Community-Acquired-Pneumonia-(CAP)社區(qū)獲得性肺炎市公開課一等獎省賽

CommunityAcquiredPneumonia(CAP)BradleyK.Harrison,M.D.1/32CAPdefinedPneumonianotacquiredinahospitaloralong-termcarefacilityHospitalacquiredpneumoniaHealthcareassociatedpneumonia:otherhealthcarefacilitiessuchasnursinghomes,dialysiscenters,andoutpatientclinics2/32IntroductionEstimated5.6millioncasesofCAPoccurannuallyintheUnitedStatesEstimatedtotalannualcostforCAPintheUnitedStatesis$8.4billion92%ofcostwithinpatienttherapyBecauseCAPistheonlyacuterespiratorytractinfectioninwhichthereisincreasedmortalityifantibiotictherapyisdelayed,diagnosticandtreatmentdecisionsneedtobemadeaccuratelyandefficientlyMortalityrateamonghospitalizedpatientswithCAPvarieseachyearandcanreach35%3/32EpidemiologyUnclearbecausefewpopulation-basedstatisticsforCAPaloneareavailableCenterforDiseaseControlandPrevention(CDC)combinespneumoniawithinfluenzawhencollectingdataonmorbidityandmortalityIn,influenzaandpneumoniacombinedwerethe7thleadingcasesofdeathintheU.S.Downfrom6thinpreviousyearsDeathrateof21.8per100,000patients4/32ClinicalPresentationPneumoniaisaninflammationorinfectionofthelungsthatcausesthemtofunctionabnormallyClassifiedastypicaloratypical,althoughtheclinicalpresentationsareoftensimilarSeveralsymptomscommonlypresentinpatientswithpneumoniaApproximately20-33%ofepisodesresultinhospitalization5/32EtiologyTypical:upto70%UsuallycausedbyStreptococcuspneumoniaeAtypical:30-40%“MyLungsContainViruses”MycoplasmapneumoniaeLegionellapneumophilaChlamydiapneumoniaeViruses:Influenza,AdenovirusMaybeco-pathogensinothercases6/32SymptomsCough,fever,chills,fatigue,dyspnea,rigors,andpleuriticchestpainDependingonthepathogen,coughmaybepersistentanddry,oritmayproducesputumOtherpresentationsmayincludeheadacheandmyalgiaCertainetiologies,suchaslegionella,alsomayproducegastrointestinalsymptomsSymptomsatpresentationarenotusefulindistinguishingCAPfromrespiratoryillnesseswithothercauses7/32Diagnosis:PhysicalExaminationDullnesstopercussionofchest,cracklesorralesonauscultation,bronchialbreathsounds,tactilefremitus,andegophany(“E”to“A”changes)PatientmayalsobetachypneicPatientswithtypicalpneumoniaaremorelikelytopresentwithdyspneaandbronchialbreathsoundsonauscultation8/32Diagnosis:RadiographyCXR(PAandLateral):AmericanThoracicSociety(ATS)guidelines,“allpatientswithsuspectedCAPshouldhaveachestradiographtoestablishthediagnosisandidentifycomplications(pleuraleffusions,multilobardisease)”Lobarconsolidation–morecommonintypicalpneumoniaBilateral,diffuseinfiltrates–commonlyseeninatypicalpneumoniaHowever,radiologistscannotreliablydifferentiatebacterialfromnonbacterialpneumoniaonthebasisoftheradiographicappearanceIfperformedearlyinthecourseofthedisease,maybenegativeThesensitivityofchestradiographydependsgreatlyonpretestprobability9/3247-year-oldsmokerpresentedafterjustafewhoursofrigorsandproductivecoughDespiteclinicalsignsofrightupperzoneconsolidation,chestx-rayshowedonlyminorabnormalitiesEmpiricaltherapyforcommunity-acquiredpneumoniawasbegun10/3212hourslaterChestx-rayshowedconsolidationintherightupperlobeconsistentwiththeearlierclinicalsignsS.pneumoniaewasisolatedfrombloodculturesThepatientrecoveredfully11/32Diagnosis:Radiography(cont.)CTCTscancouldbeperformedinpatientswithanegativechestradiographwhenthereisahighclinicalsuspicionforpneumoniaCTscan,especiallyhighresolutionCT(HRCT),ismoresensitivethanplainfilmsfortheevaluationofinterstitialdisease,bilateraldisease,cavitation,empyema,andhilaradenopathyThistechnologyisnotgenerallyrecommendedforroutineusebecausethedataforitsuseinCAParelimited,thecostishigh,andthereisnoevidencethatthisimprovesoutcomeThus,achestradiographisthepreferredmethodforinitialimaging,withCTscanorMRIreservedforfurtheranatomicaldefinition12/32Diagnosis:LaboratoryTestsHistorically:WBC,sputumcultures,twosetsofbloodcultures,andurineantigensSputumsamplesareadequateinonly52%ofpatientswithCAP,andonly44%ofthosesamplescontainpathogensLikelyduetoproblemswithretrievingsamplesfromlowerrespiratorytract,previousantibiotics,contaminationfromupperairways,orviraletiologyPositivebloodculturesobtainedinonly5-10%ofpatients,includingthosewithseverediseasePositivebloodculturehasnocorrelationwithseverityofillnessoroutcomeCurrentATSguidelinesrecommendthatpatientshospitalizedforsuspectedCAPreceive2setsofbloodcultures13/32SensitivityandSpecificityofDiagnosticTestsforCAPDiagnostictestsbypathogenSensitivity(%)Specificity(%)Chlamydia

RapidPCR(sputum,BALfluid)30to95>95Serology(fourfoldriseinserum

andconvalescenttiters)10to100-Sputumculture10to80>95Gram-negativerods

SputumGramstain15to10011to100Haemophilusinfluenzae,Moraxellacatarrhalis,

Pneumoniae

SputumcultureDiagnosticyield20to79*Diagnosticyield20to79*Influenza

RapidDFA(sputum,BALfluid)22to7590Legionellapneumophila

DFA(sputum,BALfluid)22to7590PCR(sputum,BALfluid)83to100>95Serumacutetiter10to27>85Urinaryantigen55to90>95Mycoplasmapneumoniae

Antibiotictiters75to95>90Coldagglutinins50to60-PCR(sputum,BALfluid)30to95>95Pneumococcalpneumoniae

Chestradiography(lobarinfiltrate)40?-SputumcultureDiagnosticyield

20to79*Diagnosticyield20to79*SputumGramstain15to10011to100Diagnosisandtreatmentofcommunity-acquiredpneumonia:AmFamPhysician.Feb1;73(3):442-50.

14/32TreatmentInitialtreatmentofCAPisbasedonphysicalexaminationfindings,laboratoryresults,andpatientcharacteristicsAge,chronicillnesses,smokinghistory,historyoftheillnessTherapyforpneumoniaisempiricbecausespecificpathogensusuallyarenotidentifiedatthetimetreatmentisinitiatedPhysiciansshouldbegintheirtreatmentdecisionsbyassessingtheneedforhospitalizationusingapredictiontoolforincreasedmortality,combinedwithclinicaljudgmentPneumoniaSeverityIndex15/32PneumoniaSeverityIndex(PSI)PSIwasderivedandvalidatedaspartofthePneumoniaPatientOutcomesResearchTeam(PORT)prospectivecohortstudyforthepurposeofidentifyingpatientswithCAPatlowriskformortalityThePneumoniaPORTpredictionruleusedaderivationcohortof14,199inpatientswithCAP;itwasindependentlyvalidatedin38,039inpatientswithCAPandin2,287inpatientsandoutpatientsprospectivelyThePSIrulestratifiedadultswithradiographicevidenceofpneumoniaintofiveclassesforriskofdeathfromallcauseswithin30daysofpresentationOnelimitationinthederivationofthisrulewasthatitincludedmostlypatientsseeninahospitalemergencydepartment,andincludedfewoutpatientswhowereevaluatedinaphysician'sofficeandsenthome16/32DemographicsMaleAge(years)FemaleAge(years)?10Nursinghomeresident+10ComorbidillnessNeoplasticdisease+30Liverdisease+20Congestiveheartfailure+10Cerebrovasculardisease+10Renaldisease+10PhysicalexaminationfindingsAlteredmentalstatus+20Respiratoryrate>30breathsperminute+20Systolicbloodpressure<90mmHg+20Temperature<35?C(95?F)or>40?C(104?F)+15Pulserate>125beatsperminute+10LaboratoryandradiographicfindingsArterialpH<7.35+30Bloodureanitrogen>64mgperdL(22.85mmolperL)+20Sodium<130mEqperL(130mmolperL)+20Glucose>250mgperdL(13.87mmolperL)+10Hematocrit<30percent+10Partialpressureofarterialoxygen<60mmHgoroxygenpercentsaturation<90percent+10Pleuraleffusion+10

PneumoniaSeverityIndex(PSI)Pointtotal

RiskRiskclassRecommendedsiteofcareNopredictorsLowIOutpatient≤70LowIIOutpatient71to90LowIIIInpatient(briefly)91to130ModerateIVInpatient>130HighVInpatient17/32Treatment:Outpatientvs.InpatientChoosingbetweenoutpatientandinpatienttreatmentisacrucialdecisionbecauseofthepossibleriskofdeathDecisioninfluencesdiagnostictestingandmedicationchoices,aswellasapsychologicalimpactonpatientsandfamiliesAveragecostInpatient:$7,500Outpatient:$150-350Basedonage,co-morbidities,andtheseverityofpresentingdisease18/32Treatment:Outpatientvs.Inpatient(cont.)Physicianstendtooverestimateapatient’sriskofdeath;manylow-riskpatientscouldbetreatedsafelyasoutpatientsByusingPneumoniaSeverityIndex(PSI),26-31%ofhospitalizedpatientsweregoodoutpatientcandidatesAnadditional13-19%onlyneededbriefhospitalobservationPSIcanserveasageneralguideline,clinicaljudgmentshouldalwayssupersedeprognosticscore19/32Pharmacotherapy:OutpatientConsensusguidelinesATS,InfectiousDiseaseSocietyofAmerica,andCanadianGuidelinesfortheInitialManagementofCommunity-AcquiredPneumoniaEmpiricoraltherapywithmacrolides,doxycycline,oranoralbetalactam(amoxicillin,cefuroxime[ceftin],oramoxicillin/clavulanate[augmentin]),oraflouroquinoloneTherapeuticWorkingGroupoftheCDCUseflouroquinolonessparinglybecauseofresistanceconcernsDurationoftherapyS.pneumoniae:7-10daysoruntilafebrile3daysBacteremic:10-14daysMycoplasma/Chlamydiapneumoniae:10-14days,upto21daysLegionella:10-21days20/32Pharmacotherapy:Outpatient(cont.)SeveralclassesofantibioticsareeffectiveagainstatypicalpathogensC.pneumoniaeandLegionellaspeciesareintracellularorganismsandM.pneumoniaelacksacellwall,betalactamsarenoteffectiveErythromycinandtetracyclinehavebeentraditionalchoicesforatypicalCAPNewermacrolides(azithromycin[zithromax]andclarithromycin[biaxin])havegoodatypicalactivityandaregenerallyarebettertoleratedthanerythromycinDoxycycline(Vibramcyin)iseffective,associatedwithfewergastrointestinalsideeffects,andisalessexpensivealternativeFlouroquinoloneshavedemonstratedexcellentactivityagainstatypicalsandhaveone-dailydosingandexcellentbioavailability21/32Pharmacotherapy:Outpatient(cont.)TheSanfordGuidetoAntimicrobialTherapy–36thEd.CAP,nothospitalized,nocomorbidities*Azithro0.5gPOx1,then0.25gPOQDAzithro-ER2gx1(2g/60mLsingledosebottle)Clarithro500mgPOBIDClarithro-ER1gPOQ24hDoxy100mgPOBID*Alcoholism,bronchiectasis,COPD,IVDU,Post-CVAaspiration,post-obstructionofbronchi,post-viral22/32Pharmacotherapy:Outpatient(cont.)TheSanfordGuidetoAntimicrobialTherapy–36thEd.CAP,nothospitalized,withcomorbiditiesRespiratoryflouroquinoloneGati400mgPOq24h,Gemi320mgPOq24h,Levo750mgPOq24h,Moxi400mgPOq24hTelithro800mgPOq24hAzithro/Clarithro+HDAmox,HDAM-CL,cefdinir,cefpodoxime,cefprozil23/32Pharmacotherapy:InpatientAntibiotictherapyshouldbeinitiatedwithin4hoursofhospitalizationIntravenousbetalactam(cefotaxime[claforan]orceftriaxone[rocephin])plusamacrolideoracombinationofampicillin/sulbactam(unasyn)plusamacrolideorafluoroquinolonealoneAfterclinicallystable(T<100.0,HR<100,RR<24,SBP>90,O2sat>90%)andabletotolerateoralintake,maybeswitchedtooralantibioticsforremainderoftherapySavemoney,earlierdischarge,minimizesriskofnosocomialinfections24/32Pharmacotherapy:Inpatient(cont.)TheSanfordGuidetoAntimicrobialTherapy–36thEd.CAP,hospitalized,NOTinICU,nocomorbiditiesCeftriaxone2gIVq24h+Azithro500mgIVq24hAge>65:Ceftriaxone1gIVq24hCAP,hospitalized,NOTinICU,comorbiditiesGati400mgIVq24h,Levo750mgIVq24h,Moxi400mgIVq24h25/3226/32FlouroquinolonesConservativeuseisrecommendedtominimizeresistancepatternsNewflouroquinolones(levofloxacin,gatifloxacin,moxifloxacin)shouldbeusedonlywhenpatientshavefailedrecommendedfirst-lineregimens,areallergictoalternativeagents,orhaveadocumentedinfectionwithhighlydrug-resistantpneumococci27/32PneumococcalResistanceS.pneumoniaeaccountsfor60-70%ofallbacterialCAPAffectsallpatientgroupsandcanbefatalAlarmingrateofresistancetomanycommonlyusedantibioticsPCNuncommonbefore1990Resistanceclassifiedasintermediateorhigh-levelIntermediate:28%High-level:16%Nation-wide28/32PatternsofResistancetoAntibioticsinNorthAmericaAntibioticResistance(%)Penicillins

Amoxicillin/clavulanate(Augmentin)4.1Penicillin21.3Cephalosporins

Cefepime(Maxipime)0.4Cefprozil(Cefzil)23.9Ceftriaxone(Rocephin)1.9Cefuroxime(Ceftin)24.7Macrolides

Azithromycin(Zithromax)23.0Clarithromycin(Biaxin)26.6Erythromycin28.3Fluoroquinolones

Gatifloxacin(Tequin)0.7Levofloxacin(Levaquin)0.7Moxifloxacin(Avelox)0.4Miscellaneous

Clindamycin(Cleocin)9.2Tetracycline18.8Trimethoprim/sulfamethoxazole(Bactrim,Septra)29.9Vancomycin(Vancocin)0.0AntibioticstestedagainstStreptococcuspneumoniaeisolatesResistanceratesaveragedacrossallpatientgroups29/32Cost-effectiveCareWhenchoosingatreatment,itisessentialtocomparecostsandoutcomesofallrecommendeddrugtherapiesEvaluationshouldleadtoadecisionthatwillmaximizethevalueofhealthcareservices,notsimplyreducethecostsofdrugtherapyOverallcostofeachtherapyshouldbeobtainedbycomparingtheendcostwiththeprobabilityofachievingapositiveoutcome30/32AntimicrobialTherapiesforCAPAgentDosageCostpercourse(generic)CommonadversereactionsCefotaxime(Claforan)Cefpodoxime(Vantin)Cefprozil(Cefzil)Ceftriaxone(Rocephin)Cefuroxime(Ceftin)1gIVeverysixtoeighthours200mgorallytwiceperday500mgorallytwiceperday1gIVevery24hours500mgorallytwiceperday0.75to1.5gIVeveryeighthours$355(330)124(110)192392219oral250to358IVMilddiarrheaRashClindamycin(Cleocin)300mgorallyeverysixhours600mgIVeveryeighthours238(148to168)oral250IVMilddiarrheaAbdominalpainPseudomembranouscolitisRashGatifloxacin(Tequin)Levofloxacin(Levaquin)Moxifloxacin(Avelox)400mgorallyorIVonceperday500mgorallyorIVonceperday400mgorallyonceperday98oral,3