感染病患者多重耐药菌感染风险诊断演示文稿

感染病患者多重耐药菌感染风险诊断演示文稿本文档共49页；当前第1页；编辑于星期二\15点2分（优选）感染病患者多重耐药菌感染风险诊断本文档共49页；当前第2页；编辑于星期二\15点2分DiscoveryofAntibacterialAgentsCycloserineErythromycinEthionamideIsoniazidMetronidazolePyrazinamideRifamycinTrimethoprimVancomycinVirginiamycinImipenem19301940

195019601970198019902000PenicillinProntosilCephalosporinCEthambutolFusidicacidMupirocinNalidixicacidOxazolidinonesCecropinFluoroquinolonesNeweraminoglycosidesSemi-syntheticpenicillins&cephalosporinsNewercarbapenemsTrinemsSyntheticapproachesEmpiric

screeningNewermacrolides&ketolidesRifampicinRifapentineSemi-syntheticglycopeptidesSemi-syntheticstreptograminsNeomycinPolymixinStreptomycinThiacetazoneChlortetracyclineGlycylcyclinesMinocyclineChloramphenicol本文档共49页；当前第3页；编辑于星期二\15点2分临床关注的耐药问题

ResistancesofClinicalConcerns革兰阳性细菌金匍菌–

MRSA,VISA,VRSAVRE(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)喹诺酮,头孢菌素,青霉素类,氨基糖苷,碳青霉烯类本文档共49页；当前第4页；编辑于星期二\15点2分InfectionControlAntibioticstewardshipVREMRSAABESBLK.pneumoniaeAntibioticControlandInfectionControl:TheTwoSidesoftheResistance“Coin”RekhaMurthy.ImplementationofStrategiestoControlAntimicrobialResistanceChest2001;119;405-411ControlofAntibioticResistance本文档共49页；当前第5页；编辑于星期二\15点2分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/责任所在本文档共49页；当前第6页；编辑于星期二\15点2分慢性咳嗽和黄痰-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本文档共49页；当前第7页；编辑于星期二\15点2分27-year-oldmanwithacutelymphocyticleukemia.51-year-oldmanwithchronicmyelogenousleukemia.22-year-oldwomanwithadultT-cellleukemia.67-year-oldwomanwithadultT-cellleukemia.61-year-oldmanwithinterstitialfibrosis;patientwasreceivingchlorambucilforchroniclymphocyticleukemia.COP本文档共49页；当前第8页；编辑于星期二\15点2分RapidtestsWhenavailable.Gramstain!!!Startadequateantibioticcoverage(within1hour?)TillouAetal.AmSurg2004;70:841-4DrainpurulentcollectionSamplingIncludinginvasiveprocedureswhenneeded(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本文档共49页；当前第9页；编辑于星期二\15点2分选择哪种抗菌药物

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+本文档共49页；当前第10页；编辑于星期二\15点2分-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SSSSPCP本文档共49页；当前第11页；编辑于星期二\15点2分抗菌谱(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本文档共49页；当前第12页；编辑于星期二\15点2分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

本文档共49页；当前第13页；编辑于星期二\15点2分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]本文档共49页；当前第14页；编辑于星期二\15点2分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

本文档共49页；当前第15页；编辑于星期二\15点2分中国大陆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？本文档共49页；当前第16页；编辑于星期二\15点2分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)

本文档共49页；当前第17页；编辑于星期二\15点2分NoRiskFactors

forMDROsRiskFactors

forMDREnterobacteriaceaeaRiskFactorsfor

MDRPseudomonasHealthcare

contact

NoYes!(eg,recenthospitaladmission,nursinghome,dialysis)withoutinvasiveprocedureYes,Longhospitalizationand/orinfectionfollowinginvasiveprocedures(>5days)RecentAbx

NoYes!(≥14daysinpast90days)Yes!

(≥14daysinpast90days)对Patient

characteristics

Youngfewcomorbidities≥65yrscomorbiditiessuchasTPNorrenalinsufficiencyco-morbiditiessuchasCF,structurallungdisease,advancedAIDS,neutropenia,orothersevereimmunodeficiencyDrugsofchoiceAmoxi/calvAmpicillin/sulb2ndor3rdGFQsPip/tazoCefaperazone/sulbactamertapenemCeftazidinecefepimePip/tazoCefperazone/sulbactamImipenemmeropenemaExceptnonfermenters/non-Pseudomonasspecies.AdaptedfromCarmeliY.Predictivefactorsformultidrug-resistantorganisms.In:RoleofErtapenemintheEraofAntimicrobialResistance[newsletter].Availableat:www.invanz.co.il/secure/downloads/IVZ_Carmeli_NL_2006_W-226364-NL.pdf.Accessed7April2008;DimopoulosG,FalagasME.EurInfect

Dis.2007;49–51;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-NegativePathogens本文档共49页；当前第18页；编辑于星期二\15点2分重症感染≠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PCPLD对于选择抗菌药物-耐药性

VS

严重性哪个更重要？本文档共49页；当前第19页；编辑于星期二\15点2分PCPLD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本文档共49页；当前第20页；编辑于星期二\15点2分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为例本文档共49页；当前第21页；编辑于星期二\15点2分22CravenDE.CurrOpinInfectDis.2006;19:153-160.TheChangingSpectrumofPneumonia

CAP,HCAP,HAP"Healthcare-associatedpneumoniaisarelativelynewclinicalentitythatincludesaspectrumofadultptswhohaveacloseassociationwithacute-carehospitalsorresideinchronic-caresettingsthatincreasetheirriskforpneumoniacausedbyMDRpathogens."PneumoniaCAPaHCAPbHAPc/VAPdMorbidity&MortalityRiskofMDRPathogensa.CAP=community-acquiredpneumoniab.HCAP=healthcare-associatedpneumoniac.HAP=hospital-acquiredpneumoniad.VAP=ventilator-associatedpneumonia本文档共49页；当前第22页；编辑于星期二\15点2分H.influenzaeK.pneumoniaeS.pneumoniaeM.pneumoniaeL.pneumophila

C.pneumoniae本文档共49页；当前第23页；编辑于星期二\15点2分Community-acquiredpneumoniainEurope*病原体社区治疗入院治疗ICU发表的研究数量92313肺炎链球菌19,325,921,7流感嗜血杆菌3,34,05,1军团菌1,94,97,9金匍菌0,21,47,6GNB0,42,77,5肺炎支原体11,17,52鹦鹉热衣原体1,51,91,3病毒11,710,95,1病原学不明49,843,841,5*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?√√√√??本文档共49页；当前第24页；编辑于星期二\15点2分HistoryofMRSAinU.S.‘59青霉素上市第一个MRSA菌株出现HealthcareassociatedMRSACA-MRSACA-MRSA爆发于不同人群儿童中出现没有“经典”危险因素的MRS感染‘98MMWR报告4例健康儿童死于MRSA感染‘99CA-MRSA成为SSTI的主要原因‘04‘05在美国侵袭性MRSA导致18,650死亡

本文档共49页；当前第25页；编辑于星期二\15点2分Community–AcquiredMRSAIncontrasttotheriseinnosocomialMRSAfrom1990tothepresent,growingawarenessofcommunity-acquiredMRSAhasoccurredthroughpublishedreportsofMRSAoutbreaksforwhichtraditionalriskfactorswerenotidentified.Necrotizingpneumonia,UnitedStatesandEurope1980OutbreakinDetroit,Mich2/3ofpatientswereIVDUMid1990sChildrenw/oidentifiableriskfactorsLate1990s

1998-Athletes/sportsteams1999-NativeAmericans2000

Prisonandjailpopulations2003IVDU=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.本文档共49页；当前第26页；编辑于星期二\15点2分RemainsanuncommoncauseofCAP

-CDCsurveillancestudyofinvasiveMRSA1-~0.74/100,000-EMERGEncyIDNETStudyGroup(12U.S.ERs)2

MRSAaccountedfor2.4%ofallCAP;5%ofICUCAPButhasemergedasacauseofsevereCAP

Comparedtonon-MRSACAP,patientswere2:Moreill(morelikelytobecomatose,requireintubation,pressorsanddieintheER)MoreCXRabnormalities(multipleinfiltrates,cavitation)Mortalityrate14%(upto50%insomestudies)EpidemiologyofMRSACommunity-AcquiredPneumonia(CAP)1KlevensJAMA2007;298:1763-1771;2MoranCID2012;54:1126-33本文档共49页；当前第27页；编辑于星期二\15点2分ApproachtoEmpiricTherapy:CAPEmpirictreatmentforMRSAisrecommendedforsevereCAPdefinedby:ICUadmissionNecrotizingorcavitaryinfiltratesEmpyemaDiscontinueempiricRxifculturesdonotgrowMRSA

LiuCID2011;52;285-322中国社区MRSA流行病学？我们怎么办？ValentiniAnnofClinMicro2008本文档共49页；当前第28页；编辑于星期二\15点2分CharacterizationofCA-MRSAAssociatedwithSkinandSoftTissueInfectioninBeijing:HighPrevalenceofPVL+ST398AprospectivecohortofadultswithSSTIbetween2009.01~2010.08at4hospitalsinBeijing501SSTIpatientswereenrolled-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尚无报告本文档共49页；当前第29页；编辑于星期二\15点2分EpidemiologyofMRSAH-MRSAReservoires-hospitals-LTCFs5geneticbackgroudsH-MRSAincommunity-patientswithriskfactors-contactwithpatientswithriskfactorsTruecommunity-MRSA-nohealthcare-associatedriskfactors-withPVLgeneshealthcarecommunityAcquiredOnsetH-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/利奈唑胺本文档共49页；当前第30页；编辑于星期二\15点2分PredictionofMRSAinPatientswithNon-NosocomialpneumoniaBMCInfectiousDiseases2013,13:370doi:10.1186/1471-2334-13-370RetrospectivestudyfromJanuary2008toDecember2011.943culture-positiveMRSAandnon-MRSApneumoniaoutsidethehospitalIdentifiedriskfactorsassociatedwithMRSApneumonia.本文档共49页；当前第31页；编辑于星期二\15点2分Community-acquiredpneumoniainEurope*病原体社区治疗入院治疗ICU发表的研究数量92313肺炎链球菌19,325,921,7流感嗜血杆菌3,34,05,1军团菌1,94,97,9金匍菌0,21,47,6GNB0,42,77,5肺炎支原体11,17,52鹦鹉热衣原体1,51,91,3病毒11,710,95,1病原学不明49,843,841,5*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……√√√√??本文档共49页；当前第32页；编辑于星期二\15点2分CAPduetoGNBANSORP,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,dyspneaHighermortality

18.3%vs6.1%(p<0.001)(Kangetal.EurJClinMicrobiolInfectDis2008;27:657)本文档共49页；当前第33页；编辑于星期二\15点2分PrevalenceofESBL+EnterobacteriaceaeinCAP?+=102/1052＝9.7％Invitroactivitiesofertapenemagainstdrug-resistantSpneumoniaeandotherrespiratorypathogensfrom12AsiancountriesDiagnosticMicrobiologyandInfectiousDisease56(2006)445–450.11/102＝13％91/102＝87％本文档共49页；当前第34页；编辑于星期二\15点2分高龄Advancedage误吸Aspiration护理院Nursinghomeresident(nowHCAP)基础心肺疾病Underlyingcardiopulmonarydisorders

-不包括结构性肺疾病近期抗生素暴露RecentAbx疾病严重性(hintforG–ve/legionella)CAP-革兰阴性杆菌及耐药评估CID2005本文档共49页；当前第35页；编辑于星期二\15点2分CAP-铜绿假单胞菌及耐药性评估-严重结构性肺疾病

severestructurallungdisease,(bronchiectasis,severeCOPD)-近期抗生素暴露

recentantibiotictherapy

-近期住院特别是入住ICU机械通气recentstayinhospital(especiallyintheICUforMV)AdaptedfromMandellLA,etal.ClinInfectDis.2003;37:1405–1433.-易患因素:误吸风险-老年、脑血管病等-临床综合征:吸入性肺炎、坏死性肺炎、肺脓肿、脓胸CAP-厌氧菌评估本文档共49页；当前第36页；编辑于星期二\15点2分氟喹诺酮类的地位?

-左氧氟沙星、莫西沙星、环丙沙星ß-内酰胺类＋新大环内酯类

-肺炎链球菌对大环内酯耐药并不影响其在联合治疗中的地位！

-如何选择ß-内酰胺?

CAP经验性治疗中的两个方案的实践本文档共49页；当前第37页；编辑于星期二\15点2分喹诺酮在CAP治疗中具有重要地位呼吸喹诺酮(RespiratoryFQs)

多重耐药肺链(MDRSP)

非典型病原体

ESBL阴性肠杆菌科细菌

MSSA环丙沙星/大剂量左氧氟沙星

用于铜绿假单胞菌的联合治疗√√√√本文档共49页；当前第38页；编辑于星期二\15点2分氟喹诺酮类的地位ß-内酰胺类＋新大环内酯类（如何选择ß-内酰胺?）-没有PRSP危险因素-青霉素类(!?)

-无需覆盖耐药肠杆菌科、铜绿:

抗肺链为主－酶抑制剂复合制剂－氨苄西林/舒巴坦、阿莫西林/棒酸

头孢菌素呋辛、曲松、噻肟而非哌酮、他啶抗肠杆菌科－优选他啶哌酮然后噻肟、曲松-需覆盖耐药肠杆菌科、铜绿

头孢哌酮/舒巴坦、哌拉西林/他唑巴坦、头孢他啶（铜绿）碳青霉烯（肠杆菌科优选厄他培南、非发酵菌选亚胺培南和美洛培南）本文档共49页；当前第39页；编辑于星期二\15点2分怀疑HAP、VAP或HCAP晚发(>5days)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本文档共49页；当前第40页；编辑于星期二\15点2分StratificationofHAPPatientsatRiskforMDROrganismsThedifferencesnotfirmlysettledAvailabledataindicateinspontaneouslybreathingpts-potentiallydrugresistantmicroorganismsmayplayaminorrole-GNEB(abxsusceptible),Saureus(MSSA)andSpneumoniaeasleadingpathogens-spontaneouslybreathingVSventilatedEwigS,TorresA,etal.(1999)Bacterialcolonizationpatternsinmechanicallyventilatedpatientswithtraumaticandmedicalheadinjury.Incidence,riskfactors,andassociationwithVAP.AmJRespirCritCareMed159:188–198RelloJ,TorresA(1996)MicrobialcausesofVAP.SeminRespirInfect11:24–31本文档共49页；当前第41页；编辑于星期二\15点2分MechanicalVentilationIsAssociatedWithaSignificantlyIncreasedIncidenceofRespiratoryTractMRSAInfectionPujolMetal.EurJClinMicrobiolInfectDis.1998;17:622-628.AprospectivecohortstudyconductedtodefinetheclinicalandepidemiologicalcharacteristicsofMRSAVAPacquiredduringa

large-scaleoutbreakofMRSA本文档共49页；当前第42页；编辑于星期二\15点2分TimefromHospitalization(days)TimefromIntubation(days)Late-onsetHAPEarly-onsetVAPLate-onsetVAPEarly-onsetHAP0123456701234567(AmericanThoracicSociety.AmJRespirCritCareMed2005;171:388-416)StratificationofPatientsatRiskforMDROrganisms-earlyonsetVSlate-onset本文档共49页；当前第43页；编辑于星期二\15点2分Early-onset Late-onsetpneumonia pneumonia Othersbasedon(<5days) (>5days)specificrisksS.pneumoniae P.aeruginosa AnaerobicbacteriaH.influenzae

Enterobacterspp. LegionellapneumophilaS.aureus

Acinetobacterspp.

InfluenzaAandB

Enterobacteriaceae K.pneumoniae RSV

S.marcescens Fungi E.coli

OtherGNB

S.aureus(MRSA)

GNB,Gram-negativebacilli;MRSA,methicillin-resistantS.aureusAdaptedfromAmJRespirCritCareMed.2005;171:388–416.StratificationofHAPPatientsatRiskforMDROrganisms-earlyonsetVSlate-onset本文档共49页；当前第44页；编辑于星期二\15点2分-RecentAntibioticTherapyandPseudomonalResistanceTrouilletJLetal.ClinInfectDis.2002;34:1047-1054.P.aeruginosaVAP:34isolatespiperacillinandmulti-drugresistant;101sensitiveUseofantibiotics(imipenem,thirdgenerationcephalosporinandquinolone)within15daysofVAPincreasedPAresistancetothesameagent-patient-specificabxrotationaP=.0009 bP=.003

cP=.001 dP=.05ResistanceofPaeruginosaStrainsToImipenem,Ceftazidime,orCiprofloxacin,Accordingto

PreviousTherapyWithImipenem,a3rd-generationCephalosporin,oraFluoroquinoloneNo.(%)ofpatients,bypreviousdrugtherapyreceivedImipenemThird-generationcephalosporinFluoroquinoloneStrainresistanceNo(n=114)Yes(n=21)No(n=73)Yes(n=62)No(n=100)Yes(n=35)Toimipenem

19(16.7)

11(52.4) a

12(16.4)

18(29.0)

18(18)

12(34.3) dToceftazidime

17(14.9)

7(33.3)

6(8.2)

18(29.0) b

14(14