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桂林医学院附属医院桂林医学院附属医院微生物中的“收藏家”虽然不是对抗生素天然耐药，但因为只产适量的青霉素酶染色体，被称为臭名昭著的“多耐药质粒的收藏家”肺炎克雷伯菌D类碳青霉烯酶B类碳青霉烯酶A类碳青霉烯酶桂林医学院附属医院耐药质粒编码KPCGESVIMIMPNDMOXA桂林医学院附属医院耐药进程氨基糖苷类β内酰胺类氟喹诺酮类碳青霉烯类桂林医学院附属医院泛耐药CRKP•临床使用经验有限Polymyxins多粘霉素•因广泛使用，耐药菌株已出现Fosfomycin磷霉素•？？？？Tigecycline替加环素桂林医学院附属医院Clinicalstudies,antimicrobialtherapies,andoutcomesforpatientsinfectedwithKPC-producingK.pneumoniaeReferenceCountry(yrofpublication)StudydesignNo.ofpatientswithindicatedinfectionTypeofβ-lactamase(no.ofisolates)Treatmentwithactivedrug(no.ofpatients)Outcome(no.ofsuccesses/no.offailures)182USA(2009)Caseseries3BSIsKPC-2(3)Tetracycline-aminoglycoside(1)1/0Colistin(3)1/2175Greece(2010)Case-controlstudy19BSIsKPC-2(19)Colistin(10)2/8162China(2008)Tigecycline-aminoglycoside(1)1/0Colistin-aminoglycoside(9)4/5274Greece(2011)Case-controlstudy53BSIsKPC-2(53)Carbapenem(1)0/1Colistin(7)3/4Tigecycline(5)3/2Aminoglycoside(2)2/0Colistin-aminoglycoside(2)2/0桂林医学院附属医院Clinicalstudies,antimicrobialtherapies,andoutcomesforpatientsinfectedwithMβL-producingK.pneumoniaeReferenceCountry(yrofpublication)StudydesignNo.ofpatientswithindicatedtypeofinfectionTypeofMBL(no.ofisolates)Treatment(no.ofpatients)Outcome(no.ofsuccesses/no.offailures)86Greece(2008)Tigecycline(1)1/056Spain(2008)Tigecycline-colistin(2)1/1269Taiwan(2001)Caseseries3BSIsIMP-8(3)Carbapenem(3)1/2143Taiwan(2004)Caseseries3(2pneumonias,1BSI)IMP-typeenzyme(3)Carbapenem(1)1/0240Greece(2008)Caseseries17(14BSIs,3pneumonias)VIM-1(17)Colistin(6)6/0Tigecycline(1)0/1175Greece(2010)Case-controlstudy18BSIsVIM-1(17)Colistin(10)6/4VIM-typeenzyme(1)Colistin-aminoglycoside(8)4/467Greece(2009)Prospectiveobservationalstudy67BSIsVIM-1(67)Carbapenem(14)11/3Carbapenem-colistin(8)8/0Colistin(15)11/4Noactivedrug(18)13/5桂林医学院附属医院RegimenA,combinationtherapywith≥2activedrugs,oneofwhichwasacarbapenem;regimenB,combinationtherapywith≥2activedrugs,notincludingacarbapenem;regimenC,monotherapywithanaminoglycoside;regimenD,monotherapywithacarbapenem;regimenE,monotherapywithtigecycline;regimenF,monotherapywithcolistin;regimenG,inappropriatetherapy.RegimenAwassuperiortoregimensB,E,F,andG(forAversusB,E,F,andG,thePvaluewas0.02,0.03,0.0001,and0.0001,respectively).RegimensB,C,andDweresuperiortoregimenG(forBversusG,P=0.014;forCversusG,P=0.04;andforDversusG,P=0.03).桂林医学院附属医院分析•Thedecreasedclinicaleffectivenessoftigecyclineinsevereinfectionscouldbeattributedpartlytothepharmacokinetic/pharmacodynamic(PK/PD)profileofthedrug.•替加环素在严重感染中的临床疗效减少，可能是由于药物的PK/PD•PK/PD：对不同类抗菌药物给药方案具有指导意义桂林医学院附属医院•TigecyclinedemonstratesmainlybacteriostaticactivityagainstGram-negativeorganisms,andtheattainabledrugconcentrationsatseveralanatomicsitesaresuboptimal.•替加环素对革兰氏阴性菌主要是抑菌效果•theattainabledrugconcentrationsatseveralanatomicsitesaresuboptimal•在体外药效学模式中，随着浓度超过1mg/L时，其抑菌作用保持不变，因此实现药物浓度是次重要的桂林医学院附属医院•Thepeakserumconcentrationsachievedwiththestandarddosingregimenofthedrug(50mgtwicedaily)rangefrom0.6to0.9μg/mlwhilethoseattainedintheurineandintheepithelialliningfluidareseveralfoldlower•按照替加环素的标准给药方案（50mgq12）当血药浓度达到峰值时（0.6to0.9μg/ml），其尿液和上皮表面液体中的浓度则非常低桂林医学院附属医院•Thedrugconcentrationsattainablebythisstandarddosingregimen,combinedwiththisdrug'sMICprofileforcurrentCPEisolates,renderitunlikelyfortigecyclinetocureCPEinfectionsatanatomicsiteswheredrugconcentrationsaresuboptimal.•替加环素在某些部位浓度很低，且不足以达到抑菌浓度。当CPE感染在这些部位时，则很难达到疗效。•这使得替加环素不太可能治愈CPE在这些部位的严重感染桂林医学院附属医院结论•Therefore,thisdrugshouldbeusedwithcautionagainstCPE,preferentiallyincombinationwithanotheractiveagentandafterdueconsiderationoftheattainabledrugconcentrationattheanatomicsiteofinfectionandoftheMICfortheinfectingorganism.•因此，替加环素在对待产碳青霉烯酶肠杆菌（CPE）时须谨慎使用。•综合考虑替加环素在感染部位的浓度以及其最低抑菌浓度•优先结合另一个活性药物。桂林医学院附属医院桂林医学院附属医院参考文献•产碳青霉烯酶肺炎克雷伯菌的耐药基因及流行病学研究进展•CarbapenemasesinKlebsiellapneumoniaeandOtherEnterobacteriaceae:anEvolvingCrisisofGlobalDimensions•Colistin-Resistant,KlebsiellapneumoniaeCarbapenemase(KPC)–ProducingKlebsiellapneumoniaeBelongingtotheInternationalEpidemicCloneST258