從指南談HAP/VAP的初始經(jīng)驗性抗菌治療何禮賢復(fù)旦大學(xué)附屬中山醫(yī)院

CurrentGuidelinesforHAP/VAPinEur&NorthAm●ATS/IDSA2005.AmJRespir

CritCareMed.2005;171(4):388–416●BritishSocietyforAntimicrobialChemotherapy(BSAC)2008.JAntimicrob

Chemother.2008;62(1):5–346●CanadianCriticalCaretrialsgroup(CCCTG)2008..JCritCare.2008;23(1):138–147●AssociationofMedicalMicrobiologyandInfectiousDiseaseCanada(AMMI).CanJInfectDisMedMicrobiol.2008Jan;19(1):19-53●Paul-Ehrlich-Gesellschaft(PEG)2012.Pneumologie.2012;66(12):707–765InfectionandDrugResistance2014:71–7Updateonmanagementoptionsinthetreatmentofnosocomial&ventilatorassistedpneumonia:Reviewofactualquidelinesand

ecnomicaspectoftherapy?多數(shù)指南推薦根據(jù)個體危險因素評估實施初始靜脈抗生素治療（IIAT）。無合并癥患者最常推薦Amp/BI作為一線治療，其次是3-CS,FQs,Ertapenem.?較多合并癥者推薦應(yīng)用Pip/Taz,其次Imi-&Meropenem和4-CS.?更多或嚴重合并癥者有3個指南推薦聯(lián)合治療：Pip/Taz,其次Imi-&Meropenem和4-CS+FQs、AMG或磷霉素.?如果存在MRSA危險因素所有指南均推薦萬古霉素或利奈唑胺。最新試驗認為后者治愈率高于前者，但兩組60天病死率相似.?指南遵從的初始靜脈抗生素治療（GA-IIVAT）費用節(jié)約（?28033Vs36139，p=0.006），LOS縮短（23.9Vs28.3days.p=0.022）。結(jié)論：指南強調(diào)按個體危險因素，準確選擇抗生素，初始靜脈治療，并考慮藥物經(jīng)濟學(xué)結(jié)果。InfectionandDrugResistance2014:71–7InfectDrugResist.2014;7:1–7GruppeI:bis2PunkteSubstanz

Dosierung/Tag(parenteral)EVG EGAmpicillin/Sulbactam 3x3g IaAAmoxicillin/Clavulans?ure 3x2,2g IaACefuroxim 3x1,5g IaBCefotaxim 3x2g IaBCeftriaxon 1x2g IaBLevofloxacin 1x0,5g IaAMoxifloxacin 1x0,4g IaAErtapenem1x1g IaAGruppeII:3bis5PunktePiperacillin/Tazobactam 3x4,5g IaAPiperacillin+Sulbactam 3x4g+3x1gIVBCefepim 3x2gIaADoripenem 3x0,5g IaAImipenem 3x1gIaAMeropenem 3x1gIaAChemotherJ2010;19:179–255德國按危險因素評估分值選擇抗菌治療GruppeIII:6PunkteundmehrSubstanzen

Dosierung/Tag(parenteral)EVEGPiperacillin/Tazobactam

oder 3x4,5g Ia APiperacillin+Sulbactam

oder 3x4g+3x1gIVBCeftazidim

oder 3x2g Ia BCefepim

oder 3x2gIaADoripenem

oder 3x0,5g IaAImipenem

oder 3x1g IaAMeropenem 3x1gIaAjeweils

+Ciprofloxacinoder 3x0,4IVA+Levofloxacin

oder 2x0,5g IVA+Fosfomycin

oder 3x5g IVA+Aminoglykosid

IaCChemotherJ2010;19:179–255德國按危險因素評估分值選擇抗菌治療（續(xù)）Canada:Clinicalpracticeguidelinesforhospital-acquiredpneumoniaandventilator-associatedpneumoniainadults

RecommendationsforantimicrobialtreatmentRandomizedclinicaltrialsdonotshowabenefitofanyregimenoveranotherwiththeexceptionofpooreroutcomeswithceftazidime.Combinationtherapywasnotfoundtobesuperiortomonotherapy.AshortcourseoftherapyofseventoeightdaysshouldsufficeformostcasesofHAPandVAP(C-3andA-1).ItisrecommendedthatcombinationtherapybeusedforthetreatmentofPaeruginosaHAPandVAPformoreprolongedperiodsoftime(14days)(C-3).CombinationtherapyshouldbeprescribedforaseverepresentationofHAPandVAPandstreamlinedbasedoncultureresults(C-3).CanJInfectDisMedMicrobiol.2008January;19(1):19–53.

加拿大指南：HAP分輕、中、重3組

VAP分中、重2組TreatmentofHAP:Group1Noriskfactorsforresistance+mild-moderatepresentationTreatment: 3rdgenerationnon-pseudomonalcephalosporin (eg.ceftriaxone1gq24hIV,cefotaxime1gq8hIV) or4thgenerationcephalosporin(cefepime1-2gq12hIV) OR beta-lactam/beta-lactamaseinhibitor (eg.piperacillin-tazobactam4.5gq8hIV) OR

fluoroquinolone(levofloxacin750mgIVqdormoxifloxacin400mgIVqd)

po

TreatmentofHAP:Group2

●

Riskfactorsforresistance,and/orlateonset+mild-moderatepresentation(Cont’d)

●Treatment: 3rdgenerationnon-pseudomonalcephalosporin(eg.ceftriaxone1gq24hIV,cefotaxime1gq8hIV)or4thgenerationcephalosporin(cefepime1-2gq12hIV) OR

piperacillin-tazobactam4.5gq8hIV ORimipenem500mgq6hIV ORmeropenem500mgq6hIV ORlevofloxacin750mgq24hIVORmoxifloxacin400mgq24hIV+/-

vancomycin1gq12hIVorlinezolid600mgq12hIV

TreatmentofHAP:Group2(cont’d)Treatment(cont’d): ForsuspectedP.aeruginosa: beta-lactam/beta-lactamaseinhibitor(piperacillin-tazobactam4.5gq6hIV) ORantipseudomonalcephalosporin(ceftazidime/cefepime2gq8hIV) ORcarbapenem(imipenemormeropenem1gq8hIV) +

fluoroquinolone(ciprofloxacin400mgq8hIVor750mgBIDpoorlevofloxacin750mgq24hIV/po)Riskfactorsforresistance,and/orlateonset(≥5days)+mild-moderatepresentation(Cont’d) ORaminoglycoside(gentamicinortobramycin5-7mg/kgq24hIVoramikacin15-20mg/kgq24hIV)

Severepresentation(hypotention,needforintubation,rapidprogressionofinffiltratesorendODS,&/orriskfactorforresistanceTreatmentanti-pseudomonalcephalosporin(ceftazidimeorcefepime2gq8hIV)ORbeta-lactam/beta-lactamaseinhibitor(piperacillin-tazobactam4.5gq6hIV)ORcarbapenem(imipenemormeropenem1gq8hIVor1gq8hIV)+

fluoroquinolone(ciprofloxacin400mgq8hIVorlevofloxacin750mgq24hIV)ORaminoglycoside(gentamicinortobramycin5-7mg/kgqdIVoramikacin15-20mg/kgqdIV)+/-

vancomycin1gq12hIVorlinezolid600mgq12hIVifMRSApresentorsuspectedTreatmentof

HAP:Group3TreatmentofVAP:Group4Noriskfactorsforresistance,earlyonset(<5daysofhospitalization)&moderatepresentationTreatment: 3rdgenerationnon-pseudomonalcephalosporin (eg.ceftriaxone1gq24hIV,cefotaxime1gq8hIV) OR4thgenerationcephalosporin(cefepime2gq12hIV) ORbeta-lactam/beta-lactamaseinhibitor (eg.piperacillin-tazobactam4.5gq6hIVORfluoroquinolone(levofloxacin750mgIVqd,

moxifloxacin400mgIVqd)

po

TherapyofVAP:Group5Riskfactorsforantimicrobialresistancepresent,lateonsetand/orseverepresentationTreatment:

ceftazidime2gq8hIVorcefepime2gq8hIV ORimipenem-cilastatin1gq8hIV ORmeropenem1gq8hIV ORpiperacillin-tazobactam4.5gq6hIV+ciprofloxacin400mgq8hIVorlevofloxacin750mgq24hIV ORgentamicinortobramycin5-7mg/kgq24hIVORamikacin15-20mg/kgq24hIV+/-

vancomycin1gq12hIVorlinezolid600mgq12hIVTreatmentofVAP:Group5Riskfactorsforresistancepresent+/-severepresentation(Cont’d)Treatment:

ceftazidime2gq8hIVorcefepime2gq8hIV ORimipenem-cilastatin1gq8hIV ORmeropenem1gq8hIV OR

piperacillin-tazobactam4.5gq6hIV

PLUS

ciprofloxacin400mgq8hIVorlevofloxacin750mgq24hIV OR

gentamicinortobramycin5-7mg/kgq24hIVoramikacin15-20mg/kgq24hIV+/-

vancomycin1gq12hIVorlinezolid600mgq12hIV國家抗微生物治療指南:ESBLs

菌種首選次選備注產(chǎn)ESBLs腸哌拉西林/他唑巴坦，頭孢美唑，亞胺培南/西司他桿菌科細菌頭孢哌酮/舒巴坦,頭孢米諾，汀、美羅培南、

厄他培南頭孢西丁帕尼培南/倍他隆治療有效；體外敏感的環(huán)丙沙星、頭孢他啶、

頭孢吡肟臨床可能有效。人民衛(wèi)生出版社，1912年12月。P.63臨床實踐中的幾個問題單藥治療還是聯(lián)合治療？劑量方案怎樣優(yōu)化？療程多長為宜？降階梯策略是否應(yīng)當摒棄？TapperHilfMendelsonIgraKuikka多藥聯(lián)合治療降低銅綠感染死亡率DoescombinationantimicrobialtherapyreducemortalityinGram-negativebacteraemiaAmeta-analysisLancetInfectDis2004;4:519–27聯(lián)合與單藥治療的隨機試驗參加中心:美、加28個ICU.病例數(shù):740例疑診VAP患者.方法:美羅培南1.0q8h+環(huán)丙0.4q12hVs

美羅培南1.0q8h?結(jié)果:d28病死率RR1.05;95%CI0.78-1.42;P=0.74

住ICU時間住院總時間臨床和細菌學(xué)有效率細菌耐藥率艱難梭菌出現(xiàn)率?亞組分析(銅綠,不動,MDR-GNB，N=56)足夠抗菌治療84.2%Vs18.8%，P<0.001

細菌清除率61.9%Vs29.9%,P=0.05

臨床有效率NS?結(jié)論:1.低危難治性GNB:單藥與聯(lián)合治療結(jié)果相似;2.高危難治性GNB:聯(lián)合治療可以獲得較好細菌學(xué)和臨床療效.NSHeyland

DK,et

al.CritCareMed.2008,36(3):737-744臨床實踐中的幾個問題劑量方案如何優(yōu)化？療程多長為宜？降階梯策略是否應(yīng)當摒棄？Piperacillin-tazobactamDoseOptimizationLodiseetal.Cl