疼痛科中抗生素使用（英文ppt）antibiotics and pain control课件

ExamplesofOperationalNeedStimulatingScientificInnovation AntibioticsandPainControl WWII Poole 1944 ThegreatestlessonlearnedfromWorldWarIImayhavebeenthebenefitoftheuseofpenicillinprophylacticallyinthesurgicalunitsclosetothefront Korea Scott 1954 Inanytacticalsituationwherethecasualtycannotreachtheaidstationuntil4 5hoursorlongerafterwounding antibiotictherapybytheaidmaninthefieldismostdesirable Vietnam Kell 1991 Asingleinjectionofabroad spectrumantibioticwithalonghalf lifeshouldbegivenprophylacticallytopersonnelonthebattlefieldtoprovidebactericidalcoveragefromtheearliestmomentafterinjuryoccurs Somalia Mabry 2000 4of5openfracturesofthetibiafromgunshotwoundsbecameinfected 2of2openfracturesofthefemurbecameinfected Inall 15woundinfectionsin58casualties 15hourdelaytodefinitivecare CurrentUSArmydoctrineonprehospitalcaredoesnotcallforantibioticadministrationbymedicsinthefield Whynot Antibioticsnotroutinelygiveninthefieldbycivilianpre hospitalpersonnel EMT paramedicmodelformedictraining Combatmedicsdon ttypicallyseewoundinfectionsduringthetimetheycareforthem maynotappreciatetheirdevastatingeffect Nota sexy topic IvoryTowerarrogance IncreasedRiskofInfectioninTraumaPatients DisruptionofMechanicalBarriersBacterialContaminationLocalWoundFactorsInvasiveInterventionsImpairedResistance GeneralPreventiveMeasures AdequateandTimelyResuscitationEarlyWoundCareAntibioticsTetanusImmuneProphylaxis AdequateandTimelyResuscitation A B C s Needtomaintaina nearlynormal arterialoxygentension VolumeExpansionConsiderations EarlyWoundCare EliminateDeadSpacefluid bloodDelayedPrimaryClosure DPC 4 6daysEarlyImmobilizationofFracturesSofttissuedamage SterileDressingcontamination desiccationDebridementexcisedevitalizedtissueIrrigationhighpressure solution Antibiotics Finiteperiodoftimeinwhichinfectioncanbeprevented Miles Burke Howearly nothowlong Fullen etal Boththetimingandthechoiceareimportant Thadepalli etal WhatBugs YomKippurWarPseudomonas 25 6 isolatesGmNegbacilli 70 isolatesoverallUsedpenicillinsSomaliaPseudomonasandpolymicrobialRussianAfghanistanExperienceClostridialRecommendedPCN Rifampin Metronidazole orCeftriaxoneWaterborneOpsSeaWater VibrioOverwhelmingGmNegsepsis 50 mortalityFreshWater Aeromonas OurEnvironment OurEnvironment TacticalFieldCare WhatWeWantinanAntibiotic Heat ColdResistance FireandForget LongShelfLife SingleAgent DurablePackaging EasyPreparation BroadSpectrum MultipleApplications TheEASTPracticeManagementGuidelines TheJournalofTrauma March2000Meta analysis MEDLINESearchfor1976 1997Afterdiscrimination 39articlesforreview32comparingoutcome 7comparingpharmacokinetics cost TheEASTPracticeManagementGuidelines cont LookingmostlyatClass1articles Moresuccessfulregimentsincluded cefoxinclindamycinwithgentamycintobramycinwithclindamycincefotetancefamandoleaztreonamgentamycin TheEASTPracticeManagementGuidelines cont Cefoxitinvs Clinda Gent Both24 Nicholsetal Cefoxitinvs Tobra clinda vs CefamandoleCefox18 T C29 Cefaman36 Jonesetal Cefoxitinvs CefotetanNodifferenceFabianetal Aztreonamvs Gent bothwithClinda Aztr3 Gent13 Fabianetal WhataboutUS Recommendations Consideringspecialneeds Mostapplications Cefoxitin Cefotetancancoverbothorthoandguttrauma fast stable CefoxingetsedgewithstorageCefotetanlongerhalf lifeonsetsameForPCN Allergic Cipro Clindacoversboth BUT Whynotorals Nopowdertoreconstitute Cancarryalotmore BroadSpectrum RapidAbsorptionnowavailable Onlyhesitationwouldbe PenetratingAbd Trauma Unconsciousness Shock BodyArmorhasprofoundlylessenedtorsoinjuries Therefore oralsareappropriateforvastmajorityofcasualties WhichOrals Penicillins Toomanyseriousallergicreactions Dosingrequirementstoofrequent MissmostGramNegs WhichOrals cont Flouroquinolones BloodlevelsviaPOroutesimilartoIVdosing Ciprofloxacin Goodvs Pseudomonas butnotvs anaerobes Levafloxacin BetterGmPosthanCipro butstillnotgoodforanaerobes Okayforpseudomonas WhichOrals cont Flouroquinolones cont Trovafloxacin CoversGmpos neg andanaerobes Hepatotoxicitywithprolongeduse Absorptiondelayedbymorphine Moxifloxacin CoversGmpos neg andanaerobes Goodvs ClostridiumandBacteroides samerangeasmetronidazole andsuperiortoclindamycin QDdosing Gatifloxicin CoversGmpos neg andanaerobes Verysimilartomoxifloxacin butlessexpensive QDdosing RecommendationforOralDosing Gatifloxacin 400mgPOQDforallpenetratinginjurieswhocantakeoralmeds Alternative Moxifloxacin400mgPOQD FinalRecommendationsinTacticalArena 2002 Forallopencombatwounds Gatifloxacin400mgbymouthonceaday Ifunabletotakeoralmedications shock unconsciousness penetratingabd Injury Cefotetan2gmIV slowpushover3 5min orIMevery12hours ReviewofOralAntibioticChoicestoReplaceGatifloxacin KevinC O Connor D O LTC MC USACommitteeonTacticalCombatCasualtyCareTampa FL29June2006 CurrentSituation SafetyOverview SeriousAdverseDrugEffectshaveledtowithdrawaloffourquinolones Temafloxacin immunologicalreactions Grepafloxacin cardiotoxicity Trovafloxacin hepatotoxicity Sparfloxacin cardiotoxicity Gatifloxacinassociatedwithdysglycemia Tosufluxacinassociatedwithimmunologicalreactions Gemifloxacinassociatedwithhighrateofrashes esp women 40yo Morethan100millionprescriptionswerewrittenforterfenadineandastemizolewerewrittenbeforetheywerewithdrawnforTdPandsuddendeath FrothinghamR QuinoloneSafetyandEfficacyMoreImportantthanPotency EmergingInfectiousDiseases2004 10 156 57 IanniniPB KubinR ReiterC TillotsonG ReassuringSafetyProfileofMoxifloxacin ClinicalInfectiousDiseases2001 32 4 1112 4 2002Recommendation Ingeneral moxifloxacinwasthemostpotentfluoroquinoloneforGram positivebacteriawhileciprofloxacin moxifloxacin gatifloxacin andlevofloxacindemonstratedequivalentpotencytoGram negativebacteria MatherR KarenchakLM RomanowskiEG KowalskiRP Fourthgenerationflouroquinolones newweaponsinthearsenalofopthalmicantibiotics AmJOphthalmol2002 133 463 466 O ConnorK ButlerF AntibioticsinTacticalCombatCasualtyCare2002 MilitaryMedicine2002 168 11 911 914 2002Recommendation AnotherstudyMoxifloxacinwasalmostasactiveastrovafloxacin asactiveasgatifloxacin andmoreactivethanlevofloxacinandciprofloxacinagainsttheanaerobestested includingClostridiumspecies AckermanG SchaumannR PlessB ClarosMC GoldsteinEF Rodloff Comparativeactivityofmoxifloxacininvitroagainstobligatelyanaerobicbacteria EurJClinMicrobiolInfDis2000 19 228 232 O ConnorK ButlerF AntibioticsinTacticalCombatCasualtyCare2002 MilitaryMedicine2002 168 11 911 914 2002Recommendation Gatifloxacinisagoodchoiceforsingle agenttherapybasedonitsexcellentspectrumofcoverage goodsafetyprofile andonce a daydosing Moxifloxacinwouldbeanacceptablesecondchoice Athirdchoicemightbelevofloxacin butbecauselevofloxacinhasonlylimitedactivityagainstanaerobes anotherdrugmustbeaddedtoachievecoverageagainsttheseorganisms O ConnorK ButlerF AntibioticsinTacticalCombatCasualtyCare2002 MilitaryMedicine2002 168 11 911 914 2002RecommendationRecommendationforOralDosing Gatifloxacin 400mgPOQDforallpenetratinginjurieswhocantakeoralmeds USGovt costAugust2002 1 86 Alternative Moxifloxacin400mgPOQD USGovt costAugust2002 5 09 O ConnorK ButlerF AntibioticsinTacticalCombatCasualtyCare2002 MilitaryMedicine2002 168 11 911 914 Re look SafetyTorsadesdePointes ProlongedQTinterval GrepafloxacinandSparfloxacin withdrawn 1996 2001cruderatesforTdPGatifloxacin90 xciproLevofloxacin18xciproGatifloxacin5xrateforlevoMoxifloxacin noUScases 3foreigncases ConfidenceIntervalGatifloxacinassociatedwithhighestrateofTdP Moxifloxacinassociatedwithlowest BUT Preclinicalandclinicaltrialsindicatethatlevofloxacin moxifloxacin andgatifloxacinallprolongQTinterval Smallcrossoverstudy asingleoraldoseofmoxifloxacin800mgassociatedwithgreaterQTintervalprolongation 16 18milliseconds thanciprofloxacin1500mg 2 5milliseconds orlevofloxacin1000mg 4 5milliseconds FrothinghamR Ratesoftorsadesdepointesassociatedwithciprofloxacin ofloxacin levofloxacin gatifloxacin andmoxifloxacin Pharmacotherapy2001 21 1468 72 OwensR AmproseP Torsadesdepointesassociatedwithfluoroquinolones Pharmacotherapy2002 22 5 663 672 NoelGJ NatarajanJ ChienS HuntTL GoodmanDB AbelsR EffectsofthreefluoroquinolonesonQTintervalinhealthyadultsaftersingledoses ClinicalPharmacologicalTherapeutics2003 73 292 303 SafetyDysglycemia Outpatientstudy Gatifloxacinhasbeenassociatedwithbothhypoglycemiaandhyperglycemia Ascomparedtomacrolides gatifloxacinwasassociatedwithanincreaseriskofhypoglycemia AdjustedOddsRatio4 3 95 ConfidenceInterval Levofloxacinwasalsoassociatedwithslightlyincreasedrisk AOR 1 5 95 CI Noincreasedriskwithmoxifloxacin ciprofloxacin orcephalosporins Park WyllieLYJuurlinkDN KoppA ShahBR StukelTA StumpoC DresserL LowDE MamdaniMM Outpatientgatifloxacintherapyanddysglycemiainolderadults NewEnglandJournalofMedicine2006 354 13 1352 61 SafetyDysglycemia In patientstudy Serumglucose 200or 50within72hrsofreceivingthedrug Levofloxacin Gatifloxacin CiprofloxacinorCeftriaxoneDysglycemiarates Gatifloxacin76of7540pts 1 01 Levofloxacin11of1179pts 0 93 Ceftriaxone14of7844pts 0 18 Ciprofloxacin0of545pts 0 Ofthe101patientswithdysglycemia hypoglycemiaoccurredin9 9 andhyperglycemiain92 91 Inthe17 108patientsreceivingafluoroquinoloneorceftriaxone therateofdysglycemiawasgreaterinthosereceivinglevofloxacinorgatifloxacin thaninthosereceivingCeftriaxone However therewasnostatisticallysignificantdifferencebetweenlevofloxacinandgatifloxacin MohrJF McKinnonPS PeymannPJ KentonI SeptimusE OkhuysenPC Aretrospectivecomparativeevaluationofdysglycemiasinhospitalizedpatientsreceivinggatifloxacin levofloxacin ciprofloxacinorceftriaxone Pharmacotherapy2005 25 10 1303 9 SafetyDysglycemia PhaseII IIIclinicaltrialsdatabase14 731patients 8474moxifloxacin 6257comparators Nodrug relatedhypoglycemiceventsinmoxifloxacingroup Twodrug relatedhypoglycemiceventswithlevofloxacin Onewithtrovafloxacin Sevenhyperglycemiceventsinmoxifloxacingroup 1 Onehyperglycemiceventswithcomparators 0 1 Datafromfivemoxifloxacinpostmarketingstudies 46 130subjects reportednoepisodesofhypoglycemiaandtwonon drug relatedhyperglycemicepisodes Conclusion ComprehensiveanalysisofdatapoolformoxifloxacinPhaseII IIItrialsandpost marketingstudiessuggestthatmoxifloxacinadministrationhasnorelevanteffectonbloodglucosehomeostasis GavinJR3rd KublinR ChoudhriS KubitzaD HimmelH GrossR MeyerJM Moxifloxacinandglucosehomeostasis apooled analysisoftheevidencefromclinicalandpostmarketingstudies DrugSafety2004 27 9 671 86 EfficacyPseudomonas ScheldfavorsciprofloxacinforknownorsuspectedPseudomonasaeruginosainfections FavorsmoxifloxacinforinfectionsinwhichStreptococcuspneumoniaeislikely ScheldWM Maintainingfluoroquinoloneclassefficacy reviewofinfluencingfactors EmergingInfectiousDiseases2003 9 1 9 EfficacyRespiratoryandAbdominalPathogens Moxifloxacin gatifloxacin levofloxacin andazithromycincompared in vitrosusceptibilityofcommonpathogensthatcauserespiratorytractandabdominalwoundinfections 50isolateseachMRSA E faecalis E faecium S pneumoniae S pyogenes E coli P aeruginosa H influenzae Results Moxifloxacinwasmostactivesubstancevs Gram positivepathogens Gatifloxacinmostactivevs Pseudomonas Moxifloxacin Gatifloxacincomparablevs E coliandH influenzae Conclusions Moxifloxacinandgatifloxacindisplayexcellentactivityvs respiratorypathogensaswellasnosocomialpathogenscausingabdominalwoundinfections WhentreatingPseudomonasaeruginosa theearlierfluoroquinolonessuchasciprofloxacinorofloxacinarethesubstancesofchoice WenzlerS Schmidt EisenlohrE DaschnerF Comparativeinvitroactivitiesofthreenewquinolonesandazithromycinagainstaerobicpathogenscausingrespiratorytractandabdominalwoundinfections Chemotherapy2004 50 1 40 2 EfficacyAgainstGram Positives Olderflouroquinolones i e ciprofloxacin limitedabilitytocoverGram positivebacteria CiproMIC90forS pneumoniais1 4mg L whilethemaximumconcentrationsinserumare2 3mg L Moxifloxacinhadthehighestin vitroactivityvs S pneumonia MIC90 0 25mg L MICrange0 06 0 25mg L TheMIC90valueswereonedilutionlowerthanthoseobtainedwithsparfloxacinandgrepafloxacin Threedilutionslowerthanthoseobtainedwithlevofloxacin Fourdilutionslowerthanthoseofofloxacinandciprofloxacin Moxifloxacin grepafloxacin sparfloxacin levofloxacin ofloxacin ciprofloxacin ReinertR SchlaegerJ LuttickenR Moxifloxacin acomparisonwithotherantimicrobialagentsofin vitroactivityagainstStreptococcuspneumoniae JournalofAntimicrobialChemotherapy1998 42 803 806 FrothinghamR letter inresponsetoBellomoS QuinoloneSafetyandefficacy letter EmergingInfectiousDiseases2005 11 6 985 6 EmergingInfectiousDiseases2005 11 6 986 7 EfficacyRespiratoryPathogens Gram Positives Comparisonofinvitroactivityofmoxifloxacin levofloxacinandsixotherantibioticsfrequentlyusedforURIs 1563isolatesS pneumonia S pyogenes S aureus H influenzae andM catarrhalis 21centersin10LatinAmericancountriesFindings Moxifloxacinwasthemostactivecompoundvs allthespeciesincluded Moxifloxacinwas2 4foldmoreactivethanlevofloxacinvs grampositivebacteria LopezH SaderH AmabileC PedreiraW MunozBellidoJL GarciaRodriquezJA GrupoMSP LA InvitroactivityofmoxifloxacinagainstrespiratorypathogensinLatinAmerica ArticleinSpanish RevEspQuimioter2002 15 4 325 34 ComparisonofAntibioticSpectrumNotabledifferences otherwiseratedequally MoxifloxacinE faecium Gm Clinicaltrialslackingor30 60 susc S aureus MRSA Gm Usuallyeffectiveclinicallyor 60 susc S X maltophilia Gm Usuallyeffectiveclinicallyor 60 susc Actinomycetes anaerobe Usuallyeffectiveclinicallyor 60 susc B fragilis anaerobe Clinicaltrialslackingor30 60 susc C difficile anaerobe Clinicaltrialslackingor30 60 susc LevofloxacinE faecium Gm Noteffectiveclinicallyor 30 susc S aureus MRSA Gm Noteffectiveclinicallyor 30 susc S X maltophilia Gm Clinicaltrialslackingor30 60 susc Actinomycetes anaerobe Nodataavailable B fragilis anaerobe Noteffectiveclinicallyor 30 susc C difficile anaerobe Noteffectiveclinicallyor 30 susc GilbertDN MoelleringRC EliopoulosGM SandeMA TheSanfordGuidetoAntimicrobialTherapy2004 Thirty fourthEdition 34 p 52 Costs Levofloxacin Levoquin 500mg 1 95perdose DoDpricingMoxifloxacin Avelox 400mg 1 22perdose DoDpricing Source Ms DonnaKelly PharmacyPurchasingOfficer EvansArmyCommunityHospital Ft Carson Colorado 719 526 7869 26June2006 Recommendation ReplaceGatifloxacin400mgx1withMoxifloxacin400mgx1takenorallyforallcombatwounds TacticalFieldCare Antibiotics RecommendedforallopenwoundsUsePOmoxifloxacin400mgadayifableIfcasualtyisunconscious hasanabdominalwound orisinshock Cefotetan2gmslowIVpush over3 5minutes orIMevery12hoursO ConnorK ButlerF AntibioticsinTacticalCombatCasualtyCare2003 MilitaryMedicine168 11 November2003 911 914 NOW Ertapenam1gmIV IMqD recentchange Introduction Painisamoreterriblelordofmankindthanevendeathitself AlbertSchweitzer Oligoanalgesia Termcoinedin1989byWilsonandPendleton Thephenomenathatcare giversoftenfailtoeitherrecognizeorappropriatelytreatpain PainAsInterpretedbytheCasualty Itis ofcourse acompletemyththatastandardcauseproducesastandardpain PatrickWallWallPD Pain TheScienceofSuffering London Weidenfeld1999 Fundamentals ReassuranceDistractionImmobilization TypesofMedications Non OpioidsAcetaminophenNSAIDsOtherSedativeHypnoticsDissociatives OpioidsFullagonistsPartialagonistsMixed OpioidsGeneral 1680A D amongtheremediesithaspleasedAlmightyGodtogivemantorelievehissufferings noneissouniversalandsoefficaciousasopium SyndenhamJaffeeJH MartinWR Opioidanalgesicsandantagonists InGilmanAG WallTW NeisAS etal eds Thepharmacologicbasisoftherapeutics ed8 NewYork 1993 McGraw Hill OpioidsGeneral 2002A D amongtheremediesithaspleasedAlmightyGodtogivetomantorelievehissufferings noneissouniversalandsoefficaciousasopioidderivatives O ConnorToday SOMA 2002 OpioidsGeneral DrugsofchoiceforseverepainAdverseeffectsRespiratorydepressionSedation lightheadednessNausea vomitingConstipationToleranceDependence OpioidsFullAgonists MorphinerelatedMorphineHydromorphoneOxymorphoneHeroinCodeinerelatedCodeineOxycodoneHydrocodoneDihydrocodeine SyntheticMeperidineFentanylMethadoneProproxypheneLevorphanolTramadol OpioidsFullAgonists LongActing MorphineStandardofcomparisonOnset IV 4 6minDuration 2 3hoursOnset IM 20 60minDuration 4 5hours PatientControlledAnalgesia PatientTitrationElementofControlLesstotalmedicationusedMuchimprovedpatientsatisfaction senseofpainreliefprovided OralPainMedications ProvidepainreliefwithoutalteredmentalstatusManycombatwoundswithoutbonyinjuriesonlymild moderatepainNon narcoticsmedspreservecombatantabilityofcasualty TacticalFieldCare PAIN AnalgesiaasNecessary IfAbletoFight UseoralmedsMeloxicam Mobic 15mgPOQDRofecoxib Vioxx originalrecommendation 50mgperdayNoplateletinhibitionNosulfareactionsAcetaminophen Tylenol 8hrBi layer 1300mgNOdecreaseinmentalstatusasaresultofthesemedications CombatPillPack TacticalFieldCare AnalgesiaasNecessary IfUnabletoFightMorphine5mgIV IOReassessin10minutesRepeatdoseq10minasnecessarytocontrolseverepainMonitorforrespiratorydepressionPromethazine25mgIV IO IMq4h forpainandnausea NewRec onlyPRN OralTransmucosalFentanylCitrate FentanylTransmucosalLozenge FENTANYLSynthesizedinBelgiuminthelate1950sHighlylipophilicsyntheticphenylpiperidinederivative80 100timesmorepotentthanmorphineSelectivelybindstomu 1andmu 2receptors OTFC OTFCManufacturedin1980sFDAapproval Oralet 1993 Actiq 1998Crystallineformoffentanylcitrate raspberrylozengeonaplasticstick Only50 absorbedTransmucosal 5