CommunityAcquiredPneumonia

AnnaZemke,MD.PhD.February2017

CaptainoftheMenofDeath

Historical and Regulatory Perspectives on the Treatment Effect of Antibacterial Drugs for Community-Acquired Pneumonia M. Singer, S. Nambiar, T. Valappil, K. Higgins, and S. Gitterman

ObjecCves

ReviewofATS/IDSAguidelinesonCAP(2007)

Interimdevelopments:H1N1fluoutbreak

developmentofRVPswabsdiscoveryofhumanmetapneumoviruschangesinanCmicrobialsuscepCblityremovalofXigrisfromthemarket

AnnaZemkegotaniphone

Case1

65y/omanwithCOPDon3lpmhomeoxygen.Lastadmi[ed14monthsago.NorecentanCbioCcs.Notonhomesteroids.SCllsmoking.

Presentswithcough,increasedoxygenrequirementandleukocytosis(WBC18).

WherewouldyouadmitthispaCent?

RR28,nowon6lpmoxygen,mentalstatusnormal,BUN36,WBC18,Plts150,Temp38.5,normotensive.

ICUadmissiondecision

Majorcriteria:pressors,venClator(strongrec,levelIIevidence)

ORThreeminorcriteria:RR>30,P/FraCo<250,mulClobarinfiltrate,confusion,BUN>20,WBC<4K,Plt<100K,hypothermia,hypotensionrequiringaggressivefluidsresuscitaCon(ATSdefiniConof“SevereCAP”).

WhatdiagnosCctesCngisindicated?

Bloodculturesandsputumsamplesshouldbeobtained.ICUadmissionisanindicaConforLegionellaandPneumoccalUATPleuraleffusionisanindicaConforLegionellaandPneumococcalUATIfintubated,obtainanendotrachealaspirateThoracentesisifpleuraleffusion>5cm

Top5guessforeCology?rhinovirus(8.5%) S.pneumoniae(5%)influenzaAorB(6%) S.aureus(2%)metapneumovirus(4%) M.pneumoniae(2.5%)RSV(3%) L.pneumophila(2%)parainfluenza(3%) Enterobacteriaceae(2%)Coronavirus(2%)

CAPeCology

•  EPICstudy(CDC).ChicagoandNashville2010-2012.

•  EnrolledpaCentsadmi[edwithpneumonia.21%paCentsrequiredICUadmissionand2%died(olderpeople,peopleonventandwhodiedquicklywerelesslikelytobeenrolled).

ECology–part2

Studyintheelderly(>75y/o)from1996-1999admi[edtoICUinBuffaloNY.53%withpathogensdetected.DaviesAJRCCM2001.S.pneumo(19%)Legionella(9%)S.aureus(7%)H.influenza(7%)

TreatmentRecommendaCons

Empirictreatment:potentanCpneumonoccalb-lactamandmacrolide(coverS.pneumoniaeandLegionellasp.)Doesnotnecessarilyapplytopost-influenzapneumonia(increasedriskforS.aureus),peoplewithseverestructurallungdiseaseortheimmunosuppressed.

Wouldyoutreatwithsteroids?

Manysmall-mediumsizedstudies.Metanalysis(Siemieniuk,2015).--noeffectonall-causemortality,possiblemortalitybenefitinthosewithsevereCAP.--reducestheneedformechanicalvenClaCon(RR,0.45)--reducedriskofARDS(RR,0.24.ARR5%,NNT20)--Cmetoclinicalstability(1daysless).--4%ofsubjectswithhyperglycemiarequiringtreatment.

ObjecCve2

IDSA/ATSHAP/VAPGuidelines(2016)

0/44havestrongqualityevidence7/44havemoderatequalityevidence

keepsubtracCng….

Case2:

75y/ofemaleSNFresidentwithischemiccardiomyopathy,pacerplacement,DM,gout,cogniCveimpairment.Admi[edtohospitalarerafall,atrialfibrillaCon.Developsfever,coughandinfiltrateonday3.Getsworse.CondiConC.Intubated.Nowyours.

Bronchoscope?

ShouldpaCentswithsuspectedVAPbetreatedbasedonresultsofinvasivesamplingwithquanCtaCveculture

ORnoninvasivesamplingwithsemiquanCtaCveculture?

Recommendnoninvasivesamplingoverbronchoscopy.

Weakrec,lowqualevidence

Shouldprocalcitonin,CRPorCPISbeusedtodecidewhetherornottostartanCbioCcs?

No!OneofonlytwostrongrecommendaConswithmoderateevidenceintheenCreguideline.NoneofthesetestshaveadequatesensiCvityorspecificitytoimprovedecisionmakingregardingaddiConofanCbioCcs.

ECology?Onedaysurveyofhospitalsin2010:16%S.aureus13%P.aeruginosa12%Klebsiellasp.6.4%Strepsp.5.5%S.maltophilia3.6%A.baumanniiNEJM2014,Magilletal

ShouldyouuseyourlocalanCbiogram?

Really!!!Howcananyonesaynotothis?

AnCbioCcSelecConIYoustartpip-tazo.DoessheneedMRSAcoverageaswell?

1.  PaCentwithriskfactorsforanCmicrobialresistance:--PriorIVanCbioCcsinthelast90days--sepCcshockonpresentaCon--ARDSonpresentaCon--5ormoredaysinpaCent--recentiniCaConofdialysis

OR

2.>10-20%isolatesonyourunitareMRSA

AnCbioCcSelecCon–Part2

Day2:HersputumhasheavyGNRs.She’sonlevophed.Nowwhat?

GuidelinesrecommenddoublecoverageforPseudomonasaeruginosaweakrecommendaCon,verylowqualityevidence.They’ve“limited”theatriskpopulaConto:--sputumwithheavyGNRs--bronchiectasis--sepCcshock--requiringmechanicalvenClaCon

AnCbioCcCoverageIII

SputumculturegrowsPseudomonasaeruginosasuscepCbleonlytocolisCmethate.

VAPduetoGNRsuscepCbleonlytoaminoglycosidesorpolymyxins,theysuggestaddinginhaledagentinaddiContosystemicdelivery.WeakrecommendaCon,verylowqualityevidence.TheyalsosuggestrouCnetesCngforpolymyxinsensiCvityinseungswithahighprevalenceofextensivelyresistantorganisms.

GuidelineRec’sforMDRbugsMRSA vancoorlinezolid(strongrec)

P.aeruginosa,Sonlytoaminoglycoside/polymyxin

IVandinhaleddrug

P.aeruginosa notaminoglycosidemonotherapy(poorlungpenetraCon,nostudiessupporCnguse)

ESBLGNRs getsuscepCbilitytesCng

Acinetobactersp. getsuscepCbilitytesCngcarbapenemoramp/sulbactampolymyxinsdonotaddCgayclineorrifampacinaddinhaledcolsiCmethate

Carbapenem-RGNRs IVandinhaledcolisCmethate

Howlongtotreat?Shehasbeentreatedfor6dayswithpip-tazoforapan-SP.aeruginosa.Afebrilearer2daysoftherapy,hemodynamicsimproved,nowextubated.

•  Guidelinesrecommend7daysoftherapyforallorganisms,includingP.aeruginosa.

•  Strongrec,verylowqualityevidence.•  AdmitsconCnuedtherapyforslowrespondersisreasonable.

DuraConoftherapyGuidelinesarguethatthelongercoursesofabxforPsAtreatmentwastodecreaserecurrencerate.Nochangeinmortality,LOS,duraConofvenClaCon.Subsequentstudieshaven’tconfirmedthebenefit.AlsothedefiniConofrecurrencewasunclearandsubjectsmayhavebeencolonized.Theythenconductedtheirownmetaanalysiswithintheguidelinedocument.TheyDONOTrecommendlongertherapyfornon-fermenCngGNRs(mostlyP.aeruginosa).

VenClatorAssociatedEvents

CDCstatementreleasedJan17,2017VenClator-AssociatedEvent:areraperiodofstabilityyourPEEPorFiO2requirementincreases.

VAEsubtypes

InfecCon-RelatedVAC:worseningoxygenaCon+(feverorleukocytosis)+addiConofanCbioCc.PossibleVenClator-AssociatedPneumonia:VAC+posiCvecultureorlabcerCfiedpurulentsecreConNotethatradiographicfindingsarenotdiscussed.

VAPPrevenCon

Alotofheat,notmuchlight.

Adding“HOB30%”and“CHX”toalotofnotes…

VAPPathogenesisvsProposedPrevenCveStrategies

BacterialcolonizaConoftheoropharynxand/orstomachMicroaspiraConPneumonia

DecreaseMicroaspiraConReduceoralsecreCon

InhibiCngbacterialgrowthinthemouthorstomach

StudiedMethods:

acidifiedenteralfeeds,phytotherapy(ginger),selecCvedigesCvedecontaminaCon,earlyenteralfeeds,postpyloricenteralfeeds,decreasedgastriccontents,probioCcs,ulcerprophylaxis,aerosolizedanCbioCcs,closedsucConingsystems,earlytracheotomy,humdifiers,physiotherapy,PEEP,coatedendotrachealtubes,salinetrachealinstallaCon,selecCveoraldecontaminaCon,paCentposiConing,sinusiCsprophylaxsis,subgloCcaspiraCon,trachealcuffmonitoring.

HospitalMortalityRates

CID2015:60Roquillyetal

WhatisselecCvedigesCvedecontaminaCon?

SOD:selecCveoraldecontaminaConSDD:selecCvedigesCvedecontaminaConCombinaConofPOnonabsorbableanCbioCcsandashortcourseofIVanCbioCcs.Forexample:4daysofIVcefotaximewithoral/topicalapplicaConoftobramycin,colisCnandamphotericinB.

OngoingStudies

25,000subject,clusterrandomizedstudyinCanada,UK,NZ,AUSongoing(SuDDICU).9-naConEuropeanstudy,clusterrandomizaConwithcrossovercomparingSDD,SODandoralchlorhexidine(RGNOSIS).