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ID:22077115
大小:4.80 MB
页数:33页
时间:2018-10-27
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1、ResistancetoantibioticsIntrinsicresistance(examples)penGdoesnotentergramnegativebacteriawellwhy?doesn’tpenetrate--ampicillindoesrifampindoesn’tkillfungiwhy?doesn’tgetin---weakenbarrierwithamphotericinandthenitdoesisoniaziddoesnotkillbugsthatdon’trequiresyn
2、thesisofmycolicacidsEnvironmentalresistancee.g.sulfonamideresistanceifhighpurines,methionine,thymidineavailable(suchasinanabscess)e.g.aminoglycosidesnoteffectiveinanaerobicenvironmentAcquiredResistancegeneticchanges,plasmidswithnewgenes2006AntibiogramHarbo
3、rview/UWAcquiredDrugResistance1.enzymaticinactivation(b-lactams,aminoglyc.chloramph)Bacteriakeepupwithbigpharmaintheb-lactamantibioticarmsracebacteriacanoftenexpressmorethanone-lactamaseInactivationofaminoglycosidesbyacetylation,phosphorylation,andadenyla
4、tionindrug-resistantorganismsAcquiredDrugResistance1.enzymaticinactivation(b-lactams,aminoglyc.chloramph)2.rapideffluxofdrugoutofcell(tetracyclines,ciprofloxacin)DrugexportsystemsinGram+AcquiredDrugResistance1.enzymaticinactivation(b-lactams,aminoglyc.chlo
5、ramph)2.rapideffluxofdrugoutofcell(tetracyclines,ciprofloxacin)3.decreasedconversiontoactiveform(isoniazid)4.increasedconcentrationofantagonist/competitor(sulfonamideresistancewithincreasedPABAsynthesis).5.alteredamountofreceptor(trimethoprim-DHFRamplifica
6、tion)6.alteredstructureoftargettoreducebinding(methicillinresistance,vancomycinresistance,ciprofloxacinres.)Vancomycinresistance:mechanismVancomycinresistance:mechanismResistancecanbetransferredbetweenbacteriaphagetransductiontransposableelementsplasmidtra
7、nsferduringconjugationplasmidscancontainmultipleresistancegenestransfercanoccurbetweennon-pathogenandpathogensPlasmid-mediateddrugresistancechloramphenicolaminoglycosidesulfonamidetetracyclineProblemswithAntibioticresistancemorethan50%ofantibioticsusedindo
8、mesticanimalsforsub-therapeuticeffect:breedinggroundforresistanceThereare7.5billionchickens,292millionturkeys,109millioncattleand92millionpigsintheUnitedStates.Antibioticsgiventopigsasof2000“KFCdoesnotpurchas
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