最新研究进展.docx

最新研究进展.docx

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最新研究进展

减少ICU中抗生素抵抗病原体发生率的策略

StrategiestoReducetheIncidenceofAntibiotic-ResistantPathogensintheICU

HenryMasur,MD

Introduction

Atthe32ndCriticalCareCongress,strategiestoreducethefrequencyofantibiotic-resistantpathogensreceivedconsiderableattention.MarinH.Kollef,MD,[1]ofWashingtonUniversitySchoolofMedicineinManchester,Missouri,stressedthatineveryintensivecareunit（ICU）,theincidenceofresistanceshouldbecloselymonitored,justasICUsmonitorthefrequencyofself-extubationsanddeepveinthrombosis.Collectingandreviewingdatathatindicatewhatthepathogensareinaunit,andwhattheirantimicrobialsusceptibilityis,mustbethefoundationforanICU'sprogramtoreducetheincidenceofinfectiouscomplications,andtominimizeantibioticresistance.

　AntibioticRotationintheICU

AntibioticRotationintheICU

　　Restrictingantibioticsisoneapproachtominimizingtheincidenceofantibioticresistance,butdecreasingthedurationofantibioticcoursesdeservesemphasisaswell.Cyclingandrotationofantibioticsrepresentattemptstominimizeresistanceagainstoneparticulardrug.Thisstrategycanrestoresusceptibilityoforganismstothatoneparticulardrug.Rahalandcolleagues[2]publishedabefore-and-afterstudyin1998lookingattheincidenceofcephalosporin-resistantextended-spectrumbeta-lactamase-producingKlebsielladuringaperiodoftimewhencephalosporinswerewidelyused.Theyshowedthatrestrictingtheuseofcephalosporinsinfavorofcarbapenemsreducedtheincidenceofcephalosporin-resistantKlebsielladramatically.However,theincidenceofimipenem-resistantPseudomonasincreasedsubstantially.Rahal'sapproachreallyexchangedonetypeofresistanceforanothertypeofresistance.Thisstrategyexchangesonehomogeneousstrategyofantibioticuseforanotherhomogeneousstrategy,ratherthanusingaheterogeneousstrategythatmightnotleadtosomuchresistanceagainstoneclassofdrugs.

　　Scheduledchangesofdrugusemightbeoneapproachtoproducesuchheterogeneity;changesindrugusecouldalsobemadeinresponsetochangesinsusceptibilitypatterns.Dr.Kollef[3,4]hasdonesuchastudy,andfoundadecreaseinincidenceofbacteremiasandnosocomialpneumoniasoverthefirst6monthsafteranantibioticpolicychange.However,hedidnothavedatademonstratingthatthisadvantagepersistedformorethan6months.Landmanandcolleagues[5]didasimilarstudybetween1993and1996thatrestrictedtheuseofcephalosporins,vancomycin,andclindamycininfavorofampicillin-sulbactamandpiperacillin-tazobactam.Theincidenceofcertainpathogenssuchasmethicillin-resistantStaphylococcusaureus（MRSA）declined,buttheincidenceofAcinetobacterresistanttocephalosporinsincreased.Thus,therestrictionstrategiesdonotalwayshavelong-termefficacyintermsofreducingtotalantibioticresistance.

　　Apreferableapproachmightbetomonitorantibioticresistancepatternsinrealtimeandtochangeantibioticusebasedonthesedata.DidierGrusonandcolleagues[6]haveshownthatthisstrategycanimprovepatientoutcomes,probablybyallowingclinicianstouseempiricregimensthatweremorelikelytobeactiveagainsttheoffendingpathogen（ie,allowingquickerinstitutionofactivetherapy）.Astudyreviewing5yearsofexperiencewiththisapproachwillbepublishedshortly.

　　Dr.Kollefsummarizedbyemphasizingthatcyclingorrotatingantibioticscanbebeneficial,butonlyifsuchcyclingispartofastrategyofmonitoringantibioticresistanceandrespondingwiselytochangingpatternsofcausativeorganismsandantibioticsusceptibility.

Dr.Kollefwasaskedduringthequestion-and-answerperiodwhetherthesecyclingstrategies,focusingprimarilyonGram-negativebacilli,couldalsobeusefulforGram-positiveorganisms.Dr.Kollefrepliedthatinthepast,therewerelimitedoptionsfortreatingGram-positivecocci,sothatcyclingwasnotreallyfeasible.However,withtheemergenceoflinezolid,quinupristin-dalfopristin,andperhapsdaptomycin,suchstrategiesarereasonableconsiderations.

　AntibioticUseinSepsis

AntibioticUseinSepsis

　　JonathanCohen,MD,[7]thenspokeaboutantibioticchoiceinsepsis.Itmightseemappropriatetohaveacriticalpathwaythatmandatedthesameantibioticselectionforeverypatientwhowasseptic.Thismonolithicapproachwouldbeconsistent,butwouldnotlikelymaximizeoutcome.Theappropriatechoiceofantibioticforanindividualpatientmayincreaseefficacybyincreasingthelikelihoodthatanactivedrugischosen.Knowledgeofpriorantibiotics,orpriorcolonizingorinfectingorganisms,wouldinfluencedrugselection.Theappropriatechoiceofantibioticmightalsodecreasetoxicitybyavoidingdrugsthatmightexacerbateunderlyingorgandysfunction.Inastudypublishedin1980,Kregerandcoworkers[8]demonstratedthatthechoiceofantibiotictherapythatisactiveagainstthecausativeorganismimprovespatientoutcomecomparedwithpatientswhoreceiveddrugsthatwerenotactiveagainsttheoffendingpathogen,ascliniciansmightintuitivelysuspect.MorerecentstudieshaveconfirmedKreger'sresults.

　　Dr.Cohendescribedtheutilityofatestthathasnotbeenusedformanyyearsinunderstandingoutcome.Laboratorytestscanmeasuretheabilityofantibiotic-containingserumtokillthepatient'spathogen.Thebacteridicaltiterhasbeendefinedastheconcentrationofserumthatkills95%ofaninoculum.Thesetitersassessboththeeffectofhostfactorsandtheeffectoftheantibiotic.Patientswithhigherpeaktitershavebetteroutcomesthanpatientswhohavelowerpeaktiters.However,thisassayisnotterriblypracticalbecauseofwidevariabilityinlaboratorytechniquesandresultingnonreproducibilityofresults.Morerecently,automatedbloodculturesystemsmeasurethehoursuntilgrowthofbacteriaisrecognized.Thistimeisanapproximationofbactericidalactivity.（Thisisalsoasurrogatemarkerforthequantityofcirculatingbacteria,whichisareciprocalconcept.）Theshorterthetimetoculturepositivity,theworsethepatient'sprognosis.Increasingtheamountofantibioticineachspecimen（ie,higherserumantibioticlevels）alsoleadstolongertimetoculturepositivity.

　FocusingDrugAntibioticDeliveryonInfectedTissue

FocusingDrugAntibioticDeliveryonInfectedTissue　　H.ShawWarren,MD,[9]ofMassachusettsGeneralHospitalEastinCharlestown,Massachusetts,describedsomefascinatingworkdesignedtofocusdrugdeliverytotheinfectedtissues.Dr.Warrenusedamikacin,anaminoglycosidethat（unlikegentamicin）hadaconvenientsidechainforbonding,asaligandwiththechemotacticfactorf-met-leu-fe（formyl-methionine-leucine-phenylalanine）.Thisallowedamikacintobedeliveredwithneutrophilstotheareaswherethepathogenicbacteriaelicitedaninflammatoryresponse.Analoguesofthisfactorcanaggregatewithneutrophilswithoutactivatingtheneutrophils.Thereareavarietyoftechnicalproblemsthatmustbesolvedwiththisapproach,buttheprincipleisintriguingandpreliminaryresultsinanimalmodelsarepromising.

　LimitingAntibioticUseintheICU

LimitingAntibioticUseintheICU　　JohnMarshall,MD,[10]ofTorontoGeneralHospitalinToronto,Ontario,Canada,thenfocusedonlimitingtheuseofantibioticsintheICU.Helikenedthestrategiesofantibioticcyclingandotherstrategiesthattakeadvantageofantibioticheterogeneityto"rearrangingthedeckchairsontheTitanic."Theproblemisnotwhichclassofagentisused,itisthatthereistoomuchuseofallantimicrobialagents.Normalmicrobialfloraresistthepropagationofpathogenicorganisms;whenwegiveantibioticsandalterthatnormalflora,wedisrupthomeostasis.Thereareconsiderabledatafrombothanimalandhumanstudiestosupportthisconcept.

　　esummarizedseveralstudiesthatsupportedrelativelyshort-coursetherapyforventilator-associatedpneumonia.Hedetailedonestudythatdemonstratedthatshort-courseantibiotictherapy（3days）inpatientswithnewinfiltratesandatlowriskforpneumonia（CPISscorelessthan6）decreasedtheratesofcolonizationorsuperinfectionwithresistantorganismsinanICU.[11]Asecondstudy[12]demonstratedthatpatientshadahighermortalitywhenantibioticswere　　　　　administeredforclinicalindicationscomparedwithpatientswhohadantibioticsadministeredbystrictandspecificcriteriaobtainedafterinvasivediagnostictestingwithquantitativeculturesfrombronchoscopy.Histake-homemessagewastobelieveobjectivediagnosticresultsandnottostartantibioticsunlessonehasspecificdatatoindicatethereisaninfectionwithapathogenicorganism.

　Once-DailyDosingofAminoglycosides

Once-DailyDosingofAminoglycosides　　EdwardTimm,PharmD,[13]ofAlbanyMedicalCenter,Schenectady,NewYork,reviewedthedatasupportingonce-dailydosingofaminoglycosidesinICUpatients.Heoutlinedtherationaleforsuchaonce-dailydosestrategybyemphasizing3points:

1.Thisstrategytakesadvantageofconcentration-dependentkillingofmicroorganismsandallowsformaximalantibioticefficacy;

2.Thisstrategyminimizesnephrotoxicityandototoxicityandhasanaddedadvantageofdecreasingmedicationerrorsbyusingaconsistentdosethatisnotbasedontheinterpretationofaminoglycosidelevels;and

3.Dollarcostsaredecreasedwhenthecostsofmixingandhangingdrugsmorethanonceadayandthelaboratorychargesincurredwhengettinglevelsareconsidered.

Dr.Timmsuggestedthatonce-dailyaminoglycosidetherapyisappropriateformanypatientpopulations.However,heindicatedthatnotallpatientsarecandidatesforthisdosingregimen.Specifically,therea