感染病患者多重耐药菌感染风险诊断.ppt

-谈耐药背景下的个体化抗感染治疗,感染病患者多重耐药菌感染风险的分层StratificationofInfectiousDiseasePatientsatRiskforMDROrganisms,武汉科技大学附属孝感市中心医院呼吸内科彭春燕2016年3月9日,抗感染药物发展简史,1929AlexanderFleming发现青霉素,HowardFlorey和ErnstChain分离获得青霉素，用于动物试验。,青霉素首次用于救治战伤患者，拯救了许多人的生命,1950s大量抗生素用于临床。,AposterfromWorldWarII,dramaticallyshowingthevirtuesofthenewmiracledrug,andrepresentingthehighlevelofmotivationinthecountrytoaidthehealthofthesoldiersatwar.,DiscoveryofAntibacterialAgents,CycloserineErythromycinEthionamideIsoniazidMetronidazolePyrazinamideRifamycinTrimethoprimVancomycinVirginiamycin,Imipenem,1930,1940,1950,1960,1970,1980,1990,2000,PenicillinProntosil,CephalosporinC,EthambutolFusidicacidMupirocinNalidixicacid,OxazolidinonesCecropin,Fluoroquinolones,Neweraminoglycosides,Semi-syntheticpenicillins119;405-411,ControlofAntibioticResistance,经验性抗感染治疗的基本原则耐药背景下的个体化治疗,理性回归/责任所在,慢性咳嗽和黄痰-原因,哮喘后鼻腔鼻漏病毒感染后气道高反应性胃酸返流吸烟相关的慢性支气管炎支气管扩张症弥漫性泛细支气管炎肺泡蛋白沉积症,急性发热-WBC不高/淋巴增高（无感染灶）病毒！-WBC增高/中性粒增高/核左移可能细菌！部位/病原体？原发性菌血症？慢性发热IE、布病、慢性感染灶？结核病？非感染性发热药物热、风湿病、恶性肿瘤,正确诊断是正确治疗的前提,发热的诊断与鉴别诊断,27-year-oldmanwithacutelymphocyticleukemia.,51-year-oldmanwithchronicmyelogenousleukemia.,22-year-oldwomanwithadultT-cellleukemia.,67-year-oldwomanwithadultT-cellleukemia.,61-year-oldmanwithinterstitialfibrosis;patientwasreceivingchlorambucilforchroniclymphocyticleukemia.,COP,RapidtestsWhenavailable.Gramstain!,Startadequateantibioticcoverage(within1hour?)TillouAetal.AmSurg2004;70:841-4,Drainpurulentcollection,SamplingIncludinginvasiveprocedureswhenneeded(BAL),合格标本进行微生物学检查开始经验性抗感染治疗目标治疗,经验性治疗和目标治疗的统一,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和抑菌/单药和联合/静脉和口服/疗程,经验性抗感染治疗合理选择药物-considerationsinchoosingantibioticforempirictherapy,评估病原体-有的而放矢！评估耐药性-到位不越位！,病情严重性评估,+,-个体化评估-特殊修正因子先期抗菌药物对细菌学及其耐药性影响,不同部位感染-病原体的流行病学,从病原学认识感染性疾病,SSSS,PCP,抗菌谱(coverage)组织穿透性(tissuepenetration)耐药性(resistance,specificallylocalresistance)参考代表性资料/依靠当地资料安全性(safetyprofile)药物本身/制剂/工艺/杂质费用/效益(cost/effectiveness)失败或副作用致再治疗费用更高,经验性抗感染治疗药物选择的基本原则,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-合理用药的精髓病人来源：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.aureus,Penicillin,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.aureus,CDC,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-合理用药的精髓病人来源：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,%,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解读,意义-反映了耐药趋势/告诫要谨慎使用抗菌药物-影响选择药物/考虑耐药性对疗效的影响不足-实验室收集菌株/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/不能用于指导个体化用药(年龄、基础疾病、社区/医院感染、前期抗菌药物使用情况),aExceptnonfermenters/non-Pseudomonasspecies.AdaptedfromCarmeliY.Predictivefactorsformultidrug-resistantorganisms.In:RoleofErtapenemintheEraofAntimicrobialResistancenewsletter.Availableat:www.invanz.co.il/secure/downloads/IVZ_Carmeli_NL_2006_W-226364-NL.pdf.Accessed7April2008;DimopoulosG,FalagasME.EurInfectDis.2007;4951;Ben-AmiR,etal.ClinInfectDis.2006;42(7):925934;Pop-VicasAE,DAgataEMC.ClinInfectDis.2005;40(12):17921798;ShahPM.ClinMicrobiolInfect.2008;14(suppl1):175180.,StratificationforRiskforMDRGram-NegativePathogens,重症感染耐药菌感染！重症感染革兰阴性肠杆菌科细菌感染！肺炎链球菌、化脓性链球菌、军团菌、肺孢子菌等均可致重症感染,PCP,LD,对于选择抗菌药物-耐药性VS严重性哪个更重要？,PCP,LD,耐药菌感染VS严重感染-PCP和LD告诉我们什么？,观点:-耐药性判断对于合理选择抗菌药物更重要！包括重症感染-即使重症感染,抗感染治疗方案仍需根据病原体及其耐药性评估来制定,经验性抗感染治疗的基本原则耐药背景下的个体化治疗以CAP/HAP为例,22,CravenDE.CurrOpinInfectDis.2006;19:153-160.,TheChangingSpectrumofPneumoniaCAP,HCAP,HAP,Healthcare-associatedpneumoniaisarelativelynewclinicalentitythatincludesaspectrumofadultptswhohaveacloseassociationwithacute-carehospitalsorresideinchronic-caresettingsthatincreasetheirriskforpneumoniacausedbyMDRpathogens.,a.CAP=community-acquiredpneumoniab.HCAP=healthcare-associatedpneumoniac.HAP=hospital-acquiredpneumoniad.VAP=ventilator-associatedpneumonia,H.influenzae,K.pneumoniae,S.pneumoniae,M.pneumoniae,L.pneumophila,C.pneumoniae,Community-acquiredpneumoniainEurope*,*WoodheadM.EurRespJ2002;20:Suppl.36,20-27,病原体排序肺链Spneumoniae非典型病原体atypicals流感嗜血杆菌Hinfuenzae卡他莫拉菌Mcatarrhalis金葡菌Saureus革兰阴性肠杆菌GNB,流感流行后/坏死性肺炎MRSA?,?,?,HistoryofMRSAinU.S.,59,青霉素上市,第一个MRSA菌株出现,HealthcareassociatedMRSA,CA-MRSA,CommunityAcquiredMRSA,IncontrasttotheriseinnosocomialMRSAfrom1990tothepresent,growingawarenessofcommunity-acquiredMRSAhasoccurredthroughpublishedreportsofMRSAoutbreaksforwhichtraditionalriskfactorswerenotidentified.,Necrotizingpneumonia,UnitedStatesandEurope,1980,OutbreakinDetroit,Mich2/3ofpatientswereIVDU,Mid1990s,Childrenw/oidentifiableriskfactors,Late1990s,1998-Athletes/sportsteams1999-NativeAmericans,2000,Prisonandjailpopulations,2003,IVDU=intravenousdrugusers.,GroomAVetal.JAMA.2001;286:1201-1205.HeroldBCetal.JAMA.1998;279:593-598.CDC.MorbMortalWklyRep.2001;50:919-922.,NaimiTSetal.JAMA.2003;290:2976-2984.ZetolaNetal.LancetInfectDis.2005;5:275-286.LevineDPetal.AnnInternMed.1982;97:330-338.CDC.MorbMortalWklyRep.2003;52:793-795.,GilletYetal.Lancet.2002;359:753-759.CDC.MorbMortalWklyRep.1999;48:707-710.,RemainsanuncommoncauseofCAP-CDCsurveillancestudyofinvasiveMRSA1-0.74/100,000-EMERGEncyIDNETStudyGroup(12U.S.ERs)2MRSAaccountedfor2.4%ofallCAP;5%ofICUCAPButhasemergedasacauseofsevereCAPComparedtonon-MRSACAP,patientswere2:Moreill(morelikelytobecomatose,requireintubation,pressorsanddieintheER)MoreCXRabnormalities(multipleinfiltrates,cavitation)Mortalityrate14%(upto50%insomestudies),EpidemiologyofMRSACommunity-AcquiredPneumonia(CAP),1KlevensJAMA2007;298:1763-1771;2MoranCID2012;54:1126-33,ApproachtoEmpiricTherapy:CAP,EmpirictreatmentforMRSAisrecommendedforsevereCAPdefinedby:ICUadmissionNecrotizingorcavitaryinfiltratesEmpyemaDiscontinueempiricRxifculturesdonotgrowMRSA,LiuCID2011;52;285-322,中国社区MRSA流行病学？我们怎么办？,ValentiniAnnofClinMicro2008,CharacterizationofCA-MRSAAssociatedwithSkinandSoftTissueInfectioninBeijing:HighPrevalenceofPVL+ST398,AprospectivecohortofadultswithSSTIbetween2009.012010.08at4hospitalsinBeijing501SSTIpatientswereenrolled-Cutaneousabscess(40.7%);impetigo(6.8%);cellulitis(4.8%)S.aureusaccountedfor32.7%(164/501)-5isolates(5/164,3.0%)wereCA-MRSA-mostdominantSTwasST398(17.6%)-prevalenceofPVLgenewas41.5%(66/159)inMSSA.,王辉PLoSONE,2012;7(6):e38577.,到目前为止CA-MRSA所致CAP尚无报告,EpidemiologyofMRSA,H-MRSAReservoires-hospitals-LTCFs5geneticbackgrouds,H-MRSAincommunity-patientswithriskfactors-contactwithpatientswithriskfactors,Truecommunity-MRSA-nohealthcare-associatedriskfactors-withPVLgenes,healthcare,community,AcquiredOnset,H-MRSA感染危险因素:年龄65岁，严重基础疾病，伤口广谱抗生素使用，住院时间延长，多次住院侵袭性操作（气管插管、切开/植入血管导管）,合理使用抗MRSA药物糖肽类/利奈唑胺,PredictionofMRSAinPatientswithNon-Nosocomialpneumonia,BMCInfectiousDiseases2013,13:370doi:10.1186/1471-2334-13-370,RetrospectivestudyfromJanuary2008toDecember2011.943culture-positiveMRSAandnon-MRSApneumoniaoutsidethehospitalIdentifiedriskfactorsassociatedwithMRSApneumonia.,Community-acquiredpneumoniainEurope*,*WoodheadM.EurRespJ2002;20:Suppl.36,20-27,病原体排序肺链Spneumoniae非典型病原体atypicals流感嗜血杆菌Hinfuenzae卡他莫拉菌Mcatarrhalis金葡菌Saureus革兰阴性肠杆菌GNB,?,?,CAPduetoGNB,ANSORP,2002-2004,912CAP93(10.1%)werecausedbyGNB肠杆菌科-K.pneumoniae(59),Enterobacterspp.(7),S.marcescens(1)非发酵菌-P.aeruginosa(25),A.baumannii(1),Highermorbidityandco-morbiddiseasesSepticshock,malignancy,CVdisease,smoking,hypoNa,dyspneaHighermortality18.3%vs6.1%(p5days)HAP或MDR病原体的危险因素,否,是,窄谱抗菌药物,广谱抗菌药物-针对MDR病原体,HAP初始经验性抗菌药物选择的流程图,ATS.AmJRespirCritCareMed2005;171:388-416,既往90天内曾经使用过抗菌药物住院时间为5天或更长在社区或其他医疗机构抗生素耐药出现的频率高存在HCAP相关危险因素90天内住急性病院两天及以上家庭内输液治疗（含抗生素）30天内有过持续透析家庭外伤治疗家庭成员有耐多药病原体感染免疫抑制性疾病和/或免疫抑制剂治疗,阴性预计值的价值更大,StratificationofHAPPatientsatRiskforMDROrganisms,ThedifferencesnotfirmlysettledAvailabledataindicateinspontaneouslybreathingpts-potentiallydrugresistantmicroorganismsmayplayaminorrole-GNEB(abxsusceptible),Saureus(MSSA)andSpneumoniaeasleadingpathogens,-spontaneouslybreathingVSventilated,EwigS,TorresA,etal.(1999)Bacterialcolonizationpatternsinmechanicallyventilatedpatientswithtraumaticandmedicalheadinjury.Incidence,riskfactors,andassociationwithVAP.AmJRespirCritCareMed159:188198RelloJ,TorresA(1996)MicrobialcausesofVAP.SeminRespirInfect11:2431,MechanicalVentilationIsAssociatedWithaSignificantlyIncreasedIncidenceofRespiratoryTractMRSAInfection,PujolMetal.EurJClinMicrobiolInfectDis.1998;17:622-628.,AprospectivecohortstudyconductedtodefinetheclinicalandepidemiologicalcharacteristicsofMRSAVAPacquiredduringalarge-scaleoutbreakofMRSA,TimefromHospitalization(days),TimefromIntubation(days),Late-onsetHAP,Early-onsetVAP,Late-onsetVAP,Early-onsetHAP,(AmericanThoracicSociety.AmJRespirCritCareMed2005;171:388-416),StratificationofPatientsatRiskforMDROrganisms,-earlyonsetVSlate-onset,Early-onsetLate-onsetpneumoniapneumoniaOthersbasedon(5days)specificrisksS.pneumoniaeP.aeruginosaAnaerobicbacteriaH.influenzaeEnterobacterspp.LegionellapneumophilaS.aureusAcinetobacterspp.InfluenzaAandBEnterobacteriaceaeK.pneumoniaeRSVS.marcescensFungiE.coliOtherGNBS.aureus(MRSA),GNB,Gram-negativebacilli;MRSA,methicillin-resistantS.aureus,AdaptedfromAmJRespirCritCareMed.2005;171:388416.,StratificationofHAPPatientsatRiskforMDROrganisms,-earlyonsetVSlate-onset,-RecentAntibioticTherapyandPseudomonalResistance,TrouilletJLetal.ClinInfectDis.2002;34:1047-1054.,P.aeruginosaVAP:34isolatespiperacillinandmulti-drugresistant;101sensitiveUseofantibiotics(imipenem,thirdgenerationcephalosporinandquinolone)within15daysofVAPincreasedPAresistancetothesameagent-patient-specificabxrotation,aP=.0009bP=.003cP=.001dP=.05,StratificationofPatientsatRiskforMDROrganisms,既往应用抗生素发生CRAB的风险比(OR),KimYJ,etal.JKoreanMedSci.2012May;27(5):471-5.,碳青霉烯使用是IR-MDRAB出现的唯一独立危险因素,YeJJ,etal.PLoSOne.2010Apr1;5(4):e9947,StratificationofPatientsatRiskforMDROrganisms,-RecentAntibioticTherapyandAcinetobacterResistance,RiskFactorsforInfectionsWithMultidrug-ResistantStenotrophomonasmaltophiliainPatientsWithCancer.CANCER。2007；109（12）：2615-22,StratificationofPatientsatRiskforMDROrganisms,-RecentAntibioticTherapyandSmaltophilia,医院获得性肺炎细菌学演变-抗生素选择性压力的体现,早期(Early),中期(Middle),晚期(Late),135101520,肺链,流感嗜血杆菌,MSSAMRSA,肠杆菌科细菌(抗生素敏感)肠杆菌科细菌(抗生素不敏感),肺克,大肠肺克,大肠,铜绿假单胞菌MDRXDRPDR,不动杆菌MDRXDRPDR,嗜麦芽窄食单胞菌,抗生素选择性压力,二代头孢菌素三代头孢菌素/酶抑制剂复合制剂碳青霉烯+抗MRSA,135101520,hospital/ICUadmmission,LOS4d),Early(4d),50,LeadingPathogens,SlideLibrary,TimeofOnset,医院获得性肺炎细菌学演变-抗生素治疗的方向,早期(Early),中期(Middle),晚期(Late),肺链,流感嗜血杆菌,MSSAMRSA,肠杆菌科细菌(抗生素敏感)肠杆菌科细菌(抗生素不敏感),肺克,大肠肺克,大肠,铜绿假单胞菌MDRXDRPDR,不动杆菌MDRXDRPDR,嗜麦芽窄食单胞菌,二代头孢菌素三代头孢菌素/酶抑制剂复合制剂碳青霉烯+抗MRSA酶抑制剂复合制剂,135101520,耐药背景下的个体化抗感染治疗-小结,正确诊断是正确治疗的前提努力实现经验性治疗和目标治疗之统一经验性抗感染治疗的两种能力-评估病原体流行病学/个体化评估/从病原学识别感染性疾病-评估耐药性流行病学基础上的个体化评估耐药菌感染:高龄/基础疾病/近期住院(ICU)/晚发医院感染/抗生素暴露,Nosimplisticpolicy,Homogenousprotocol,Mixing,ThankYou,