感染病患者多重耐藥菌感染風(fēng)險(xiǎn)診斷

抗感染藥物發(fā)展簡(jiǎn)史1929AlexanderFleming發(fā)現(xiàn)青霉素

HowardFlorey和ErnstChain分離獲得青霉素，用于動(dòng)物試驗(yàn)。青霉素首次用于救治戰(zhàn)傷患者，拯救了許多人的生命1950’s

大量抗生素用于臨床。AposterfromWorldWarII,dramaticallyshowingthevirtuesofthenewmiracledrug,andrepresentingthehighlevelofmotivationinthecountrytoaidthehealthofthesoldiersatwar.現(xiàn)在是1頁\一共有50頁\編輯于星期三DiscoveryofAntibacterialAgentsCycloserineErythromycinEthionamideIsoniazidMetronidazolePyrazinamideRifamycinTrimethoprimVancomycinVirginiamycinImipenem19301940

195019601970198019902000PenicillinProntosilCephalosporinCEthambutolFusidicacidMupirocinNalidixicacidOxazolidinonesCecropinFluoroquinolonesNeweraminoglycosidesSemi-syntheticpenicillins&cephalosporinsNewercarbapenemsTrinemsSyntheticapproachesEmpiric

screeningNewermacrolides&ketolidesRifampicinRifapentineSemi-syntheticglycopeptidesSemi-syntheticstreptograminsNeomycinPolymixinStreptomycinThiacetazoneChlortetracyclineGlycylcyclinesMinocyclineChloramphenicol現(xiàn)在是2頁\一共有50頁\編輯于星期三臨床關(guān)注的耐藥問題

ResistancesofClinicalConcerns革蘭陽性細(xì)菌金匍菌–

MRSA,VISA,VRSAVRE(地理上差別)肺炎鏈球菌

–青霉素和大環(huán)內(nèi)酯耐藥

革蘭陰性細(xì)菌腸桿菌科ESBLs-喹諾酮,頭孢菌素,青霉素類,氨基糖苷類碳青霉烯酶（KPC,NDM-1?）-碳青酶烯耐藥在中國(guó)出現(xiàn)和蔓延非發(fā)酵菌(假單孢菌/不動(dòng)桿菌)喹諾酮,頭孢菌素,青霉素類,氨基糖苷,碳青霉烯類現(xiàn)在是3頁\一共有50頁\編輯于星期三InfectionControlAntibioticstewardshipVREMRSAABESBLK.pneumoniaeAntibioticControlandInfectionControl:TheTwoSidesoftheResistance“Coin”RekhaMurthy.ImplementationofStrategiestoControlAntimicrobialResistanceChest2001;119;405-411ControlofAntibioticResistance現(xiàn)在是4頁\一共有50頁\編輯于星期三經(jīng)驗(yàn)性抗感染治療的基本原則耐藥背景下的個(gè)體化治療理性回歸/責(zé)任所在現(xiàn)在是5頁\一共有50頁\編輯于星期三慢性咳嗽和黃痰-原因哮喘后鼻腔鼻漏病毒感染后氣道高反應(yīng)性胃酸返流吸煙相關(guān)的慢性支氣管炎支氣管擴(kuò)張癥彌漫性泛細(xì)支氣管炎肺泡蛋白沉積癥急性發(fā)熱

-WBC不高/淋巴增高（無感染灶）－病毒！

-WBC增高/中性粒增高/核左移－可能細(xì)菌！－部位/病原體？－原發(fā)性菌血癥？慢性發(fā)熱

－IE、布病、慢性感染灶？結(jié)核病？－非感染性發(fā)熱藥物熱、風(fēng)濕病、惡性腫瘤正確診斷是正確治療的前提發(fā)熱的診斷與鑒別診斷現(xiàn)在是6頁\一共有50頁\編輯于星期三27-year-oldmanwithacutelymphocyticleukemia.51-year-oldmanwithchronicmyelogenousleukemia.22-year-oldwomanwithadultT-cellleukemia.67-year-oldwomanwithadultT-cellleukemia.61-year-oldmanwithinterstitialfibrosis;patientwasreceivingchlorambucilforchroniclymphocyticleukemia.COP現(xiàn)在是7頁\一共有50頁\編輯于星期三RapidtestsWhenavailable.Gramstain!!!Startadequateantibioticcoverage(within1hour?)TillouAetal.AmSurg2004;70:841-4DrainpurulentcollectionSamplingIncludinginvasiveprocedureswhenneeded(BAL…)

合格標(biāo)本進(jìn)行微生物學(xué)檢查開始經(jīng)驗(yàn)性抗感染治療

目標(biāo)治療經(jīng)驗(yàn)性治療和目標(biāo)治療的統(tǒng)一現(xiàn)在是8頁\一共有50頁\編輯于星期三選擇哪種抗菌藥物

感染部位的常見病原學(xué)選擇能夠覆蓋病原體的抗感染藥物

-抗菌譜/組織穿透性/耐藥性/安全性/費(fèi)用考慮藥代動(dòng)力學(xué)/藥效動(dòng)力學(xué)考慮病人生理和病理生理狀態(tài)

高齡/兒童/孕婦/哺乳腎功不全/肝功不全/肝腎功能聯(lián)合不全其它因素

殺菌和抑菌/單藥和聯(lián)合/靜脈和口服/療程

經(jīng)驗(yàn)性抗感染治療－合理選擇藥物

-considerationsinchoosingantibioticforempirictherapy

評(píng)估病原體

-有的而放矢！評(píng)估耐藥性

-到位不越位！病情嚴(yán)重性評(píng)估+現(xiàn)在是9頁\一共有50頁\編輯于星期三-個(gè)體化評(píng)估-特殊修正因子

先期抗菌藥物對(duì)細(xì)菌學(xué)及其耐藥性影響

不同部位感染-病原體的流行病學(xué)從病原學(xué)認(rèn)識(shí)感染性疾病SSSSPCP現(xiàn)在是10頁\一共有50頁\編輯于星期三抗菌譜(coverage)組織穿透性(tissuepenetration)耐藥性(resistance,specificallylocalresistance)－參考代表性資料/依靠當(dāng)?shù)刭Y料安全性(safetyprofile)

－藥物本身/制劑/工藝/雜質(zhì)費(fèi)用/效益(cost/effectiveness)－失敗或副作用致再治療費(fèi)用更高經(jīng)驗(yàn)性抗感染治療－藥物選擇的基本原則現(xiàn)在是11頁\一共有50頁\編輯于星期三評(píng)價(jià)病原體耐藥可能？

是否耐藥菌？

-了解耐藥病原體流行狀況

參考代表性治療/依靠當(dāng)?shù)刭Y料-個(gè)體化用藥-合理用藥的精髓病人來源：社區(qū)、養(yǎng)老院、醫(yī)院高齡、基礎(chǔ)疾病、近期抗菌藥物、近期住院、侵襲性操作、晚發(fā)醫(yī)院感染

現(xiàn)在是12頁\一共有50頁\編輯于星期三S.aureusPenicillin[1944]Penicillin-resistantS.aureus金黃色葡萄球菌耐藥的發(fā)生發(fā)展過程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]現(xiàn)在是13頁\一共有50頁\編輯于星期三評(píng)價(jià)病原體耐藥可能？

是否耐藥菌？

-了解耐藥病原體流行狀況

參考代表性治療/依靠當(dāng)?shù)刭Y料-個(gè)體化用藥-合理用藥的精髓病人來源：社區(qū)、養(yǎng)老院、醫(yī)院高齡、基礎(chǔ)疾病、近期抗菌藥物、近期住院、侵襲性操作、晚發(fā)醫(yī)院感染

現(xiàn)在是14頁\一共有50頁\編輯于星期三中國(guó)大陸ESBL的發(fā)生率%

WangH,ChenM.DiagnosMicrobiolInfectDis,2005,51,201-208CMSS/SEANIR/CARES.year細(xì)菌耐藥監(jiān)測(cè)結(jié)果如何解讀？現(xiàn)在是15頁\一共有50頁\編輯于星期三實(shí)驗(yàn)室藥物敏感性監(jiān)測(cè)的解讀意義-反映了耐藥趨勢(shì)/告誡要謹(jǐn)慎使用抗菌藥物

-影響選擇藥物/考慮耐藥性對(duì)療效的影響不足

-實(shí)驗(yàn)室收集菌株/大型教學(xué)醫(yī)院/ICU

抗生素選擇壓力導(dǎo)致耐藥性高估！-沒有臨床背景資料/不能用于指導(dǎo)個(gè)體化用藥

(年齡、基礎(chǔ)疾病、社區(qū)/醫(yī)院感染、前期抗菌藥物使用情況)

現(xiàn)在是16頁\一共有50頁\編輯于星期三aExceptnonfermenters/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現(xiàn)在是17頁\一共有50頁\編輯于星期三重癥感染≠耐藥菌感染！重癥感染≠革蘭陰性腸桿菌科細(xì)菌感染！肺炎鏈球菌、化膿性鏈球菌、軍團(tuán)菌、肺孢子菌等均可致重癥感染PCPLD對(duì)于選擇抗菌藥物-耐藥性

VS

嚴(yán)重性哪個(gè)更重要？現(xiàn)在是18頁\一共有50頁\編輯于星期三PCPLD耐藥菌感染

VS

嚴(yán)重感染-PCP和LD告訴我們什么？觀點(diǎn):

-耐藥性判斷對(duì)于合理選擇抗菌藥物更重要！

[包括重癥感染]-即使重癥感染,抗感染治療方案仍需根據(jù)病原體及其耐藥性評(píng)估來制定現(xiàn)在是19頁\一共有50頁\編輯于星期三經(jīng)驗(yàn)性抗感染治療的基本原則耐藥背景下的個(gè)體化治療以CAP/HAP為例現(xiàn)在是20頁\一共有50頁\編輯于星期三21CravenDE.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現(xiàn)在是21頁\一共有50頁\編輯于星期三H.influenzaeK.pneumoniaeS.pneumoniaeM.pneumoniaeL.pneumophila

C.pneumoniae現(xiàn)在是22頁\一共有50頁\編輯于星期三Community-acquiredpneumoniainEurope**WoodheadM.EurRespJ2002;20:Suppl.36,20-27病原體排序肺鏈

Spneumoniae非典型病原體

atypicals

流感嗜血桿菌

Hinfuenzae卡他莫拉菌

Mcatarrhalis金葡菌

Saureus革蘭陰性腸桿菌

GNB……流感流行后/壞死性肺炎MRSA?√√√√??現(xiàn)在是23頁\一共有50頁\編輯于星期三HistoryofMRSAinU.S.‘59青霉素上市第一個(gè)MRSA菌株出現(xiàn)HealthcareassociatedMRSACA-MRSACA-MRSA爆發(fā)于不同人群兒童中出現(xiàn)沒有“經(jīng)典”危險(xiǎn)因素的MRS感染‘98MMWR報(bào)告4例健康兒童死于MRSA感染‘99CA-MRSA成為SSTI的主要原因‘04‘05在美國(guó)侵襲性MRSA導(dǎo)致18,650死亡

現(xiàn)在是24頁\一共有50頁\編輯于星期三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.現(xiàn)在是25頁\一共有50頁\編輯于星期三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現(xiàn)在是26頁\一共有50頁\編輯于星期三ApproachtoEmpiricTherapy:CAPEmpirictreatmentforMRSAisrecommendedforsevereCAPdefinedby:ICUadmissionNecrotizingorcavitaryinfiltratesEmpyemaDiscontinueempiricRxifculturesdonotgrowMRSA

LiuCID2011;52;285-322中國(guó)社區(qū)MRSA流行病學(xué)？我們?cè)趺崔k？ValentiniAnnofClinMicro2008現(xiàn)在是27頁\一共有50頁\編輯于星期三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.王輝

PLoSONE,2012;7(6):e38577.到目前為止CA-MRSA所致CAP尚無報(bào)告現(xiàn)在是28頁\一共有50頁\編輯于星期三EpidemiologyofMRSAH-MRSAReservoires-hospitals-LTCFs5geneticbackgroudsH-MRSAincommunity-patientswithriskfactors-contactwithpatientswithriskfactorsTruecommunity-MRSA-nohealthcare-associatedriskfactors-withPVLgeneshealthcarecommunityAcquiredOnsetH-MRSA感染危險(xiǎn)因素:年齡>65歲，嚴(yán)重基礎(chǔ)疾病，傷口廣譜抗生素使用，住院時(shí)間延長(zhǎng)，多次住院侵襲性操作（氣管插管、切開/植入血管導(dǎo)管）合理使用抗MRSA藥物糖肽類/利奈唑胺現(xiàn)在是29頁\一共有50頁\編輯于星期三PredictionofMRSAinPatientswithNon-NosocomialpneumoniaBMCInfectiousDiseases2013,13:370doi:10.1186/1471-2334-13-370RetrospectivestudyfromJanuary2008toDecember2011.943culture-positiveMRSAandnon-MRSApneumoniaoutsidethehospitalIdentifiedriskfactorsassociatedwithMRSApneumonia.現(xiàn)在是30頁\一共有50頁\編輯于星期三Community-acquiredpneumoniainEurope**WoodheadM.EurRespJ2002;20:Suppl.36,20-27病原體排序肺鏈

Spneumoniae非典型病原體

atypicals

流感嗜血桿菌

Hinfuenzae卡他莫拉菌

Mcatarrhalis金葡菌

Saureus革蘭陰性腸桿菌

GNB……√√√√??現(xiàn)在是31頁\一共有50頁\編輯于星期三CAPduetoGNBANSORP,2002-2004,912CAP93(10.1%)werecausedbyGNB腸桿菌科-K.pneumoniae(59),Enterobacterspp.(7),S.marcescens(1)非發(fā)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)現(xiàn)在是32頁\一共有50頁\編輯于星期三PrevalenceofESBL+EnterobacteriaceaeinCAP?+=102/1052＝9.7％Invitroactivitiesofertapenemagainstdrug-resistantSpneumoniaeandotherrespiratorypathogensfrom12AsiancountriesDiagnosticMicrobiologyandInfectiousDisease56(2006)445–450.11/102＝13％91/102＝87％現(xiàn)在是33頁\一共有50頁\編輯于星期三高齡Advancedage誤吸Aspiration護(hù)理院Nursinghomeresident(nowHCAP)基礎(chǔ)心肺疾病Underlyingcardiopulmonarydisorders

-不包括結(jié)構(gòu)性肺疾病近期抗生素暴露RecentAbx疾病嚴(yán)重性(hintforG–ve/legionella)CAP-革蘭陰性桿菌及耐藥評(píng)估CID2005現(xiàn)在是34頁\一共有50頁\編輯于星期三CAP-銅綠假單胞菌及耐藥性評(píng)估-嚴(yán)重結(jié)構(gòu)性肺疾病

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

recentantibiotictherapy

-近期住院特別是入住ICU機(jī)械通氣recentstayinhospital(especiallyintheICUforMV)AdaptedfromMandellLA,etal.ClinInfectDis.2003;37:1405–1433.-易患因素:誤吸風(fēng)險(xiǎn)-老年、腦血管病等-臨床綜合征:吸入性肺炎、壞死性肺炎、肺膿腫、膿胸CAP-厭氧菌評(píng)估現(xiàn)在是35頁\一共有50頁\編輯于星期三氟喹諾酮類的地位?-左氧氟沙星、莫西沙星、環(huán)丙沙星?-內(nèi)酰胺類＋新大環(huán)內(nèi)酯類

-肺炎鏈球菌對(duì)大環(huán)內(nèi)酯耐藥并不影響其在聯(lián)合治療中的地位！

-如何選擇?-內(nèi)酰胺?

CAP經(jīng)驗(yàn)性治療中的兩個(gè)方案的實(shí)踐現(xiàn)在是36頁\一共有50頁\編輯于星期三喹諾酮在CAP治療中具有重要地位呼吸喹諾酮(RespiratoryFQs)

多重耐藥肺鏈(MDRSP)

非典型病原體

ESBL陰性腸桿菌科細(xì)菌

MSSA環(huán)丙沙星/大劑量左氧氟沙星

用于銅綠假單胞菌的聯(lián)合治療√√√√現(xiàn)在是37頁\一共有50頁\編輯于星期三氟喹諾酮類的地位?-內(nèi)酰胺類＋新大環(huán)內(nèi)酯類（如何選擇?-內(nèi)酰胺?）-沒有PRSP危險(xiǎn)因素-青霉素類(!?)

-無需覆蓋耐藥腸桿菌科、銅綠:

抗肺鏈為主－酶抑制劑復(fù)合制劑－氨芐西林/舒巴坦、阿莫西林/棒酸

頭孢菌素呋辛、曲松、噻肟而非哌酮、他啶抗腸桿菌科－優(yōu)選他啶哌酮然后噻肟、曲松-需覆蓋耐藥腸桿菌科、銅綠

頭孢哌酮/舒巴坦、哌拉西林/他唑巴坦、頭孢他啶（銅綠）碳青霉烯（腸桿菌科優(yōu)選厄他培南、非發(fā)酵菌選亞胺培南和美洛培南）現(xiàn)在是38頁\一共有50頁\編輯于星期三懷疑HAP、VAP或HCAP晚發(fā)(>5days)HAP或

MDR病原體的危險(xiǎn)因素否是窄譜抗菌藥物廣譜抗菌藥物-針對(duì)MDR病原體HAP初始經(jīng)驗(yàn)性抗菌藥物選擇的流程圖ATS.AmJRespirCritCareMed2005;171:388-416既往90天內(nèi)曾經(jīng)使用過抗菌藥物住院時(shí)間為5天或更長(zhǎng)在社區(qū)或其他醫(yī)療機(jī)構(gòu)抗生素耐藥出現(xiàn)的頻率高存在HCAP相關(guān)危險(xiǎn)因素90天內(nèi)住急性病院兩天及以上家庭內(nèi)輸液治療（含抗生素）30天內(nèi)有過持續(xù)透析家庭外傷治療家庭成員有耐多藥病原體感染免疫抑制性疾病和/或免疫抑制劑治療陰性預(yù)計(jì)值的價(jià)值更大現(xiàn)在是39頁\一共有50頁\編輯于星期三StratificationofHAPPatientsatRiskforMDROrganismsThedifferencesnotfirmlysettledAvailabledataindicateinspontaneouslybreathingpts-potentiallydrugresistantmicroorganismsmayplayaminorrole-GNEB(abxsusceptible),Saureus(MSSA)andSpneumoniaeasleadingpathogens-spontaneouslybreathingVSventilatedEwigS,TorresA,etal.(1999)Bacterialcolonizationpatternsinmechanicallyventilatedpatientswithtraumaticandmedicalheadinjury.Incidence,riskfactors,andassociationwithVAP.AmJRespirCritCareMed159:188–198RelloJ,TorresA(1996)MicrobialcausesofVAP.SeminRespirInfect11:24–31現(xiàn)在是40頁\一共有50頁\編輯于星期三MechanicalVentilationIsAssociatedWithaSignificantlyIncreasedIncidenceofRespiratoryTractMRSAInfectionPujolMetal.EurJClinMicrobiolInfectDis.1998;17:622-628.AprospectivecohortstudyconductedtodefinetheclinicalandepidemiologicalcharacteristicsofMRSAVAPacquiredduringa

large-scaleoutbreakofMRSA現(xiàn)在是41頁\一共有50頁\編輯于星期三TimefromHospitalization(days)TimefromIntubation(days)Late-onsetHAPEarly-onsetVAPLate-onsetVAPEarly-onsetHAP0123456701234567(AmericanThoracicSociety.AmJRespirCritCareMed2005;171:388-416)StratificationofPatientsatRiskforMDROrganisms-earlyonsetVSlate-onset現(xiàn)在是42頁\一共有50頁\編輯于星期三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現(xiàn)在是43頁\一共有50頁\編輯于星期三-RecentAntibioticTherapyandPseudomonalResistanceTrouilletJLetal.ClinInfectDis.2002;34:1047-1054.P.aeruginosaVAP:34isolatespiperacillinandmulti-drugresistant;101sensitiveUseofantibiotics(imipenem,thirdgenerationcephalosporinandquinolone)within15daysofVAPincreasedPAresistancetothesameagent-patient-specificabxrotationaP=.0009 bP=.003

cP=.001 dP=.05StratificationofPatientsatRiskforMDROrganisms現(xiàn)在是44頁\一共有50頁\編輯于星期三既往應(yīng)用抗生素發(fā)生CRAB的風(fēng)險(xiǎn)比(OR)KimYJ,etal.JKoreanMedSci.2012May;27(5):471-5.碳青霉烯使用是IR-MDRAB出現(xiàn)的唯一獨(dú)立危險(xiǎn)因素YeJJ,etal.PLoSOne.2010Apr1;5(4):e9947StratificationofPatientsatRiskforMDROrganisms-RecentAntibioticTherapyandAcinetobacterResistance現(xiàn)在是45頁\一共有50頁\編輯于星期三RiskFactorsforInfectionsWithMultidrug-ResistantStenotrophomonasmaltophiliainPatientsWithCancer.CANCER。2007；109（12）：2615-22StratificationofPatientsatRiskforMDROrganisms-RecentAntibioticTherapyandSmaltophilia現(xiàn)在是46頁\一共有50頁\編輯于星期三醫(yī)院獲得性肺炎細(xì)菌學(xué)演變-抗生素選擇性壓力的體現(xiàn)早期(Early)中期(Middle)

晚期(Late)135101520肺鏈流感嗜血桿菌MSSAMRSA腸桿菌科細(xì)菌(抗生素敏感)

腸桿菌科細(xì)菌(抗生素不敏感)肺克,大腸肺克,大腸銅綠假單胞菌MDRXDRPDR不動(dòng)桿菌MDRXDRPDR嗜麥芽窄食單胞菌抗生素選擇性壓力

二代頭孢菌素三代頭孢菌素/酶抑制劑復(fù)合制劑碳青霉烯+抗MRSA135