Antimicrobial Agents Introduction & Cell Wall Inhibitors - Introduction & Cell wall Inhibitors PDF

Antimicrobial agents 1. Principles of Anti-microbial Therapy 2. Anti-microbial agents Antibacterial A. Cell Wall Inhibitors B. Protein Synthesis Inhibitors C. Anti-metabolites Anti-fungal agents Antiviral Agents PRINCIPLES OF ANTIMICROBIA...

Antimicrobial agents 1. Principles of Anti-microbial Therapy 2. Anti-microbial agents Antibacterial A. Cell Wall Inhibitors B. Protein Synthesis Inhibitors C. Anti-metabolites Anti-fungal agents Antiviral Agents PRINCIPLES OF ANTIMICROBIAL THERAPY  Infection associated factors Age: young and elderly Exposure to pathogen (bacteria, virus, pesification M themicroorganisimi fungi.;;;) lackingfor pdue Distruption of normal barriers sterilization Decrease immunological defensedueto d1 oid.dk immune system Impaired circulation (diabetes) diseases or iftheywhere Poor nutritional state elderly  Antibacterials/Antibiotics Medications used to treat bacterial the know we infections. shouldbacteria weofthe Before starting antibiotic therapy type wantffffation Suspected areas of infection should be cultured to identify the causative organism Potential antibiotic susceptibilities. Ensitivities resistent sensitive tyamosisin WWW8 gjj8  Principles of Anti-microbial Therapy Pathogen-directed therapy: drug administration after bacterial identification according to susceptibility testing suscept ftibioticddk.fm ictypeusedwhentreating emergencesituation Empiric therapy: treatment of an infection before t.im specific culture information has been reported or obtained L Broad-spectrum therapy may be needed: Initially for serious infections when the identity of the organism is unknown or The site makes a polymicrobial infection likely Prophylactic therapy: treatment with antibiotics to prevent an infection, as in intra-abdominal surgery Gthere isnoinfectionhere so we usethistypebeforesurgeriestopreventinfections  due to contaminations Eg therelativesorfamilyof a tuberclosispatient because theyhavehighrisktobepatients Emperictherapy Weusebroadspectrumalso here Post surgery I use it when I wanttotreatemergencystate Eg aurinarytract Infection a menegitis patient a UTI patient severepneumoniapatient Fighypainful infection thesepatientsif I wantto letthem waituntilspecification ofthebacteriaoccur thedisease will be highly progressed or eventhepatientwill die Depending on whatthedrugwillbe prescribed 1Theexperienceofthedoctor Thedoctorsupposed topredictthecausitiveagent forthe situation aww III live.info ww81 bdb.w301 2 Broadspectrum agentsthat can beused to most all typesof pathogenesis gram ve gram ve aerobes anaerobes __ Afteranalysisofthemicroorganismtheantibioticmayberight so we continue usingit or maybewrong so we use theright instead or we multiple may have apolypathogens so we use antibiotics Selection of Antimicrobial Agents 1. The organisms susceptibility to a particular agent 2. The site of the infection localinfectionsystemicinfection 3. Patient factors, history age genderpregnancy lactation 4. The safety and efficacy of the drug and 5. The cost of therapy. However, most patients require empiric therapy (immediate administration of drug(s) prior to bacterial identification and susceptibility testing).  Patients factors taken into consideration when selecting an antimicrobial agents: 1. Immune system 2. Renal and hepatic dysfunction 3. Poor perfusion 4. Age 5. Pregnancy and lactation  Route of administration: compliance ofthepatient Oral route is chosen for mild infections, and is favorable for outpatients not hospitalized Parenteral route is used for more serious infections, or when anti-microbial agent of choice has poor GI absorption  Effect of the site of infection on therapy: the blood–brain barrier The penetration In and concentration of an antibacterial agent in the CSF are particularly influenced by the following 1. Lipid solubility highlipidsolubility rossthemembrane required 2. Molecular weight bilityto twoweight11isms distribute 3. Protein binding iwIi distributions binding 4. pumps ww.s Susceptibility to transporters or efflux fcoproten distribution 2 silk  Bacteriostatic vs. Bactericidal drugs Bacteriostatic drugs arrest the growth and replication of bacteria, which Will eventually lead to bacterial death inhibitthegrowthofthebacteria Keep bacteriain stationary Bacteriostaticdrugsusedin highdose phase ofgrowth could bebacteriocidal Bactericidal drugs kill bacteria at drug serum levels achievable in the patient. III 0 1 It damagethestructureofthebacteria sideeffectforthe hostcell Direct killing ofthebacteria Concentration dependentbacterial killing occursonlywhentherat extentofkilling  increase with p ogressively gherandb cteria concen aliens withno Minimum inhibitory concentration (MIC) (for bacteriostatic agents): The lowest concentration of antibiotic that inhibits bacterial growth. Minimum bactericidal concentration (MBC) (for bactericidal agents): Determines the minimum concentration of antibiotic that kills the bacteria under investigation. Spectrum of antibiotic Narrow spectrum: a chemotherapeutic agents acting only on a limited group of microorganisms. Broad spectrum: a chemotherapeutic agents acting on a wide variety of microbial species. SITES OF ANTIMICROBIAL ACTIONS  used be rarelytoemergency in β ofcell tinhibitors membraneare thedrugsthathave because  I 5 g d cyn an beau her are g Sim y y between humanandbacterialcellmembranesoantibiotics bacterial cellmembr affecting willaffecthuman Whendoestheantimicrobial agent killthebacteriaandwhen ones it inhibitsitsgrowth works Depending on where it inhibitors arebacteriostatic DNA synthesisinhibitors protein synthesis cell membranedamage agentsthatdamagethecellmembraneand outofthecell are leads it to be leaky or letthecellularcontentstoget 4 bacteriocidal the bacterial cell especially these different mechanisms haveselectivetoxicityon inhibitory when itisused inthetheraputic Conc thats whywedon'tusetheminimum inhighdoses becauseweincreasetheriskoftoxicity aswhenweincreasethe Conc human concofbacteriostatictomake itbactericidal weincreasethedirecttoxicityon Butwhydo antibacterial haveselectivetoxicityonbacteria andsmall agents directtoxicityon human hasverylowdirect Because whenwetalkaboutcell wall inhibitors it because Eukaryotesdon'thave cell wall toxicityon human When we talk about DNA synthesis inhibitors theprocess involvedin DNAsynthesis of DNAsynthesis andenzymesthatare for bacteria is highlydifferentfrom human Ribosomes When we talk about protein synthesis inhibitors areresponsiblefor proteinsynthesis andbacterial ribosomes arehighlydifferentfrom humanribosomes  Complications of Antibiotic Therapy Injectabledrugshavehigherchancetocausehypersensitivity A. Hypersensitivity morethananyother routebecauseinjectabledrugsinterthe Hypersensitivity reactions to antimicrobial drugs orbodyinhig Conc their metabolic products frequently occur. iTereactia For example, Penicillin's.sulfadrugs willbevery rapid Mor When antibacterialagentshavedirect toxicityonhuman dangerous B. Direct toxicity High serum levels of certain antibiotics may cause issue toxicity by directly affecting cellular processes in the II im host. dosed I For example, aminoglycosides can cause ototoxicity É Gthisdrugevenifitisatnormaldoselnormalconc.lt neededdose mitochondria  s direct loxelyonhehascells chon a Weusethesedrugsin lossofchoicescases whenthereisnosafer drugisavaliableto treatthisinfection thisdrugisgivenundermonitorforserumlevelsignssymptoms Complications of Antibiotic Therapy othertypeofmicroorganismotherthanthe go type I'mtreatingit opportunisticinfection itis a infection Hecondaryinfection microorganisms C. Super-infections: over growth of normal flora due to antibiotic treatment of an initial treatment. especiallythe oralantibiotic With Broad-spectrum antimicrobials Combinations of agents multi antibioticsused May result in alterations of the normal microbial flora permitting the overgrowth of opportunistic organisms, especially fungi or resistant bacteria. Duration antibiotics  on Blee nn rma s ogIngerduaoJanb I emo a Opportunistic infection Occurswhenantibiotictreatment kills offthenormalflora sopathogenscan taketheopportunitytogrowandmultiply Infectionfrom a microorganism differentthanthetype ofmicroorganism I'm treating If a resistantstrainofbacteriaremaincausinginfection herethepatientfirstly shows improvement butthenthesymptomeswill return again Why Becausetheantibioticaffectsthesensitivestrainforthebacteriaand theresistantstrainwhichhastheabilitytogrowremainandreinfect butherewearetalkingaboutinfectionfrom thesametypeof microorganism that I wastreating But 2 infection opportunisticinfection superinfection Comes as aresultofirradication of normalflora Eg Oralsyrupantibioticssuppressestheoralnormalfloraand andgrow in the fungi in theabsence ofnormalflora mouthcavitycausingfungalinfection Alsomostofantibiotics afterusingitfor2weeksforexample willcausediarrhea because microorganisms causeinfectionthat causediarrhea bloodydiarrhea abdominalpain isSittfound Whywhen Istoptheantibiotictreatment thesuperinfectionprobability Becausenormalfloraafterbeingirradiatedneedstime returntoitsnormal to Conc amongthistimethepatient isstillhavinghighrisktobeaffectedagain General mechanisms ofresistance Bacteriacandevelopresistance bymultiplemechanism itiscalled multidrugresistancebacteria