产KPC酶肺炎克雷伯菌的文献阅读报告

KPC-ProducingKlebsiella

pneumoniae

andTreatment-----关于产KPC酶肺炎克雷伯菌的文献阅读报告药学部万隽碳青霉烯酶分类碳青霉烯酶的水解能力KPC种类

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

YigitH,QueenanAM,AndersonGJ,etal.AntimicrobAgentsChemother.2008;52(2).Carbapenemases:theVersatileb-Lactamases2006-2008年间我国已报道的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.产KPC酶肺炎克雷伯菌流行病学调查KPC传播--质粒转导Thegeneconferringresistance,blaKPC-1,wasfoundtoresideonalargeplasmidthatwasresponsibleforresistancetothecarbapenems,extended-spectrumcephalosporinsandaztreonam.KPC传播--质粒转导BratuS,MootyN,NichaniSetal.AntimicrobAgentsChemother2005;49:3018–20.KPC传播--质粒转导方式：通过耐药菌性菌毛和敏感菌菌体直接沟通，由耐药菌将耐药质粒边复制边转移给敏感菌。细菌：革兰阴性菌，特别是肠道细菌。临床意义：可造成耐药菌的爆发流行。肠杆菌科－碳青霉烯类CLSI折点的历史演变改良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