產(chǎn)KPC酶肺炎克雷伯菌的文獻(xiàn)閱讀報(bào)告

KPC-ProducingKlebsiella

pneumoniae

andTreatment-----關(guān)于產(chǎn)KPC酶肺炎克雷伯菌的文獻(xiàn)閱讀報(bào)告藥學(xué)部萬雋碳青霉烯酶分類碳青霉烯酶的水解能力KPC種類

KPC-1&KPC-2ArecentcorrectioninthegenesequenceofKPC-1revealedthatKPC-1andKPC-2wereinfactidenticalenzymes;hence,theKPC-1designationisnolongerused.

YigitH,QueenanAM,AndersonGJ,etal.AntimicrobAgentsChemother.2008;52(2).Carbapenemases:theVersatileb-Lactamases2006-2008年間我國已報(bào)道的KPC型碳青酶烯酶1.SrinivasanA,PatelJB.InfectControlHospEpidemiol2008;29:1107–9.

2.BratuS,LandmanD,HaagRetal.ArchInternMed2005;165:1430–5.

3.LomaestroBM,TobinEH,ShangWetal.ClinInfectDis2006;43:e26–8.Dataonhealthcare-associatedinfectionsreportedtotheCDCfrom2007indicatedthat8%ofallKlebsiellaisolateswerecarbapenem-resistantK.pneumoniae(CRKP),incomparisonwith,1%in2000.KPC-producingisolateshavenowbeenreportedfromseveralcountriesoutsidetheUSA.France,China,Sweden,Norway,Colombia,Brazil,Scotland,TrinidadTobago,andPolandhaveallidentifiedpathogensharbouringKPCs.EpidemicsituationshavealsobeenreportedinIsraelandandGreece.產(chǎn)KPC酶肺炎克雷伯菌流行病學(xué)調(diào)查KPC傳播--質(zhì)粒轉(zhuǎn)導(dǎo)Thegeneconferringresistance,blaKPC-1,wasfoundtoresideonalargeplasmidthatwasresponsibleforresistancetothecarbapenems,extended-spectrumcephalosporinsandaztreonam.KPC傳播--質(zhì)粒轉(zhuǎn)導(dǎo)BratuS,MootyN,NichaniSetal.AntimicrobAgentsChemother2005;49:3018–20.KPC傳播--質(zhì)粒轉(zhuǎn)導(dǎo)方式：通過耐藥菌性菌毛和敏感菌菌體直接溝通，由耐藥菌將耐藥質(zhì)粒邊復(fù)制邊轉(zhuǎn)移給敏感菌。細(xì)菌：革蘭陰性菌，特別是腸道細(xì)菌。臨床意義：可造成耐藥菌的爆發(fā)流行。腸桿菌科－碳青霉烯類CLSI折點(diǎn)的歷史演變改良Hodge(MHT)CLSI：M100-S22.P52－60InvitrosusceptibilityTothetetracyclines(i.e

doxycycline),itisimportanttonotethatMIC90valuesareoftenatorneartheCLSIsusceptibilitybreakpoint(4mg/L).

Clinicallyachievabledrugconcentrationsatthesiteofinfectionshouldbetakenintoaccountbeforeusingthisclassofagents.1.BratuS,MootyN,NichaniSetal.AntimicrobAgentsChemother2005;49:3018–20.2.BratuS,TolaneyP,KarumudiUetal.JAntimicrob

Chemother2005;56:128–32.3.CastanheiraM,SaderHS,DeshpandeLMetal.AntimicrobAgentsChemother2008;52:570–3.AsystematicreviewofpublishedstudiesandreportsoftreatmentoutcomesofKPCinfectionsusingMEDLINE(2001–2011）Atotalof38articlescomprising105caseswereincludedintheanalysis.ThemajorityofinfectionswereduetoK.pneumoniae(89%).

Themostcommonsiteofinfectionwasblood(52%),followedbyrespiratory(30%),andurine(10%).

CombinationversusmonotherapyOveralltreatmentfailureratesThreemostcommonantibiotic-classcombinations:polymyxinpluscarbapenem,30%polymyxinplustigecycline,29%polymyxinplusaminoglycoside25%（p=0.6）tripleantimicrobialtherapy（3case）doripenempluspolymyxinBplusrifampin

（1case）

tigecyclinepluscolistinplus

garamycin（2case）Atotalof15papersinvolving55uniquepatientcaseswerereviewed.Tigecyclineandtheaminoglycosideswereassociatedwithpositiveoutcomesinthemajorityofcases.Clinicalsuccessrateswerelowwhenthepolymyxinswereusedasmonotherapy,butweremuchhigherwhentheywereusedincombination.Bloodstreaminfectionscaused

byKPC-producingKlebsiella

pneumoniaeBloodstreaminfectionscaused

byKPC-producingKlebsiella

pneumoniaeBloodstreaminfectionscaused

byKPC-producingKlebsiella

pneumoniaeItisevidentthatKPC-KPBSIsareassociatedwithhighmortalityrates.Itisofnotethatinfectionmortalityamongpatientswhoreceivedcolistin

monotherapyissimilartothatinthosewhoreceivedinappropriateantimicrobialtreatment.Accordingtotheresultsofthemultivariateanalysis,themajorpredictorsofinfectionmortalitywere:

severityofthebaselinecondition（higherAPACHEIIscore）,olderageANDinappropriatetreatment.

Inacohortof41patientswithKPC-Kpneumoni

aebacteremia----

improved28-daymortality.

Themostcommonsuccessfulcombination:apolymyxinincombinationwitheithertigecyclineoracarbapenem.AstudyinthreeItalianhospitals,combinationtherapy,particularlyatriple-drugregimen---improvedsurvival.

Tigecycline+colistin+acarbapenem.Inapreviouspoolof55individualcases，combinationtherapywasassociatedwithsuccessfuloutcomesComparedtomonotherapy,particularly

ifpolymyxinswerepartoftheregimen.Leeetallookedat16patientsfoundthatthreeoftwelvetreatedwithpolymyxin

monotherapy

developedpolymyxinresistanceduringtreatment.CombinationversusmonotherapyInfectionwithPanresistant

Klebsiella

pneumoniae:AReportof2CasesandaBriefReviewoftheLiteratureTigecycline,aglycylcyclineshowntohavepotentinvitroactivityagainstKPCbacteria,isnotapprovedforthetreatmentofblood-streaminfections.

Itsuseinurinarytractinfections(UTIs)isalsoquestionableduetolowconcentrationsfoundintheurine.

ReportsofsuccessfultreatmentofUTIscausedbymultidrug-resistantisolatesutilizingoff-label‘high-dose’tigecycline

(200mgforonedose,then100mgevery12h)havebeenpublished.Theaminoglycosidesmaynotbeoptimalforthetreatmentofabscessesorintra-abdominalinfectionscausedbyKPCbacteriaduetotheirlowpenetrationinacidicenvironments.Pharmacokinetic/pharmacodynamic

considerationshuman-simulatedtreatment:

ertapenemat1gq24hwasaddedtodoripenemat2gq8h(ertapenemistheleastactivecarbapenemagainstKPC,andthus,itisusedasanindicatoragenttoidentifytheorganism.)3CASE

bacteremia(2patients)andurinarytractinfection(1patient)TREATMENT

Ertapenemplusdoripenemormeropenem

CONCLUSIONAllrespondedsuccessfully,withoutrelapseatfollow-up.

(ertapenem'sincreasedaffinityforthecarbapenemaseshinderingdoripenem/meropenemdegradationintheenvironmentofthemicroorganism)1.OmpK35&ompK36

porinconfigurationmayaffectentryofcarbapenems.

2.Carbapenem

MICs

increasedwith

decreasingexpressionofompK36

.

3.IsolatesofKPC-possessingK.

pneumoniaethatexpress

ompK36tendtohavelowerMICsto

carbapenems

BothblaKPCcopynumberanddeletionsintheupstreamgeneticenvironmentaffectthelevelofKPCproductionandmaycontributetohigh-levelcarbapenemresistanceinKPC-producingK.pneumoniae,particularlywhencoupledwithOmpK36porinloss.Colistin-carbapenemcombinationsmayprovideoptimalactivityagainstKPCK.pneumoniae,includingcolistin-resistantisolates.Screeningforporinexp