Pneumococcalpneumoniainadults

Authors
ThomasJMarrie,MD
ElaineITuomanen,MD
SectionEditor
DanielJSexton,MD
DeputyEditor
AnnaRThorner,MD
Contributordisclosures
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Mar2016.|Thistopiclastupdated:Sep22,2014.
INTRODUCTIONOftheapproximatelyfourmillioncasesofpneumoniaeachyearintheUnited
States,thepneumococcus(Streptococcuspneumoniae)isthemostcommonagentleadingto
hospitalizationinallagegroups[1].Formanydecades,bacteremicpneumococcalpneumoniahas
accountedfor9to18casesper100,000adults[13].(See"Epidemiology,pathogenesis,and
microbiologyofcommunityacquiredpneumoniainadults".)
Ageneraloverviewofpneumococcalpneumoniawillbepresentedhere.Theepidemiology,
microbiology,diagnosis,andtreatmentofcommunityacquiredpneumoniaarediscussedseparately.
(See"Diagnosticapproachtocommunityacquiredpneumoniainadults"and"Epidemiology,
pathogenesis,andmicrobiologyofcommunityacquiredpneumoniainadults"and"Treatmentof
communityacquiredpneumoniainadultsintheoutpatientsetting"and"Treatmentof
communityacquiredpneumoniainadultswhorequirehospitalization".)
EPIDEMIOLOGYAlthoughS.pneumoniaeisthemostcommoncauseofcommunityacquired
pneumonia(CAP),manystudieshavereportedisolationoftheorganisminonly5to18percentof
cases.Therateofisolationincreaseswhenmoreinvasivemethodsareusedforobtainingspecimens,
suchastranstrachealaspiration,whicheliminatescontaminatingoropharyngealflora[2].Itiscurrently
believedthatmanyculturenegativecasesofCAParecausedbypneumococcus.Thefollowing
observationssupportthisbelief:
Thesputumcultureisnegativeinabout50percentofpatientswithconcurrentpneumococcal
bacteremia[4].
Adiscriminantfunctionalanalysis,inwhichcasesofunknownetiologywereevaluatedaccordingto
theclinicalcharacteristicsofS.pneumoniae,Mycoplasmapneumoniae,orotherorganisms,predicted
thatthemajorityofcaseswereduetopneumococcus[5].
Amajorityofcasesofunknownetiologyrespondtotreatmentwithpenicillin[3].
StudiesusingtranstrachealaspirationshowhighyieldsofS.pneumoniae.
S.pneumoniaeaccountsfor66percentofbacteremicpneumonias[6].
Therehasbeenaresurgenceofoutbreaksofpneumococcalpneumonia,particularlyinchroniccare
facilitiesandinvolvingantibioticresistantstrains.Inonereport,forexample,pneumococcalpneumonia
developedin11of84residentsofanursinghome,threeofwhomdied[7
].Thestrain,whichcolonized
23percentoftheresidentsofthefacilityandsomestaffmembers,wasresistanttomultipleantibiotics,
includingpenicillinandcefotaxime.
Riskfactors
InfluenzainfectionInfluenzainfectiongreatlypredisposestosecondarypneumococcalpneumonia
[8].Thisisdiscussedindetailseparately.(See" Clinicalmanifestationsofseasonalinfluenzain
adults",sectionon'Secondarybacterialpneumonia'.)
AlcoholabuseAlcoholabusewasassociatedwithanincreasedriskofinfectionwithS.pneumoniae
inaprospectiveanalysisof1347patientshospitalizedwithCAP[9].TheassociationbetweenS.
pneumoniaeandalcoholismappliedtobothcurrentalcoholics(dailyalcoholintake>80ginmenor>60
ginwomen)andformeralcoholabusers(1yearofabstinence).
SmokingInvasivepneumococcaldiseasewasassociatedwithcigarettesmoking(oddsratio[OR]
4.1,95%CI2.47.3)andwithpassivesmokeexposure(OR2.5,95%CI1.25.1)inacasecontrol
study[10].Adoseresponserelationshipwasdemonstrablefornumberofcigarettessmokedperday,
packyearsofsmoking,andtimesincequitting.
COPDandasthmaPatientswithchronicobstructivepulmonarydisease(COPD)haveincreased
ratesofhospitalizationduetopneumococcalpneumonia[11].Thereareconflictingdataregardingthe
riskamongpatientswithasthma.Inacasecontrolstudy,patientswithasthmahadatwofoldincrease
inriskforinvasivepneumococcaldiseasecomparedwithnonasthmatics[12],althoughinaseparate
cohortstudy,asthmaticsdidnothaveincreasedratesofhospitalizationforpneumococcalpneumonia
[11].(See' Riskfactors'aboveand"Invasivepneumococcal(Streptococcuspneumoniae)infections
andbacteremia",sectionon'Riskfactorsforinfection'.)
HyposplenismorsplenectomySeveralsplenicfunctionsprotectthehostagainstinfectionwith
encapsulatedorganisms,includingpneumococcus[13].Thesefunctionsincludetheroleofthespleen
inantibodyproduction,activationofthealternativecomplementpathway,andphagocytosisof
unopsonizedparticulatematter.
Surgicalremovalofthespleen(fortrauma,diseasestaging,ortherapeutic)orfunctionalhyposplenism
(sicklecelldisease,thalassemia,lymphoproliferativediseases,bonemarrowtransplantation,andtotal
irradiation)increasetheriskforoverwhelmingpneumococcalinfection[14].Patientswithdisease
involvingthereticuloendothelialsystemareatgreaterriskthanthosewhounderwentsplenectomyfor
traumaticinjury.Allpatientswhohaveundergonesplenectomyshouldreceivepneumococcalvaccine.
Ifsplenectomyisperformedasanelectiveprocedure,pneumococcalvaccineshouldbeadministered
atleasttwoweeks,andpreferablyonemonth,priortotheprocedure.(See"Preventionofsepsisinthe
asplenicpatient".)
ImmunocompromiseThereisa50to100foldincreaseininvasivepneumococcaldiseaseamong
personsinfectedwithHIV[15,16].ForHIVinfectedpatientswhowerevaccinatedwithconjugatedS .
pneumoniaepolysaccharidevaccineinchildhood,therehasbeenadecreaseininvasivepneumococcal
diseasecausedbyvaccineserotypesbutanincreaseindiseaseduetononvaccineserotypes[17].The
incidenceofinvasivepneumococcaldiseaseinHIVinfectedindividualsremainssignificantlyhigher
thaninnonHIVinfectedpersonsdespitethewidespreaduseofhighlyeffectiveantiretroviraltherapy
[18].
Othercausesofimmunocompromisearealsoassociatedwithincreasedriskforpneumococcal
disease.Forpatientswithprimaryimmunodeficiencysyndromes,riskisgreatestforthosewithBcell
defects[19].Otherconditionsinclude:
Multiplemyeloma[20,21]
Systemiclupuserythematosus[22]
Transplantrecipients[2 325]and,inparticular,bonemarrowtransplantrecipientswithchronic
graftversushostdisease[26]
OtherfactorsAdditionalriskfactorsinclude[2730]:
Homelessness
Incarceration
Pregnancy
Crackcocaineuse
Weldingasanoccupation,especiallyifthewelderisatobaccosmoker[3 1]
AntibioticresistanceResistanceofS.pneumoniaetomultipleantibioticsisanincreasinglyimportant
clinicalproblem.Adiscussionofpneumococcaldrugresistanceispresentedseparately.(See
"ResistanceofStreptococcuspneumoniaetobetalactamantibiotics"and"Resistanceof
Streptococcuspneumoniaetothemacrolides,azalides,lincosamines,andketolides"and"Resistance
ofStreptococcuspneumoniaetothefluoroquinolones,doxycycline,and
trimethoprimsulfamethoxazole".)
Areportoftheemergenceofvancomycintoleranceinthepneumococcusisadisturbingevent,as
vancomycinisconsideredtheantibioticoflastresortforthisorganism[32].
NasopharyngealcolonizationPneumococciareacquiredbyaerosolinhalation,leadingto
colonizationofthenasopharynx.Colonizationispresentin40to50percentofhealthyadultsand
persistsforfourtosixweeks[33].Carriagemayinvolvemorethanoneserotypeatatime.Disease
occursmostfrequentlyuponacquisitionofaserotypedifferentfromthosewithwhichanindividualmay
becolonized[34].Pneumococcalcarriageismorecommoninsmokersthannonsmokers[35].
Colonizationwithpneumococcusismorecommoninchildrenthanadults[36,37],andyoungchildren
areresponsibleforthemajorityofnewserotypesintroducedintoahousehold[38].Asymptomatic
pneumococcalcolonizationinchildrenhasbeenimplicatedasareservoirforpenicillinor
antibioticresistantstrains[39].However,someresistantstrainsdonotappeartobeeasilytransmitted
toadults,asillustratedinastudyfromakibbutzinIsrael[40].Serotypingandpulsedfieldgel
electrophoresistodeterminetherelatednessofpneumococcididnotfindthatchildrenindaycare
centerspassedtheirresistantstrainstotheirparentsorotheradultsinthekibbutz.
ProlongedcoursesofantibioticsmayincreasethelikelihoodofcolonizationwithantibioticresistantS.
pneumoniae.Asanexample,astudyevaluatedtheriskofcarriageofpenicillinnonsusceptible
pneumococciinchildrenreceivinga5daycourseofhighdoseamoxicillinversusastandard10day
regimenofamoxicillinforthetreatmentofrespiratorytractinfections[41].Theriskofcarriageofstrains
thatwerenotsusceptibletoeitherpenicillinortrimethoprimsulfamethoxazolewaslowerinthegroup
receivingtheshortercourseofhighdoseamoxicillintheoverallriskofcarriageofnonsusceptible
strainswasincreasedinbothgroupsthatreceivedantibioticscomparedwithbaseline.
Althoughchildrenaremorefrequentlycolonizedthanadults,outbreaksofpneumococcalpneumoniain
nursinghomeshavedemonstratedhighratesofnasopharyngealcarriageamongresidents[7].

CLINICALMANIFESTATIONSClassically,thepatientwithpneumococcalpneumoniabecomesill
abruptlywithfever,chills,cough,andpainintheside,oftensosevereastolimitrespiratory
movements.Thisclassicalpresentation,however,typicallyoccursinyoungerpatients.W ithincreasing
ageofthepopulation,olderpatientsmorefrequentlydeveloppneumococcalpneumoniaandexhibit
fewersymptoms[49].
Tachypneaandincreasingsystemictoxicityfollowinitialsymptomonset.Thedegreeofdistressisnot
directlyrelatedtotheextentofpulmonarypathology,suggestingthathypoxiaisnotthecauseofthese
symptoms,althoughhypoxiaandcyanosismaydevelopinseverecases.
Presentationmaydifferforpatientswithandwithoutbacteremia.Inamulticenterstudy,56patients
withbacteremicpneumococcalpneumonia(BPP)werecomparedwith394patientswith
communityacquiredpneumonia(CAP)andnegativebloodcultures.TheBPPpatientswereyounger
(55.6yearsversus63.4years),hadahighermeanoraltemperatureatpresentation,higherpulserate,
andmorebandformsoncompletebloodcount(CBC22.1percentbandversus14.2percent).Thetime
fromonsetofsymptomsuntiladmissiontohospitalwasshorterforBPPpatients,4.63.7daysversus
7.013.9days[50].
Pneumococcalpneumoniamaypresentatypically,especiallyinolderadultswhereconfusionordelirium
maybeaninitialmanifestation[51].Infrequently,jaundicemayoccur,leadingthecliniciantosuspect
hepatobiliarydisease[52].
Theclassicdescriptionofthesputuminlobarpneumococcalpneumoniais"rusty,"duetomixedblood
cellsandhemoglobininthesputum,asdescribedina1939textbyHeffron[5 3].
Auscultatoryfindingsofralesandbronchialbreathsoundsarelocalizedtotheinvolvedsegmentor
lobe.Thesefindingsmaydisappearattheheightofconsolidationandreappearonresolution(redux
crepitus).Consolidationisassociatedwithphysicalfindingsofdullnessonpercussion,bronchialbreath
sounds,egophony,andwhisperedpectoriloquy.
Inadditiontoclassiclobarpneumonia(alveolarinfectionleadingtoconsolidationofthegreaterpartor
allofoneormorelobes,typicallywithairbronchograms),pneumococcicancausebronchopneumonia
(infectionofthebronchiwithamoresegmentalpatternandwithoutairbronchograms).Theprevalence
ofthesetwodiseasepatternsdiffersbyserotype,suggestingthatunderlyingpneumococcal
componentsmaycontributetovariationsindiseaseprogression.Lobarpneumoniaisassociatedwith
serotypes1,2,3,5,7,and8,andbronchopneumoniaisassociatedwithserotypes3,7,8,10,18,and
20inadults[42].Inamulticenterinternationalstudyof844patientsfrom10countries(theUnited
States,SouthAfrica,Sweden,Spain,NewZealand,Taiwan,Argentina,Brazil,HongKong,and
France),serotypes14,4,6,and3werethemostcommon,indecreasingorderofprevalence[54].
SpectrumofillnessPneumococcalpneumoniamaycausemilddisease,butthereisawiderangein
severity,includingpatientswithoverwhelmingsepsisinwhomthemortalityratemaybegreaterthan25
percent[55].However,forthosewhosurvivetheinfection,thereisusuallycompleterecoveryofnormal
pulmonaryfunction.
Ascoringsystemhasbeendefinedtocategorizeseverityofillnessinpatientswithpneumonia,based
ondemographicfactors,comorbidity,andfindingsfromphysicalexaminationandlaboratoryand
radiographicstudies[56].PatientsinclassesIthroughIIIareatlowriskfordeathorcomplications,
withincreasingmortalityratesforclassesIVandV.Applyingthisscoringsystemtoaseriesof158
patientswithpneumococcalpneumonia(including65bacteremicpatients),29percentwereclassIV
with2percentmortality,and15percentwereclassVwith30percentmortalityinonestudy[5 7].Intwo
otherstudiesofhospitalizedpopulations,slightlyover50percentofpatientswerecategorizedin
classesIVorV[27,58].

DIAGNOSISThehistory,physicalfindings,andthefindingofanopacityonchestradiographusually
establishthediagnosisofpneumonia.Althoughlobarconsolidationissuggestiveofbacterial
pneumonia,radiographscannotreliablydifferentiatebacterialfromnonbacterialpneumonia[3 ].(See
"Diagnosticapproachtocommunityacquiredpneumoniainadults".)
SputumGramstainandcultureItisoftendifficulttodeterminethemicrobiologiccauseof
pneumonia.Asanexample,anetiologicagentwasidentifiedin51percentof154patientswith
communityacquiredpneumonia(CAP)requiringhospitalization[68]andin49percentofpatientswith
CAPtreatedonanambulatorybasis[69].
Twoproblemscontributetothedifficultyinidentifyinganorganism:15to30percentofpatientsare
unabletoproduceasputumspecimenandapproximately25percentofpatientshavereceived
antibioticspriortoproducingaspecimen[2,3,70].Inonestudy,amongpatientswithbacteremic
pneumococcalpneumoniawhohadbeentreatedwithantibioticsforover24hoursbeforesubmittinga
sputumsample,theGramstainwaspositiveinoneofsevensamples,andculturepositiveintwoof
sevensputumsamples[71].Forpatientswhohadnotbeenpreviouslytreatedandwhowereableto
produceasputumsample(n=51),Gramstainsuggestedpneumococcalinfectionin63percent.
Fortheseandotherreasons,theutilityofsputumGramstainandcultureremainsasourceof
controversy,andmostpatientswithcommunityacquiredpneumoniaaretreatedempirically.
Nevertheless,whenapropersputumsampleisobtained,aGramstainmaygiveimmediateetiologic
informationandisuseful.Thefindingofapredominantorganism(eg,grampositivediplococci)may
supporttheetiologyofthepneumoniaaspneumococcus(picture1).(See"Diagnosticapproachto
communityacquiredpneumoniainadults".)
The2007InfectiousDiseasesSocietyofAmerica/AmericanThoracicSociety(IDSA/ATS)guidelines
forthetreatmentofCAPrecommendbloodculturesforpatientswithCAPrequiringadmissiontothe
hospitalunderthefollowingcircumstances[72]:
Intensivecareadmission
Cavitaryinfiltrates
Leukopenia
Activealcoholabuse
Chronicsevereliverdisease
Asplenia
Positivepneumococcalurineantigentest
Pleuraleffusion
Inthepreantibioticera,about25percentofpatientswithlobarpneumoniahadbloodculturespositive
forS.pneumoniae[73].Currently,6to10percentofpatientsrequiringhospitalizationfortreatmentof
CAParebacteremic,and60percentoftheseareduetoS.pneumoniae[3].
PneumococcalurinaryantigenTheneedforimprovedspeedandaccuracyinthediagnosisof
pneumoniahasledtothedevelopmentofaurinaryassayforpneumococcalcellwallcomponents[74].
ThereportedsensitivityoftheBinaxNOWurinaryassayrangesfrom70to90percent,witha
specificityof80to100percentinadultswithpneumonia[75,76].Thespecificityislowerinthesetting
ofnasopharyngealcarriagewithoutinfection[75]andappearstobeincreasedinpatientswith
bacteremiaorsevereinfection[76].Inaprospectivestudythatincluded171adultshospitalizedwith
CAPcausedbyS.pneumoniae,themajorityofwhomdidnothaveS.pneumoniaeisolatedfromblood
cultures,thesensitivityofthepneumococcalurinaryantigenwas71percentandthespecificitywas96
percent[77].AmongpatientswithadefinitediagnosisofpneumococcalCAP,thesensitivityofurinary
antigentestingwas78percentcomparedwith57percentinthosewithaprobablediagnosis.Adefinite
diagnosiswasdefinedasS.pneumoniaeisolatedfromabloodcultureorpleuralfluidcultureor
detectedbypolymerasechainreaction(PCR)frompleuralfluid,whereasaprobablediagnosisrequired
S.pneumoniaetobethepredominantorganisminagoodqualitysputumsamplewithanaccompanying
positiveGramstain.PneumococcalCAPwasdiagnosedexclusivelybytheurinaryantigentestin75
cases(44percent).Theresultsoftheurinaryantigentestledclinicianstoreducethespectrumof
antibioticsin41of474patientswithCAP(9percent).Thisstudysuggeststhat,althoughthesensitivity
ofthepneumococcalurinaryantigentestislowerinpatientswhoarenotbacteremic,thepresenceofa
positiveurinaryantigentestinanonbacteremicpatientcanbehelpfulfortailoringtherapy.
The2007IDSA/ATSguidelinesforthemanagementofCAPrecommenduseofthepneumococcal
urinaryantigeninthefollowingcircumstances[72]:
Intensivecareadmission
Failureofoutpatientantibiotictherapy
Leukopenia
Activealcoholabuse
Asplenia
Pleuraleffusion
FuturedirectionsPolymerasechainreactiontestsfordetectingpneumococcalautolysinor
pneumolysinhavebeendeveloped[74,78].However,noneofthesetestshasyetbeenproventobe
sufficientlysensitiveorspecifictohavebeenadoptedfordiagnosticuse[7 8,79].

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