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AntimicrobialDrugs AntimicrobialDrugs Chemotherapy TheuseofdrugstotreatadiseaseAntimicrobialdrugs InterferewiththegrowthofmicrobeswithinahostAntibiotic Substanceproducedbyamicrobethat insmallamounts inhibitsanothermicrobeSelectivetoxicity AdrugthatkillsharmfulmicrobeswithoutdamagingthehostItiseasiertofindagentstoxictoprokaryoticcellsthatdonotharmeukaryotichoststhantoeukaryoticpathogens fungi parasites etc Thedawnofantibiotics PaulErlich 1910 Wantedtofindthe magicbullet forsyphilisproposedtheideaofthebloodbrainbarrierWorkedatstainingtissuesandfirsttocomeupwiththeideabehind selectivetoxicity NobelPrizein1908 AlexanderFleming AphysicianwhostudiedbacterialactionofbloodandantisepsisDiscoveredandnamedLysozymeDiscoveredmoldgrowingonanaganplate 1928 1945NobelPrizeinPhysiologyorMedicinealongwithChainandFlorey ChainandFlorey 1940developedasystemforgrowingPenicilliumandpurifyingthedrugTestedthedruginmice passedalltrialsReceivedtheNobelPrizein1945withAlexanderFlemingfortheirwork Antibiotics AsubstanceproducedbyamicroorganismthatinhibitsorkillsothermicrobesBacteriostaticBacteriocidal Theraputicindex toxicity lowestdosetoxictopatientdividedbydoseusedfortherapy ifhigh lesstoxic Microbesthatproduceantibiotics Rangeofactivity Narrowrange targetonegroupofmicrobesBroadrange targetawidegroupofdifferentmicrobesWhichoneisthebest SuperinfectionClostridiadifficile AntibioticAssociatedColitisYeast Spectrumofactivity Targetsofantibiotics Inhibitionofcellwallsynthesis peptidoglycanInhibitionofproteinsynthesis ribosomesInjuresplasmamembrane changespermeabilityInhibitsnucleaicacidsynthesis interferewithreplicationandtranscriptionInhibitssynthesisofessentialmetabolites competitivelyinhibitedbysimilarsubstance Targetsofantimicrobialdrugs Somedrugstargetproteinsynthesis Howdoespenicillinwork Inhibitsformationoftetrapeptidesidechains whichmeans Whathappensifyouputacellinasolutionwithpenicillin Penicillinweakensthecellwall PenicillinPenicilinase resistantpenicillinsExtended spectrumpenicillinsPenicillins lactamaseinhibitorsCarbapenemsMonobactam AntibacterialAntibioticsInhibitorsofCellWall Penicillins Howorganismsdegradepenicillins Inhibitorsofcellwallsynthesis Cephalosporins2nd 3rd and4thgenerationsmoreeffectiveagainstgram negatives Figure20 9 InhibitorsofCellWallSynthesis PolypeptideantibioticsBacitracinTopicalapplicationAgainstgram positivesVancomycinGlycopeptideImportant lastline againstantibioticresistantS aureus AntibioticsforMycobacterium AntimycobacteriumantibioticsIsoniazid INH InhibitsmycolicacidsynthesisEthambutolInhibitsincorporationofmycolicacid ChloramphenicolBroadspectrumBinds50Ssubunit inhibitspeptidebondformationAminoglycosidesStreptomycin neomycin gentamycinBroadspectrumChangesshapeof30Ssubunit InhibitorsofProteinSynthesis TetracyclinesBroadspectrumInterfereswithtRNAattachmentMacrolidesGram positivesBinds50S preventstranslocationErythromycinGram positivesBinds50S preventstranslocation InhibitorsofProteinSynthesis StreptograminsGram positivesBinds50Ssubunit inhibitstranslationSynercidGram positivesBinds50Ssubunit inhibitstranslationOxazolidinonesLinezolidGram positivesBinds50Ssubunit preventsformationof70Sribosome InhibitorsofProteinSynthesis PolymyxinBTopicalCombinedwithbacitracinandneomycininover the counterpreparation InjurytothePlasmaMembrane RifamycinInhibitsRNAsynthesisAntituberculosisQuinolonesandfluoroquinolonesCiprofloxacinInhibitsDNAgyraseUrinarytractinfections InhibitorsofNucleicAcidSynthesis Sulfonamides sulfadrugs FirstsyntheticdrugstotreatmicrobialinfectionsUsedtotreaturinarytractinfections UTIs Combinationoftrimethoprimandsulfamethoxazole TMP SMZ exampleofsynergism Sulfonamides Sulfadrugs InhibitfolicacidsynthesisBroadspectrum CompetitiveInhibitors Figure5 7 TMP SMZ Testsformicrobialsensitivity MICMinimalinhibitoryconcentrationMBCMinimalbactericidalconcentration Testsformicrobialsensitivity Kirby Bauer diskdiffusionmethod WedidthisinlabEtest determinestheminimuminhibitoryconcentration MICDilutiontestsforMIC Kirby Bauertestsforsensitivity E testforMIC MICtesting Synergismoccurswhentheeffectoftwodrugstogetherisgreaterthantheeffectofeitheralone Antagonismoccurswhentheeffectoftwodrugstogetherislessthantheeffectofeitheralone EffectsofCombinationsofDrugs EffectsofCombinationsofDrugs Figure20 22 Developmentofantibioticresistantbacteria Drugresistance DestructionorinactivationofthedrugPreventionofpenetrationtotargetsiteAlterationoftargetsite mutation Pumpingofthedrugoutofthebacterialcell rapidejectionofdrugResistancegenesareoftenonplasmidsortransposonsthatcanbetransferredbetweenbacteria Ex
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