產(chǎn)KPC酶肺炎克雷伯菌的文獻閱讀報告

KPC-ProducingKlebsiella

pneumoniae

andTreatment-----關于產(chǎn)KPC酶肺炎克雷伯菌的文獻閱讀報告藥學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調查KPC傳播--質粒轉導Thegeneconferringresistance,blaKPC-1,wasfoundtoresideonalargeplasmidthatwasresponsibleforresistancetothecarbapenems,extended-spectrumcephalosporinsandaztreonam.KPC傳播--質粒轉導BratuS,MootyN,NichaniSetal.AntimicrobAgentsChemother2005;49:3018–20.KPC傳播--質粒轉導方式：通過耐藥菌性菌毛和敏感菌菌體直接溝通，由耐藥菌將耐藥質粒邊復制邊轉移給敏感菌。細菌：革蘭陰性菌，特別是腸道細菌。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