistance

inGram-positiveCocciS.aureusPenicillin[1940s]Penicillin-resistantS.aureusMethicillin[1960s]Methicillin-resistantS.aureus(MRSA)Vancomycin-resistantenterococcus(VRE)Vancomycin[1997]Vancomycin(glycopeptide)intermediate-resistantS.aureusVancomycin-resistantS.aureusCiprofloxacin1987[2002]CLASSIFICATIONOFS.AUREUSRESISTANCETypeofS.aureusCommentOxacillin-susceptible(OSSA)Susceptibletooxacillin,nafcillin,cephalosporins,and-lactaminhibitorcombinations.Borderline-resistant(BRSA)BorderlineoxacillinMICsduetohyperproductionof-lactamase,abnormalPBPs,orheterogeneousmecAproduction.Oxacilin-resistant(ORSA)Oxacillin

>4ug/mLduetolowaffinityPBP(PBP-2’).Resistanttoallpenicillins,cephalosporins,carbapenems.Glycopeptide-intermediate(GISA)VancomycinMIC8-16ug/mL;alsointermediatetoteicoplanin.Mechanism=thickenedcellwall.Clinicallyresistanttovancomycin.

Vancomycin-resistant(VRSA)VancomycinMIC>32ug/mL.Mechanism=vanAgenefromVREE.faecalisORSA:Prevalenceofco-resistancetootherdrugs,U.S.,1997-1999:MRSAwithCo-ResistanceDiekemaDJetal.CID.2001;32:S114-S132.ORSAstrainsshowedresistancetomean3.5(median3)additionaldrugclasses36%89%93%79%26%24%ErythromycinCiprofloxacin

GentamicinClindamycinTMP-SMZGatifloxacinTetracycline16%IncreasingPrevalenceofMRSAin

S.aureusBloodstreamInfectionsDiekemaDJetal.CID.2001;32:S114-S132.%MRSAUnitedStates,Saureusisolates(N=4405)EPIDEMIOLOGICANDCLINICALFEATURESCommunity-acquiredstrainsdemonstrateincreasedsusceptibilitytoantibioticsandmultipleclonaltypesClinicalfeaturesandepidemiologicfeaturesofcommunity-acquiredcasessimilartohealthcareassociatedSkinandsofttissueinfectionspredominateFamilialtransmissionofMRSAdescribedOutbreaksdescribed(e.g.,highschoolwrestingteam)ANTIBIOTICRESISTANCEINTHECOMMUNITY:

FACTORSCONTRIBUTINGTOSPREADINTHECOMMUNITYFactorscontributingtospreadofantibioticresistanceSelectionofantibiotic-resistancegenesIncreasein“high-risk”(immunodeficient)populationProlongedsurvivalofpersonswithchronicdiseasesCongregatefacilities(e.g.,jails,daycarecenters)Lackofrapid,accuratediagnosticteststodistinguishbetweenviralandbacterialinfectionsIncreaseduseofantibioticsinanimals&agricultureSource:Segal-MaurerS.IDClinNA1996;10:939-957.ANTIBIOTICRESISTANCE:

PhysicianpracticescontributingtoinappropriateantibioticuseProvidingantibacterialdrugstotreatviralillnessesUsinginadequatediagnosticcriteriaforinfectionsthatmayhaveabacterialetiologyProvidingexpensive,broad-spectrumagentsthatareunnecessaryPrescribingantibioticsatanimproperdoseordurationANTIBIOTICPRESCRIBING,CHILDRENDiagnosisOfficeVisits(x1000)AntibioticPrescriptions(x1000)%TotalAntibioticPrescriptionsOtitismedia20,82016,15030URI14,0686,50912Pharyngitis7,4355,24610Bronchitis6,4184,6649Sinusitis3,2542,3564NyquistA-C,etal.JAMA1998;279:875ANTIBIOTICPRESCRIBING,ADULTSDiagnosisOfficeVisits(x1000)AntibioticPrescriptions(x1000)%TotalAntibioticPrescriptionsSinusitis13,3697,49412Bronchitis10,2356,76211URI11,0335,84210Pharyngitis7,4125,6349UTI4,8582,7985Otitismedia4,2262,0033GonzolesR,etal.JAMA1997;278:901FREQUENCYOFANTIBIOTICUSEDiagnosisChildrenAdultCommoncold44%51%URI46%52%Bronchitis75%66%StreptococcusPneumoniae:

RegionalTrendsinAntibioticResistance%NonsusceptibleData:B.Schwartz,EmergingInfectionsProgram,CDC;ICAAC‘98=regionalrange01020304050AtlantaBaltimoreConn.MetroTenn.MinneapolisPortlandSanFran.RegionBeta-lactamMacrolideStreptococcusPneumoniae:

RiskforAntibioticResistanceisGreaterwith

IncreasedOutpatientAntibioticUseControlledforregionData:B.Schwartz,EmergingInfectionsProgram,CDC;ICAAC‘98DecreasedSusceptibilityofS.pneumoniaetoFluoroquinolonesinCanada:

RelationshipofResistancetoAntibioticUseOverallprevalenceofFQRSP1.0%NoreducedsusceptibilityinchildrenFQRSPprevalencehigherintheelderlyandinOntarioHighestFQuseintheelderlyandinOntarioChenet.al.,NEJM1999;341:233-9KEYNOSOCOMIALPATHOGENSNationalNosocomialInfectionsSurveillance(NNIS)Report:ICUInfections1986-1997CDC.AmJInfectControl.1997;25:477-487.BloodstreamInfectionCoNS*S.aureusEnterococcusC.albicansEnterobacterOther*CoNS=coagulase-negativestaphylococciPneumoniaP.aeruginosaS.aureusEnterobacterK.pneumoniaeH.influenzaeOtherSurgicalSiteInfectionEnterococcusCoNS*S.aureusP.aeruginosaEnterobacterOtherPercentPercentPercentRISKFACTORSFORHEALTHCARE-ASSOCIATEDINFECTIONSHAZARDSINTHEICUWeinsteinRA.AmJMed1991;91(suppl3B):180SPREVALENCE:ICU(EUROPE)Studydesign:Pointprevalencerate17countries,1447ICUs,10,038patientsFrequencyofinfections:4,501(44.8%)Community-acquired:1,876(13.7%)Hospital-acquired:975(9.7%)ICU-acquired:2,064(20.6%)Pneumonia:967(46.9%)Otherlowerrespiratorytract:368(17.8%)Urinarytract:363(17.6%)Bloodstream:247(12.0%)VincentJ-L,etal.JAMA1995;274:639RISKFACTORSFORICUACQUIREDINFECTIONS(1.01-1.43)(1.16-1.57)(1.20-1.60)(1.19-1.69)(1.51-2.03)(1.75-2.44)(95%CI)RISKFACTORSFORICUACQUIREDINFECTIONS(1.56-4.13)(5.51-14.70)(9.33-24.14)(19.43-48.67)(37.90-96.25)(48.18-120.06)(95%CI)EMERGINGDRUGRESISTANCEINNOSOCOMIALPATHOGENSEMERGINGRESISTANTPATHOGENS:

HEALTHCAREFACILITIESStaphylococcusaureus:Oxacillin,vancomycin,linezolidEnterococcus:Penicillin,aminoglycosides,vancomycin,linezolid,dalfopristin-quinupristinEnterobacteriaceae:ESBLproducers,carbapenemsCandidaspp.:FluconazoleMycobacteriumtuberculosis:INH,rifampinCurrentstatusofresistanceintheICU:

(NNIS,2002vs1997–2001)Resistance(%)0102030405060708090Vancomycin/EnterococciMethicillin/S.aureusMethicillin/CNS3rdCeph/E.coli3rdCeph/K.pneumoniaeImipenem/P.aeruginosaQuinolone/P.aeruginosa3rdCeph/P.aeruginosa3rdCeph/Enterobacterspp.+11+13+1+14–2+32+27+22–5Changein

resistance(%)Jan–Dec20021997–2001(±sd)Ceph=cephalosporin;

NNIS=NationalNosocomialInfections

SurveillanceSystem;CNS=coagulase-negativestaphylococciNNIS.AmJInfect

Control2003;31:481–98ORSA,SENTRY,1997-1999DiekemaD,etal.CID2001;32(S-2):S114ENTEROCOCCALRESISTANCEIntrinsicResistanceSemisynthetic

penicillinsCephalosporinsClindamycinTrimethoprim-SulfamethoxazoleMonobactamsAminoglycosidesCarbapenems(E.faecium)AcquiredAminoglycosides(HighLevel)ChloramphenicolErythromycinPenicillinTetracyclineVancomycinandTeicoplaninLinezolidSynercidIncreasingVREOverTimeVancomycinIntroducedC.difficiledescribed“PROBLEM”GRAM-NEGATIVEPATHOGENSP.aeruginosaESBL-producingGNRE.coliKlebsiellapneumoniaeEnterobacterspp.Acinetobacterspp.StenotrophomonasmaltophilaP.AERUGINOSASUSCEPTIBILITY

US,1999(SENTRY)GalesA,etal.CID2001;32(S-2);146WhatisanExtended-Spectrum-Lactamase(ESBL)?VariantofstandardTEMandSHV-lactamasesResultofpointmutationsinTEM-1andSHV-1genesAltersactivebindingsiteofenzymeExtendsspectrumofthemutated-lactamaseAllowseffectivehydrolyzationofthird-generationcephalopsorinsTransmittedviaplasmidsRiceLB.Pharmacotherapy.1999;19(8Pt2):120S-128S.Evolutionof-Lactamase

Plasmid-MediatedTEMandSHVEnzymesAmpicillin1965TEM-1E.coliS.paratyphi1970sTEM-1Reportedin

28gram-negative

species1983ESBLinEurope1987ESBLin

United

States2001>150ESBLsworldwide1963Third-generationcephalosporins1980sESBLsDetectionMethods:

InhibitionbyClavulanicAcid©RonaldJ.Jones(ReprintedwithPermissionofAuthor).ESBL®EtestPrescribingInformation–ABBIODISKANTIMICROBIALRESISTANCERATES-GNR,ICARE/AUR,JANUARY1998–JUNE2003CDC.AJIC2003;31:881-98.ACINETOBACTERSUSCEPTIBILITY

US&CANADA,1997-1999(SENTRY)GalesAC,etal.ClinInfectDis2001;32(Suppl2):S104-113STENOTROPHOMONASRESISTANCE

US,1997-1999(SENTRY)GalesAC,etal.ClinInfectDis2001;32(Suppl2):S104-113ANTIBIOTICRESISTANCEINHOSPITALS:

FACTORSCONTRIBUTINGTOSPREADINHOSPITALSGreaterseverityofillnessofhospitalizedpatientsMoreseverelyimmunocompromisedpatientsNewerdevicesandproceduresinuseIncreasedintroductionofresistantorganismsfromthecommunityIneffectiveinfectioncontrol&isolationpractices(esp.compliance)IncreaseduseofantimicrobialprophylaxisIncreaseduseofpolymicrobialantimicrobialtherapyHighantimicrobialuseinintensivecareunitsSource:ShalesD,etal.ClinInfectDis1997;25:684-99.PRINCIPLESOFANTIBIOTICRESISTANCE

(LevySB.NEJM,1998)Givensufficienttimeanddruguse,antibioticresistancewillemerge.Resistanceisprogressive,evolvingfromlowlevelsthroughintermediatetohighlevels.Organismsresistanttooneantibioticarelikelytobecomeresistanttootherantibiotics.Onceresistanceappears,itislikelytodeclineslowly,ifatall.Theuseofantibioticsbyanyonepersonaffectsothersintheextendedaswellastheimmediateenvironment.FACTORSASSOCIATEDWITH

RESISTANTPATHOGENSAllresistanceislocalHospitaldemographicsSizeTeachingversusnon-teachingLocationCareinanintensivecareunitDurationofhospitalizationanduseofaninvasivemedicaldevice(centralvenouscatheter,endotrachealtubeformechanicalventilation,urinarycatheter)PriorantimicrobialuseANTIMOCROBIALRESISTANCE,US,1999-2000DiekemaDJ,etal.ClinInfectDis2004;38:7885ANTIMOCROBIALRESISTANCE,US,1999-2000DiekemaDJ,etal.ClinInfectDis2004;38:7885ANTIMICROBIALRESISTANCERATES-GPC,ICARE/AUR,JANUARY1998–JUNE2003CDC.AJIC2003;31:881-98.ANTIMICROBIALRESISTANCERATES-GNR,ICARE/AUR,JANUARY1998–JUNE2003CDC.AJIC2003;31:881-98.ICU(NNIS,1989-99):PrimaryBloodstreamInfectionBlackbar=pooledpercentageresistanceduringhospitalizationOpenbars<7dayshospitalizationClosedbars>7dayshospitalizationICU(NNIS,1989-99):Ventilator-AssociatedPneumoniaFridkinSK.CritCareMed2001;29:N67Blackbar=pooledpercentageresistanceduringhospitalizationOpenbars<7dayshospitalizationClosedbars>7dayshospitalizationICU(NNIS,1989-99):UrinaryTractInfectionFridkinSK.CritCareMed2001;29:N67RESISTANACEASAFUNCTIONOFPRIORANTIBIOTICUSEANDDURATIONOFHOSPITALIZATION

135consecutivecasesofVAP,FrenchICUsPotentially“resistant”bacteria{highermortality}:P.aerugninosa,Acinetobacter

baumannii,Stenotrophomonas

maltophilia,ORSARiskfactorsforresistantbacteriaDurationmechanicalventilation>7d,OR=6.0Priorantibioticuse,OR=13.5Broadspectrumantibiotic,OR=4.1 Source:Troullet,AJRCCM1998;157:531PATHOGENSASAFUNCTIONOFDURATIONOFVAPTrouilletJ,etal.AmJRespirCritCareMed1998;157:608-613.EffectofMechanicalVentilationandPriorAntibioticUseonDevelopmentofMultiresistantPathogensNumbersandpercentagesofmicroorganismsresponsiblefor135VAPepisodesclassifiedaccordingtodurationofmechanicalventilation(MV)andpriorantibiotictherapy(ABT)OrganismsGroup1(n=22)

MV<7ABT=noGroup2(n=12)MV<7ABT=yesGroup3(n=17)MV7ABT=noGroup4(n=84)MV7ABT=yesMultiresistantbacteria0*6(30)4(12.5)†89(58.6)P.aeruginosa04(20)2(6.3)33(21.7)A.baumannii01(5)1(3.1)20(13.2)S.maltophilia0006(3.9)MRSA01(5)1(3.1)30(19.7)Otherbacteria41(100)14(70)28(87.5)63(41.4)*p<0.02versusGroups2,3,or4†p<0.0001versusGroup4AdaptedfromTrouilletJL,etal.AmJRespirCritCareMed.1998;157:531-539IMPACTOFDRUGRESISTANTPATHOGENSIMPACTOFDRUGRESISTANTPATHOGENSProlongedhospitalizationIncreaseddifficultywithplacementinanextendedcarefacilityNeedofisolationprecautions(maynegativelyimpactonqualityofpatientcare)IncreasedcostHighermortalityEXCESSMORTALITYASSOCIATEDWITHORSA:TWOMETA-ANALYSES*CosgroveSEetal.CID.2003;36:53-59.†WhitbyMetal.MJA.2001;175:264-267.1980–2000*n=39631990–2000†n=2209%

Mortality36%29%23%12%P<.001P<.001

EXCESSMORTALITYASSOCIATEDWITHVRE%

Mortalityp<0.001CDC.MMWR1993;42:597-599FAILUREOFCEPHALOSPORINS(byMIC)WITH

ESBL+E.coliANDK.pneumoniae

BACTEREMIAModifiedfromPatersonDLetal.JClinMicrobiol.2001;39:2206-2212.54%(15/28)failurewhenorganismsusceptible100%failurewhenorganismintermediate%(no./total)ofpatientswhoMIC(g/mL)FailedoncephalosporintherapyDied<14daysofbacteremia8100(6/6)33(2/6)467(2/3)0(0/3)233(1/3)0(0/3)127(3/11)18(2/11)WHYANTIBIOTICSAREUSED

ANDOVERUSEDIMPACTOFANTIMICROBIALSKollefChest115:462,1999HAP:TheImportanceofInitialEmpiricAntibioticSelectionAlvarez-LermaF.IntensiveCareMed1996May;22(5):387-94.RelloJ,GallegoM,MariscalD,etal.AmJRespir

CritCareMed1997Jul;156(1):196-200.LunaCM,VujacichP,NiedermanMSetal.Chest1997;111:676-685.KollefMHandWardS.Chest1998Feb;113(2):412-20.PreventionandControlStrategies

fortheNewMillenniumHandwashing/InfectionControlAntimicrobialUseControlofAntibioticResistanceInfectionControlAntibioticControlVREMRSAESBLK.pneumoniaeKEYINTERVENTIONSININFECTIONCONTROLFORRESISTANTPATHOGENSHandhygieneSurveillanceContactprecautionsGloveswhenenteringtheroomGownforclosecontactwithpatientorenvironmentEnvironmentaldisinfectionEFFECTIVENESSOFHANDHYGIENEPittetD,etal.Lancet2000;356:1307-12.ANTIMICROBIALSTEWARDSHIPAsystemofinformatics,datacollectionmethods,personnel,andpolicy/procedureswhichpromotestheoptimalselection,dosing,anddurationoftherapyforantibioticsPreventorslowtheemergenceofantimicrobialresistanceOptimizeselection,doseanddurationofRxReducemorbidityandmortalityReducelengthofstayReducehealthcareexpendituresReduceadversedrugeventsANTIMICROBIALSTEWARDSHIP:

GOALSPRSP:InterventionstoImproveAntimicrobialUse

RuralAlaskaVillagesStudiedchildren<5yrsold,3400persons3ruralregions:1study

2controlEducationalinterventiontoparentsandprovidersonjudiciousantibioticuseinstudyregionFocusedonrespiratorytractinfectionsPeterson,ICCAC,1999Rx’s

Resp

PNSP

PRSP

visits

NPcarriageKEYINTERVENTIONSINANTIOBIOTICCONTROLFORRESISTANTPATHOGENSDon’ttreatnon-bacterialinfectionsornon-infectiousdiseaseswithantibioticsDon’tprolongthedurationofbeyondwhatisneededAvoidprophylacticantibioticsunlessbenefitdemonstratedUsethenarrowestspectrumagentavailableRISKSTRATIFICATIONPriorTxwithABXwhileinHospitalProlongedLOSPresenceofIn-DwellingDeviceHIGHRISKPTSWITHSERIOUSINFECTIONSHospital-AcquiredPneumoniaBloodstreaminfections-Lactam+AminoglycosideorFluoroquinolone+VancomycinorLinezolidModifyRegimenasNecessarySelectAppropriateEmpiricTherapyPseudomonasaeruginsoaAcinetobacterspp.Methicillin-resistantStaphylococcusaureusSpecimensforCultureClinicalRe-assessmentMicrobiologicalDataDURATIONOFTHERAPY:

STUDYDESIGNAuthors:ChastreJ,etal.JAMA2003;290:2988Studygoal:Compare8vs15daysoftherapyforVAPDesign:Prospective,randomized,double-blind(untilday8),clinicaltrialVAPdiagnosedbyquantitativeculturesobtainedbybronchoscopyLocation:51FrenchICUs(N=401patients)Outcomes:Assessed28daysafterVAPonset(ITTanalysis)Primarymeasures=deathfromanycauseMicrobiologicallydocumentedpulmonryinfectionrecurrenceAntibioticfreedaysDURATIONOFTHERAPY:

RESULTSPrimaryoutcomes(8vs15days)Similarmortality,18.8%vs17.2%Similarrateofrecurrentinfection,28.9%vs26.0%MRSA,33.3%vs42.9%

NonfermentingGNR,40.6%vs25.4%(p<0.05)Moreantibioticfreedays,13.1%vs8.7%(p<0.001)Secondaryoutcomes(8vs15days)Similarmechanicalventilation-freedays,8.7vs9.1Similarnumberoforganfailure-freedays,7.5vs8.0SimilarlengthofICUstay,30.0vs27.5Similarfrequencydeathatday60,25.4%vs27.9%Multi-resistantpathogen(recurrentinfection),42.1%vs62.0%(p=0.04)MORTALITYANTIMICROBIALSTEWARDSHIP:

INTERVENTIONSAntimicrobialrestrictionsandcontrolsAssistanceinantimicrobialdosingFeedbacktoMDtooptimizetherapyImmediatefeedbackwheninformaticsdetectsantimicrobial/pathogenmismatchIdentifycandidatesforearlyIVtoPOswitchAutomaticStopOrdersTherapeuticSubstitutionsCycling(Benefitunproven)Restrictionof3rdGenerationCephalosporinsBradley,etal-1998Goal-toreducetheriskofVREinpatientsinleukemiaunits.Situation-50%VREcarriageinoncologyunits.MethodsPhaseI-nointerventions-ceftazidimeusedasempirictherapyforfebrileneutropenicpatientPhase2aandb-2-4monthintervalssubstitutingpiperacillin/tazobactamforceftazidimeasempirictherapyforthefebrileneutropenicpatient.Phase3-4monthsvalidationsubstitutingceftazidimeforpiperacillin/tazobactamasinPhaseIJAntimicrob

Chemother.1999.Restrictionof3rdGenerationCephalosporinsBradley,etal.-1998(continued)ResultsPhase1-57%VREcolonizationwith6weeksofadmission-5clinicalinfections.Phase2-rateofcolonizationfellgraduallyto29%inphase2a.Last3months(phase2b)thecolonizationratewas8%withnoclinicalinfections.Phase1vs2b-p<0.0001Phase3-VREcolonizationincreasedbackto36%with3clinicalinfections.JAntimicrob

Chemother.1999.IncreasingESBL-MediatedResistanceDat