感染的治疗（英文ppt）treatmentof

TreatmentofInfection ProfessorMarkPallen TreatmentofInfectionHowDoAntimicrobialsWork Keyconcept selectivetoxicitytheantimicrobialagentblocksorinhibitsametabolicpathwayinamicro organismwhichiseitherabsentorisradicallydifferentinthemammaliancellsofthehumanhost Principleofantibioticspectrum Differentantibioticstargetdifferentkindsofbacteriai e differentspectrumofactivityExamples PenicillinG originalpen mainlystreptococci narrowspectrum VancomycinonlyGram positivebacteria intermediatespectrum Carbapenemsmanydifferentbacteria verybroadspectrum TreatmentofInfectionAnti MicrobialDrugTargets Antimicrobialsactingonthebacterialcellwall Interferewithsynthesisofpeptidoglycanlayerincellwalleventuallycausecelllysisbindtoandinhibitactivityofenzymesresponsibleforpeptidoglycansynthesisaka penicillin bindingproteins Antimicrobialsactingonthebacterialcellwall Beta lactams Penicillinsbenzylpenicillinflucloxacillinampicillinpiperacillin Antimicrobialsactingonthebacterialcellwall Beta lactams CephalosporinsOrallyactivecephradinecephalexinBroadspectrumcefuroximecefotaxmeceftriaxoneceftazidime Antimicrobialsactingonthebacterialcellwall Unusualbeta lactamsCarbapenemsImipenem meropenemverywidespectrumMonobactamsAztreonamonlyGram negativesGlycopeptidesonlyGram positives butbroadspectrumvancomycinteicoplanin Antimicrobialsactingonnucleicacidsynthesis InhibitorsOfPrecursorSynthesissulphonamides trimethoprimaresynthetic bacteriostaticagentsusedincombinationinco trimoxazoleSulphonamidesinhibitearlystagesoffolatesynthesisdapsone ananti leprosydrug actsthiswaytooTrimethopriminhibitsfinalenzymeinpathway dihydrofolatesynthetase pyramethamine ananti toxoplasmaandanti PCPdrugactsthiswaytoo Antimicrobialsactingonnucleicacidsynthesis InhibitorsofDNAreplicationQuinolones e gciprofloacin inhibitDNA gyraseOrallyactive broadspectrumDamagetoDNAMetronidazole anti anaerobes nitrofurantoin UTI InhibitorsofTranscriptionrifampicin keyanti TBdrug inhibitsbacterialRNApolymeraseflucytosineisincorporatedintoyeastmRNA Antimicrobialsactingonproteinsynthesis Bindingto30sSubunitaminoglycosides bacteriocidal streptomycin gentamicin amikacin tetracyclinesBindingtothe50ssubunitchloramphenicolfusidicacidmacrolides erythromycin clarithromycin azithromycin Antimicrobialsactingonthecellmembrane amphotericinbindstothesterol containingmembranesoffungipolymyxinsactlikedetergentsanddisrupttheGramnegativeoutermembrane Notusedparenterallybecauseoftoxicitytomammaliancellmembranefluconazoleanditraconazoleinterferewiththebiosynthesisofsterolinfungi Mechanismsofresistance Resistancecanarisefromchromosomalmutations orfromacquisitionofresistancegenesonmobilegeneticelementsplasmids transposons integronsResistancedeterminantscanspreadfromonebacterialspeciestoanother acrosslargetaxonomicdistancesMultipleresistancedeterminantscanbecarriedbythesamemobileelementTendtostackuponplasmids Impactofantibioticresistance Infectionsthatusedtobetreatablewithstandardantibioticsnowneedrevised complexregimens e g penicillin resistantStrep pneumoniaenowrequiresbroad spectrumcephalosporinInsomeinstances hardlyanyantibioticsleft e g MultiresistantPseudomonasaeruginosae g Vancomycin resistantStaph aureusResistanceratesworldwideincreasing MimsCetal MedicalMicrobiology 1998 Mechanismsofresistance Enzymesmodifyantibioticwidespread carriedonmobileelementsbeta lactamaseschloramphenicol modifyingenzymesaminoglycoside modifyingenzymesPermeabilityantibioticcannotpenetrateorispumpedoutchromosomalmutationsleadstochangesinporinseffluxpumpswidespreadandmobile Mechanismsofresistance ModificationorbypassoftargetbymutationoracquisitionofextrinsicDNAS aureusresistancetoflucloxacillinacquiresanextraPBP2tobecomeMRSAS aureusresistancetomupirocinChromosomalmutationsinlow levelresistancePlasmid borneextraILTSgeneinhigh levelresistanceRifampicinresistanceinM tuberculosisPointmutationsinRNApolymerasegene Antibioticsusceptibilitytestinginthelaboratory BacterialculturestestedonartificialmediaTeststheabilitytogrow or bekilled inthepresenceofdefinedantibioticsProvidesguidanceforongoingtherapyProvidesresistanceratesforempirictherapyProblems notallresultscorrespondwithclinicalsuccessorfailure DeterminationofMICandMBC MimsCetal MedicalMicrobiology 1998 Diskdiffusiontesting Cohen Questionstoaskbeforestartingantibiotics Doesthispatientactuallyneedantibiotics Whatisbesttreatment Whatarethelikelyorganisms Whereistheinfection Howmuch howoften whatroute forhowlong Howmuchdoesitcost Arethereanyproblemsinusingantibioticsinthispatient Haveyoutakenbacteriologyspecimensfirst Clinicaluseofantibiotics GillespieSH BamfordKB 2003 Medicalmicrobiology infectionataglance Doesthispatientneedantibiotics Isthepatienteveninfected e g urethralsyndromevsUTIIsitaviralinfection e g thecommoncoldIstheinfectiontrivialorself limiting mostdiarrhoeaAretheremoreappropriatetreatments physiotherapyforbronchitistreatmentofpusisdrainagetreatmentofforeignbodyinfectionisremovingtheforeignbody Bestantibiotic s fortheseorganisms Forsomeorganismssensitivitiesareentirelypredictablee g Streptococcuspyogenesalwayspenicillin sensitiveFormostorganisms sensitivitytestscontributetorationaltherapye g coliformsinUTIKnowledgeoflocalresistanceproblemscontributestochoiceofempiricaltherapy Bestantibiotic s forthissiteofinfection Dependsonpenetrationofantibioticintotissuese g gentamicingivenivdoesnotenterCSForgutE g azithromycinaccumulatesincellseventhoughlevelslowinserumDependsonmodeofexcretione g amoxycillinexcretedinmassiveamountsinurine Arethereanyproblemswiththisregimeninthispatient Allergyusuallyonlyaproblemwithpenicillins and lessoften withcephalosporins 10 crosssensitivity AmpicillinRashdevelopsifpatienthasglandularfeverorlymphomaNotrelatedtogeneralpenicillinallergy Arethereanyproblemswiththisregimeninthispatient SideEffectssomeoccurwithalmostanyantibioticGastricupsetAntibiotic associateddiarrhoeaC difficileinfectionpseudo membranouscolitisanbefatalOvergrowthofresistantorganisms Thrush inthecommunityVRE s MRS A s CandidainITU Arethereanyproblemswiththisregimeninthispatient Organ specificsideeffectsdamagetokidneys ears liver bonemarrowchloramphenicolproducesrareaplasticanaemiavancomycin