ICU常見(jiàn)的易發(fā)感染的疾病及其診療思路-M3課件

ICU常見(jiàn)的易發(fā)感染的疾病及其

診療思路JianguoTang

Trauma-Emergency-CriticalCareMedicineCenter(T-E-CCMC)內(nèi)容提要ICU常見(jiàn)的易發(fā)感染的疾病ICU獲得性感染病原特征ICU常見(jiàn)的易發(fā)感染病原學(xué)ICU常見(jiàn)感染抗生素選擇策略ICU常見(jiàn)感染抗生素應(yīng)用要點(diǎn)內(nèi)容提要ICU常見(jiàn)的易發(fā)感染的疾病ICU獲得性感染病原特征ICU常見(jiàn)的易發(fā)感染病原學(xué)ICU常見(jiàn)感染抗生素選擇策略ICU常見(jiàn)感染抗生素應(yīng)用要點(diǎn)75countries1265ICUS13796patients7087(51.4%)infectedpatients9084(71%)receivingantibioticsICUmortalityrate25%(infected)&11%(non-infected)(P<.001)Infectionaccountedfor40%oftotalICUexpendituresSiteofinfectionDistributionofNosocomialInfectionsbySiteinMedical-SurgicalICUinUSInfectControlHospEpidemiol2000;21:510-515.

83%ofepisodesofnosocomialpneumoniawereassociatedwithMV25%VAP27%VAP內(nèi)容提要ICU常見(jiàn)的易發(fā)感染的疾病ICU獲得性感染病原特征ICU常見(jiàn)的易發(fā)感染病原學(xué)ICU常見(jiàn)感染抗生素選擇策略ICU常見(jiàn)感染抗生素應(yīng)用要點(diǎn)ICU感染的病原學(xué)細(xì)菌(G+;G-;厭氧菌)不典型細(xì)菌真菌病毒etc…Mohnarin2011ICU&Non-ICU非ICUICU病原菌%病原菌%大腸埃希菌19.4鮑氏不動(dòng)桿菌20.7肺炎克雷伯菌11.9銅綠假單胞菌

13.3銅綠假單胞菌

11.8肺炎克雷伯菌11.2金黃色葡萄球菌9.7金黃色葡萄球菌9.8鮑氏不動(dòng)桿菌8.8大腸埃希菌7.8陰溝腸桿菌3.6嗜麥芽寡養(yǎng)單胞菌5表皮葡萄球菌3.3屎腸球菌4屎腸球菌3.1表皮葡萄球菌3糞腸球菌2.8洋蔥伯克霍爾德菌2.8嗜麥芽寡養(yǎng)單胞菌2.4陰溝腸桿菌2.218ICUs18-monthstudy105episodesIFIsoccurredin5,561PatientsCandida:16.5cases/1,000admissionsFilamentousfungi:2.3cases/1,000admissionsFilamentousfungi:mainlyinvasivepulmonaryaspergillosisSEMINARSINRESPIRATORYANDCRITICALCAREMEDICINE.2010.31(1):79-86JournalofIntensiveCareMedicine.2010,25(2):78-92MainpathogensinICUEEnterococcus

faeciumE

E.coliSStaphylococcusaureusKKlebsiella

pneumoniaeAAcinetobacter

baumaniiPPseudomonasaeruginosaEEnterobacterspeciesS

Stenotrophomonas

maltophiliaACandidaalbican;AspergillosisESKAPESEAESKAPE2球菌+2真菌+3腸桿菌科+3非發(fā)酵菌Badbugs，NoDrugsNoESKAPE

大腸埃希菌ESBL+肺炎克雷伯菌ESBL+

非ICUICU非ICUICU200965.573.84564.1201068.668.541.979201171.9/48.2/

MRSAMRSCoN

非ICUICU非ICUICU200954.372.48095.4201048.979.464.273.9201147.978.982.290.4Mohnarin2009-2011ICU&Non-ICUMohnarin2011ICU&Non-ICU

銅綠假單胞菌體外藥敏比較ICU獲得性感染病原特征G-60-65%;G+35-40%;Fungal15-25%SEAESKAPEICU:non-fermentingAntimicrobial-ResistanceorganismsinICU內(nèi)容提要ICU常見(jiàn)的易發(fā)感染的疾病ICU獲得性感染病原特征ICU常見(jiàn)的易發(fā)感染病原學(xué)ICU常見(jiàn)感染抗生素選擇策略ICU常見(jiàn)感染抗生素應(yīng)用要點(diǎn)ThepathogensofcommonHAIPneumonia(oftenventilator-associatedpneumonia,VAP)Catheter-associatedurinarytractinfection(UTI)Bloodstreaminfection(BSI)Intra-abdominalinfection(IAI)中國(guó)16家大型教學(xué)醫(yī)院HAP臨床調(diào)查(599例分離到694株菌)病原菌菌株數(shù)%病例數(shù)Sort鮑曼不動(dòng)桿菌17529.221銅綠假單胞菌12520.872金黃色葡萄球菌7712.853肺炎克雷伯桿菌589.684白色念珠菌355.845嗜麥芽窄食單胞菌274.516大腸埃希菌203.347陰溝腸桿菌132.178醋酸鈣不動(dòng)桿菌40.6720其他不動(dòng)桿菌屬81.3412不動(dòng)桿菌屬占所有病例數(shù)31.23%；占總GNB的38.56%致病原分離情況

早發(fā)性HAPvs遲發(fā)性HAPESBL53.1%ESBL37.5%ThepathogensofcommonHAIPneumonia(oftenventilator-associatedpneumonia,VAP)Catheter-associatedurinarytractinfection(UTI)Bloodstreaminfection(BSI)Intra-abdominalinfection(IAI)ClinicalInfectiousDiseases2004;39:309–171995-2002Nosocomialbloodstreamisolates(SCOPEStudy)ClinicalInfectiousDiseases2004;39:309–17NosocomialBloodstreamIsolates(SCOPEStudy)9.8%23.2%67.0%ThepathogensofcommonHAIPneumonia(oftenventilator-associatedpneumonia,VAP)Catheter-associatedurinarytractinfection(UTI)Bloodstreaminfection(BSI)Intra-abdominalinfection(IAI)MicrobiologyofPeritonitis1.LarocheM,HardingG.EurJClinMicrobiolInfectDis.1998;17:542-550.2.BariePS.JChemother.1999;11:464-477.B.fragilisgroupClostridiumspp.EnterococciS.EpidermidisMRSAPseudomonas+A.baumanniiCandidaB.fragilisgroupClostridiumspp.

E.coliKlebsiellaspp.StreptococcusEnterococcusspp.CandidaE.coliKlebsiellaspp.Streptococcusspp.Tertiary(Polymicrobial)2Secondary(Polymicrobial)1,2Primary(Monomicrobial)1S.anginosus?Copyright2005gbf.de/AllrightsreservedE.coli?Copyright2005/AllrightsreservedB.fragilis?Copyright2005/AllrightsreservedS.epidermidis?Copyright2005/Allrightsreserved最初1-4周病原特征MicrobiologyofCA&HCA-IAI1.LarocheM,HardingG.EurJClinMicrobiolInfectDis.1998;17:542-550.2.BariePS.JChemother.1999;11:464-477.Enterobacterspp.Pseudomonas+A.baumanniiEnterococcusspp.MRSACandidaE.coliStreptococcusHCA/HA-IAICA-IAIS.anginosus?Copyright2005gbf.de/AllrightsreservedE.coli?Copyright2005/AllrightsreservedB.fragilis?Copyright2005/AllrightsreservedS.epidermidis?Copyright2005/AllrightsreservedThepathogensofcommonHAIPneumonia(oftenventilator-associatedpneumonia,VAP)

非發(fā)酵菌、金葡菌、腸桿菌科Catheter-associatedurinarytractinfection(UTI)

ESBL+腸桿菌科、腸球菌、念珠菌Bloodstreaminfection(BSI)

G+、G-、念珠菌Intra-abdominalinfection(IAI)

繼發(fā)/第三類(lèi)型/院內(nèi)：非發(fā)酵/腸桿菌科、腸球菌、念珠菌內(nèi)容提要ICU常見(jiàn)的易發(fā)感染的疾病ICU獲得性感染病原特征ICU常見(jiàn)的易發(fā)感染病原學(xué)ICU常見(jiàn)感染抗生素選擇策略ICU常見(jiàn)感染抗生素應(yīng)用要點(diǎn)ICU常見(jiàn)感染抗生素選擇策略細(xì)菌耐藥與抗生素選擇策略不同耐藥菌抗生素選擇策略MDR(多)-XDR(泛)-PDR(全)MDR

isdefinedasnon-susceptibilitytoatleastoneagentin3ormoreantimicrobialcategories[allpenicillinsandcephalosporins(includinginhibitorcombinations),fluroquinolones,andaminoglycosidesXDRisdefinedasnon-susceptibilitytoatleast1agentinallbut2orfewerantimicrobialcategories(i.e.bacterialisolatesremainsusceptibletoonlyoneortwocategories).PDRisdefinedasnon-susceptibilitytoallagentsinallantimicrobialcategories(i.e.noagentstestedassusceptibleforthatorganism)JGlobInfectDis.2010Sep–Dec;2(3):291–304耐藥機(jī)制酶：水解酶或鈍化酶或修飾酶靶位改變(如核糖體和核蛋白)(Targetalteration)：點(diǎn)發(fā)生突變使抗生素?zé)o法結(jié)合發(fā)揮作用或被修飾使之與抗生素的結(jié)合不緊密主動(dòng)外排泵機(jī)制(Effluxpumps)

細(xì)菌細(xì)胞膜膜孔蛋白發(fā)生改變(Outermembraneporins:OMP)

細(xì)菌菌膜(Biofilm)的形成，使抗生素?zé)o法進(jìn)入胞內(nèi)的耐藥機(jī)制水解酶或鈍化酶

NEnglJMed.2010;362:1804-13膜孔蛋白

NEnglJMed.2010;362:1804-13靶位改變

NEnglJMed.2010;362:1804-13PBP外排泵

NEnglJMed.2010;362:1804-131940s2000sPenicillinsNarrow-spectrumcephemsExpanded-spectrumcephemsCarbapenemsAmpC-typeβ-lactamasesExtended-spectrumβ-lactamases(ESBLs)CarbapenemasesPenicillinasesBroad-spectrumβ-lactamases水解酶或鈍化酶b-lactamaseβ-LactamasesandantibioticsKoreanjinternmed.2012,27:128-242A類(lèi)B類(lèi)D類(lèi)?β-Lactamasesandantibioticsβ-LactamasesOptionsESBL?-lactam/?-lactamaseinhibitorCarbapenemsColistin

Tigecyclline

Amikacin？

Fosfomycin？CefamycinsAmpC4-generationcephalosporinsCarbapenemasesCeftazidime(Dcategories)？

Aztreonam(BcategoriesOXA)？ICU常見(jiàn)感染抗生素選擇策略細(xì)菌耐藥與抗生素選擇策略不同耐藥菌抗生素選擇策略感染？病原菌G+orG-orFungalG+G-腸桿菌科非發(fā)酵菌耐藥評(píng)估、危險(xiǎn)因素評(píng)估嚴(yán)重程度感染部位？FungalCandidaAspergillosisStaphyl-ococcusEntero-coccusLocalecology感染？病原菌G+orG-orFungalG+G-腸桿菌科非發(fā)酵菌耐藥評(píng)估、危險(xiǎn)因素評(píng)估嚴(yán)重程度感染部位？FungalCandidaAspergillosisStaphyl-ococcusEntero-coccusMakeyourempiricalantibioticsmoreappropriated

-腸桿菌科頭霉素、磷霉素、阿米卡星、替加環(huán)素、多粘菌素？NEnglJMed.2010,362;1804-13碳青霉烯不敏感腸桿菌科體外藥敏實(shí)驗(yàn)MarianaC,etal.AAC.2008:570-573Makeyourempiricalantibioticsmoreappropriated

-

PDR-肺克/大腸多粘菌素替加環(huán)素亞胺培南/美洛培南劑量/輸注時(shí)間磷霉素利福平氟喹諾酮氨基糖苷米諾環(huán)素、多西環(huán)素

聯(lián)合用藥替加環(huán)素+多粘菌素替加環(huán)素+磷霉素替加環(huán)素+氨基糖苷類(lèi)碳青霉烯類(lèi)+氨基糖苷類(lèi)碳青霉烯類(lèi)+多粘菌素碳青霉烯類(lèi)+喹諾酮類(lèi)感染？病原菌G+orG-orFungalG+G-腸桿菌科非發(fā)酵菌耐藥評(píng)估、危險(xiǎn)因素評(píng)估嚴(yán)重程度感染部位？FungalCandidaAspergillosisStaphyl-ococcusEntero-coccusMDR/XDR/PDR?CRPA?CRAB?Makeyourempiricalantibioticsmoreappropriated

-非發(fā)酵菌MDR/XDR/PDR?CRPA?CRAB?Makeyourempiricalantibioticsmoreappropriated

-非發(fā)酵菌-銅綠假單胞菌抗假單胞菌青霉素類(lèi)哌拉西林/他唑巴坦、哌拉西林、替卡西林/克拉維酸抗假單胞菌頭孢菌素類(lèi)頭孢哌酮/舒巴坦、頭孢他啶、頭孢吡肟、頭孢哌酮、氨曲南碳青霉烯類(lèi)美羅培南、亞胺培南氨基糖苷類(lèi)阿米卡星、妥布霉素、慶大霉素氟喹諾酮類(lèi)環(huán)丙沙星、左氧氟沙星

-磷霉素

-其他抗生素：多粘菌素B\E多為聯(lián)合或上述藥過(guò)敏而選用厄他培南：對(duì)非發(fā)酵菌無(wú)效；替加環(huán)素：對(duì)銅綠無(wú)效Makeyourempiricalantibioticsmoreappropriated

-非發(fā)酵菌-鮑曼不動(dòng)桿菌CurrentOpinioninInfectiousDiseases2010,23:332–339NEnglJMed.2010,362;1804-13CRAB:

Colistin

Sulbactam6g/dayIncreaseto9g/day

Tigecycline

Meropenam1-2g@3hq8h

Imipenam.5-1g@3hq8h+rifampin/minocycline/doxycycline/azithromycin藥物方案劑量（菌株及嚴(yán)重程度）舒巴坦單用/聯(lián)合4g/d，可增至6~8g，分3~4次（國(guó)外）頭胞哌酮/舒巴坦單用/聯(lián)合3g（2:1）q8h或q6h碳青霉烯類(lèi)單用/聯(lián)合IMP或MP1gq8h或q6hCNS中MP可加至2gq8h多西環(huán)素聯(lián)合100mgq12h靜脈或口服氨基糖苷類(lèi)（丁卡）聯(lián)合15~20mg/kg/d（國(guó)外）0.6/d（國(guó)內(nèi)）嚴(yán)重感染且腎功能正常加至0.8/d多粘菌素E聯(lián)合2.5~5mg/kg/d或200~400萬(wàn)u，分2~4次替加環(huán)素聯(lián)合100mg首劑，以后50mgq12h2011年《中國(guó)鮑曼不動(dòng)桿菌感染診治與防控專(zhuān)家共識(shí)》Makeyourempiricalantibioticsmoreappropriated

-非發(fā)酵菌-鮑曼不動(dòng)桿菌Makeyourempiricalantibioticsmoreappropriated

-非發(fā)酵菌-鮑曼不動(dòng)桿菌感染？病原菌G+orG-orFungalG+G-腸桿菌科非發(fā)酵菌耐藥評(píng)估、危險(xiǎn)因素評(píng)估嚴(yán)重程度感染部位？FungalCandidaAspergillosisStaphyl-ococcusEntero-coccusExpandedoff-labelindicationsofnewestantimicrobialagentsforresistantGPCDrugSSTIUTIBSIHAP/CAPIEB/JIEye/CNSIAANotesLinezolid√√E.F√

NotCR-BSIDaptomycin√⊙√X√XNotPneu↓CSFTigecycline√?⊙X√CAP⊙X√N(yùn)otHAP(esp.VAP)Serumcon?CSF?TeicoplaninX↓CSFVancomycin√√√√√√√IDSA√VREMICCreep感染？病原菌G+orG-orFungalG+G-腸桿菌科非發(fā)酵菌耐藥評(píng)估、危險(xiǎn)因素評(píng)估嚴(yán)重程度感染部位？FungalCandidaAspergillosisStaphyl-ococcusEntero-coccusMayoClinProc.2011;86(8):805-817InvasiveCandidiasisICU常見(jiàn)感染抗生素選擇策略細(xì)菌耐藥與抗生素選擇策略

ESBL/AmpC/Carbapenemases不同耐藥菌抗生素選擇策略腸桿菌科非發(fā)酵菌：銅綠/鮑曼

G+FungalCandida/aspergillosis內(nèi)容提要ICU常見(jiàn)的易發(fā)感染的疾病ICU獲得性感染病原特征ICU常見(jiàn)的易發(fā)感染病原學(xué)ICU常見(jiàn)感染抗生素選擇策略ICU常見(jiàn)感染抗生素應(yīng)用要點(diǎn)AntimicrobialtherapyforsevereHAIGetitrightthefirsttimeHithardupfrontBroad-spectrumantibiotics(appropriatespectrum)Shortperiod/durationDe-escalationorstoppedPk-PdindividualizationIndicationsandbesttimingforstartingantibiotictherapyEmergentUrgentDelayedAntimicrobialtherapyforsevereHAIGetitrightthefirsttimeHithardupfrontBroad-spectrumantibiotics(appropriatespectrum)Shortperiod/durationDe-escalationorstoppedPk-PdindividualizationMakeyourempiricalantibioticsmoreappropriatedHostcharacteristicsThesiteofinfectionKnowledgeoflocalecologyTheseverityofthediseaseMDR?Severity?CoverG+?Antifungal?De-escalation?Fungal?AntimicrobialtherapyforsevereHAIGetitrightthefirsttimeHithardupfrontBroad-spectrumantibiotics(appropriatespectrum)

Shortperiod/duration

（8d&15d）

De-escalationorstoppedPk-PdindividualizationPredetermineddurationofantibiotictherapybyIDSAguidelinesAntimicrobialtherapyforsevereHAIGetitrightthefirsttimeHithardupfrontBroad-spectrumantibiotics(appropriatespectrum)

Shortperiod/durationDe-escalationorstoppedPk-PdindividualizationAlgorithmforde-escalationdecision-makingatday3inanimprovingpatientCritCareClin.2011,27:149-162CritCareClin.2011,27:149-162AntimicrobialtherapyforsevereHAIGetitrightthefirsttimeHithardupfrontBroad-spectrumantibiotics(appropriatespectrum)

Shortperiod/durationDe-escalationorstoppedPk-PdindividualizationInterrelationshipamongPk-PdVargheseJM,etal.CritCareClin.2011,27:19-34Pk&PdparametersofantibioticsonaC-TcurveRobertsJA,etal.Pharmacokineticissuesforantibioticsinthecriticallyillpatient.CritCareMed.2009,37:840-851.Pharmacodynamic

propertiesRobertsJA,etal.Pharmacokineticissuesforantibioticsinthecriticallyillpatient.CritCareMed.2009,37:840-851.KillcharacteristicsT-DT-D(moderate-prolongedT1/2orPAE)C-DC-D(moderate-prolongedT1/2orPAE)Antibioticsβ-lactamsCarbapenemsAztrecnamErythromycinClarithromycinLincosamidesClindamycinLinezolidTigecyclineLinezolidQuinupristin/dalfopristinAzithromycinTetracyclinesGlycopeptidesTigecyclineAminoglycosideMetronidazoleTelithromycinDaptomycinColistinFluoroquinolonDaptomycinPk-PdT>MICAUC/MICCmax/MICAUC/MICT-D:Time-dependent;C-D:Concentration-dependentPk-PdofnewestantimicrobialagentsforresistantGPCDrugClassDosageEliminationDoseadjustmentProteinbindingT1/2VdLinezolidOxazolidinone600mg12hH65%Non-enzyme30%(R)NDoseafterDialysis31%4-6h0.8L/kg(40-50L)TigecyclineGlycylcyclines100mgIV,50mgq12hBiliary60%R20-40%(Unchanged)H-Y71-89%36h10L/kgDaptomycin

Lipopeptide4–6mg,-10mg/kgqdR78%R-Y92%8-9h0.1L/kg