抗菌药(Clinical_Uses_of_Antimicrobial Agents——方三华

ClinicalUsesofAntimicrobialAgents,San-HuaFang,PhD方三华Dept.ofPharmacology,SchoolofMedicine,ZhejiangUniversityfshfbzxhq,1.Formulatingapathogenicdiagnosisearly,whichdependsonclinicaldiagnosis,microbiologicdiagnosisandtestingresultsinvitro.2.Choicenessofantimicrobialagentsdependsonpharmacologicalfactorsandhostfactors.3.Theusesofantimicrobialagentsisstrictlycontrolledinsomesituations.,Basicprinciples,EmpiricTherapy,VastmajorityofallantimicrobialtherapyShouldbeapproachedrationallySyndromeLikelypathogensKnownresistancepatternsHostfactors,IdentificationofInfectingOrganism,StainingofclinicalspecimensGramstain,Acid-faststain,silverstainsAntigendetection(e.g.ELISA)Nucleicaciddetection(e.g.PCR)CulturemethodsObtainculturematerialpriortoantimicrobialtherapy,ifpossible,inbroth,pharmacologicalfactorsinclude:kineticsofabsorption,distribution,andelimination;Bacteriostaticvsbactericidalactivityconcentration-dependentkilling(eg.aminoglycosidesandquinolones)time-dependentkilling(eg.b-lactamsandvancomycin);C.thepotentialtoxicityofanagent;D.pharmacodynamicorpharmacokineticinteractionwithotherdrugs.,Basicprinciples,BactericidalvsBacterostatic,hostfactorsinclude:SiteofinfectiontheageandpregnancystatusHepaticorrenalfunctionThefunctionalstateofhostdefensemechanismIndividualvariation,Basicprinciples,HostFactors,SiteofinfectionAdequateconcentrationsofantimicrobialsmustbedeliveredtothesiteofinfectionLocalconcentrationsgreaterthanMICExcretionUrineAminoglycosides,fluoroquinolonesBileCeftriaxone(头孢曲松)PenetrationintovarioussitesCentralnervoussystemLungBone,HostFactors,AgeGastricaciditylowinyoungchildrenandelderlyRenal,hepaticfunctionvarywithageDoseadjustmentforcreatinineclearanceandhepaticdysfunctioniscriticaltoavoidtoxicitiesDevelopingboneandteethTetracyclinesstainteethQuinolonesmayimpairboneandcartilagegrowth,HostFactors,GeneticandmetabolicabnormalitiesIsoniazidacetylationvariesgreatlyG-6-PDdeficiencyandriskofhemolysisSulfonamides,nitrofurantoinPregnancyTeratogenicityandothertoxicitytothefetusOthertoxicreactions(lacticacidosis,pancreatitis)ExcretioninbreastmilkImmunocompromise,ResistancePatterns,AntibiogramsLocalpatternsofsusceptibilityHospital,state,country,ProportionofinvasionS.aureusisolatesresistanttooxacillin(orequivalent)EARSS,2004,FormulateaclinicaldiagnosisofmicrobialinfectionObtainspecimensforlaboratoryexaminationFormulateamicrobiologicdiagnosisDeterminethenecessityforempiricaltherapyInstitutetreatment,TherapeuticapplicationsofAnti-infectives,Theusesofantimicrobialagentsisstrictlycontrolledin:ViralinfectionsFevercausedbyunidentifiedreasonsTopicalapplicationsAntimicrobialprophylaxisAntimicrobialagentscombinations,TherapeuticapplicationsofAnti-infectives,Nonsurgicalprophylaxis1)Rheumaticfever(风湿热)2)Meningococcalinfection3)Tuberculosis4)Newbornophthalmia(新生儿眼炎)5)Malaria(疟疾)6)Urinarytractinfections,ProphylaxisuseofAnti-infectives,SurgicalprophylaxisNationalresearchcouncilexpectedinfectionwoundclassificationcriteriarateClean2%Cleancontaminated10%Contaminatedabout20%Dirtyabout40%,ProphylaxisuseofAnti-infectives,Surgicalprophylaxis1)Cardiacoperation2)Noncardiac,thoracicoperation3)Vascular(abdominalandlowerextremity)operation4)Headandneckoperation5)Gastroduodenalorbiliaryoperation6)Orthopedicoperation(withhardwareinsertion)7)Penetratingtrauma8)Burnwound9)Colorectaloperation10)Appendectomy,ProphylaxisuseofAnti-infectives,Antimicrobialagentscombinations,?,Antimicrobialagentscombinations,Accordingtotheiractions,antimicrobialagentscanbeclassified:bactericidalagentsforgrowingbacteriabactericidalagentsforrestingbacteriafastbacteriostaticagentsslowbacteriostaticagents,Antimicrobialagentscombinations,Accordingtotheiractions,antimicrobialagentscanbeclassified:bactericidalagentsforgrowingbacteriabactericidalagentsforrestingbacteriafastbacteriostaticagentsslowbacteriostaticagents+:synergism+:antagonism+:additionorindifference+:addition,Mechanismofsynergisticaction:BlockadeofsequentialstepsinametabolicsequenceInhibitionofenzymaticinactivationEnhancementofantimicrobialagentuptakeInhibitionofdifferentresistantstrainrespectively,Twoisbetterthanone?EmpirictherapyPolymicrobialinfectionIncreaseefficacy-synergismPreventemergenceofresistanceCombinationtherapyMycobacteriumtuberculosisHIVPseudomonasaeruginosa?Invasiveaspergillosis（侵入性曲霉菌病）,Antimicrobialagentscombinations,Antimicrobialagentsdosinginpatientswithhepaticimpairment,Ithasnosuitablemarkersofhepaticfunction.So,druguseinpatientswithliverdiseasemusttakeintoaccount3generalprinciples:(1)Pharmaco