肠杆菌科的beta内酰胺类抗生素耐药

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1、Resistancetob-lactamantibioticswithintheEnterobacteriaceaePaulD.Fey,Ph.D.UniversityofNebraskaMedicalCenterObjectivesUnderstandthemechanismsof-lactamresistanceinGNRsUnderstandhow-lactamasesaretransferred.Knowthecharacteristicsofthreeclassesof-lactamasesESBLsAmpCKPCMechanismof-LactamA

2、ctionBactericidal-lactamsbindandinhibitpenicillinbindingproteins(PBPs)PBPsareresponsibleforassembly,maintenance,andregulationofpeptidoglycan(cellwall)metabolism.DisruptionofpeptidoglycansynthesisMechanismsofGNRResistanceto-lactamsPorin-mediatedresistanceAntibioticdoesnotreachtarget.b

3、-lactamaseMajorityofresistancetob-lactamantibioticsmediatedthroughb-lactamases.Manydifferenttypesofb-lactamaseswithdifferentsubstrate(antibiotic)specificities.Common-LactamasesinGNRsNEJM352:4.2005Howareb-lactamasestransferred?TransferofPlasmids.ExtrachromosomalDNAUsuallycarryantibiotic

4、resistancegenesThesegenescanbeencodedontransposons,whicharealsomobile.TEM-1hasbeentransferredbetweentheEnterobacteriaceaeandH.influenzaeandtheNeisseriaceaeb-lactamantibioticsPenicillinsAmpicillinPiperacillinBeta-lactam/beta-lactamaseinhibitorsAmpicillin/sulbactamAmoxicillin/clavulanateT

5、icarcillin/clavulanatePiperacillin/Tazobactamb-lactamantibioticsFirstGenerationcephalosporinsCefazolinCephalothinSecondGenerationoralantibioticsCefuroxime(manyothers)SecondGenerationcephamycinsCefoxitinCefotetanb-lactamantibioticsThirdgenerationcephalosporinsCefotaximeCeftriaxoneCeftazi

6、dimeFourthgenerationcephalosporinsCefepimeMonobactamsAztreonamb-lactamantibioticsCarbapenemsImipenemMeropenemErtapenemDoripenemESBLsEnzymescapableofhydrolyzingthird-generationcephalosporins.Plasmid-mediatedDerivatives(mutants)oforiginalTEM-1andSHV-1b-lactamases.Susceptiblein-vitrotoclav

7、ulanateandcefoxitin.E.colisusceptibilityReportAmpicillinRPiperacillinRCephalothinRCefoxitinSCefotaximeRCeftazidimeICeftriaxoneRAztreonamICefepimeSPip/TazoIImipenemSLaboratorydetectionofESBLsResistanceorintermediatetothird-generationcephalosporins.Cefoxitinandcefotetansusceptibl