抗菌疗法的原则(英文)Foundations-in-Microbiology课件

Variolavirus(Smallpox)Randommicrobeoftheweek!!!Variolavirus(Smallpox)Random2PrinciplesofAntimicrobialTherapyAdministeradrugtoaninfectedpersonthatdestroystheinfectiveagentwithoutharmingthehost’scellsAntimicrobialdrugsareproducednaturallyorsynthetically2PrinciplesofAntimicrobialT33445OriginsofAntimicrobialDrugsAntibioticsarecommonmetabolicproductsofaerobicbacteriaandfungiBacteriaingeneraStreptomycesandBacillusMoldsingeneraPenicilliumandCephalosporiumByinhibitingtheothermicrobesinthesamehabitat,antibioticproducershavelesscompetitionfornutrientsandspace5OriginsofAntimicrobialDrug667InteractionsBetween

DrugandMicrobeAntimicrobialdrugsshouldbeselectivelytoxic–drugsshouldkillorinhibitmicrobialcellswithoutsimultaneouslydamaginghosttissuesAsthecharacteristicsoftheinfectiousagentbecomemoresimilartothevertebratehostcell,completeselectivetoxicitybecomesmoredifficulttoachieveandmoresideeffectsareseen7InteractionsBetween

Drugan8MechanismsofDrugActionInhibitionofcellwallsynthesisBreakdownofcellmembranestructureorfunctionInhibitionofnucleicacidsynthesis,structureorfunctionInhibitionofproteinsynthesisBlocksonkeymetabolicpathways8MechanismsofDrugActionInhi99101011TheSpectrumofan

AntimicrobicDrugSpectrum–rangeofactivityofadrugNarrow-spectrum–effectiveonasmallrangeofmicrobesTargetaspecificcellcomponentthatisfoundonlyincertainmicrobesBroad-spectrum–greatestrangeofactivityTargetcellcomponentscommontomostpathogens(ribosomes)11TheSpectrumofan

Antimicr12AntimicrobialDrugsThatAffecttheBacterialCellWallMostbacterialcellwallscontainpeptidoglycanPenicillinsandcephalosporinsblocksynthesisofpeptidoglycan,causingthecellwalltolyseActiveonyoung,growingcellsPenicillinsthatdonotpenetratetheoutermembranearelesseffectiveagainstgram-negativebacteriaBroadspectrumpenicillinsandcephalosporinscancrossthecellwallsofgram-negativebacteria12AntimicrobialDrugsThatAff131314AntimicrobialDrugsThatDisruptCellMembraneFunctionAcellwithadamagedmembranediesfromdisruptioninmetabolismorlysisThesedrugshavespecificityforaparticularmicrobialgroup,basedondifferencesintypesoflipidsintheircellmembranesPolymyxinsinteractwithphospholipidsandcauseleakage,particularlyingram-negativebacteriaAmphotericinBandnystatinformcomplexeswithsterolsonfungalmembraneswhichcausesleakage14AntimicrobialDrugsThatDis151516DrugsThatAffect

NucleicAcidSynthesisMayblocksynthesisofnucleotides,inhibitreplication,orstoptranscriptionChloroquinebindsandcross-linksthedoublehelix;quinolonesinhibitDNAhelicasesAntiviraldrugsthatareanalogsofpurinesandpyrimidinesinsertinviralnucleicacid,preventingreplication16DrugsThatAffect

Nucleic17DrugsThatBlockProteinSynthesisRibosomesofeukaryotesdifferinsizeandstructurefromprokaryotes;antimicrobicsusuallyhaveaselectiveactionagainstprokaryotes;canalsodamagetheeukaryoticmitochondriaAminoglycosides(streptomycin,gentamycin)insertonsitesonthe30SsubunitandcausemisreadingofmRNATetracyclinesblockattachmentoftRNAontheAacceptorsiteandstopfurthersynthesis17DrugsThatBlockProteinSyn181819DrugsthatAffectMetabolicPathwaysSulfonamidesandtrimethoprimblockenzymesrequiredfortetrahydrofolatesynthesisneededforDNAandRNAsynthesisCompetitiveinhibition–drugcompeteswithnormalsubstrateforenzyme’sactivesiteSynergisticeffect–theeffectsofacombinationofantibioticsaregreaterthanthesumoftheeffectsoftheindividualantibiotics19DrugsthatAffectMetabolic2020212122SurveyofMajor

AntimicrobialDrugGroupsAntibacterialdrugsAntibioticsSyntheticdrugsAntifungaldrugsAntiprotozoandrugsAntiviraldrugsAbout260differentantimicrobialdrugsareclassifiedin20drugfamilies22SurveyofMajor

AntimicrobiAntibacterialDrugsthat

ActontheCellWallBeta-lactamantimicrobials-allcontainahighlyreactive3carbon,1nitrogenringPrimarymodeofactionistointerferewithcellwallsynthesisGreaterthan½ofallantimicrobicdrugsarebeta-lactamsPenicillinsandcephalosporinsmostprominentbeta-lactams23AntibacterialDrugsthat

Act24PenicillinandItsRelativesLargediversegroupofcompoundsCouldbesynthesizedinthelaboratoryMoreeconomicaltoobtainnaturalpenicillinthroughmicrobialfermentationandmodifyittosemi-syntheticformsPenicillium

chrysogenum–majorsourceAllconsistof3parts:ThiazolidineringBeta-lactamringVariablesidechaindictatingmicrobialactivity24PenicillinandItsRelatives2525262627SubgroupandUsesofPenicillinsPenicillinsGandVmostimportantnaturalformsPenicillinisthedrugofchoiceforgram-positivecocci(streptococci)andsomegram-negativebacteria(meningococciandsyphilisspirochete)Semisyntheticpenicillins–ampicillin,carbenicillin,andamoxicillinhavebroaderspectra–Gram-negativeinfectionsPenicillinase-resistant–methicillin,nafcillin,cloxacillinPrimaryproblems–allergiesandresistantstrainsofbacteria27SubgroupandUsesofPenicil28CephalosporinsAccountforone-thirdofallantibioticsadministeredSyntheticallyalteredbeta-lactamstructureRelativelybroad-spectrum,resistanttomostpenicillinases,andcausefewerallergicreactionsSomearegivenorally;manymustbeadministeredparenterallyGenericnameshaveroot–cef,ceph,orkef28CephalosporinsAccountforon29Cephalosporins4generationsexist:eachgroupmoreeffectiveagainstgram-negativesthantheonebeforewithimproveddosingscheduleandfewersideeffectsFirstgeneration–cephalothin,cefazolin–mosteffectiveagainstgram-positivecocciandfewgram-negativeSecondgeneration–cefaclor,cefonacid–moreeffectiveagainstgram-negativebacteriaThirdgeneration–cephalexin,ceftriaxone–broad-spectrumactivityagainstentericbacteriawithbeta-lactamasesFourthgeneration–cefepime–widestrange;bothgram-negativeandgram-positive29Cephalosporins4generations303031AdditionalBeta-lactamDrugsCarbapenemsImipenem–broad-spectrumdrugforinfectionswithaerobicandanaerobicpathogens;lowdose,administeredorallywithfewsideeffectsMonobactamsAztreonam–narrow-spectrumdrugforinfectionsbygram-negativeaerobicbacilli;maybeusedbypeopleallergictopenicillin31AdditionalBeta-lactamDrugs32NonBeta-lactamCellWallInhibitorsVancomycin–narrow-spectrum,mosteffectiveintreatmentofStaphylococcalinfectionsincasesofpenicillinandmethicillinresistanceorifpatientisallergictopenicillin;toxicandhardtoadminister;restricteduseBacitracin–narrow-spectrumproducedbyastrainofBacillussubtilis;usedtopicallyinointmentIsoniazid(INH)–worksbyinterferingwithmycolicacidsynthesis;usedtotreatinfectionswithMycobacteriumtuberculosis32NonBeta-lactamCellWallInAntibioticsThatDamageBacterialCellMembranesPolymixins,narrow-spectrumpeptideantibioticswithauniquefattyacidcomponentTreatdrugresistantPseudomonasaeruginosaandsevereUTI33AntibioticsThatDamageBacterDrugsthatActonDNAorRNAFluoroquinolones–workbybindingtoDNAgyraseandtopoisomeraseIVBroadspectrumeffectivenessConcernshavearisenregardingtheoveruseofquinolinedrugsCDCisrecommendingcarefulmonitoringoftheirusetopreventciprofloxacin-resistantbacteria34DrugsthatActonDNAorRNAFl35DrugsThatInterferewith

ProteinSynthesisAminoglycosides–composedofoneormoreaminosugarsandanaminocyclitol(6C)ring;bindsribosomalsubunitProductsofvariousspeciesofsoilactinomycetesingeneraStreptomycesandMicromonosporaBroad-spectrum,inhibitproteinsynthesis,especiallyusefulagainstaerobicgram-negativerodsandcertaingram-positivebacteriaStreptomycin–bubonicplague,tularemia,TBGentamicin–lesstoxic,usedagainstgram-negativerodsNewer–tobramycinandamikacingram-negativebacteria35DrugsThatInterferewith

P363637TetracyclineAntibioticsBroad-spectrum,blockproteinsynthesisbybindingribosomesTreatmentforSTDs,RockyMountainspottedfever,Lymedisease,typhus,acne,andprotozoaGenerictetracyclineislowincostbutlimitedbyitssideeffects37TetracyclineAntibioticsBroa383839ChloramphenicolPotentbroad-spectrumdrugwithuniquenitrobenzenestructureBlockspeptidebondformationandproteinsynthesisEntirelysynthesizedthroughchemicalprocessesVerytoxic,restricteduses,cancauseirreversibledamagetobonemarrowTyphoidfever,brainabscesses,rickettsial,andchlamydialinfections39ChloramphenicolPotentbroad-404041MacrolidesandRelatedAntibioticsErythromycin–largelactoneringwithsugars;attachestoribosomal50ssubunitBroad-spectrum,fairlylowtoxicityTakenorallyforMycoplasmapneumonia,legionellosis,Chlamydia,pertussis,diphtheriaandasaprophylacticpriortointestinalsurgeryForpenicillin-resistant–gonococci,syphilis,acneNewersemi-syntheticmacrolides–clarithromycin,azithromycin41MacrolidesandRelatedAntib424243DrugsThatBlockMetabolicPathwaysMostaresynthetic;mostimportantaresulfonamides,orsulfadrugs-firstantimicrobicdrugsNarrow-spectrum;blockthesynthesisoffolicacidbybacteriaSulfisoxazole–shigellosis,UTI,protozoaninfectionsSilversulfadiazine–burns,eyeinfectionsTrimethoprim–givenincombinationwithsulfamethoxazole–UTI,PCP43DrugsThatBlockMetabolicPStructureofsulfonamides44Structureofsulfonamides4445NewlyDeveloped

ClassesofAntimicrobialsFormulatedfrompre-existingdrugclassesThreenewdrugtypes:Fosfomycintrimethamine–aphosphoricacideffectiveasalternatetreatmentforUTIs;inhibitscellwallsynthesisSynercid–effectiveagainstStaphylococcusandEnterococcusthatcauseendocarditisandsurgicalinfections;usedwhenbacteriaisresistanttootherdrugs;inhibitsproteinsynthesisDaptomycin–directedmainlyagainstgram-positive;disruptsmembranefunction45NewlyDeveloped

Classesof46NewlyDeveloped

ClassesofAntimicrobialsKetolides–telitromycin(Ketek),newdrugwithdifferentringstructurefromErythromycin;usedforinfectionwhenresistanttomacrolidesOxazolidinones–linezolid(Zyvox);syntheticantimicrobialthatblockstheinteractionofmRNAandribosomeUsedtotreatmethicillinresistantStaphylococcusaureus(MRSA)andvancomycinresistantEnterococcus(VRE)46NewlyDeveloped

Classesof47AgentstoTreatFungalInfectionsFungalcellsareeukaryotic;adrugthatistoxictofungalcellsalsotoxictohumancellsFiveantifungaldruggroups:MacrolidepolyeneAmphotericinB–mimiclipids,mostversatileandeffective,topicalandsystemictreatmentsNystatin–topicaltreatmentGriseofulvin–stubborncasesofdermatophyteinfections,nephrotoxicSyntheticazoles–broad-spectrum;ketoconazole,clotrimazole,miconazoleFlucytosine–analogofcytosine;cutaneousmycosesorincombinationwithamphotericinBforsystemicmycosesEchinocandins–damagecellwalls;capsofungin47AgentstoTreatFungalInfec484849AntiparasiticChemotherapyAntimalarialdrugs–quinine,chloroquinine,primaquine,mefloquineAntiprotozoandrugs–metronidazole(Flagyl),quinicrine,sulfonamides,tetracyclinesAntihelminthicdrugs–immobilize,disintegrate,orinhibitmetabolismMebendazole,thiabendazole–broad-spectrum–inhibitfunctionofmicrotubules,interfereswithglucoseutilizationanddisablesthemPyrantel,piperazine–paralyzemusclesNiclosamide–destroysscolex49AntiparasiticChemotherapyAn50AntiviralChemotherapeuticAgentsSelectivetoxicityisalmostimpossibleduetoobligateintracellularparasiticnatureofvirusesBlockpenetrationintohostcellBlockreplication,transcription,ortranslationofviralgeneticmaterialNucleotideanalogsAcyclovir–herpesvirusesRibavirin–aguanineanalog–RSV,hemorrhagicfeversAZT–thymineanalog–HIVPreventmaturationofviralparticlesProteaseinhibitors–HIV50AntiviralChemotherapeuticA515152DrugsforTreatingInfluenzaAmantadine,rimantidine–restrictedalmostexclusivelytoinfluenzaAviralinfections;preventfusionofviruswithcellmembraneRelenzaandtamiflu–slightlybroaderspectrum;blocksneuraminidaseininfluenzaAandB52DrugsforTreatingInfluenza53AntiherpesDrugsManyantiviralagentsmimicthestructureofnucleotidesandcompeteforsitesonreplicatingDNAAcyclovir–ZoviraxValacyclovir–ValtrexFamiciclovir–FamvirPeniciclovir–DenavirOralandtopicaltreatmentsfororalandgenitalherpes,chickenpox,andshingles53AntiherpesDrugsManyantivir54DrugsforTreating

HIVInfectionsandAIDSRetrovirusoffers2targetsforchemotherapy:InterferencewithviralDNAsynthesisfromviralRNAusingnucleosidereversetranscriptaseinhibitors(nucleotideanalogs)InterferencewithsynthesisofDNAusingnonnucleosidereversetranscriptaseinhibitorsAzidothymidine(AZT)–firstdrugaimedattreatingAIDS,thymineanalog54DrugsforTreating

HIVInfe55Interferons(INF)Human-basedglycoproteinproducedprimarilybyfibroblastsandleukocytesTherapeuticbenefitsinclude:ReduceshealingtimeandsomecomplicationsofinfectionsPreventsorreducessymptomsofcoldandpapillomavirusSlowstheprogressofcertaincancers,leukemias,andlymphomasTreatmentofhepatitisC,genitalwarts,Kaposi’ssarcoma55Interferons(INF)Human-based56TheAcquisitionof

DrugResistanceAdaptiveresponseinwhichmicroorganismsbegintotolerateanamountofdrugthatwouldordinarilybeinhibitory;duetogeneticversatilityorvariation;intrinsicandacquiredAcquiredresistance:SpontaneousmutationsincriticalchromosomalgenesAcquisitionofnewgenesorsetsofgenesviatransferfromanotherspeciesOriginatesfromresistancefactors(plasmids)encodedwithdrugresistance,transposons56TheAcquisitionof

DrugRes575758MechanismsofDrugResistanceDruginactivationbyacquiredenzymaticactivity–penicillinasesDecreasedpermeabilitytodrugorincreasedeliminationofdrugfromcell–acquiredormutationChangeindrugreceptors–mutationoracquisitionChangeinmetabolicpatterns–mutationoforiginalenzyme58MechanismsofDrugResistanc595960NaturalSelectionandDrugResistanceLargepopulationsofmicrobeslikelytoincludedrugresistantcellsduetopriormutationsortransferofplasmids–nogrowthadvantageuntilexposedtodrugIfexposed,sensitivecellsareinhibitedordestroyedwhileresistancecellswillsurviveandproliferate.Eventuallypopulationwillberesistant–selectivepressure–naturalselectionWorldwideindiscriminateuseofantimicrobialshasledtoexplosionofdrugresistantmicroorganisms60NaturalSelectionandDrugR61Amodelofnaturalselectionfordrugresistance61Amodelofnaturalselection626263InteractionsBetween

DrugandHostEstimatethat5%ofallpersonstakingantimicrobialswillexperienceaseriousadversereactiontothedrug–sideeffectsMajorsideeffects:DirectdamagetotissueduetotoxicityofdrugAllergicreactionsDisruptioninthebalanceofnormalflora-superinfectionspossible63InteractionsBetween

Druga64646565666667ConsiderationsinSelectinganAntimicrobialDrugIdentifythemicroorganismcausingtheinfectionTestthemicroorganism’ssusceptibility(sensitivity)tovariousdrugsinvitrowhenindicatedTheoverallmedicalconditionofthepatient67ConsiderationsinSelecting68IdentifyingtheAgentIdentificationofinfectiousagentshouldbeattemptedassoonaspossibleSpecimensshouldbetakenbeforeantimicrobialsareinitiated68IdentifyingtheAgentIdentif69TestingforDrugSusceptibilityEssentialforgroupsofbacteriacommonlyshowingresistanceKirby-BauerdiskdiffusiontestE-testdiffusiontestDilutiontests–minimuminhibitoryconcentration(MIC)–smallestconcentrationofdrugthatvisiblyinhibitsgrowthProvideprofileofdrugsensitivity69TestingforDrugSusceptibil70707171727273TheMICandTherapeuticIndexInvitroactivityofadrugisnotalwayscorrelatedwithinvivoeffectIftherapyfails,adifferentdrug,combinationofdrugs,ordifferentadministrationmustbeconsideredBesttochoseadrugwithhighestlevelofselectivitybutlowestleveltoxicity–measuredbytherapeuticindex–theratioofthedoseofthedrugthatistoxictohumansascomparedtoitsminimumeffectivedoseHighindexisdesirable73TheMICandTherapeuticIndeVariolavirus(Smallpox)Randommicrobeoftheweek!!!Variolavirus(Smallpox)Random75PrinciplesofAntimicrobialTherapyAdministeradrugtoaninfectedpersonthatdestroystheinfectiveagentwithoutharmingthehost’scellsAntimicrobialdrugsareproducednaturallyorsynthetically2PrinciplesofAntimicrobialT76377478OriginsofAntimicrobialDrugsAntibioticsarecommonmetabolicproductsofaerobicbacteriaandfungiBacteriaingeneraStreptomycesandBacillusMoldsingeneraPenicilliumandCephalosporiumByinhibitingtheothermicrobesinthesamehabitat,antibioticproducershavelesscompetitionfornutrientsandspace5OriginsofAntimicrobialDrug79680InteractionsBetween

DrugandMicrobeAntimicrobialdrugsshouldbeselectivelytoxic–drugsshouldkillorinhibitmicrobialcellswithoutsimultaneouslydamaginghosttissuesAsthecharacteristicsoftheinfectiousagentbecomemoresimilartothevertebratehostcell,completeselectivetoxicitybecomesmoredifficulttoachieveandmoresideeffectsareseen7InteractionsBetween

Drugan81MechanismsofDrugActionInhibitionofcellwallsynthesisBreakdownofcellmembranestructureorfunctionInhibitionofnucleicacidsynthesis,structureorfunctionInhibitionofproteinsynthesisBlocksonkeymetabolicpathways8MechanismsofDrugActionInhi829831084TheSpectrumofan

AntimicrobicDrugSpectrum–rangeofactivityofadrugNarrow-spectrum–effectiveonasmallrangeofmicrobesTargetaspecificcellcomponentthatisfoundonlyincertainmicrobesBroad-spectrum–greatestrangeofactivityTargetcellcomponentscommontomostpathogens(ribosomes)11TheSpectrumofan

Antimicr85AntimicrobialDrugsThatAffecttheBacterialCellWallMostbacterialcellwallscontainpeptidoglycanPenicillinsandcephalosporinsblocksynthesisofpeptidoglycan,causingthecellwalltolyseActiveonyoung,growingcellsPenicillinsthatdonotpenetratetheoutermembranearelesseffectiveagainstgram-negativebacteriaBroadspectrumpenicillinsandcephalosporinscancrossthecellwallsofgram-negativebacteria12AntimicrobialDrugsThatAff861387AntimicrobialDrugsThatDisruptCellMembraneFunctionAcellwithadamagedmembranediesfromdisruptioninmetabolismorlysisThesedrugshavespecificityforaparticularmicrobialgroup,basedondifferencesintypesoflipidsintheircellmembranesPolymyxinsinteractwithphospholipidsandcauseleakage,particularlyingram-negativebacteriaAmphotericinBandnystatinformcomplexeswithsterolsonfungalmembraneswhichcausesleakage14AntimicrobialDrugsThatDis881589DrugsThatAffect

NucleicAcidSynthesisMayblocksynthesisofnucleotides,inhibitreplication,orstoptranscriptionChloroquinebindsandcross-linksthedoublehelix;quinolonesinhibitDNAhelicasesAntiviraldrugsthatareanalogsofpurinesandpyrimidinesinsertinviralnucleicacid,preventingreplication16DrugsThatAffect

Nucleic90DrugsThatBlockProteinSynthesisRibosomesofeukaryotesdifferinsizeandstructurefromprokaryotes;antimicrobicsusuallyhaveaselectiveactionagainstprokaryotes;canalsodamagetheeukaryoticmitochondriaAminoglycosides(streptomycin,gentamycin)insertonsitesonthe30SsubunitandcausemisreadingofmRNATetracyclinesblockattachmentoftRNAontheAacceptorsiteandstopfurthersynthesis17DrugsThatBlockProteinSyn911892DrugsthatAffectMetabolicPathwaysSulfonamidesandtrimethoprimblockenzymesrequiredfortetrahydrofolatesynthesisneededforDNAandRNAsynthesisCompetitiveinhibition–drugcompeteswithnormalsubstrateforenzyme’sactivesiteSynergisticeffect–theeffectsofacombinationofantibioticsaregreaterthanthesumoftheeffectsoftheindividualantibiotics19DrugsthatAffectMetabolic9320942195SurveyofMajor

AntimicrobialDrugGroupsAntibacterialdrugsAntibioticsSyntheticdrugsAntifungaldrugsAntiprotozoandrugsAntiviraldrugsAbout260differentantimicrobialdrugsareclassifiedin20drugfamilies22SurveyofMajor

AntimicrobiAntibacterialDrugsthat

ActontheCellWallBeta-lactamantimicrobials-allcontainahighlyreactive3carbon,1nitrogenringPrimarymodeofactionistointerferewithcellwallsynthesisGreaterthan½ofallantimicrobicdrugsarebeta-lactamsPenicillinsandcephalosporinsmostprominentbeta-lactams96AntibacterialDrugsthat

Act97PenicillinandItsRelativesLargediversegroupofcompoundsCouldbesynthesizedinthelaboratoryMoreeconomicaltoobtainnaturalpenicillinthroughmicrobialfermentationandmodifyittosemi-syntheticformsPenicillium

chrysogenum–majorsourceAllconsistof3parts:ThiazolidineringBeta-lactamringVariablesidechaindictatingmicrobialactivity24PenicillinandItsRelatives98259926100SubgroupandUsesofPenicillinsPenicillinsGandVmostimportantnaturalformsPenicillinisthedrugofchoiceforgram-positivecocci(streptococci)andsomegram-negativebacteria(meningococciandsyphilisspirochete)Semisyntheticpenicillins–ampicillin,carbenicillin,andamoxicillinhavebroaderspectra–Gram-negativeinfectionsPenicillinase-resistant–methicillin,nafcillin,cloxacillinPrimaryproblems–allergiesandresistantstrainsofbacteria27SubgroupandUsesofPenicil101CephalosporinsAccountforone-thirdofallantibioticsadministeredSyntheticallyalteredbeta-lactamstructureRelativelybroad-spectrum,resistanttomostpenicillinases,andcausefewerallergicreactionsSomearegivenorally;manymustbeadministeredparenterallyGenericnameshaveroot–cef,ceph,orkef28CephalosporinsAccountforon102Cephalosporins4generationsexist:eachgroupmoreeffectiveagainstgram-negativesthantheonebeforewithimproveddosingscheduleandfewersideeffectsFirstgeneration–cephalothin,cefazolin–mosteffectiveagainstgram-positivecocciandfewgram-negativeSecondgeneration–cefaclor,cefonacid–moreeffectiveagainstgram-negativebacteriaThirdgeneration–cephalexin,ceftriaxone–broad-spectrumactivityagainstentericbacteriawithbeta-lactamasesFourthgeneration–cefepime–widestrange;bothgram-negativeandgram-positive29Cephalosporins4generations10330104AdditionalBeta-lactamDrugsCarbapenemsImipenem–broad-spectrumdrugforinfectionswithaerobicandanaerobicpathogens;lowdose,administeredorallywithfewsideeffectsMonobactamsAztreonam–narrow-spectrumdrugforinfectionsbygram-negativeaerobicbacilli;maybeusedbypeopleallergictopenicillin31AdditionalBeta-lactamDrugs105NonBeta-lactamCellWallInhibitorsVancomycin–narrow-spectrum,mosteffectiveintreatmentofStaphylococcalinfectionsincasesofpenicillinandmethicillinresistanceorifpatientisallergictopenicillin;toxicandhardtoadminister;restricteduseBacitracin–narrow-spectrumproducedbyastrainofBacillussubtilis;usedtopicallyinointmentIsoniazid(INH)–worksbyinterferingwithmycolicacidsynthesis;usedtotreatinfectionswithMycobacteriumtuberculosis32NonBeta-lactamCellWallInAntibioticsThatDamageBacterialCellMembranesPolymixins,narrow-spectrumpeptideantibioticswithauniquefattyacidcomponentTreatdrugresistantPseudomonasaeruginosaandsevereUTI106AntibioticsThatDamageBacterDrugsthatActonDNAorRNAFluoroquinolones–workbybindingtoDNAgyraseandtopoisomeraseIVBroadspectrumeffectivenessConcernshavearisenregardingtheoveruseofquinolinedrugsCDCisrecommendingcarefulmonitoringoftheirusetopreventciprofloxacin-resistantbacteria107DrugsthatActonDNAorRNAFl108DrugsThatInterferewith

ProteinSynthesisAminoglycosides–composedofoneormoreaminosugarsandanaminocyclitol(6C)ring;bindsribosomalsubunitProductsofvariousspeciesofsoilactinomycetesingeneraStreptomycesandMicromonosporaBroad-spectrum,inhibitproteinsynthesis,especiallyusefulagainstaerobicgram-negativerodsandcertaingram-positivebacteriaStreptomycin–bubonicplague,tularemia,TBGentamicin–lesstoxic,usedagainstgram-negativerodsNewer–tobramycinandamikacingram-negativebacteria35DrugsThatInterferewith

P10936110TetracyclineAntibioticsBroad-spectrum,blockproteinsynthesisbybindingribosomesTreatmentforSTDs,RockyMountainspottedfever,Lymedisease,typhus,acne,andprotozoaGenerictetracyclineislowincostbutlimitedbyitssideeffects37TetracyclineAntibioticsBroa11138112ChloramphenicolPotentbroad-spectrumdrugwithuniquenitrobenzenestructureBlockspeptidebondformationandproteinsynthesisEntirelysynthesizedthroughchemicalprocessesVerytoxic,restricteduses,cancauseirreversibledamagetobonemarrowTyphoidfever,brainabscesses,rickettsial,andchlamydialinfections39ChloramphenicolPotentbroad-11340114MacrolidesandRelatedAntibioticsErythromycin–largelactoneringwithsugars;attachestoribosomal50ssubunitBroad-spectrum,fairlylowtoxicityTakenorallyforMycoplasmapneumonia,legionellosis,Chlamydia,pertussis,diphtheriaandasaprophylacticpriortointestinalsurgeryForpenicillin-resistant–gonococci,syphilis,acneNewersemi-syntheticmacrolides–clarithromycin,azithromycin41MacrolidesandRelatedAntib11542116DrugsThatBlockMetabolicPathwaysMostaresynthetic;mostimportantaresulfonamides,orsulfadrugs-firstantimicrobicdrugsNarrow-spectrum;blockthesynthesisoffolicacidbybacteriaSulfisoxazole–shigellosis,UTI,protozoaninfectionsSilversulfadiazine–burns,eyeinfectionsTrimethoprim–givenincombinationwithsulfamethoxazole–UTI,PCP43DrugsThatBlockMetabolicPStructureofsulfonamides117Structureofsulfonamides44118NewlyDeveloped

ClassesofAntimicrobials