Anti-bacteria Medicine. . Anti-bacteria medicinen nAntibiotics:ThesubstancederivedfromAntibiotics:Thesubstancederivedfromfungiandbacteriawhichcanselectivelyfungiandbacteriawhichcanselectivelykillorinhibitbacteriagrowthkillorinhibitbacteriagrowthn nAnti-bacteriamedicine:ChemicallyAnti-bacteriamedicine:Chemicallysynthesizedmedicinewhichcansynthesizedmedicinewhichcanselectivelykillorinhibitbacteriagrowthselectivelykillorinhibitbacteriagrowth. . . Antibacteria medicinen nSulfonamiden nQuilononesn nothers. . .Antibiotics and drugs targeting nucleic acid biosynthesis and functions. .Antibiotics and drugs targeting nucleic acid biosynthesis and functions1.Sulphonamides&Trimethoprim(TMP)1.Sulphonamides&Trimethoprim(TMP)PABAfalsestructurePABAfalsestructureInhibitionofDihydrofolatereductaseInhibitionofDihydrofolatereductaseDihydrofolateDihydrofolatetetrahydrofolatetetrahydrofolate. . .2.QuinolonesBacterialtopoisomerase2.QuinolonesBacterialtopoisomeraseII-GyraseII-Gyrasen nNalidixicacidNalidixicacidn nOfloxacinOfloxacinn nCiprofloxacinCiprofloxacinAntibiotics and drugs targeting nucleic acid biosynthesis and functions. . .3.Rifampicin(fromrifamycin)subunitofDNA-primedRNApolymeaseAntibiotics and drugs targeting nucleic acid biosynthesis and functions. .! Rifampicin must be given by a “cocktail” of drugs.Antibiotics and drugs targeting nucleic acid biosynthesis and functions. . . . . .Problem of antibiotics which inhibit protein synthesis . . . Antibiotics: From isolation of strain to clinical applicationn nSelectionofapotentialproductn n1、efficacyn n2、metaboliccharacterizationn n3、toxicityandadverseeffectn n4、Potentialityofindustrialproduction. .Antibiotics: from strain isolation to clinical applicationn nSemi-synthesis:themostpopularapproachofproductionn nMarketingpotentialityn nLife-spanofmarketinganditsimpact. . .% verlevarePenicillinObehandladeDagarPenicillin increased the chance of survival from 10% to 90%Patients withpneumonia and bacteria in blood. .“It is not difficult to make microbes resistant to penicillin “ “The time may come when penicillin can be bought by anyone in the shops “Alexander Flemings Nobel Lecture, 1945 . . . The Global Challenge Antibiotics have saved millions of livesAntibiotics are rapidly losing their effect . .WhatisAntibioticResistance?. .Bacterial Resistance to Antibiotics Enzymessecreted(exo-enzyme)Enzymessecreted(exo-enzyme) Enzymesnotsecreted(endo-enzymes)Enzymesnotsecreted(endo-enzymes) DeletionoftargetmoleculesDeletionoftargetmolecules ChangeincellpermeabilityChangeincellpermeability ChangeintargetmoleculeaffinityChangeintargetmoleculeaffinity Speed-upofsynthesisandmetabolismSpeed-upofsynthesisandmetabolism OthersOthers. .Mechanism of resistance n nSelectionpressure(notonlyinhealthinstitutions)n nGeneticrecombination(especiallyconjugationmediatedbyplasmid). . Improper prescription of antibioticsn nAntibioticprescriptionfornon-bacterialAntibioticprescriptionfornon-bacterialinfectioninfectionn nProphylaxisapplicationofantibioticsProphylaxisapplicationofantibioticsn nLocalapplicationofantibioticsLocalapplicationofantibioticsn nOveruseofwide-spectrumantibioticsOveruseofwide-spectrumantibioticsn nLong-termuseofantibioticsLong-termuseofantibioticsn nAntibioticabuseinagricultureAntibioticabuseinagricultureproductionproduction. .Hip replacementOrgan transplantsCancer chemotherapyCare of preterm babiesModern Medicine Is Not Possible Without Effective Antibiotics. . The survival of the fittest. . .Horisontal spread of resistance genesSpread of resistance between species. . Barrier to the development of new antibioticsn nShortmarketinglifeoftheproductbecauseShortmarketinglifeoftheproductbecauseofresistanceofresistancen nDifficultR&DDifficultR&Dn n11、qualifiedstrainqualifiedstrainn n22、resourcestosupportR&DresourcestosupportR&Dn n33、longtermresearchandtranslationlongtermresearchandtranslationn nAdversereactionsAdversereactionsn nExpenseforhealthcareExpenseforhealthcare. .The outcome of resistance development The outcome of resistance development (From the view point of bacteria cells)(From the view point of bacteria cells) UneconomicstateofcellmetabolismUneconomicstateofcellmetabolism Slow-downofproliferationSlow-downofproliferation deletionofsomepathogenicabilitiesdeletionofsomepathogenicabilities AvoidingharmsfromdrugsAvoidingharmsfromdrugs. . .Antibiotic sensitivity test MIC & MBC Broth dilution Agar dilution Disk diffusion Standard requirements. . .Antibiotic sensitivity testStandardrequirements:a.Depth:4mmb.Inoculates:105cell/mlc.Incubation:37,18hours. .Antibiotic Sensitivity TestHowtoexplaintheresults?Howtoavoidmisleadingofclinicians?Howtostandardizethetest?. . Reading and evaluation of sensitivity test1 1、PhysicalandchemicalprofileofthePhysicalandchemicalprofileofthemedicinemedicine2 2、MetabolicprocessMetabolicprocess3 3、Identificationofsensitivity&Identificationofsensitivity&resistanceresistance4 4、Q.C.Q.C.5 5、Whoisresponsibleforthosework?Whoisresponsibleforthosework?. . .