XDR耐藥菌感染的治療策略

XDR耐藥菌感染的治療策略2臨床分離細(xì)菌的分布

--“陰盛陽(yáng)衰”革蘭陰性菌72.6％（57320/78955）革蘭陽(yáng)性菌27.4％（21635/78955）CHINET2014TheGreekViewoftheAppropriateDefinitionsBased

ontheChaosofResistanceMechanismsWHO發(fā)布全球耐藥性細(xì)菌報(bào)告：情況極為嚴(yán)峻！2014年4月，世衛(wèi)組織（WHO）發(fā)布了史上最完整的基于114個(gè)WHO會(huì)員國(guó)資料的《2014全球抗菌藥物耐藥調(diào)查的報(bào)告》報(bào)告顯示：抗菌藥物的廣泛耐藥性，已經(jīng)出現(xiàn)在世界上每一個(gè)角落《Nature》關(guān)注末日危機(jī)：后抗生素時(shí)代即將到來(lái)！“在后抗生素時(shí)代，即使是普通感染和輕傷也有可能致命。而這已經(jīng)不是什么關(guān)于世界末日的幻想故事，這種情況很可能就在二十一世紀(jì)發(fā)生”

耐藥菌的挑戰(zhàn)已經(jīng)成為公共衛(wèi)生的熱點(diǎn)523,000死亡/年

1架巨型噴氣式飛機(jī)墜機(jī)/周在美國(guó)，每年有：世界其他地區(qū)的評(píng)估數(shù)據(jù)與此類似Thetermsusedtodescribetheselevelsarerare(<0.1%),verylow(0.1%to1%),low(>1%to10%),moderate(>10%to20%),high(>20%to50%),veryhigh(>50%to70%),extremelyhigh(>70%).3個(gè)威脅級(jí)別18種耐藥菌10BADBUG,

NODRUG,

NOESKAPEEnterococcusStaphylococcusKlebsiellaAcinetobacterPseudomonasEnterobacter11ProportionofVancomycinResistant(R)Enterococcus

faeciumIsolatesinEU2005-2014年CHINET

VRE檢出率132014年CHINET糞腸球菌(3129株)和屎腸球菌(3312株)的耐藥率（%）屎腸球菌對(duì)抗菌藥的耐藥率高于糞腸球菌，但氯霉素反之。132株VRE中，糞腸球菌12株、屎腸球菌120株可分型101株VRE中，vanA38株（均為屎腸）、vanB40株（10株糞腸+30株屎腸）、 vanM23株（均為屎腸）15ProportionMRSAisolatesinEU200520132005-2014年CHINET金葡菌中MRSA檢出率2014年CHINET

MSSA(4022株)與MRSA(3172株)的耐藥率（%）MRSA對(duì)抗菌藥的耐藥率高于MSSA，但除外復(fù)方磺胺甲噁唑未發(fā)現(xiàn)萬(wàn)古霉素、利奈唑胺和替考拉寧耐藥的菌株。MRSA對(duì)復(fù)方磺胺甲噁唑的耐藥率較低，為7.0%；對(duì)其他均近50%或以上。Untreatableandhard-to-treatinfectionsfromcarbapenem-resistantEnterobacteriaceae(CRE)bacteriaareontheriseamongpatientsinmedicalfacilities.AlmosthalfofhospitalpatientswhogetbloodstreaminfectionsfromCREbacteriadiefromtheinfectionCRE在美國(guó)發(fā)生率：肺炎克雷伯菌11%大腸埃希菌2%ProportionofCarbapenemsResistant(R+I)Klebsiella

pneumoniae

IsolatesinEUCHINET2005～2014CRE的檢出情況

2005-2014年CHINET耐藥監(jiān)測(cè)肺炎克雷伯菌

碳青霉烯類耐藥率（%）2014年CHINET

11308株克雷伯菌屬耐藥率（%）AcinetobacterisolatesresistanttocarbapenemsMYSTIC2004Countriesthathavereportedanoutbreakofcarbapenem-resistantAcinetobacter

baumannii.Redsignifiesoutbreaksreportedbefore2006,andyellowsignifiesoutbreaksreportedsince2006.2005-2014年CHINET耐藥監(jiān)測(cè)不動(dòng)桿菌屬

碳青霉烯類耐藥率（%）year%耐藥率2014年CHINET

8769株不動(dòng)桿菌屬(鮑曼不動(dòng)93.0%)的耐藥率（%）29ProportionofCarbapenemsResistant(R+I)Pseudomonasaeruginosa

IsolatesinEU2005-2014年CHINET耐藥監(jiān)測(cè)銅綠假單胞菌

對(duì)碳青霉烯類的耐藥率（%）2014年CHINET

7471株銅綠假單胞菌耐藥率（%）2014年CHINET

3418株腸桿菌屬細(xì)菌耐藥率（%）AmpCde-repressors(“SPACE”organisms)S:Serratiaspp.P:Providenciaspp.A:Aeromonasspp.C:Citrobacterspp.E:Enterobacterspp.2014年CHINET

35788株腸桿菌科細(xì)菌耐藥率（%）抗菌藥物耐藥敏感替加環(huán)素3.778.3亞胺培南5.392.4美羅培南5.494.0厄他培南5.492.0阿米卡星5.593.3哌拉西林/他唑巴坦7.486.9頭孢哌酮/舒巴坦9.176.5頭孢吡肟22.867.0頭孢他啶27.468.4慶大霉素33.665.0環(huán)丙沙星38.657.72014年CHINET

19967株糖不發(fā)酵菌的耐藥率（%）抗菌藥物耐藥敏感頭孢哌酮/舒巴坦27.253.4阿米卡星29.368.0哌拉西林/他唑巴坦38.952.1環(huán)丙沙星40.955.2頭孢他啶42.851.5美羅培南44.153.1頭孢吡肟44.543.6亞胺培南47.548.9Colistin:ThephoenixarisesStudiesthatprimarilyassessedtheefficacyand/ortoxicityofintravenouspolymyxins多黏菌素臨床有效率57%~>80%，腎及神經(jīng)系統(tǒng)毒性發(fā)生率分別為10%~38%和～7%Worldwidereportsofcolistin

heteroresistanceandresistanceofA.baumannii異質(zhì)性耐藥率為18.7%～100%耐藥率為0%～46.4%Tigecycline

TheObscurePositioninTheRealWorldofMultidrug-ResistanceGlobalinvitroactivityoftigecyclineandcomparatoragents:TigecyclineEvaluationandSurveillanceTrial2004–2013AntimicrobialactivityofantimicrobialagentsagainstAcinetobacter

baumanniicollectedgloballybetween2004-2013

意大利2004-2011年

鮑曼不動(dòng)桿菌敏感性的變化藥物20042005200620072008200920102011替加環(huán)素11212221阿莫西林克拉維酸≥64≥64≥64≥64≥64≥64≥64≥64哌拉西林他唑巴坦≥256≥256≥256≥256≥256≥256≥256≥256頭孢他啶≥64≥64≥64≥64≥64≥64≥64≥64頭孢曲松≥128≥128≥128≥128≥128≥128≥128≥128亞胺培南≥3281616161616美羅培南≥1616≥16≥16≥16≥16阿米卡星≥12864≥128≥128≥128≥128≥128≥128各抗生素對(duì)臨床分離的鮑曼不動(dòng)桿菌體外藥敏試驗(yàn)中MIC90的值（μg/ml）Probabilityoftargetattainment(PTA)

oftigecyclinebyMonteCarlosimulationMICs≤0.25mg/l>99%MICof0.5mg/l:0%and67.98%MIC>0.5mg/l:0cSSSIcIAIMICs≤0.5mg/l100%MICof1mg/l:12.93%and96.6%MIC>2mg/l:0Intheabsenceofnewdrugsonthehorizon,ratherthanusingasinglefixeddosingregimen,tigecyclinedosingneedstobeoptimizedinordertoachievethedesiredsuccessfulclinicalresponseandtopreventanescalationindrugresistance.2000HAPTestArticleAdministration

TigecyclineIV*150mgloadthen75mgq12h

TigecyclineIV*200mgloadthen100q12hImipenem-cilastatinIV**1gq8h

1:1:1Randomization*TigecyclineAdjunctiveRx:ceftazidime2gIVq8handaminoglycoside

(tobramycin7mg/kgdailyoramikacin20mg/kgdaily)**Imipenem-cilastatinAdjunctiveRx:vancomycin15mg/kgIVq12and

aminoglycoside(tobramycin7mg/kgdailyoramikacin20mg/kgdaily)7-14days10-21daysafterLDOTLDOTVisitTOCVisitLDOT:Lastdoseoftherapy;TOC:testofcureDePascaleetal.CriticalCare2014,18:R90DePascaleetal.CriticalCare2014,18:R90Effectivenessandsafetyofhigh-dose(200mgdaily)tigecycline-containingregimensforthetreatmentofseverebacterialinfections8studies(263patients;58%criticallyill):1RCT,4non-randomisedcohortsand3casereportsKlebsiella

pneumoniaewasthemostcommonlyisolatedMostofthedatacomefromcriticallyillpatientswithdifficult-to-treatinfections,includingVAPandcomplicatedintra-abdominalinfections.IntheRCT,responseintheclinicallyevaluablepatientswas85.0%(17/20)inthe100mgevery12h(q12h)groupand69.6%(16/23)inthe75mgq12hgroup(P=0.4).Moreepisodesofdiarrhoea,treatment-relatednauseaandvomitingdevelopedinthehigh-dosegroup(14.3%vs.2.8%,8.6%vs.2.8%and5.7%vs.2.8%,respectively;P>0.05forallcomparisons).Thecohortstudies:Mortalitywithhigh-dosetigecycline(100mgq12h)inthecohortstudiesrangedfrom8.3%to26