multi-drug resistant pathogens课件

Multi drugresistantpathogens HelmutAlbrecht MDDivisionofInfectiousDiseases Disclosures Grant ResearchSupport MSD J J VIIF Gilead nopaymenttome Consultant FranceFoundation nonprofitprojectwithDuke VIIF Gilead nohonoraria Speaker sBureau nohonoraria Agenda StateoftheunionTheplayers Resistantpathogens Whattodoaboutthem Antibiotics DeathsintheUSdeclinedby220per100 000withtheintroductionofsulfonamidesandpenicillin Thisfaroutweighsanyothermedicaladvanceinthepastcentury Armstrongetal JAMA1999 6 61ffFrom1983to2010 FDAapprovalofnewantibioticshascontinuouslydeclined from4peryearintheearly1980stolessthan1antibioticperyearnowThelastclassofdrugswithanovelmechanismofactionagainstGNbacteriagoesback40years Areviewofdrugscurrentlyintrialsrevealednosuchnewdrugs FortheUS antibioticresistanceisresponsiblefornearly100 000deathscausedbyhospital acquiredinfectionsperyearatanestimatedannualcostof 23billion RobertsetalCID2009 49 1175ff Whydoweseemoreresistance SickerinpatientpopulationPatientschronicallyillLargerimmunocompromisedpopulationMoreinstrumentation newproceduresPresenceofdevicesIncreasingresistanceincommunityEmergingpathogensComplacencyregardingantibioticsIncreaseduseof empiric broad spectrumantibioticsIneffectiveinfectioncontrolandcomplianceCrowdingofpatientsinconfinedareasDecreasingnurse patientratio Whydoweseemoreresistance SickerinpatientpopulationPatientschronicallyillLargerimmunocompromisedpopulationMoreinstrumentation newproceduresPresenceofdevicesIncreasingresistanceincommunityEmergingpathogens Superbugs ComplacencyregardingantibioticsIncreaseduseof empiric broad spectrumantibioticsIneffectiveinfectioncontrolandcomplianceCrowdingofpatientsinconfinedareasDecreasingnurse patientratio Mypatientisreallyill WhatisthepriceofprescribingalittlemorethanneededifIdonotwanttothinkthathard Healthcaredollars irrelevant iftitletrue C difficile potentiallydeadly Sideeffects potentiallydeadly Resistance relevant GettingItRightBloodstreamInfections Mortality GettingItRightVentilator associatedPneumonia Mortality Itisalotmoredifficulttogetitrightifthebacteriaaremulti drugresistant Scopeoftheproblem Nosocomialinfections 8millionexcesshospitaldaysApproximately80 000deaths 75 resistanttoatleastonedrugclass 50 ofinpatientsreceiveantibiotics30 50 ofthesereceivetheminappropriatelyCostofres pathogens100million 30billionUS yearPhelpsMedCare1989 NEWSUPERBUGS AdaptedfromLivermoreandWoodford TrendsinMicrobiol 2006 TheGramNegativeCellWall Porinchannels Effluxsystem PBPs B lactamases Bushclassificationof lactamasesinGNbacteria SubstrateProfile PenicillinaseCephalosporinaseBroadspectrumExtendedbroadspectrumCarbapenemase SubstrateProfile PenicillinaseCephalosporinaseBroadspectrumExtendedbroadspectrumCarbapenemase 19MonthsESBLKlebsiellapneumoniaeOutbreakNewYorkHospitalMedicalCenterofQueens 432ceftazidime resistantKlebsiellapneumoniae155patientscolonized 61 orinfected 39 53 crudemortalityrateNotdetectedfor12months Meyeretal Ann Int Med 119 353 3581993 SubstrateProfile PenicillinaseCephalosporinaseBroadspectrumExtendedbroadspectrumCarbapenemase IsKlebsiellabad Itdepends MostKlebsiellainfectionsareeasytodealwith butsomeareworsethanothersBecausethehostisbad Becausethebugisbad Becausethedrugsarebad SusceptibilityProfileofKPC ProducingK pneumoniae DrugswithMostReliableActivityAgainstESBL producingEnterobacteriaceae Carbapenems Cephamycins Fluoroquinolones CarbapenemResistance Mechanisms Carbapenemases CarbapenemasesintheU S KlebsiellaPneumoniaeCarbapenemase KPCisaclassAb lactamaseConfersresistancetoallb lactamsincludingextended spectrumcephalosporinsandcarbapenemsOccursinEnterobacteriaceaeMostcommonlyinKlebsiellapneumoniaeAlsoreportedin K oxytoca Citrobacterfreundii Enterobacterspp Escherichiacoli Salmonellaspp Serratiaspp AlsoreportedinPseudomonasaeruginosa Columbia thankfullywearetalkingthecountry notus SusceptibilityProfileofKPC ProducingK pneumoniae KPCEnzymes Locatedonplasmids conjugativeandnonconjugativeblaKPCisusuallyflankedbytransposonsequencesblaKPCreportedonplasmidswith Normalspectrumb lactamasesExtendedspectrumb lactamasesAminoglycosideresistance GeographicalDistributionofKPC Producers FrequentOccurrenceSporadicIsolate s KPCOutsideofUnitedStates France Nassetal 2005 AAC49 4423 4424 Singapore reportfromsurvey PuertoRico ICAAC2007 Columbia Villegasetal 2006 AAC50 2880 2882 ICAAC07 Brazil ICAAC2007 Israel Navon Veneziaetal 2006 AAC50 3098 3101 China WeiZ etal 2007 AAC51 763 765 Inter Institutional Inter StateSpreadofKPC ProducingK pneumoniae Carbapenemase ProducingEntericGNR U K 40 resistanttotigecycline 90 susceptibletocolistin NDM1Carbapenemase FirstdescribedfromIndia2008NovelresistancemechanismGenecompatiblewithmultipletypesofplasmids greatlyenhancesglobalspreadAlreadyinCalifornia IllinoisandMass Somestrainssensitivetoonlypolymyxins highlyneuroandnephro toxic orTigecyclineNonewdrugsclosetorelease PhenotypicTestsforCarbapenemaseActivity ModifiedHodgeTest100 sensitivityindetectingKPC alsopositivewhenothercarbapenemasesarepresent100 specificity ProceduredescribedbyLeeetal CMI 7 88 102 2001 Newtransmissionmechanisms NDM 1 77casesin13Europeancountries60 fromEnglandTraveltoIndia includingmedicaltourism ESBLsTravellersdiarrheaFoodborneoutbreakAdoption 25 ofE coliESBL 3 Europe 79 India 50 Egypt 22 Thailand Antibioticusenotpredictiveexceptforciprofloxacin5 21persistentlycolonized 156ptsaffected35 ofkitchensurfacescolonized6of44 14 offoodworkersfecalcarriers2y o fromChinaAdoptedSecondarytransmissioninfamily ModifiedHodgeTest LawnofE coliATCC259221 10dilutionofa0 5McFarlandsuspension Imipenemdisk Testisolates DescribedbyLeeetal CMI 7 88 102 2001 Whichismoredangerous Resistanceingram positiveorganisms 199019972000PRSP4 30 50 48 VTSP 0 2 3 6 5 1 MRSA20 25 25 50 GISA0 0 1 0 1VRE 0 11521 EvolutionofE faeciumresistance MIC90ofE faecium19681969 881989 90Penicillin864512Ampicillin232128 VRE0061 Graysonetal AAC Communityacquired ca MRSAstrainsgenerallyCANNOTbedistinguishedfromhospitalacquiredstrainsbythepresenceof MEC AgeneSCCpatternPanton Valentineleukocidin Whyisthisdifferent OutbreaksinnewpopulationsDifferentdiseasespectrum boils CAP SpiderbitehistorySpecificclonesSCCmectypeIVPanton ValentineLeukocidin PVL Susceptibletomanyantibiotics Populationswithca MRSA ChildrenInmatesMilitaryrecruitsNativepopulationsMSMHIV patientsReligiouscommunities FootballteamsWrestlersGymnastsFencingteamsIDUHomeless ClinicallyRelevantCA MRSADisease GA MD MNn 1 674 78 Fridkinetal NEJM 2005 MRSAskininfection differentialdiagnosis Commonmisdiagnosis spiderbite completewithhistoryofhavingbeenbitten Rangeofthebrownrecluse d j vu Phagetype80 81 PCN RcloneofSANeonataloutbreaksinAustraliain50 sBecamepandemicinadults childreninhospitals communitiesHighlytransmissibleandvirulentCarriedleukocidinRobinsonetalPhagetype80 81carriedPVLMLST30CurrentSWPcloneofCA MRSAdescendant acquiredSCCIV d j vuII Okumaetal JClinMicro2002 DistributionofVirulenceandResistanceDeterminantsCA MRSA France Switzerland USA Oceania Vandeneschetal EIDAug2003 PVLassociatedwithseveredisease NecrotizingpneumoniasSepticsyndromeEmpyemaMostCA MRSAstrainsPVL Causalroleinseverediseasepresentationsisnotproven CentersforDiseaseControlCampaign12stepstopreventantimicrobialresistance PreventInfectionVaccinateRemovecathetersDiagnoseandTreatEffectivelyTargetthepathogenAccesstheexpertsUseAntimicrobialsWiselyPracticeantimicrobialcontrolUselocaldataTreatinfection notcolonizationKnowwhentosaynotovancomycinStoptreatmentwheninfectioniscuredorunlikelyPreventtransmissionIsolatethepathogenBrakethechainofcontagion HowToPreventResistance Adequateinfectioncontrol Appropriateuseofantibiotics StrategiesforManagingOutbreaksofResistance AhmadMetal ClinInfectDis1999 29 352 355 OptimalUseofAntimicrobial It sRoleinPreventingResistance Willoptimaluse includingcontrolofantibioticuse preventorslowtheemergenceofresistance Itisunlikelythattheresistanceproblemwillrapidlywane simplybybeingmoreprudentinouruseofantimicrobialagents ontheotherhand itiscertainthatifwedonotcutbackontheuseoftheseagents theresistanceproblemwillworsen WilliamsScience1998 279 1153 Whattodotoslowantibioticresistance AggressivelyattackmisuseAnimalfeedsand treatment ofinanimateobjectsUpperrespiratorytractinfection Colds Sinusitis Pharyngitis Bronchitis acuteFeverwithoutevidenceofbacterialinfections ICUs Children Chroniccarefacilities AppropriateUseofAntibiotics TheappropriateempirictreatmentforthepatientwithSneezococcuscongestiiCoughobacillussnifficileisTylenol decongestantsandantitussivesnotantibioticsIfthepatientisreallysickandmayhavepneumoniawithTyrannococcusrexorothersuperbugsyoumaywanttoconsiderBumfacillinorGorillamycin SHEAandIDSARecommendationforHospitals ImplementationofasystemforperiodicmonitoringofantimicrobialresistanceincommunityandnosocomialisolatesImplementationofasystemforperiodicmonitoringofantibioticuseaccordingtohospitallocationand orprescribingserviceMonitoringofrelationshipbetweenantibioticuseandresistance assignmentofresponsibilitythroughpracticeguidelinesorotherinstitutionalpoliciesApplicationofcontactisolationprecautionsinpatientsknownorsuspectedtobecolonizedorinfectedwithepidemiologicallyimportantmicroorganisms Canwewintheglobalbattle KeepondevelopingnewantibioticsSurpriseyouropponent combination rotation UsetheoptimaldoseoftherightantibioticfortheappropriatedurationoftherapyKnowasmuchaboutantibioticsasyourIDfolksalternativelycallthemtohelpyou Doublecoverage Reasonabledataforsomegram positivesNogooddataforgram negativesMaystillbereasonabletocover2organismsandinspecificsituationsDoublecoverageacrossthebo