抗生素英文課件-Choosing-Antibiotics-Before-and-After-t

ChoosingAntibiotics:

BeforeandAftertheCultureResultsGopiPatel,MDAugust20,2010ChoosingAntibiotics:

BeforeProphylaxisEmpiricTargetedPickingAntibioticsWhathasthepatientgrownbefore?Whatisthepatientgrowingnow?Whatisthepatientatriskforgrowing?Whatarethepatient’ssignsandsymptoms?ProphylaxisEmpiricTargetedPickAntibioticselectionRiskfactorsfordrugresistanceRecentantimicrobialexposuresUnderlyingcomorbiditiesAllergiesRecentinterventionsAvailableandpreviousculturedataHistoryofMRSA,VRE,PseudomonasESBL-producingGNRThefloraandfaunaofthehospitalAndperhapseventheunit…Howsickisthepatient?Canalways“gobig”andnarrowasyougetmoreinformation…AntibioticselectionRiskfactoJusttorefreshyourmemory…Justtorefreshyourmemory…Cephalosporins*1stCefazolinCephalexinGram-positivecocci(e.g.,MSSA,GBS)

E.coli,K.pneumoniae,P.mirabilis2ndCefuroximeCefoxitinCefotetanCefuroxime-H.influenzaeCephamycins-Bacteroidesspp3rdCefotaximeCeftriaxoneCeftazidimeSomeanaerobiccoverageCeftazidime-Pseudomonas

CrossestheBBBPotentinducersofβ-lactamases4thCefepime

Pseudomonas

CrossestheBBBStableagainstmanyβ-lactamases*DoNOTcoverEnterococcus,Listeria,Legionella,orMRSACephalosporins*1stCefazolinGrCase148MIVDAadmittedwithfeversandchillsFreshtrackmarksonLeftarmFebrileto39BP70/55HR11293%RAIII/VIsystolicmurmuratLLSBB/LcracklesChestX-ray-CongestionB/LEmpiricantibiotics?Case148MIVDAadmittedwithAsexpectedAt14hoursbothsetsofbloodculturesaregrowingGram-positivecocciinclustersPrevioushistoryofMRSATTEcan’truleoutvegetationonmitralvalveTEErefusedPatientgrowsMRSAVancomycincontinuedAsexpectedAt14hoursbothseVancomycinDiscoveredin1956MechanismofactionInhibitsbacterialcellwallsynthesisBindsfirmlytoD-Ala-D-Alaofthepeptidoglycan,preventingelongationandcross-linkingMechanismofresistanceAlteredpeptidoglycanbindingsiteD-Ala-D-AlaisreplacedbyD-Ala-D-lactateThickenedcellwallVancomycinDiscoveredin1956ToxicityNephrotoxicityMostofteninthesettingofothernephrotoxicagentsandunstablerenalfunctionHypersensitivityreactions1RedmansyndromeAnaphylaxisRarereactionsOtotoxicityNeutropeniaand/orthrombocytopenia2LinearIgAbullousdermatosis1CritCare.2003;7(2)119-202NEJM.2007;356(9)904-910ToxicityNephrotoxicity1CritCLinearIgABullousDermatosisLinearIgABullousDermatosisDosingDosingDosingCrCl(mL/min)DosingRegimen>7015mg/kgevery8-12hours40-6915mg/kgevery12-24hours<3915mg/kgx1,thenre-dosebylevelUseactualbodyweighttodoseRoundtothenearest250mgAmJHealth-SystPharm.2009;66:82-98UseCockcroft-GaulttocalculateCreatinineClearanceNOTMDRD(GivenbyEDRorSCC)DosingCrCl(mL/min)DosingRegiMonitoringTroughsaremostaccurateandpractical

Obtaintroughjustpriortothenextdoseatsteady-state(usuallyafter4thdose)Levelsshouldbemaintained>10mg/LMinimumtroughsof15-20mg/Larerecommendedforsevereorcomplicatedinfections(endocarditis,osteomyelitis,meningitis,andpneumonia)1AmJRespCritCareMed.2005;171:338.2ClinInfectDis.2004;39:1267-84.3Circulation.2005;111:e394-e433.MonitoringTroughsaremostaccWhatifapersoncan’t“tolerate”Vanco?AnaphylaxisPatient“refuses”drugCan’tgettherightlevelsEaseofdosingWhatifapersoncan’t“toleraDaptomycinFDAapprovedin2003DepolarizesthecellmembraneandisrapidlybactericidalagainstGram-positivesApprovedforthetreatmentofcomplicatedskinandskinstructureinfectionsS.aureus(includingMRSA),GAS,Streptococcusagalactiae,andvanco-susceptibleEnterococcusfaecalisNotapprovedforE.faecium(CLSIbreakpoint<4)Non-inferiortovancoandanti-staphpenicillinsinS.aureusbacteremiaandright-sidedendocarditis1Juryisoutforleft-sidedendocarditisNOTindicatedfortreatmentofpneumonia1NEJM.2006;355(7):652-65DaptomycinFDAapprovedin2003DosingUseactualbodyweightForserious,life-threateninginfectionsdosingregimensof8to12mg/kghavebeenused1Requires24-hourAntibioticApprovalIndicationCrCl(mL/min)DoseSSTI≥30<30(HD)4mg/kgevery24hrs4mg/kgevery48hrsBacteremia≥30<30(HD)6mg/kgevery24hrs6mg/kgevery48hrs1CID.2009;49:177-80DosingUseactualbodyweightInToxicityRhabdomyolysisandmyopathyMonitorforclinicalevidenceofmyopathyCheckCK/CPKlevelseveryweekEspeciallyifonhigherdoseorinrenalfailureMaybeatincreasedriskfortoxicitywithstatinsToxicityRhabdomyolysisandmyoMicrobiologicFailureResistancecandeveloptodaptomycinduringtreatmentandmaybeinfluencedbyexposuretovancomycinSeeninbothS.aureusandEnterococcussppNEJMnon-inferioritystudy:15%ofpatientsindaptoarmwithclinicalfailure6/19(32%)withincreaseddaptomycinMICShouldnotbeusedif1°sourcenotremovedMicrobiologicFailureResistancWhatifthepatientgrewMSSA?NafcillinNafcillin2gIVQ4hoursNoadjustmentCefazolin2gIVQ8hoursfor“normal”renalfunctionWhatifthepatientgrewMSSA?S.aureus:itsownlecturePleasecallanIDconsultforMSSAorMRSAbacteremiaHighriskformetastaticdiseaseFuturenoonconferencetofollow(10/13/10)S.aureus:itsownlecturePleaAnotherrefresher…Anotherrefresher…B-lactam/B-lactamaseinhibitorsAmpicillin-sulbactamAmpicillin-susceptibleEnterococcusspp.AnaerobesSinusitis,dogandcatbites,humanbites,community-acquiredlungabscessSulbactamcomponenthasactivityagainstAcinetobacterspp.Piperacillin-tazobactamPseudomonasaeruginosa

Ampicillin-susceptibleEnterococcusspp.AnaerobesB-lactam/B-lactamaseinhibitorCase257FtransferredfromoutsidehospitalafteradmissionfornewjaundiceandincreasingabdominalgirthDiagnosedwith“cryptogeniccirrhosis”Transferredonpiperacillin-tazobactamandvancomycinCase257FtransferredfromouCase2Patientgivenvancomycin1gramx1doseandcontinuedonpiperacillin-tazobactamHD#2developsworseningencephalopathyCXRBloodculturesU/AandurinecultureDiagnosticparacentesisattemptedCase2PatientgivenvancomycinCase2InterncallsOSHandfindsthatpatient’sbloodculturestherearegrowingGPCinpairsandchainsPatientonbothvancoandpip-tazoatthetimethecultureswereobtainedHint:WhatGPCisnotbeingcovered?ChangeAntibiotics?Case2InterncallsOSHandfinEnterococcusspeciesAmpicillin-susceptibleE.faecalis

PenicillinandampicillinslowlybactericidalAmpicillin,piperacillin,penicillin,imipenemVancomycin(whensusceptible)88%ofE.faecalisisvancosusceptibleatMSH20%ofE.faeciumUseofaminoglycosidesforsynergyinthesettingofseriousinfections(e.g.,endocarditis)EnterococcusspeciesAmpicillinVREFDAapprovedagentsLinezolidQuinupristin/Dalfopristin(E.faeciumONLY)AlternativeagentsDaptomycinTigecyclineVREFDAapprovedagentsLinezolidFDAapprovedin2000forcomplicatedskinandskinstructureinfections,pneumonia,andbloodstreaminfectionsGram-positiveorganismsNocardia,non-tuberculousmycobacteria,TBMechanismofactionInhibitsinitiationofproteinsynthesisbybinding50SribosomeOralformulationwith100%bioavailabilityLinezolidFDAapprovedin2000Dosing600mgIV/POevery12hoursNodose-adjustmentforrenalinsufficiencyorliverdiseaseDosing600mgIV/POevery12hoToxicitySafetyconcernswithprolongeduseThrombocytopeniaandneutropeniaLacticacidosisPeripheralneuropathyOpticneuritisSerotoninsyndromeincombinationwithSSRIsToxicitySafetyconcernswithpSerotoninSyndromeDescribedbyatriadofsymptomsMentalstatuschangeAutonomichyperactivityFever,hyperreflexiaNeuromuscularabnormalitiesSerotoninSyndromeDescribedbyBoyerEandShannonM.NEnglJMed2005;352:1112-1120SpectrumofClinicalFindingsBoyerEandShannonM.NEnglLinezolidresistanceRarebuthasbeenreportedwithS.aureusandEnterococcusspeciesLinezolidresistanceRarebuthLinezolid-pneumonia“Intrapulmonarypharmacokinetics”Requirevancotrough≥20toachieveappropriatealveolarlevels?In2RCTs(2001and2003)comparedvancov.linezolidforpneumoniaanddemonstratednodifferenceinoutcomes(aztreonamforGNRcoverage)ControversialsubsetanalysissuggestedsuperiorityoflinezolidforS.aureuspneumoniaLinezolid-pneumonia“IntrapulmCase352MwithHCVcirrhosisadmittedwithlargevolumehematemesisHistoryofSBPonciprofloxacinprophylaxisIntubatedtomaintainairways/pEGDwithbandingofvaricesStartedonceftriaxone1gevery24hoursforSBPprophylaxisHD#2febrileto38.5Case352MwithHCVcirrhosisCase3BloodculturessentanddiagnosticparacentesisperformedPatientgiven1gofvancomycinandchangedfromceftriaxonetocefepimeRBC1260WBC54090%NGramstain:fewWBCandnoorganismsBloodcultureswithGNRat13hoursinaerobicbottleCase3BloodculturessentandPreviousculturedataAnastutePGY-2looksbackatpreviousculturesandfindsthat8monthsearlierthepatientgrewthisinhisurine…PreviousculturedataAnastuteURINECULTURE01/02/10>100,000CFU/mLGRAMNEGATIVEBACILLIIsolate01Klebsiellapneumoniae,anESBLproducerCONTACTPRECAUTIONSANTIBIOTICSMicSYSTEMICURINE Aztreonam>16 R Ceftriaxone<8 R* Ceftazidime16 R Cefotaxime8 R Cefazolin>16 R* Cefepime<8 R* Ampicillin>16 R* Cefuroxime16 R* Tetracycline<4 S Ertapenem<2 S Gentamicin<4 S Imipenem<4 S Levofloxacin<2 S Trimethoprim/Sulf<2/38 S

抗生素英文課件——Choosing-Antibiotics-Before-and-After-tAnychanges?A.ContinuecefepimeB.ChangecefepimetolevofloxacinC.ChangecefepimetoimipenemD.GiveadoseofgentamicinE.CallIDforaconsultbecauseliverisgoingtoaskyoutodothatanywaysAnychanges?A.ContinuecefepiESBLExtended-spectrumbeta-lactamase(ESBL)producingorganismsfirstdescribedin1983AssociatedwithuseofbroadspectrumantibioticsLikeceftriaxone,ceftazidime,pip-tazoResistanttopenicillins,cephalosporins,andmonobactams(aztreonam)CarbapenemsarethedrugofchoiceClinicalfailuresassociatedwithalternativeagents(likefluoroquinolones)Increasedmorbidityandmortalityassociatedwithdelayedadministrationof“appropriate”antibioticsESBLExtended-spectrumbeta-lacCarbapenemsImipenem1987Activityvs.AcinetobacterMeropenem1996Activityvs.BurkholderiaspeciesFDAapprovedformeningitisErtapenem2001NotforPseudomonasorAcinetobacterMinimalactivityvs.EnterococcusFDAapprovedforintra-abdominalinfections/UTIs/CAP/skininfectionsDoripenem2007MostpotentagainstPseudomonasFDAapprovedforcomplicatedUTIs/Intra-abdominalinfectionsCarbapenemsImipenem1987ActiviCarbapenemsExcellentanaerobiccoverageIntrinsicresistanceEnterococcusfaecium

MRSAStenotrophomonasmaltophiliaBurkholderiacepacia(exceptmeropenem)Penicillin-resistantStreptococcuspneumoniaeAdverseeventsNephrotoxicityNeurotoxicityCarbapenemsExcellentanaerobicBLOODCULTURE08/02/10GRAMNEGATIVEBACILLIINAEROBICBOTTLEAFTER13HOURSIsolate01Klebsiellapneumoniae,anESBLproducerANTIBIOTICSMicSYSTEMICURINE Aztreonam>16 R Ceftriaxone<8 R* Ceftazidime16 R Cefotaxime8 R Cefazolin>16 R* Cefepime<8 R* Ampicillin>16 R* Cefuroxime16 R* Tetracycline<4 S Ertapenem<2 S Gentamicin<4 S Imipenem<4 S Levofloxacin>2 R Trimethoprim/Sulf<2/38 S

抗生素英文課件——Choosing-Antibiotics-Before-and-After-tIfyoueverseethis…Ifyoueverseethis…BLOODCULTURE07/02/10GRAMNEGATIVEBACILLIINBOTHBOTTLESAFTER7HOURS.Isolate01Klebsiellapneumoniae07/04/10-ThisOrganismIsProducingaKPC-typeCarbapenemase.AllBeta-LactamAntibioticsShouldBeInterpretedAsResistant.SusceptibilitytestingresultsforPolymyxinBmaybeusedtopredicttheactivityofColistin(PolymyxinE).-CONTACTPRECAUTIONSANTIBIOTICSMICSYSTEMICURINE Amox/Clavulanate>16/8 R Aztreonam>16 R Ceftriaxone>32 R Ceftazidime>16 R Ciprofloxacin>2 R Cefepime>16 R Amikacin>32 R Ertapenem>4 R Gentamicin<4 S Imipenem>8 R Levofloxacin>4 R Meropenem>8 R Piperacillin/tazo>64 R Trimethoprim/Sulf>2/38 R Tetracycline>4 R Tobramycin>8 RBLOODCULTURECallanIDfellow…CallanIDfellow…抗生素英文課件——Choosing-Antibiotics-Before-and-After-tSusceptibilitiesatMSH2009CarbapenemGentAmikTobraE.coli99%K.pneumoniae64%(E)76%70%55%P.aeruginosa86%(M)76%93%93%A.baumannii21%(I)29%45%40%E.cloacae76%(E)73%97%70%SusceptibilitiesatMSH2009CaOthersusceptibilitiesTigecyclinePolymyxinK.pneumoniae75%84%A.baumannii13%97%E.cloacae58%92%A.baumannii-38%susceptibletosulbactamcomponentofamp-sulbactamOthersusceptibilitiesTigecyclCase455FDM,HTN,PVD,ESRDonHDAdmittedwithhyperglycemia/HONKTransferredoutofMICUto9WafterstabilizedonHD#3OnHD#5febrileto38.7andlethargicCXRorderedBloodculturessentU/AandUrineculturesorderedCase455FDM,HTN,PVD,ESRDCXRCXRLateralLateralEmpiricAntibioticsHospital-AcquiredPneumonia≥48hoursafteradmissionVentilator-AssociatedPneumoniaHealthcare-AssociatedPneumoniaEmpiricAntibioticsHospital-AcHealthcare-associatedPneumoniaMostrecentguidelinesemphasizeobtaininglowerrespiratorytractculturesEarly,appropriatebroad-spectrumantibioticsattheadequatedosesMicrobiologyvariesfromonehospitaltoanotherandoneunittoanotherNarrowingcoverageShorterdurationsTheroleforanaerobiccoverageand“aspirationpneumonia”Healthcare-associatedPneumoniPip-tazovs.CefepimePip-TazoProsAmpicillin-susceptibleEnterococcusAnaerobesConsPotentinducerofbeta-lactamaseproduction“Highersaltload”CefepimeProsMorestableagainstmanybeta-lactamasesincludingsomeESBLsBetterGNRdrughereatMSH?(personalopinion)CheaperConsNoactivityagainstEnterococcusorAnaerobesPip-tazovs.CefepimePip-TazoC“Aspiration”andtheAnaerobeDoyouneedtoaddmetronidazoleorclindamycin?RarelynecessaryLevofloxacinandceftriaxonehavesomeanaerobicactivityMostpneumoniaarisesfromaspirationofbacteriacolonizingtheoropharynx/nasopharynxAwfuldentition(differentfromlackofdentition)AbscessformationUsuallyamoreindolentpresentationChemicalpneumonitisAspirationofgastriccontentsvs.aspirationofbowelcontentsWheredoanaerobeslive?“Aspiration”andtheAnaerobeD抗生素英文課件——Choosing-Antibiotics-Before-and-After-tUseantibioticswiththoughtUseantibioticswiththoughtHelpfulHintsWhathasthepatientgrownbefore?PreviousantibioticexposuresIfthepatientisincontactisolationfromadmissionchancesaretheygrewsomethinginthepastSCCisprobablythebestsystemtolookatculturesWhatisthepatientatriskforgrowingnow?PreviousantibioticexposuresRecentinterventionsWhatisthepatientgrowingnow?NarrowcoverageLimitingantibioticexposuresHelpfulHintsWhathasthepati抗生素英文課件——Choosing-Antibiotics-Before-and-After-tCallforadviceAntibioticApproval9407GeneralID0649TransplantID8679CallforadviceAntibioticApprPopQuiz47yoFs/palloSCT8/08complicatedbyGVHDoftheskinandgut,CMVviremia,andpresumedaspergilluswithworseningshortnessofbreathandB/LnodularinfiltratesIntubatedon11CandcomestoMICUonLinezolid,Imipenem,Tigecycline,Gentamicin,Azithromycin,Ambisome,andGanciclovirPopQuiz47yoFs/palloSCT8PopQuizSputumgramstainwith1-9PMNsBloodcultureswithGNRinaerobicbottleat5hoursWhatdoyouadd?A.BactrimB.InhaledcolistinC.LevofloxacinD.PalliativecareconsultPopQuizSputumgramstainwithStenotrophomonasmaltophiliaInherentlyresistanttoCarbapenemsDrugofchoiceisTMP-SMXTMP-SMXLevoCeftazS.maltophilia98%88%47%StenotrophomonasmaltophiliaInChoosingAntibiotics:

BeforeandAftertheCultureResultsGopiPatel,MDAugust20,2010ChoosingAntibiotics:

BeforeProphylaxisEmpiricTargetedPickingAntibioticsWhathasthepatientgrownbefore?Whatisthepatientgrowingnow?Whatisthepatientatriskforgrowing?Whatarethepatient’ssignsandsymptoms?ProphylaxisEmpiricTargetedPickAntibioticselectionRiskfactorsfordrugresistanceRecentantimicrobialexposuresUnderlyingcomorbiditiesAllergiesRecentinterventionsAvailableandpreviousculturedataHistoryofMRSA,VRE,PseudomonasESBL-producingGNRThefloraandfaunaofthehospitalAndperhapseventheunit…Howsickisthepatient?Canalways“gobig”andnarrowasyougetmoreinformation…AntibioticselectionRiskfactoJusttorefreshyourmemory…Justtorefreshyourmemory…Cephalosporins*1stCefazolinCephalexinGram-positivecocci(e.g.,MSSA,GBS)

E.coli,K.pneumoniae,P.mirabilis2ndCefuroximeCefoxitinCefotetanCefuroxime-H.influenzaeCephamycins-Bacteroidesspp3rdCefotaximeCeftriaxoneCeftazidimeSomeanaerobiccoverageCeftazidime-Pseudomonas

CrossestheBBBPotentinducersofβ-lactamases4thCefepime

Pseudomonas

CrossestheBBBStableagainstmanyβ-lactamases*DoNOTcoverEnterococcus,Listeria,Legionella,orMRSACephalosporins*1stCefazolinGrCase148MIVDAadmittedwithfeversandchillsFreshtrackmarksonLeftarmFebrileto39BP70/55HR11293%RAIII/VIsystolicmurmuratLLSBB/LcracklesChestX-ray-CongestionB/LEmpiricantibiotics?Case148MIVDAadmittedwithAsexpectedAt14hoursbothsetsofbloodculturesaregrowingGram-positivecocciinclustersPrevioushistoryofMRSATTEcan’truleoutvegetationonmitralvalveTEErefusedPatientgrowsMRSAVancomycincontinuedAsexpectedAt14hoursbothseVancomycinDiscoveredin1956MechanismofactionInhibitsbacterialcellwallsynthesisBindsfirmlytoD-Ala-D-Alaofthepeptidoglycan,preventingelongationandcross-linkingMechanismofresistanceAlteredpeptidoglycanbindingsiteD-Ala-D-AlaisreplacedbyD-Ala-D-lactateThickenedcellwallVancomycinDiscoveredin1956ToxicityNephrotoxicityMostofteninthesettingofothernephrotoxicagentsandunstablerenalfunctionHypersensitivityreactions1RedmansyndromeAnaphylaxisRarereactionsOtotoxicityNeutropeniaand/orthrombocytopenia2LinearIgAbullousdermatosis1CritCare.2003;7(2)119-202NEJM.2007;356(9)904-910ToxicityNephrotoxicity1CritCLinearIgABullousDermatosisLinearIgABullousDermatosisDosingDosingDosingCrCl(mL/min)DosingRegimen>7015mg/kgevery8-12hours40-6915mg/kgevery12-24hours<3915mg/kgx1,thenre-dosebylevelUseactualbodyweighttodoseRoundtothenearest250mgAmJHealth-SystPharm.2009;66:82-98UseCockcroft-GaulttocalculateCreatinineClearanceNOTMDRD(GivenbyEDRorSCC)DosingCrCl(mL/min)DosingRegiMonitoringTroughsaremostaccurateandpractical

Obtaintroughjustpriortothenextdoseatsteady-state(usuallyafter4thdose)Levelsshouldbemaintained>10mg/LMinimumtroughsof15-20mg/Larerecommendedforsevereorcomplicatedinfections(endocarditis,osteomyelitis,meningitis,andpneumonia)1AmJRespCritCareMed.2005;171:338.2ClinInfectDis.2004;39:1267-84.3Circulation.2005;111:e394-e433.MonitoringTroughsaremostaccWhatifapersoncan’t“tolerate”Vanco?AnaphylaxisPatient“refuses”drugCan’tgettherightlevelsEaseofdosingWhatifapersoncan’t“toleraDaptomycinFDAapprovedin2003DepolarizesthecellmembraneandisrapidlybactericidalagainstGram-positivesApprovedforthetreatmentofcomplicatedskinandskinstructureinfectionsS.aureus(includingMRSA),GAS,Streptococcusagalactiae,andvanco-susceptibleEnterococcusfaecalisNotapprovedforE.faecium(CLSIbreakpoint<4)Non-inferiortovancoandanti-staphpenicillinsinS.aureusbacteremiaandright-sidedendocarditis1Juryisoutforleft-sidedendocarditisNOTindicatedfortreatmentofpneumonia1NEJM.2006;355(7):652-65DaptomycinFDAapprovedin2003DosingUseactualbodyweightForserious,life-threateninginfectionsdosingregimensof8to12mg/kghavebeenused1Requires24-hourAntibioticApprovalIndicationCrCl(mL/min)DoseSSTI≥30<30(HD)4mg/kgevery24hrs4mg/kgevery48hrsBacteremia≥30<30(HD)6mg/kgevery24hrs6mg/kgevery48hrs1CID.2009;49:177-80DosingUseactualbodyweightInToxicityRhabdomyolysisandmyopathyMonitorforclinicalevidenceofmyopathyCheckCK/CPKlevelseveryweekEspeciallyifonhigherdoseorinrenalfailureMaybeatincreasedriskfortoxicitywithstatinsToxicityRhabdomyolysisandmyoMicrobiologicFailureResistancecandeveloptodaptomycinduringtreatmentandmaybeinfluencedbyexposuretovancomycinSeeninbothS.aureusandEnterococcussppNEJMnon-inferioritystudy:15%ofpatientsindaptoarmwithclinicalfailure6/19(32%)withincreaseddaptomycinMICShouldnotbeusedif1°sourcenotremovedMicrobiologicFailureResistancWhatifthepatientgrewMSSA?NafcillinNafcillin2gIVQ4hoursNoadjustmentCefazolin2gIVQ8hoursfor“normal”renalfunctionWhatifthepatientgrewMSSA?S.aureus:itsownlecturePleasecallanIDconsultforMSSAorMRSAbacteremiaHighriskformetastaticdiseaseFuturenoonconferencetofollow(10/13/10)S.aureus:itsownlecturePleaAnotherrefresher…Anotherrefresher…B-lactam/B-lactamaseinhibitorsAmpicillin-sulbactamAmpicillin-susceptibleEnterococcusspp.AnaerobesSinusitis,dogandcatbites,humanbites,community-acquiredlungabscessSulbactamcomponenthasactivityagainstAcinetobacterspp.Piperacillin-tazobactamPseudomonasaeruginosa

Ampicillin-susceptibleEnterococcusspp.AnaerobesB-lactam/B-lactamaseinhibitorCase257FtransferredfromoutsidehospitalafteradmissionfornewjaundiceandincreasingabdominalgirthDiagnosedwith“cryptogeniccirrhosis”Transferredonpiperacillin-tazobactamandvancomycinCase257FtransferredfromouCase2Patientgivenvancomycin1gramx1doseandcontinuedonpiperacillin-tazobactamHD#2developsworseningencephalopathyCXRBloodculturesU/AandurinecultureDiagnosticparacentesisattemptedCase2PatientgivenvancomycinCase2InterncallsOSHandfindsthatpatient’sbloodculturestherearegrowingGPCinpairsandchainsPatientonbothvancoandpip-tazoatthetimethecultureswereobtainedHint:WhatGPCisnotbeingcovered?ChangeAntibiotics?Case2InterncallsOSHandfinEnterococcusspeciesAmpicillin-susceptibleE.faecalis

PenicillinandampicillinslowlybactericidalAmpicillin,piperacillin,penicillin,imipenemVancomycin(whensusceptible)88%ofE.faecalisisvancosusceptibleatMSH20%ofE.faeciumUseofaminoglycosidesforsynergyinthesettingofseriousinfections(e.g.,endocarditis)EnterococcusspeciesAmpicillinVREFDAapprovedagentsLinezolidQuinupristin/Dalfopristin(E.faeciumONLY)AlternativeagentsDaptomycinTigecyclineVREFDAapprovedagentsLinezolidFDAapprovedin2000forcomplicatedskinandskinstructureinfections,pneumonia,andbloodstreaminfectionsGram-positiveorganismsNocardia,non-tuberculousmycobacteria,TBMechanismofactionInhibitsinitiationofproteinsynthesisbybinding50SribosomeOralformulationwith100%bioavailabilityLinezolidFDAapprovedin2000Dosing600mgIV/POevery12hoursNodose-adjustmentforrenalinsufficiencyorliverdiseaseDosing600mgIV/POevery12hoToxicitySafetyconcernswithprolongeduseThrombocytopeniaandneutropeniaLacticacidosisPeripheralneuropathyOpticneuritisSerotoninsyndromeincombinationwithSSRIsToxicitySafetyconcernswithpSerotoninSyndromeDescribedbyatriadofsymptomsMentalstatuschangeAutonomichyperactivityFever,hyperreflexiaNeuromuscularabnormalitiesSerotoninSyndromeDescribedbyBoyerEandShannonM.NEnglJMed2005;352:1112-1120SpectrumofClinicalFindingsBoyerEandShannonM.NEnglLinezolidresistanceRarebuthasbeenreportedwithS.aureusandEnterococcusspeciesLinezolidresistanceRarebuthLinezolid-pneumonia“Intrapulmonarypharmacokinetics”Requirevancotrough≥20toachieveappropriatealveolarlevels?In2RCTs(2001and2003)comparedvancov.linezolidforpneumoniaanddemonstratednodifferenceinoutcomes(aztreonamforGNRcoverage)ControversialsubsetanalysissuggestedsuperiorityoflinezolidforS.aureuspneumoniaLinezolid-pneumonia“IntrapulmCase352MwithHCVcirrhosisadmittedwithlargevolumehematemesisHistoryofSBPonciprofloxacinprophylaxisIntubatedtomaintainairways/pEGDwithbandingofvaricesStartedonceftriaxone1gevery24hoursforSBPprophylaxisHD#2febrileto38.5Case352MwithHCVcirrhosisCase3BloodculturessentanddiagnosticparacentesisperformedPatientgiven1gofvancomycinandchangedfromceftriaxonetocefepimeRBC1260WBC54090%NGramstain:fewWBCandnoorganismsBloodcultureswithGNRat13hoursinaerobicbottleCase3BloodculturessentandPreviousculturedataAnastutePGY-2looksbackatpreviousculturesandfindsthat8monthsearlierthepatientgrewthisinhisurine…PreviousculturedataAnastuteURINECULTURE01/02/10>100,000CFU/mLGRAMNEGATIVEBACILLIIsolate01Klebsiellapneumoniae,anESBLproducerCONTACTPRECAUTIONSANTIBIOTICSMicSYSTEMICURINE Aztreonam>16 R Ceftriaxone<8 R* Ceftazidime16 R Cefotaxime8 R Cefazolin>16 R* Cefepime<8 R* Ampicillin>16 R* Cefuroxime16 R* Tetracycline<4 S Ertapenem<2 S Gentamicin<4 S Imipenem<4 S Levofloxacin<2 S Trimethoprim/Sulf<2/38 S

抗生素英文課件——Choosing-Antibiotics-Before-and-After-tAnychanges?A.ContinuecefepimeB.ChangecefepimetolevofloxacinC.ChangecefepimetoimipenemD.GiveadoseofgentamicinE.CallIDforaconsultbecauseliverisgoingtoaskyoutodothatanywaysAnychanges?A.ContinuecefepiESBLExtended-spectrumbeta-lactamase(ESBL)producingorganismsfirstdescribedin1983AssociatedwithuseofbroadspectrumantibioticsLikeceftriaxone,ceftazidime,pip-tazoResistanttopenicillins,cephalosporins,andmonobactams(aztreonam)CarbapenemsarethedrugofchoiceClinicalfailuresassociatedwithalternativeagents(likefluoroquinolones)Increasedmorbidityandmortalityassociatedwithdelayedadministrationof“appropriate”antibioticsESBLExtended-spectrumbeta-lacC