XXXX-01-16-细菌耐药的临床对策-TZC-final

陈佰义中国医科大学第一医院感染病科/感染管理办公室辽宁省医院感染管理质控中心[e-mail]细菌耐药的临床对策-谈耐药时代的个体化治疗与抗菌药物的临床管理抗感染药物发展简史1929AlexanderFleming发现青霉素1939HowardFlorey和ErnstChain分离获得青霉素，用于动物试验。1942青霉素首次用于救治战伤患者，拯救了许多人的生命1950’s大量抗生素用于临床。AposterfromWorldWarII,dramaticallyshowingthevirtuesofthenewmiracledrug,andrepresentingthehighlevelofmotivationinthecountrytoaidthehealthofthesoldiersatwar.DiscoveryofAntibacterialAgentsCycloserineErythromycinEthionamideIsoniazidMetronidazolePyrazinamideRifamycinTrimethoprimVancomycinVirginiamycinImipenem19301940195019601970198019902000PenicillinProntosilCephalosporinCEthambutolFusidicacidMupirocinNalidixicacidOxazolidinonesCecropinFluoroquinolonesNeweraminoglycosidesSemi-syntheticpenicillins&cephalosporinsNewercarbapenemsTrinemsSyntheticapproachesEmpiricscreeningNewermacrolides&ketolidesRifampicinRifapentineSemi-syntheticglycopeptidesSemi-syntheticstreptograminsNeomycinPolymixinStreptomycinThiacetazoneChlortetracyclineGlycylcyclinesMinocyclineChloramphenicolResistantStrainsRareResistantStrainsDominantAntimicrobialExposureSelectionforAntimicrobial-ResistantStrains抗生素选择压力耐药菌的播散临床关注的耐药问题ResistancesofClinicalConcerns革兰阳性细菌金匍菌–MRSA,VISA,VRSAVRE(地理上差别)肺炎链球菌–青霉素和大环内酯耐药革兰阴性细菌肠杆菌科ESBLs-喹诺酮,头孢菌素,青霉素类,氨基糖苷类碳青霉烯酶（KPC,NDM-1?）-碳青酶烯耐药在中国出现和蔓延非发酵菌(假单孢菌+/-不动杆菌)-常见/CRAB50％喹诺酮,头孢菌素,青霉素类,氨基糖苷,碳青霉烯类－寻找新的抗感染药物-新药越来越少－限制人以外(畜牧业)使用-减少对人类的影响－优化抗感染药物－预防VS治疗－优化抗感染药物临床管理－加强医院感染的控制-减少耐药菌传播细菌耐药的临床对策-MeasurestoResistance-减少抗生素选择性压力OriginofEmergingofResistance-SWAB,NethMap-2003;最大程度减少耐药克隆是阻击耐药的第一步几个问题经验性抗感染治疗的基本原则-ESBLs介导多重耐药肠杆菌科治疗中哌拉西林/他唑巴坦地位-从指南看哌拉西林/他唑巴坦在经验性治疗中的地位抗菌药物临床管理与细菌耐药控制-ESBL＋肠杆菌科细菌-碳青酶烯耐药铜绿假单胞菌FightingInfectionInTheFirsthoursRapidtestsWhenavailable.Gramstain!!!Startadequateantibioticcoverage(within1hour?)TillouAetal.AmSurg2004;70:841-4DrainpurulentcollectionSamplingIncludinginvasiveprocedureswhenneeded(BAL…)经验性治疗和目标治疗的统一留取标本进行微生物学检查开始经验性抗感染治疗目标治疗选择哪种抗菌药物感染部位的常见病原学选择能够覆盖病原体的抗感染药物-抗菌谱/组织穿透性/耐药性/安全性/费用考虑药代动力学/药效动力学考虑病人生理和病理生理状态高龄/儿童/孕妇/哺乳肾功不全/肝功不全/肝肾功能联合不全其它因素杀菌/抑菌/单药/联合/静脉/口服/疗程经验性抗感染治疗－药物选择-considerationsinchoosingantibioticforempirictherapy评估病原体-有的而放矢评估耐药性-到位不越位减少/避免随意使用广谱/超广谱抗菌药物/联合多种药物联合MouthPeptococcusPeptostreptococcusActinomycesSkin/SoftTissueS.aureusS.pyogenesS.epidermidisPasteurellaBoneandJointS.aureusS.epidermidisStreptococciN.gonorrhoeaeGram-negativerodsAbdomenE.coli,ProteusKlebsiellaEnterococcusBacteroidessp.UrinaryTractE.coli,ProteusKlebsiellaEnterococcusStaphsaprophyticusUpperRespiratoryS.pneumoniaeH.influenzaeM.catarrhalisS.pyogenesLowerRespiratoryCommunityS.pneumoniaeH.influenzaeK.pneumoniaeLegionellapneumophilaMycoplasma,ChlamydiaLowerRespiratoryHospitalK.pneumoniaeP.aeruginosaEnterobactersp.Serratiasp.S.aureusMeningitisS.pneumoniaeN.meningitidisH.influenzaGroupBStrepE.coliListeria注意特殊修正因子/特别是先期抗菌药物对细菌学的影响不同感染部位的常见感染性病原体Possiblepathogensonsiteofinfection评价病原体耐药可能？是否耐药菌？-了解耐药病原体流行状况参考代表性治疗/依靠当地资料-个体化用药病人来源：社区、养老院、医院高龄、基础疾病、近期抗菌药物、近期住院、侵袭性操作、晚发医院感染S.aureusPenicillin[1944]Penicillin-resistantS.aureus金黄色葡萄球菌耐药的发生发展过程Methicillin[1962]Methicillin-resistantS.aureus(MRSA)Vancomycin-resistantenterococci(VRE)Vancomycin[1990s][1997]VancomycinintermediateS.aureus(VISA)[2002]Vancomycin-resistantS.aureusCDC,MMWR2002;51(26):565-567[1960]评价病原体耐药可能？是否耐药菌？-了解耐药病原体流行状况参考代表性治疗/依靠当地资料-个体化用药－合理用药的核心病人来源：社区、养老院、医院高龄、基础疾病、近期抗菌药物、近期住院、侵袭性操作、晚发医院感染中国大陆ESBL的发生率28.645.75954.657.86060.260.225.734.947.736.640.451.53845.701020304050607020012002200320042005200620072008E.coliK.pneumoniae%WangH,ChenM.DiagnosMicrobiolInfectDis,2005,51,201-208CMSS/SEANIR/CARES.year细菌耐药监测结果如何解读？实验室药物敏感性监测的意义及缺陷意义-反映了耐药趋势-告诫我们要合理用药/遏制耐药-提示我们选择抗菌药物时要考虑耐药性对治疗的影响缺陷-实验室收集到的菌株/大型教学医院/ICU抗生素选择压力导致耐药性高估！-没有临床背景资料/不利用于个体化用药(年龄、基础疾病、社区/医院感染、前期抗菌药物使用情况)NoRiskFactorsforMDRPathogensRiskFactorsforMDREnterobacteriaceaeaRiskFactorsforMDRPseudomonasHealthcarecontactNoYes!(eg,recenthospitaladmission,nursinghome,dialysis)withoutinvasiveprocedureYes,Longhospitalizationand/orinfectionfollowinginvasiveprocedures(5days)RecentAbxNoYes!(≥14daysinpast90days)Yes!(≥14daysinpast90days)PatientcharacteristicsYoungfewcomorbidities≥65yrscomorbiditiessuchasTPNorrenalinsufficiencyco-morbiditiessuchasCF,structurallungdisease,advancedAIDS,neutropenia,orothersevereimmunodeficiencyaExceptnonfermenters/non-Pseudomonasspecies.AdaptedfromCarmeliY.Predictivefactorsformultidrug-resistantorganisms.In:RoleofErtapenemintheEraofAntimicrobialResistance[newsletter].Availableat:–51;Ben-AmiR,etal.ClinInfectDis.2006;42(7):925–934;Pop-VicasAE,D’AgataEMC.ClinInfectDis.2005;40(12):1792–1798;ShahPM.ClinMicrobiolInfect.2008;14(suppl1):175–180.StratificationforRiskforMDRGram-NegativePathogensEpidemiologyofMRSAH-MRSA•Reservoires-hospitals-LTCFs•5geneticbackgroudsH-MRSAincommunity-patientswithriskfactors-contactwithpatientswithriskfactorsTruecommunity-MRSA-nohealthcare-associatedriskfactors-withPVLgeneshealthcarecommunityAcquiredOnsetH-MRSA感染危险因素:年龄65岁，严重