Microbiology and Treatment of Acute Apical Abscesses - Clinical

19 Pages·2013·1.57 MB·English

Microbiology and Treatment of Acute Apical Abscesses
JoséF.Siqueira,Jr.,IsabelaN.Rôças
DepartmentofEndodonticsandMolecularMicrobiologyLaboratory,EstáciodeSáUniversity,RiodeJaneiro,Brazil
SUMMARY..................................................................................................................................................255
INTRODUCTION............................................................................................................................................255
THEDISEASEPROCESS.....................................................................................................................................256
ComplicationsStemmingfromAcuteApicalAbscesses.................................................................................................256
MICROBIOLOGYOFACUTEAPICALABSCESSES ..........................................................................................................257
MicrobiologyDiagnosticMethods.......................................................................................................................257
Culture.................................................................................................................................................257
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Molecularmethods....................................................................................................................................257
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MicrobialDiversityinAcuteApicalAbscesses............................................................................................................258 w
Gram-negativebacteria................................................................................................................................258 n
Gram-positivebacteria.................................................................................................................................259 lo
As-yet-uncultivatedphylotypes.......................................................................................................................261 a
Pyrosequencinganalysisofabscesssamples..........................................................................................................262 d
e
BacterialSpeciesandAcuteInfections:IsThereaSingleCulprit?........................................................................................262 d
TheCommunity-as-PathogenConcept..................................................................................................................263 f
Bacterialcommunitypatternsrelatedtoacuteinfections.............................................................................................263 ro
GeographicDifferencesintheAbscessMicrobiota......................................................................................................264 m
THEHOSTSIDEOFTHESTORY.............................................................................................................................264
h
FACTORSINFLUENCINGTHEDEVELOPMENTOFACUTEINFECTION.....................................................................................265 t
t
DifferenceinVirulenceamongClonalTypesoftheSameSpecies.......................................................................................265 p
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BacterialInteractionsResultinginCollectivePathogenicity..............................................................................................265 //
BacterialLoad............................................................................................................................................265 c
m
Environment-RegulatedExpressionofVirulenceFactors.................................................................................................265
r
HostResistanceandDiseaseModifiers...................................................................................................................266 .a
TREATMENTOFTHEACUTEAPICALABSCESS.............................................................................................................266 s
FUTUREDIRECTIONS.......................................................................................................................................267 m
REFERENCES................................................................................................................................................268 .o
AUTHORBIOS..............................................................................................................................................273 r
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SUMMARY andproposesfuturedirectionsinresearch,diagnosis,andthera-
p
Acuteapicalabscessisthemostcommonformofdentalabscess peuticapproachestodealwiththisdisease. ril
and is caused by infection of the root canal of the tooth. It is 1
3
usuallylocalizedintraorally,butinsomecasestheapicalabscess INTRODUCTION ,

2
mayspreadandresultinseverecomplicationsorevenmortality. Apical periodontitis is an inflammatory disease affecting the 0
The reasons why dental root canal infections can become 1
tissuessurroundingtherootendofatoothandiscausedby 9
symptomatic and evolve to severe spreading and sometimes
rootcanal(endodontic)infection.Thediseasecanmanifestitself b
life-threateningabscessesremainelusive.Studiesusingculture y
indifferentclinicalways,includingthedevelopmentofanacute
g
andadvancedmolecularmicrobiologymethodsformicrobial
abscess(1).Thefactorsinfluencingthedevelopmentoftheacute u
identificationinapicalabscesseshavedemonstratedamultispe- e
formofthediseasehavebeenthesubjectofcontinuousinterest s
ciescommunityconspicuouslydominatedbyanaerobicbacteria. t
(2–4).Arecurrentthemeinthisregardistheassociationofcertain
Species/phylotypescommonlyfoundintheseinfectionsbelongto
bacterialspecieswithclinicalsignsandsymptoms.However,the
the genera Fusobacterium, Parvimonas, Prevotella, Porphyromo-
searchforasingleorevenasmallgroupofspeciestobeconsidered
nas, Dialister, Streptococcus, and Treponema. Advances in DNA themajorpathogeninvolvedwithacuteendodonticinfectionshas
sequencing technologies and computational biology have sub- provenfruitless.Recentstudiesinthefieldsofmolecularandcel-
stantially enhanced the knowledge of the microbiota associated lularmicrobiologyandimmunologyhaveprovidedinformation
withacuteapicalabscessesandshedsomelightontheetiopathog- toimplicateamultitudeoffactorsinthepathogenesisofsymp-
enyofthisdisease.Speciesrichnessandabundanceandtheresult- tomaticapicalperiodontitis,includingitsmostsevereform,the
ing network of interactions among community members may acute apical abscess. Understanding the factors that make a
affectthecollectivepathogenicityandcontributetothedevelop-
mentofacuteinfections.Diseasemodifiers,includingtransientor
permanenthost-relatedfactors,mayalsoinfluencethedevelop- AddresscorrespondencetoJoséF.Siqueira,Jr.,[email protected].
mentandseverityofacuteabscesses.Thisreviewfocusesonthe Copyright©2013,AmericanSocietyforMicrobiology.AllRightsReserved.
currentevidenceabouttheetiologyandtreatmentofacuteapical doi:10.1128/CMR.00082-12
abscessesandhowtheprocessisinfluencedbyhost-relatedfactors
April2013 Volume26 Number2 ClinicalMicrobiologyReviews p.255–273 cmr.asm.org 255
SiqueiraandRôças
FIG1(A)Anindividualwithspreadacuteapicalabscess.(B)Aboneradiolucentlesionisvisiblearoundtherootapexesofthemandibularsecondmolar,which
isthesourceofinfection.(C)Incisionaldrainageisessentialformanagementoftheseconditions.Inthiscomplicatedcase,itwasperformedextraorally.
(CourtesyofCraigBaumgartner.)
D
chronic asymptomatic endodontic infection evolve to an acute acutereactiontoendodonticinfectionmaydevelopveryquickly, o
w
abscess,sometimeswithseverecomplications,mayhelpestablish theinvolvedtoothmaynotshowradiographicevidenceofperira- n
betterstrategiestopreventanddealwiththeseconditions.This dicular bone destruction. When a periradicular radiolucency is lo
a
reviewfocusesonthemicrobiologyandtreatmentofacuteapical radiographicallyobserved,theabscessisusuallytheresultofex-
d
abscessesandhowthediseasedevelopmentisinfluencedbyhost- acerbationofapreviouschronicasymptomaticcondition(Fig.1). e
d
relatedfactors.Futuredirectionsinresearchandtherapeuticap- Inmostcases,thetoothisextremelysensitivetopercussion.
f
proachestodealwiththisdiseasearealsodiscussed. Thepurulentexudateformedinresponsetorootcanalinfec- ro
m
tionspreadsthroughthemedullarybonetoperforatethecortical
THEDISEASEPROCESS boneanddischargeintothesubmucousorsubcutaneoussofttis- h
t
Anabscessconsistsofacollectionofpusintoacavityformedby sue.Inmanycases,swellingdevelopsonlyintraorally(8).Inthe tp
tissue liquefaction. The terms dental abscess, dentoalveolar ab- maxilla,acuteapicalabscessesdrainthroughthebuccalorpalatal :/
/
c
scess, and odontogenic abscess are often used synonymously to boneintotheoralcavityoroccasionallyintothemaxillarysinusor m
describe abscesses formed in the tissues around the tooth. The thenasalcavity.Apicalabscessesofmandibularteethmaydrain r
.
causemaybeanendodonticinfection(acuteapicalabscess)ora throughthebuccalorlingualboneintotheoralcavity.However, a
s
periodontal infection (periodontal abscess and pericoronitis). theinfectiousprocessmayalsoextendintofascialspacesofthe m
Theacuteapicalabscessisthemostcommonformofdentalab- headandneckandresultincellulitisandsystemicsignsandsymp- .o
scessesandisthesubjectofthisreview. toms,withconsequentcomplications. rg
Endodonticinfectiondevelopsonlyinrootcanalsofteethde- /
o
voidofavitalpulp.Thismaybeduetonecrosisofthedentalpulp ComplicationsStemmingfromAcuteApicalAbscesses n

asaconsequenceofcariesortraumatothetoothortoremovalof Almost60%ofallnontraumaticdentalemergenciesareasso- A
p
thepulptissueforpreviousrootcanaltreatment.Oncetheinfec- ciated with acute apical abscesses and toothaches (9). Acute r
tionisestablishedintherootcanal,bacteriamaycontacttheperi- dentalabscesseshavebeenreportedtocauseseverecomplica- il
1
radiculartissuesviaapicalandlateralforaminaorrootperfora- tions and even mortality (10–12). Mortality is more likely a 3
,
tionsandinduceachronicoracuteinflammatoryresponse(5). resultofsepsisorairwayobstruction(13,14),butdeathdueto 2
Thechronicresponseisusuallyasymptomaticandalmostinvari- aspreadinginfectionleadingtomassivehemorrhagefromthe 0
1
ablyleadstoboneresorptionaroundtherootapex,whichisthe subclavianveinintothepleuralcavityhasbeenreported(10). 9

typicalradiographicfeatureofapicalperiodontitis.Acuteperira- Thespreadofbacteriafromendodonticabscessestoothertis- b
y
dicular inflammation in turn usually gives rise to signs and/or sues may give rise to fascial plane infections (15). The most
g
symptoms,includingpainandswelling.Theacute(symptomatic) commonlyaffectedfascialspacesarethesublingual,subman- u
e
processmaydevelopwithoutpreviouschronicinflammationor dibular,buccalandpterygomandibularspaces,butotherssuch s
t
maybetheresultofexacerbationofapreviouslychronicasymp- asthetemporal,masseteric,lateralpharyngeal,andretropha-
tomaticlesion.Ithasbeenestimatedthattheincidenceofexacer- ryngealspacescanbeoccasionallyinvolved(8).
bationsofapicalperiodontitis(i.e.,asymptomaticlesionsbecom- Thespreadofinfectionsofendodonticoriginintothefascial
ingsymptomatic)isabout5%peryear(6). spacesoftheheadandneckisdeterminedbythelocationofthe
Theacuteabscesscanberegardedasanadvancedstageofthe rootendoftheinvolvedtoothinrelationtoitsoverlyingbuccalor
symptomatic form of apical periodontitis. In acute endodontic lingualcorticalplate,thethicknessoftheoverlyingbone,andthe
infections,notonlyaretheinvolvedbacterialocatedintheroot relationshipoftheapextotheattachmentofamuscle.Forexam-
canal,buttheyinvadetheperiradiculartissuesandhavethepo- ple,ifamandibularmolarisaffectedanditsrootapicesliecloser
tentialtospreadtootheranatomicalspacesofheadandneckto tothelingualcorticalplateandabovetheattachmentofthemy-
form a cellulitis or phlegmon, which is a disseminating diffuse lohyoidmuscle,thepurulentexudatecanbreakthroughthelin-
inflammatoryprocesswithpusformation(7). gual cortical plate into the sublingual space. If the root apices
Clinically, the patient with acute apical abscess experiences instead lie below the attachment of the mylohyoid muscle, the
mild to severe pain and swelling (Fig. 1). Trismus may occur. infection can spread into the submandibular space. If infection
Systemic manifestations may also develop, including fever, affectsthesublingualandsubmandibularspacesbilaterallyaswell
lymphadenopathy, malaise, headache, and nausea. Because the asthesubmentalspace,aconditionknownasLudwig’sanginais
256 cmr.asm.org ClinicalMicrobiologyReviews
MicrobiologyofDentalAbscesses
diagnosed.SwellingfromLudwig’sanginacangiverisetodiffi- oftheculturemediumitself,(iv)inhibitionbyotherspeciespres-
cultybreathingandpotentiallylethalairwayobstruction(16–18). entinthesample,(v)metabolicdependenceonotherspecies,(vi)
Anotherexampleofabscesscomplicationsinvolvesinfections disruptionofnaturalbacterialquorum-sensingsystems,and(vii)
ofthemidface,whichcanbeverydangerousandresultincavern- cellsina“viable-but-noncultivable”state(51,59,60).Effortshave
oussinusthrombosis.Thisisalsoalife-threateninginfection,in beenexpendedtowardthedevelopmentofapproachesthatallow
whichathrombusformedinthecavernoussinusbreaksfreeand cultivationofas-yet-uncultivatedbacteria(61–64).Thisisofgreat
leads to spread of the infection. Under normal conditions, the importance for description of novel species and study of their
angularandophthalmicveinsandthepterygoidplexusofveins ecologicalandpathogenicpotential,aswellasthepatternsofsus-
flowintothefacialandexternaljugularveins.Ifaninfectionhas ceptibilitytoantimicrobialdrugs.
spreadintothemidfacialarea,however,edemaandtheresultant Successful cultivation does not ensure successful identifica-
increasedpressurecausethebloodtobackupintothecavernous tion. Culture-dependent identification is based on phenotypic
sinus. Once in the sinus, the blood can stagnate and clot. The traitsreportedforreferencestrains,withpredictablebiochemical
resultantinfectedthrombiremaininthecavernoussinusores- andphysicalpropertiesunderoptimalgrowthconditions.How-
capeintothecirculation(19,20). ever,thereareseveralphenotype-relatedfactorsthatcanleadto
Other reported complications of disseminating dental infec- difficulties in identification and even to misidentification. They D
tionsincludebrainabscess(21–24),septicemiainapatientwith include(i)strainsofthesamespeciesshowingadivergentpheno- o
w
multiplemyeloma(25),deepneckinfection(26,27),mediastinitis typicbehavior(65,66),(ii)strainsofdifferentspeciesshowinga
n
(14,28–30),necrotizingfasciitis(31–33),orbitalabscess(34–36), convergentphenotypicbehavior(51,65),(iii)analteredpheno- lo
andcervicalspondylodiscitiswithspinalepiduralabscess(37).It typeinresponsetoconditionssuchasstress(67,68),(iv)strains a
d
hasbeensuggestedthatsomehost-relatedfactorsmaycontribute showingdifferentresultsafterrepeatedtests(69),(v)incomplete e
d
towardincreasedmorbidityandmortalityassociatedwithacute databasesnotincludingnewlynamedspeciesandas-yet-unchar-
f
dentalabscesses,includingdiabetes,chronicalcoholandtobacco acterized species, (vi) the fact that even small alterations in the ro
consumption,malnourishment,andtheuseofillicitsubstances assay may lead to false results (70), and (vii) the fact that test m

(26,27,33). resultsrelyonindividualinterpretationandexpertise(70). h
t
Complicationsofdentalabscessescanbesevereenoughtore- Molecularmethods.Toolsandproceduresbasedonmolecular tp
quirehospitalization.Alargenumberofhospitalizationsdueto biologyhavebecomeavailabletosidestepthelimitationsofcul- :/
/
c
oralabscesses/cellulitiswitharesultingsubstantialeconomicbur- tureandhavebeensubstantiallyimprovedtoachieveamorere- m
denhavebeenrecorded(38).Forinstance,in2007,7,886hospi- alisticdescriptionofthemicrobialcommunitiesofdifferentenvi- r
.
talizations were attributed primarily to abscesses of endodontic ronmentswithouttheneedforcultivation.Onegenethathasbeen a
s
origin, with total hospital charges on the order of $100 million widelyusedforrapididentificationofknownandunknownbac- m
(39). terialspeciesistheoneencodingthe16SrRNA(71).Therearea .o
myriadofmolecularmethodsforthestudyofbacteriainabscess rg
MICROBIOLOGYOFACUTEAPICALABSCESSES samples,andthechoiceofaparticularapproachdependsonthe o/
questionstobeanswered.Molecularmethodsfordiagnosticmi- n
MicrobiologyDiagnosticMethods crobiologycanbeusedforspecificdetectionoftargetspecies(spe- A
p
Culture.Culturemethodshavebeentraditionallyusedtoinves- cies-specificorclosed-endedanalysis),identificationofallorthe r
tigatethemicrobiotaofacuteapicalabscessesandhaveprovideda mostdominantspeciesinasample(broad-rangeoropen-ended il
1
substantialbodyofinformationaboutthebacterialetiologyand analysis), or profiling of the microbial community structure 3
,
thespeciesinvolved.However,someimportantlimitationsofcul- (communityanalysis)(72).Broad-rangePCRfollowedbycloning 2
turemakeitdifficulttoachieveacomprehensiveanalysisofthe andsequencingandmorerecentlythemassiveparallel454pyro- 0
1
apicalabscessmicrobiota.Becauseanaerobicbacteriaaredomi- sequencingapproachcanbeusedtounravelthebreadthofbacte- 9

nantinapicalabscesses(40–49),samplesforresearchorclinical rial diversity in a site. DNA hybridization arrays (e.g., checker- b
y
diagnosisusingcultureshouldbecollectedandtransportedtothe boardarraysandmicroarrays),species-specificPCR,nestedPCR,
g
laboratoryunderconditionsthatfavorthesurvivalofthesebac- multiplex PCR, and quantitative real-time PCR can be used to u
e
teria.Thelaboratorythatwillanalyzethesampleshastobeprop- surveylargenumbersofsamplesforthepresenceoftargetspecies. s
t
erlypreparedandequippedtoisolate,cultivate,andidentifyan- Bacterialcommunitystructurescanbeanalyzedviathepyrose-
aerobes. The procedures for isolation and identification can be quencingtechnologyandbyfingerprintingtechniques,suchasthe
laboriousandtime-consuming,andmanyanaerobicspeciesmay denaturinggradientgelelectrophoresis(DGGE)andterminalre-
requiremultiplephenotype-basedtestsforreliableidentification strictionfragmentlengthpolymorphism(T-RFLP)assays.Aswith
(50). anyothertechnology,molecularmethodshavetheirownlimita-
Moreimportant,thedifficultiesinculturingalargenumberof tions. However, variations in virtually every technique have
oral bacteria or even in identifying many species are of special emerged to circumvent or minimize limitations, or sometimes
concern(51).Asearlyestimatedbycorrelativemicroscopicand morethanoneapproachisrequiredforreliableinformationtobe
culturing analyses (52) and further elegantly demonstrated and obtained.
specifiedbymolecularbiologytechniques(53–58),40%to70%of The chronology of the microbiological study of acute apical
theoralbacterialspeciesremaintobecultivatedandphenotypi- abscessescanbedidacticallydividedintofivegenerationsofstud-
callycharacterized.Themostpossiblereasonsforthefactthata ies based on different strategic diagnostic approaches (73). The
largenumberoforalbacteriastillhavetobecultivatedinclude(i) first generation involves studies of the abscess microbiota con-
lack of essential nutrients or growth factors in the culture me- ducted using open-ended (or broad-range) culture methods,
dium,(ii)overfeedingconditionsduringcultivation,(iii)toxicity which disclosed many cultivable species in association with the
April2013 Volume26 Number2 cmr.asm.org 257
SiqueiraandRôças
disease(41–49).Thesecondgenerationconsistedofstudiesem- (e.g.,generaFusobacteriumandLeptotrichia),Actinobacteria(e.g.,
ployingclosed-endedmoleculardetectionmethods,suchasspe- generaActinomycesandPropionibacterium),Spirochaetes(e.g.,ge-
cies-specificPCRanditsderivativesaswellastheoriginalcheck- nus Treponema), Synergistetes (e.g., genus Pyramidobacter and
erboardhybridizationassay,totargetcultivablebacteria(74–82). some as-yet-uncultivated phylotypes), and Proteobacteria (e.g.,
Thesemethodsallowedtheinclusionofsomedifficult-to-culture genera Campylobacter and Eikenella ) (Fig. 2). Regardless of the
species in the set of candidate abscess pathogens. Next, a third studyandmethodofidentification,thephylaFirmicutesandBac-
generation of studies adopted open-ended molecular methods, teroidetes together contribute to more than 70% of the species
suchasbroad-rangePCRfollowedbycloningandsequencingor found in abscesses (Fig. 3). Representatives of Spirochaetes and
T-RFLP,whichallowedanevenmorecomprehensiveinvestiga- Synergisteteshavebeenrevealedonlybyculture-independentmo-
tionofthebacterialdiversityinabscesses(83–87).Bytheseap- lecular methods (Fig. 3). Diverse groups of Gram-negative and
proaches,notonlycultivablespeciesbutalsoas-yet-uncultivated Gram-positive bacteria have been identified, and the most fre-
anduncharacterizedbacteriahavebeenidentified.Technicalhur- quentgeneraandspeciesidentifiedinabscessesandregardedas
dles make it difficult to analyze a large number of samples by putativepathogensaredescribednext.Thefactthatmanygenera
cloningandsequencing,butcataloguingbacterialspeciesinthe haveundergonereclassificationsovertheyearsmakesinterpreta-
oral cavity by this approach provided 16S rRNA gene sequence tionof“old”studiesdifficult,especiallywhenidentificationswere D
data that could be used to design primers or oligonucleotide restrictedtothegenuslevel. o
w
probestotargetbothcultivableandas-yet-uncultivatedbacteria. Gram-negative bacteria. Dark-pigmented anaerobic bacteria
n
Thefourthgenerationofstudiesinvolvedclosed-endedmolecular havebeencloselyassociatedwithacutesymptomsofendodontic lo
analyseswithPCRandDNAhybridizationassays(e.g.,reverse- infections,includingabscesses(41,47,96–100).Twoculturestud- a
d
capturecheckerboard)inlarge-scaleclinicalstudiestoinvestigate ies(42,101)foundthatvirtuallyallabscessesofendodonticorigin e
d
the prevalence and association of cultivable and as-yet-unculti- harboredoneormorespeciesofthisgroup.Dark-pigmentedan-
f
vatedbacteriawithabscesses(88–90).Afifthgenerationhasbeen aerobicbacteriaareusuallyfoundinmixedinfection,whichmay ro
possiblyheraldedbytheuseofpyrosequencingtechnologyfora berequiredfortheiroptimalgrowthandcontributestoasignifi- m

deep-coverage open-ended analysis of abscess samples (91, 92) cant increase in their pathogenicity (102–106). This bacterial h
t
(seebelow). groupcomprisestwogenera:Prevotella(containingsaccharolytic tp
Ingeneral,cultureanalysesofabscessesresultedintheestab- species)andPorphyromonas(containingasaccharolyticspecies). :/
/
c
lishmentofasetofspeciesthoughttoplayanimportantroleinthe The genus Prevotella also includes some nonpigmented species. m
pathogenesis of the disease. Not only have molecular methods ThePrevotellaspeciesfrequentlyfoundinapicalabscesssamples r
.
confirmedandevenstrengthenedtheassociationofmanyculti- includeP.intermedia,P.nigrescens,P.baroniae,andP.oris,andin a
s
vablebacterialspecieswithabscesses,buttheyalsorevealednew moststudiestheyareamongthemostprevalentand/ordominant m
suspected pathogens (93). The list of candidate pathogens has species(40,42,43,75,83,86,87,101,107).OfthePorphyromonas .o
expanded to include difficult-to-culture species or even as-yet- species,P.endodontaliswasfirstisolatedfromendodonticinfec- rg
uncultivatedbacteriathathadneverbeenpreviouslyfoundinab- tions(108)andhasbeenconsistentlyencounteredinabscesssam- /
o
scessesbyculturingapproaches(Fig.2).Consequently,themicro- ples,withincreasedprevalenceinmolecularstudies(42,77,90, n

biota of apical abscesses has been refined and redefined by 101,109,110).Porphyromonasgingivalisisoneofthemostimpor- A
p
molecularmethods(93).Althoughmolecularmethodshavebeen tantperiodontalpathogens(111,112)andhasalsobeendetected r
widelyusedforresearchpurposes,theystillhaveyettobeimple- in association with endodontic abscesses (74, 77, 101, 113). P. il
1
mentedforclinicaldiagnosis.Thereisagreatpotentialforthese gingivalisfimAgenotypevariantsII,III,andIVandtypeIhave 3
,
methodstobeusedforrapididentificationofpotentialpathogens beenreportedinabscessaspirates(114). 2
concomitantlywithspecificantibioticsusceptibility,whichwould Fusobacteriumnucleatumisananaerobicspindle-shapedrod 0
1
allowimmediateandmoreappropriatepatientcarewithpossibly thatisoneofthemostcommonlydetectedGram-negativespecies 9

reducedmorbidityormortality(87,94).Thisapplicationwillbe in the large majority of culture and molecular studies of acute b
y
furtherdiscussedinthesectionFutureDirections. apicalabscesses(40,45,85,90),reachingprevalencevaluesashigh
g
asapproximately70%(42,75)oreven86%(83)ofthesamples. u
MicrobialDiversityinAcuteApicalAbscesses Thisspeciesinducessevereabscesslesionsinanimalsinbothpure es
t
Samples for microbiological analyses of abscesses can be taken and mixed cultures (115–118). Four subspecies (F. nucleatum
eitherfromtherootcanalsofaffectedteethorbyaspirationofthe subsp. nucleatum, F. nucleatum subsp. polymorphum, F. nuclea-
purulentexudatefromtheswollenmucosa/skin.Cultureandmo- tumsubsp.vincentii,andF.nucleatumsubsp.animalis)havebeen
lecular microbiology studies have clearly demonstrated that the identifiedinapicalabscesses(74,86),butthefrequencyofeach
apicalabscessmicrobiotaismixedandconspicuouslydominated onehasyettobeaccuratelydetermined.ThespeciesFusobacte-
byanaerobicbacteria(42,43,49,83,87,95–96).Table1provides riumperiodonticumhasalsobeendetectedinabscessaspiratesbya
acompilationofthemainmicrobiologicalfindingsfrommostof studyusingthecheckerboardhybridizationassay(74).
thesestudies.Itisnoteworthythatwhilesomebacterialspeciesor Inaseminalstudyofendodonticinfectionspublishedin1894
groupsarereportedinmanystudies,themostprevalentspecies (119),WilloughbyDaytonMillersuggestedthatspirochetescould
varyfromstudytostudy. play a role in the etiology of abscesses. Nevertheless, it was not
At a broader taxonomic level, the large majority of the fre- untiltheintroductionofmolecularmethodsinendodonticmi-
quentlydetectedbacterialspeciesbelongtosevendifferentbacte- crobiologyresearchthatthepotentialinvolvementofspirochetes
rialphyla,namely,theFirmicutes(e.g.,generaStreptococcus,Di- withthisdiseasewasconfirmed.Oralspirochetesfallwithinthe
alister, Filifactor, and Pseudoramibacter), Bacteroidetes (e.g., genus Treponema and have been linked to several oral diseases
genera Porphyromonas, Prevotella, and Tannerella), Fusobacteria (120–123). Molecular methods have revealed the occurrence of
258 cmr.asm.org ClinicalMicrobiologyReviews
MicrobiologyofDentalAbscesses
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FIG2Bacterialspecies/phylotypesfrequentlydetectedinacuteapicalabscesses.Aphylogenetictreebasedon16SrRNAgenecomparisons,showingseveral y

candidatepathogensandtheirrespectivephyla,isshown.Thescalebarshowsthenumberofnucleotidesubstitutionspersite. g
u
e
s
t
treponemes in 61% to 89% of endodontic abscess samples (79, Anotherexampleofbacteriathathavebeenconsistentlydetected
80).Ofthe10cultivableandvalidlynamedoralTreponemaspe- inapicalabscessesonlyaftertheadventofmolecularmethodsis
cies,theasaccharolyticspeciesT.denticolaandT.mediumaswell theasaccharolyticanaerobicGram-negativeDialisterspecies,es-
asthesaccharolyticspeciesT.socranskiiandT.maltophilumhave peciallyD.pneumosintesandD.invisus(76,83,86,88).
beenmostfrequentlydetected(80,109,124),withprevalenceval- OtherGram-negativebacteriathathavebeendetectedinab-
uesinstudiesusingspecies-specificnestedPCRofupto75%for scessed samples in some culture or molecular studies include
T.socranskii(125)and79%forT.denticola(79).Oraltreponemes Campylobacterspp.(42),Catonellamorbi(129),Veillonellapar-
have been demonstrated to induce abscesses and disseminating vula(48,130),andEikenellacorrodens(90,130).
infectionswheninoculatedinanimals(126–128). Gram-positive bacteria. Several Gram-positive bacteria have
AssociationofotherGram-negativebacterialspecieswithab- alsobeenfrequentlydetectedinacuteapicalabscessesbyculture
scesseshasalsobeensuggestedbasedonmolecularstudies.One andmolecularmethods.AlongwiththeGram-negativebacteria
example is Tannerella forsythia, a fastidious obligate anaerobic of the genera Prevotella, Porphyromonas, and Fusobacterium,
rod,whichisanimportantperiodontalpathogenandwasnever Gram-positive cocci, specifically peptostreptococci and strepto-
previouslydetectedinapicalabscessesbyculture(74,78,90,109). cocci,comprisethemostprevalentbacteriainmoststudies.Pep-
April2013 Volume26 Number2 cmr.asm.org 259
SiqueiraandRôças
TABLE1Microbiologicalfindingsforacuteapicalabscesses
Studytypeandauthors No.ofabscess Meanno.ofspecies
(reference) casesexamined Method perabscesssample Mostprevalentspecies(%)
Culture(openended)
Heimdahletal.(40) 58 Culture 3.4 Fusobacteriumnucleatum(45),“Streptococcusmilleri”
(31),Parvimonasmicra(29),Prevotellaruminicola
(29),Prevotellamelaninogenica(26)
Sabistonetal.(44) 58 Culture 3.8 Streptococcusspp.(71),Fusobacteriumnucleatum
(24),Parvimonasmicra(22),Actinomycesspp.(17)
Williamsetal.(45) 10 Culture 4 Fusobacteriumnucleatum(60),Bacteroidesspp.(60),
Parvimonasmicra(50)
Lewisetal.(41) 50 Culture 3.3 Peptostreptococcusspp.(64),Peptococcusspp.(64),
Streptococcus“milleri”(50),Prevotellaoralis(40)
Sundqvistetal.(42) 17 Culture 8.5 Fusobacteriumnucleatum(71),Lactobacillusspp.
(65),Prevotellaintermedia/nigrescens(59),
Parvimonasmicra(53),Peptostreptococcus
anaerobius(53),Eggerthellalenta(47)
Brooketal.(46) 32 Culture 2.4 Alpha-hemolyticstreptococci(34),Porphyromonas
D
gingivalis(22),Parvimonasmicra(19),
o
Fusobacteriumnucleatum(16)
w
Kulekçietal.(47) 13 Culture 5.4 Peptostreptococcusspp.(92),alpha-hemolytic
n
streptococci(69),Prevotellaintermedia/nigrescens lo
(69),Fusobacteriumnucleatum(38)
a
Sakamotoetal.(48) 23 Culture 4.9 Peptostreptococcusspp.(52),Fusobacteriumspp.(43), d
Prevotellaoris(39),Streptococcusconstellatus(35), e
Streptococcusintermedius(35) d
deSousaetal.(49) 30 Culture 3.9 Anaerococcusprevotii(43),Parvimonasmicra(30), f
r
Gemellamorbillorum(30),Fusobacterium o
necrophorum(23),Streptococcusconstellatus(20) m
Khemaleelakuletal.(43) 17 Culture 7.5 Prevotellaintermedia(35),Prevotellabaroniae(35),
h
Streptococcusconstellatus(29),Prevotellabuccae t
t
(29),Prevotellamelaninogenica(29) p
:
/
/
Molecular c
Closedended,severaltarget m
species r.
Siqueiraetal.(74) 27 Conventionalcheckerboard Notapplicable Tannerellaforsythia(30),Porphyromonasgingivalis a
s
(49targetspecies) (30),Streptococcusconstellatus(26),Prevotella m
intermedia(22),Prevotellanigrescens(22)
.
SiqueiraandRôças(90) 42 Reverse-capturecheckerboard Notapplicable Fusobacteriumnucleatum(64),Parvimonasmicra o
(81targetspecies) (52),Porphyromonasendodontalis(48),Olsenella rg
uli(45),Streptococcusspp.(38),Eikenellacorrodens /

(38),BacteroidetescloneX083(36),Prevotella o
n
baroniae(36),Treponemadenticola(36)

SiqueiraandRôças(230) 22 NestedPCR(40target Notapplicable Treponemadenticola(77),Porphyromonas A
species) endodontalis(68),Dialisterpneumosintes(64), p
r
(T5a9n)n,eDreialllaisftoerrsiyntvhiisau(s6(45)3,)P,oFriplihfaycrtoomraolnoacsisg(i4n2gi)v,alis il 1
Fusobacteriumnucleatum(41),Streptococcusspp. 3
(41) ,
2
Openended
0
Sakamotoetal.(83) 7 T-RFLP;PCR,cloning,and 13.3 Fusobacteriumnucleatum(86),Parvimonasmicra 1
sequencing (57),Lachnospiraceaclone55A-34(57),Prevotella 9
intermedia(43),Prevotellabaroniae(43),Dialister b
pneumosintes(43),EubacteriumcloneBP1-89 y
(43),LachnospiraceacloneMCE7_60(43) g
Flynnetal.(86) 9 PCR,cloning,andsequencing 7.4 Parvimonasmicra(78),Dialisterpneumosintes(78), u
Prevotellaoris(67),Eubacteriumbrachy(56), e
s
Fusobacteriumnucleatumsubsp.nucleatum(44) t
Openended,next-generation
sequencing
Santosetal.(91) 9 Pyrosequencing 114 Fusobacteriumspp.(89),Parvimonasspp.(78),
Dialisterspp.(78),Atopobiumspp.(78),
Eubacteriumspp.(67),Porphyromonasspp.(67),
Prevotellaspp.(67)
Hsiaoetal.(92) 8 Pyrosequencing 77(genera) Fusobacteriumspp.(100),Streptococcusspp.(100),
Phocaeicolaspp.(100),Prevotellaspp.(100),
Porphyromonasspp.(100)
tostreptococci have been subjected to several recent taxonomic samples(40,42,44,45,49,83,90),reachingupto78%ofthecases
reclassifications,andnewgenerahaveemerged,suchasParvimo- (86).Thisspecieshasbeenrevealedtobepathogenicinanimal
nasandAnaerococcus.Parvimonasmicra(formerlyPeptostrepto- studies,especiallyinmixedinfections(115,116,131,132).
coccusmicros)isanasaccharolyticanaerobicsmallcoccusthathas The predominant streptococci associated with abscesses be-
beenisolatedfromordetectedinahighnumberofapicalabscess longtotheStreptococcusanginosusgroup(alsoreferredtoasthe
260 cmr.asm.org ClinicalMicrobiologyReviews
MicrobiologyofDentalAbscesses
D
o
w
n
lo
a
d
e
d

f
r
o
m

h
t
t
p
:
/
/
c
m
r
.
a
s
m
.
o
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/

o
n

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p
r
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y

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u
e
FIG3Bacterialphylawithrepresentativesinacuteapicalabscessesasrevealedbystudiesusingeitherculture(A)ormolecular(B)open-endedmethods.Data s
t
refertothenumberofdifferenttaxafoundineachphylum.Notethatregardlessofthestudyandmethod,themajorityofspeciesdetectedbelongtothephyla
FirmicutesandBacteroidetes.RepresentativesofthephylaSynergistetesandSpirochaeteswererevealedonlybymolecularmethods.(Referencecitationscorre-
spondtoreferences43,45,49,83,86,and87.)
“S.milleri”groupinsomestudies)(40,41,43,48,49,74,133). (42, 90), Olsenella uli (88, 90), Mogibacterium timidum (42),
Thisgroupiscomposedofthemicroaerophilicoranaerobicspe- Granulicatellaadiacens(88),Eubacteriumspecies(E.brachyandE.
cies S. anginosus, S. constellatus, and S. intermedius, which have infirmum)(86,90),Gemellamorbillorum(49),andanaerobiclac-
beenshowntocausepurulentinfectionsinanimalmodels(104, tobacilli(42).
115,117,134,135).MembersoftheS.anginosusgrouphavebeen As-yet-uncultivatedphylotypes.In1894,Miller(119)wrote,
oftenreportedinavarietyofabscessesinotherbodysites(94,136, “Itmuststrikeeveryonethattheresultsofthecultureexperiments
137). donottallywiththoseofthemicroscopicalexamination.Whilea
OtherGram-positivebacteriathathavealsobeendetectedin careful microscopical examination of the diseased pulp almost
apical abscesses included Filifactor alocis (78, 89, 90, 138–139), invariablyrevealedamixedinfection,thepureculturesshow,in
Actinomycesspecies(44,90,140),Pseudoramibacteralactolyticus the majority of cases, either only cocci or only bacilli.” One of
April2013 Volume26 Number2 cmr.asm.org 261
SiqueiraandRôças
Miller’spossibleexplanationsforthisfindingwasthat“manyspe- Arecentstudyused454pyrosequencingtocomparethemi-
ciesofbacteriaoccurringinthediseasedpulp,vibriones,spiro- crobiotaofendodonticinfectionsassociatedwithacuteabscesses
chaetes,thestiffpointedbacilliandthreads,havenotbeenfound andasymptomaticchronicapicalperiodontitis,anditfoundop-
cultivableonartificialmediaanyway;andpossiblytherearestill erational taxonomic units (at 3% divergence) belonging to 13
otheruncultivablepulp-bacteria.”Thedevelopmentofmethods phyla (91). The most abundant phyla in acute infections were
for anaerobic cultivation showed that the bacterial diversity in Firmicutes (52%), Fusobacteria (17%), and Bacteroidetes (13%),
endodontic infections was underestimated by previous culture whilethedominantphylainasymptomaticinfectionswereFirmi-
studiesbyexcludingahighnumberofspeciesthatcomposethe cutes (59%), Bacteroidetes (14%), and Actinobacteria (10%).
largestproportionofthebacterialcommunityintheseinfections. Members of Fusobacteria were much more prevalent in acute
Furtherbreakthroughsinmicrobialidentificationrepresentedby (89%)thaninchronic(50%)infections.Ofthe49generadetected
moleculartechnologiesrevealedthatevenadvancesinanaerobic inacutecases,themostabundantwereFusobacterium,Parvimo-
culturingleftalargeproportionofthemicrobiotaundisclosed. nas,andPeptostreptococcus.Fusobacteriumwasalsothemostprev-
Indeed, molecular investigations of the bacteria involved in alent,followedbyParvimonas,Dialister,andAtopobium.Thebac-
abscessesunveiledafarmorecomplexpicturethananticipatedby terial communities in abscesses were significantly more diverse
culturestudies.Noteworthyisthecommonoccurrenceofas-yet- thanthoseinchronicinfections,andapatternrelatedtothepres- D
uncultivatedbacterialphylotypes,whichcanberegardedasspe- ence of symptoms was apparently evident through community o
w
cies-level bacteria known only by a 16S rRNA gene sequence. analysis.Theoveralldiversityofabscessesasrevealedbypyrose-
n
Open-endedmolecularanalysisofacuteapicalabscessesrevealed quencing was much higher than previously reported. Most of lo
that,intermsofrichness,as-yet-uncultivatedphylotypesencom- these findings were confirmed by another study using pyrose- a
d
passapproximately24%to46%ofthetaxafound(83,86),while quencing,whichrevealedrepresentativesof11phylaandFusobac- e
d
in terms of abundance, they collectively represent from 6% to teriumasthemostabundantgenus(92).
f
morethan30%oftheclonessequenced(83,87). ro
Several of the as-yet-uncultivated phylotypes are suspected BacterialSpeciesandAcuteInfections:IsThereaSingle m
pathogensbasedonassociationdata.Forinstance,aphylotypeof Culprit? h
t
the Bacteroidetes phylum known as oral clone X083 has been A matter of intense debate and investigation is why only some tp
foundin14%to36%ofapicalabscessaspirates(90,107).Oral selectedcasesevolvetoacuteinfectionswithseveresymptomsand :/
/
c
Synergistetesphylotypes,whichhadbeenoriginallyassignedtothe potentialcomplications.Inthiscontext,thedesiretofindasingle m
Flexistipes or Deferribacteres groups, are another example of as- speciesoratleastagroupofmajorspeciesthatisassociatedwith r
.
yet-uncultivatedbacteriathathavebeenfrequentlyencountered acute symptoms is an ever recurrent topic in the study of end- a
s
inabscesses(88–90).ThegreatmajorityofSynergistetesbacteria odontic infections. In his milestone study, Miller (119) was the m
remainuncultivated(141),andthiscanbetheprimaryreasonfor firstonetosuggesttheinvolvementofaspecificgroupofbacteria .o
thefactthattheirpresenceinabscesseshasbeenoverlookedby with endodontic symptoms: spirochetes were associated with rg
culture studies. Some Synergistetes phylotypes have been culti- acuteabscesses.However,thefirstconsistentreportontheasso- /
o
vatedandgivenaspeciesname;oneofthem,Pyramidobacterpis- ciationofagivenspecieswithendodonticsymptomscamefrom n

colens(previouslyoralcloneBA121),isprobablythemostpreva- theclassicPh.D.thesisofGoranSundqvist(99),whofounddark- A
p
lent representative of the Synergistetes phylum in abscess cases pigmentedbacteria(formerlyBacteroidesmelaninogenicus)inas- r
(88–90).PhylotypesfromthefamilyLachnospiraceaeorthegenera sociation with acute symptoms. Further culture and molecular il
1
Eubacterium, Megasphaera, Leptotrichia, Oribacterium, Pepto- studiesreportedontheassociationwithsymptomsofseveralspe- 3
,
streptococcus, Prevotella, Selenomonas, and Solobacterium have cies,withthemostfrequentbelongingtothegeneraPorphyromo- 2
beendisclosedinpussamplesfromapicalabscesses(83,86,87). nas,Fusobacterium,Parvimonas,andPrevotella(Table2).Never- 0
1
Thereisnoreasontobelievethatthesepreviouslyunrecognized theless, these findings have not been consistently confirmed by 9

andoverlookedbacteriadonotplayaroleinthepathogenesisof otherstudies,becausebasicallythesamespeciescanalsobefound b
y
thedisease. intherootcanalsofteethwithasymptomaticapicalperiodontitis
g
Pyrosequencing analysis of abscess samples. Advances in insimilarprevalences(74,93,100,147–151). u
e
DNA sequencing technologies and computational biology have Asignificantlimitationofvirtuallyallthemicrobiologicalstud- s
t
substantially enhanced molecular phylogenetic surveys of hu- iesofacuteendodonticinfectionsistheircross-sectionalnature.
man-associatedmicrobialcommunitiesinhealthanddisease,of- Restrictionismostlybecauseofobviousethicalreasonsandpre-
fering a great depth of coverage at a very high analytical speed cludesanystrongconclusionaboutinvolvementofcertainspecies
(142,143).The454pyrosequencingmethodisoneofthesead- presentinamixedconsortiumincausationofacutesymptoms.As
vancedDNAsequencingtechniquesthathasbeenwidelyusedin a consequence, only association with symptoms, instead of a
medical microbiology. This technology is a sequencing-by-syn- cause-and-effectrelationship,canbeinferredfromthesehuman
thesismethodthatinvolvesacombinationofemulsionPCRand studies.Thismakesthespeciesassociatedwithacuteinfectionbe
pyrosequencing.Pyrosequencingreliesonthedetectionofpyro- referredtoas“candidate,”“suspected,”or“putative”pathogens.
phosphatereleaseandconsequentlightgenerationasnucleotides Animalstudieshavegivensomesupporttothepotentialrolein
areincorporatedinagrowingchainofDNA(144,145).Oneofthe abscesscausation.Forinstance,theabilitytocausepurulentin-
greatestadvantagesofthepyrosequencingapproachoverthecon- fectionsinanimalmodelsstrengthensthepossiblecausativerole
ventional Sanger sequencing method is that hundreds of thou- ofcertainspeciesclinicallyassociatedwithsymptomaticdisease.
sandsofsequencereadscanbeobtainedinasinglerun,generating Manycandidateendodonticpathogens,aloneorincombinations,
sequence information data that are orders of magnitude larger havebeenshowntocauseabscessesinanimalmodels(104,105,
(146). 116,126,152).Oneofthemainproblemswiththeanimalmodel
262 cmr.asm.org ClinicalMicrobiologyReviews
MicrobiologyofDentalAbscesses
TABLE2Bacterialspeciesassociatedwithsignsandsymptomsofacuteendodonticinfections
Studyauthor(s)
Species Signsandsymptoms Method (reference)
Spirochetes Pain,purulentexudate Microscopy Miller(119)
Prevotellaintermedia,Porphyromonasendodontalis Pain Culture Sundqvist(99)
Prevotellaspp.,Porphyromonasspp. Pain Culture Griffeeetal.(231)
Prevotellaspp.,Porphyromonasendodontalis Pain Culture Sundqvistetal.(42)
Porphyromonasendodontalis,Porphyromonasgingivalis Pain Culture Haapasaloetal.(100)
Finegoldiamagna Pain Culture Yoshidaetal.(232)
Peptostreptococcusspp.,Eubacteriumspp.,Porphyromonasspp. Pain Culture Hashiokaetal.(233)
Parvimonasmicra,Prevotellaspp. Pain,swelling Culture Gomesetal.(234)
Fusobacteriumnecrophorum,Prevotellaloescheii,Streptococcusconstellatus Purulentexudate Culture Gomesetal.(235)
Streptococcusspp. Pain PCR Fouadetal.(150)
Streptococcusconstellatus Pain,swelling,purulent Checkerboard Siqueiraetal.(236)
exudate
Prevotellaloescheii,Peptostreptococcusspp.,Anaerococcusprevotii Pain Culture Jacintoetal.(207) D
o
Bifidobacteriumspp.,Actinomycesspp.,Streptococcusconstellatus Tendernesstopercussion Culture Jacintoetal.(207) w
Fusobacteriumnucleatum Swelling Culture Jacintoetal.(207) n
Parvimonasmicra,Prevotellaintermedia/nigrescens,Eubacteriumspp. Pain Culture Gomesetal.(237) lo
Porphyromonasspp.,Fusobacteriumspp.,Peptostreptococcusspp. Tendernesstopercussion, Culture Gomesetal.(237) a
d
purulentexudate e
Porphyromonasspp.,Peptostreptococcusspp.,Enterococcusspp. Swelling Culture Gomesetal.(237) d

Treponemadenticola Pain PCR Foschietal.(238) fr
o
Filifactoralocis Pain,swelling,purulent PCR Gomesetal.(78) m
exudate
h
Tannerellaforsythia Tendernesstopercussion, PCR Gomesetal.(78) t
t
purulentexudate p
:
Fusobacteriumnucleatum,Prevotellaintermedia,Dialisterpneumosintes, Pain,swelling,purulent PCR,cloning,and Sakamotoetal.(83) //
c
PrevotellacloneE9_42,Prevotellabaroniae,EubacteriumcloneBP1-89, exudate sequencing m
LachnospiraceaecloneMCE7_60 r
.
Tannerellaforsythia Pain Checkerboard Sassoneetal.(188) a
s
Porphyromonasgingivalis Pain,swelling,purulent PCR Siqueiraetal.(113) m
exudate .
o
Selenomonassputigena Pain Checkerboard Rôçasetal.(187) r
g
Fusobacteriumspp.,Parvimonasspp.,Atopobiumspp.,Dialisterspp., Pain,swelling,purulent Pyrosequencing Santosetal.(91) /

Porphyromonasspp.,Prevotellaspp. exudate o
n

A
p
r
isthatonlycultivablebacteriahavebeentested,eitherinsingle principlethatteamworkiswhateventuallycounts.Thebehavior il 1
culture or in combinations of two or a few species. Thus, any ofthecommunityandtheoutcomeofthehost/bacterialcommu- 3
,
speculationaboutextensionoftheseresultstoaclinicalcondition nityinteractionwilldependonthespeciescomposingthecom- 2
0
wherethereisanetworkofinteractingspecies(10ormore),in- munityandhowthemyriadofassociationsthatcanoccurwithin 1
cludingas-yet-uncultivatedphylotypes,mayleadtooversimplifi- thecommunityaffectandmodulatethevirulenceofinvolvedspe- 9

cation. cies.Thevirulenceofagivenspeciesisallegedlydifferentwhenit by

isinpureculture,inpairs,oraspartofalargebacterial“society” g
TheCommunity-as-PathogenConcept u
(community).Inmixedcommunities,abroadspectrumofrela- e
Pathogenicityhastraditionallybeenassumedonthebasisof“guilt tionshipsmayarisebetweenthecomponentspecies,rangingfrom s
t
byassociation,”andsomeclassicdiseases,suchastetanus,gonor-
noeffect(rare)orreducedpathogenicitytoadditiveorsynergistic
rhea,cholera,andsyphilis,havebeendeterminedashavinga“sin-
pathogeniceffects.Acuteapicalabscessesareexamplesofpolymi-
gle-speciesetiology.”Unlikethesediseases,endodonticinfections
crobialinfectionswherebybacterialspeciesthatindividuallymay
aresimilartoseveralotherhumanendogenousinfectionsinthat
havelowvirulenceandareunabletocausediseasecandosowhen
nosinglepathogenbutasetofspecies,usuallyorganizedinmul-
inassociationwithothersaspartofamixedconsortium(patho-
tispecies biofilm communities, is involved (83, 99, 153–155).
genicsynergism)(105,157,158).
Mountingevidenceindicatesthatwhilethereislittlespecificityas
Bacterial community patterns related to acute infections.
totheinvolvementofsinglenamedspeciesintheetiologyofapical
periodontitis, specificity becomes more evident when bacterial Bacterialcommunityprofilesareessentiallydeterminedbyspecies
communityprofilesaretakenintoaccount.Thisisbecausewhile richnessandabundanceandhavebeenrecentlyinvestigatedinthe
associationsofanyspecificspecieswithanyformofapicalperio- different types of endodontic infections. Community profiling
dontitis is seldom, if ever, confirmed, the bacterial community analysesoftheendodonticmicrobiotahavedisclosedagreatin-
profilesseemtofollowsomepatternsrelatedtothedifferentpre- terindividual variability in endodontic communities associated
sentationsofapicalperiodontitis(156). with the same clinical disease (95, 159); i.e., no two root canal
The concept of the community as pathogen is based on the infections are the same in terms of species richness and abun-
April2013 Volume26 Number2 cmr.asm.org 263
SiqueiraandRôças
dance.Thisindicatesthattheetiologyofapicalperiodontitis,in- microbiologicalfactors,thepossibilitycertainlyexiststhathost-
cludingtheacuteforms,isheterogeneous(95,160). related factors (disease modifiers) can influence the severity of
Ofgreatinterestisthatbacterialcommunitiesseemtofollowa apicalperiodontitislesions.Examplesofdiseasemodifiersinclude
specificpatternaccordingtotheclinicalcondition(e.g.,asymp- systemic conditions (e.g., diabetes, herpesvirus infection, stress,
tomaticversussymptomaticdisease)(95).Therefore,theseverity autoimmunediseases,anddiseasesthatweakentheimmunere-
ofapicalperiodontitismayberelatedtotheoverallbacterialcom- sponse)andthegeneticbackground(e.g.,genepolymorphism).
munitycomposition.Inotherwords,fromtheperspectiveofthe Diabetic individuals have been shown to develop complica-
single-pathogenconcept,apicalperiodontitiscanbeconsidered tionsfromabscessesmorefrequentlyandtohavealongerdura-
to be of no specific microbial etiology. However, based on the tionofhospitalstaythannondiabetics(27,33).Similarly,diabetic
community-as-pathogenconcept,itispossibletoinferthatsome patientscanexhibitabouttwicetherateofinterappointmentex-
communitiesaremorerelatedtocertainformsofthedisease,such acerbations (flare-ups) following endodontic intervention (165,
asabscesses(83,95).Achallengethatarisesfromthisnotionisthe 166).Furthermore,diabeticanimalsdevelopapicalperiodontitis
needtounravelthespecificgenotypicandphenotypiccharacter- lesionsthatarelargerandmoreseverethanthoseinnondiabetic
isticsoftheseabscess-relatedbacterialcommunities. controls (167). Type 2 diabetes mellitus has been found to be
Acuteapicalabscessesarecharacterizedbyaconcomitantin- significantlyassociatedwithincreasedprevalenceofapicalperio- D
fectionoftherootcanalandtheperiradiculartissues,asthelatter dontitis (168, 169). Although diabetic patients are apparently o
w
isanextensionoftheformer.Evenso,studieshavereportedsome more prone to develop severe forms of apical periodontitis, no
n
discrepanciesbetweenbacterialcommunityprofilesformatched study so far has reported on the prevalence of endodontic ab- lo
samplestakenfromtherootcanalandabscessaspirates(92,161). scessesindiabeticindividuals. a
d
The differences observed suggest that some selection of species Potentially, genetic polymorphism is another factor that can e
d
occursastheinfectionadvancesfromthecanaltotheperiradicu- makeindividualsmoresusceptibletodevelopacuteinfections.De
f
lartissues.This“filtering”processishighlylikelytobearesultof Sáetal.(170)investigatedtheassociationofacuteapicalabscesses ro
thedifferentenvironmentsfacedbytheinfectingbacteria:froma withpolymorphismsinthegenesforinterleukin-1(cid:1)(IL-1(cid:1)),IL-6, m
siterelativelyprotectedfromhostdefenses(necroticrootcanal)to IL-10,tumornecrosisfactoralpha(TNF-(cid:2)),andCD14.Individ- h
t
asitewithanexuberantacuteinflammatoryresponse(highlyvas- ualswithasymptomaticapicalperiodontitis,withoutpreviousex- tp
cularizedperiradiculartissues).Moreover,differencesinthetis- acerbation, were included as controls. A significant association :/
/
c
sueinvasionabilityoftheinvolvedspeciesmaycontributetothe wasobservedbetweentheoccurrenceoftheGGgenotypeortheG m
selectiveprocessofspeciespresentinpusaspirates. alleleexpressionoftheIL-6geneandacuteabscessesinwomen r
.
andinindividualsyoungerthan35years.TheGalleleisassociated a
s
GeographicDifferencesintheAbscessMicrobiota with high levels of IL-6 production compared with the C allele m
Acuriousobservationwhenanalyzingseparatestudiesperformed (171).Intermediate-andhigh-producerIL1Bgenotypesandlow- .o
in different countries is the different prevalences of species in- producerTNFAgenotypealsoshowedsomeassociationwithab- rg
volved in abscesses. Variations in microbiological diagnostic scesses,althoughnotasstrongasobservedforIL-6.Otherstudies /
o
methodologiesmayaccountformostofthesedifferences,buta areneededtoconfirmandexpandthesefindingstoanalyzeother n

geographicalvariationinbacterialcompositioncannotbedisre- potentialinflammation-relatedgenes. A
p
garded,asitalsooccursforotherhumanbodysites(162–164). Ithasbeenhypothesizedthatherpesviruses,especiallyhuman r
Molecularstudieshavebeenconductedtodirectlycomparethe cytomegalovirus(HCMV)andEpstein-Barrvirus(EBV),maybe il
1
bacterial community structures and prevalences of some target implicatedinthepathogenesisofapicalperiodontitisasadirect 3
,
speciesinabscessesfrompatientsresidingindifferentgeographic result of virus infection and replication or as a result of virally 2
locations.IntwostudiescomparingsamplesfromPortland,OR, inducedimpairmentoflocalhostdefenses,whichmightgiverise 0
1
andRiodeJaneiro,Brazil(75,89),species-specificPCRanalyses toovergrowthofpathogenicbacteriaintheveryapicalpartofthe 9

revealedthattherewasasignificantdifferenceinprevalencebe- rootcanalsystem(172).InfectionbyHCMVandEBVhasbeen b
y
tweenthetwogeographicallocationsforP.intermedia,P.nigre- morefrequentlyobservedinsymptomaticlesions(173,174),and
g
scens, Prevotella tannerae, F. nucleatum, and P. gingivalis, all of anassociationhasbeensuggested.However,datarelatedtothe u
e
whichmorefrequentinPortlandsamples,whileT.denticolaand occurrence of herpesviruses in acute apical abscesses are rather s
T.forsythiaweremoreprevalentinRiodeJaneirosamples.Open- inconclusive.Chenetal.(175)foundherpesvirusesinlowpreva- t
endedDGGEanalysisofthebacterialcommunityprofilesinacute lencesandlowcopynumbersinabscesssamplesandconcluded
apicalabscessesfromthesametwolocationsalsodisclosedage- that herpesviruses may be present but are not required for the
ography-relatedpattern(160).Severalspecieswereexclusivefor developmentofabscessesandcellulitisofendodonticorigin.Fer-
eachlocation,andotherssharedbythetwolocationsshowedgreat reiraetal.(176)evaluatedthepresenceofhumanherpesviruses1
differencesinprevalence.Theoccurrenceofgeographicalvaria- to8andhumanpapillomavirusinacuteapicalabscessesandre-
tionswasconfirmedwhencomparingabscesssamplesfromRio portedthatabout60%ofthesampleswerepositiveforatleastone
deJaneiroandSeoul,SouthKorea(110).Thesedifferenceshave target virus. Human herpesvirus 8 (HHV-8) occurred at a high
thepotentialtotranslateintorelevanttherapeuticimplications, prevalence(48%),followedbyhumanpapillomavirus(13%)and
specificallyincasesrequiringsystemicantibiotictherapy. varicella-zoster virus and HHV-6 (9%). Viral coinfection oc-
curred in some cases. In another study, the same group (109)
THEHOSTSIDEOFTHESTORY found positive (but weak) associations between candidate end-
Giventhemicrobialetiologyofapicalperiodontitis,development odonticbacterialpathogensandhumanvirusesinsamplesfrom
ofacutesymptomshasbeentraditionallysearchedforcandidate acuteapicalabscesses.Althoughthesefindingsmaysuggestarole
microbial risk factors. Although there is a clear implication of forvirusesintheetiologyofendodonticabscesses,thepossibility
264 cmr.asm.org ClinicalMicrobiologyReviews