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Candidavulvovaginitis
OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate

Candidavulvovaginitis
Author
JackDSobel,MD

SectionEditors
RobertLBarbieri,MD
CarolAKauffman,MD

DeputyEditor
KristenEckler,MD,FACOG

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jul2016.|Thistopiclastupdated:May25,2016.
INTRODUCTIONVulvovaginalcandidiasisreferstoadisordercharacterizedbysignsandsymptomsofvulvovaginal
inflammationinthepresenceofCandidaspecies.Itisthesecondmostcommoncauseofvaginitissymptoms(after
bacterialvaginosis)andaccountsforapproximatelyonethirdofvaginitiscases[1].Incontrasttooropharyngeal
candidiasis,itisgenerallynotconsideredanopportunisticinfection,and,unliketrichomonasvaginitis,itisnotconsidered
asexuallytransmitteddisease.
PREVALENCECandidaspeciescanbeidentifiedinthelowergenitaltractin10to20percentofhealthywomeninthe
reproductiveagegroup,6to7percentofmenopausalwomen,and3to6percentofprepubertalgirls[2,3].However,
identificationofvulvovaginalCandidaisnotnecessarilyindicativeofcandidaldisease,asthediagnosisofvulvovaginitis
requiresthepresenceofvulvovaginalinflammation.
Theprevalenceofvulvovaginalcandidiasisisdifficulttodeterminebecausetheclinicaldiagnosisisoftenbasedon
symptomsandnotconfirmedbymicroscopicexaminationorculture(asmanyasonehalfofclinicallydiagnosedwomen
mayhaveanothercondition[4]).Inaddition,thewidespreaduseofoverthecounterantimycoticdrugsmakes
epidemiologicstudiesdifficulttoperformandculturewithoutclinicalcorrelationislikelytooverestimatetheprevalenceof
disease.
Insurveys,theprevalenceofvulvovaginalcandidiasisishighestamongwomenintheirreproductiveyears:55percentof
femaleuniversitystudentsreporthavinghadatleastonehealthcareproviderdiagnosedepisodebyage25years,29to49
percentofpremenopausalwomenreporthavinghadatleastonelifetimeepisode,and9percentofwomenreporthaving
hadfourormoreinfectionsina12monthperiod(ie,recurrentvulvovaginalcandidiasis[RVVC])[5,6].Inwomenwithan
initialinfection,theprobabilityofRVVCwas10percentbyage25years,and25percentbyage50years[6].
TheprevalenceincreaseswithageuptomenopauseandishigherinAfricanAmericanwomenthaninotherethnicgroups.
Thedisorderisuncommoninpostmenopausalwomen,unlesstheyaretakingestrogentherapy.Itisalsouncommonin
prepubertalgirls,inwhomitisfrequentlyoverdiagnosed.
MICROBIOLOGYCandidaalbicansisresponsiblefor80to92percentofepisodesofvulvovaginalcandidiasis[7]and
C.glabrataaccountsforalmostalloftheremainder[8].Some,butnotall,investigatorshavereportedanincreasing
frequencyofnonalbicansspecies,particularlyC.glabrata[9,10],possiblyduetowidespreaduseofoverthecounter
drugs,longtermuseofsuppressiveazoles,andtheuseofshortcoursesofantifungaldrugs.
AllCandidaspeciesproducesimilarvulvovaginalsymptoms,althoughtheseverityofsymptomsismilderwithC.glabrata
andC.parapsilosis.
Incontrasttobacterialvaginosis,vulvovaginalcandidiasisisnotassociatedwithareductioninvaginallactobacilli[1114].
PATHOGENESISCandidaorganismsprobablyaccessthevaginaviamigrationfromtherectumacrosstheperianal
area[15]culturesofthegastrointestinaltractandvaginaoftenshowidenticalCandidaspecies.Lesscommonly,the
sourceofinfectionissexualorrelapsefromavaginalreservoir.
Symptomaticdiseaseisassociatedwithanovergrowthoftheorganismandpenetrationofsuperficialepithelialcells[16
18].ThemechanismbywhichCandidaspeciestransformfromasymptomaticcolonizationtoaninvasiveformcausing
symptomaticvulvovaginaldiseaseiscomplex,involvinghostinflammatoryresponsesandyeastvirulencefactors.(See
"BiologyofCandidainfections".)
RecurrentvulvovaginalcandidiasisRecurrentvulvovaginalcandidiasisisdefinedasfourormoreepisodesof
symptomaticinfectionwithinoneyear[16].LongitudinalDNAtypingstudiessuggestthat,inmostwomen,recurrent
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diseaseisduetorelapsefromapersistentvaginalreservoiroforganismsorendogenousreinfectionwiththeidentical
strainofsusceptibleC.albicans[19,20].Rarely,infectionisduetoadifferentCandidaspecies.
Recurrentvulvovaginalcandidiasishasbeenassociatedwithdecreasedinvivoconcentrationofmannosebindinglectin
(MBL)andincreasedconcentrationofinterleukin4.Twospecificgenepolymorphisms,variantsintheMBLandinterleukin
4alleles,canaccountforthisfindinginsomewomen.TheprevalenceofavariantMLBgeneishigherinwomenwith
recurrentvulvovaginalcandidiasisthanincontrolswithoutcandidiasis[21,22].SincethedirectinteractionofMBLwithC.
albicansisanimportantcomponentofthehost'sabilitytoresistcandidiasis,impairmentofthisinteractioninMBL
deficientindividuals,suchasthosewithcertainMBLpolymorphisms,appearstopredisposethesewomentorecurrent
vulvovaginalcandidalinfection[21,2326].Thesewomenmountastronginflammatoryresponsewhenexposedtosmall
amountsofCandida,whereasnormalwomenmaynotmountanyinflammatoryresponseandremainasymptomatic.
Interleukin4blockstheantiCandidaresponsemediatedbymacrophages,thuselevatedIL4levelsresultininhibitionof
localdefensemechanisms.
RISKFACTORSSporadicattacksofvulvovaginalcandidiasisusuallyoccurwithoutanidentifiableprecipitatingfactor.
Nevertheless,anumberoffactorspredisposetosymptomaticinfection[27,28]:
DiabetesmellitusWomenwithdiabetesmellituswhohavepoorglycemiccontrolaremorepronetovulvovaginal
candidiasisthaneuglycemicwomen[29,30].Inparticular,womenwithType2diabetesappearpronetononalbicans
Candidaspecies[31].
AntibioticuseUseofbroadspectrumantibioticssignificantlyincreasestheriskofdevelopingvulvovaginal
candidiasis[32].Asmanyasonequartertoonethirdofwomendevelopthedisorderduringoraftertakingthese
antibioticsbecauseinhibitionofnormalbacterialflorafavorsgrowthofpotentialfungalpathogens,suchasCandida.
Administrationoflactobacillus(oralorvaginal)duringandforfourdaysafterantibiotictherapydoesnotprevent
postantibioticvulvovaginitis[33].
IncreasedestrogenlevelsVulvovaginalcandidiasisappearstooccurmoreofteninthesettingofincreased
estrogenlevels,suchasoralcontraceptiveuse(especiallywhenestrogendoseishigh),pregnancy,andestrogen
therapy.
ImmunosuppressionCandidalinfectionsaremorecommoninimmunosuppressedpatients,suchasthosetaking
glucocorticoidsorotherimmunosuppressivedrugs,orwithhumanimmunodeficiencyvirus(HIV)infection[34].
ContraceptivedevicesVaginalsponges,diaphragms,andintrauterinedeviceshavebeenassociatedwith
vulvovaginalcandidiasis,butnotconsistently.SpermicidesarenotassociatedwithCandidainfection.
BehavioralfactorsVulvovaginalcandidiasisisnottraditionallyconsideredasexuallytransmitteddisease(STD)
sinceitoccursincelibatewomenandsinceCandidaspeciesareconsideredpartofthenormalvaginalflora.This
doesnotmeanthatsexualtransmissionofCandidadoesnotoccurorthatvulvovaginalcandidiasisisnotassociated
withsexualactivity.Forexample,anincreasedfrequencyofvulvovaginalcandidiasishasbeenreportedatthetime
mostwomenbeginregularsexualactivity[5,27,35].Inaddition,partnersofinfectedwomenarefourtimesmore
likelytobecolonizedthanpartnersofuninfectedwomen,andcolonizationisoftenthesamestraininbothpartners.
However,thenumberofepisodesofvulvovaginalcandidiasisawomanhasdoesnotappeartoberelatedtoher
lifetimenumberofsexualpartnersorthefrequencyofcoitus[27,36,37].
Thetypeofsexmaybeafactor.Infectionmaybelinkedtoorogenitaland,lesscommonly,anogenitalsex.Evidence
ofalinkbetweenvulvovaginalcandidiasisandhygienichabits(eg,douching,useoftampons/menstrualpads)or
wearingtightorsyntheticclothingisweakandconflicting[27,3845].
RecurrentvulvovaginalcandidiasisTheriskfactorsdescribedaboveareapparentinonlyaminorityofwomenwith
recurrentdisease(see'Riskfactors'above).Intheremainder,factorsthatpredisposetorecurrentinfectionlikelyinvolve
abnormalitiesinlocalvaginalmucosalimmunity[46]andgeneticsusceptibility(see'Recurrentvulvovaginalcandidiasis'
above).
Theroleofsexualtransmissioninrecurrentinfectionremainsunresolved,butdoesnotappeartobeamajorfactorasthe
bulkofevidencefromrandomizedtrialsdoesnotsupporttreatmentofsexualpartners[4750].

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CLINICALFEATURESVulvarpruritusisthedominantfeatureofvulvovaginalcandidiasis[8,17,5153].Vulvarburning,
soreness,andirritationarealsocommon,andcanbeaccompaniedbydysuria(typicallyperceivedtobeexternalorvulvar
ratherthanurethral)ordyspareunia.Symptomsareoftenworseduringtheweekpriortomenses[53].Theintensityof
signsandsymptomsvariesfrommildtosevere,exceptamongwomenwithC.glabrataorC.parapsilosisinfection,who
tendtohavemildorminimalclinicalfindings[54].
Physicalexaminationoftheexternalgenitalia,vagina,andcervixoftenrevealserythemaofthevulvaandvaginalmucosa
andvulvaredema.Vulvarexcoriationandfissuresarepresentinaboutonequarterofpatients.Therecanbelittleorno
dischargewhenpresent,itisclassicallywhite,thick,adherent,andclumpy(curdlikeorcottagecheeselike)withnoor
minimalodor.However,thedischargemaybethinandloose,watery,homogeneous,andindistinguishablefromthatin
othertypesofvaginitis.Thecervixusuallyappearsnormal.
DIAGNOSISThegeneraldiagnosticapproachtowomenwithvaginalcomplaintsisreviewedseparately.(See
"Approachtowomenwithsymptomsofvaginitis".)
ThediagnosisofvulvovaginalcandidiasisisbasedonthepresenceofCandidaonwetmount,Gramsstain,orcultureof
vaginaldischargeinawomanwithcharacteristicclinicalfindings(eg,vulvovaginalpruritus,burning,erythema,edema,
and/orcurdlikedischargeattachedtothevaginalsidewall)andnootherpathogenstoaccountforhersymptoms.(See
'Clinicalfeatures'above.)Becausenoneoftheclinicalmanifestationsofvulvovaginalcandidiasisispathognomonic,
suspectedclinicaldiagnosisshouldalwaysbeconfirmedbylaboratorymethods.Importantly,althoughvulvarpruritusisa
cardinalsymptomofthedisorder,lessthan50percentofwomenwithgenitalpruritushavevulvovaginitiscandidiasis[55].
OfficediagnosisThevaginalpHinwomenwithCandidainfectionistypicallynormal(4to4.5),whichdistinguishes
candidiasisfromtrichomoniasisorbacterialvaginosis(table1).Candidaspeciescanbeseenonawetmountofthe
dischargeadding10percentpotassiumhydroxidedestroysthecellularelementsandfacilitatesrecognitionofbudding
yeast,pseudohyphae,andhyphae(picture1andpicture2andpicture3andpicture4andpicture5andpicture6)[56].
UseofSwartzLamkinsfungalstain(potassiumhydroxide,asurfactant,andbluedye)mayfacilitatediagnosisbystaining
theCandidaorganismsbluesotheyareeasiertoidentify[57].However,microscopyisnegativeinupto50percentof
patientswithcultureconfirmedvulvovaginalcandidiasis[16].
Microscopyisalsoimportantforlookingforcluecellsormotiletrichomonads,whichindicatebacterialvaginosisand
trichomoniasis,respectively,asalternativediagnoses,coinfection,ormixedvaginitis[58].
RoleofcultureWerecommendnotculturingallpatientsbecausecultureisnotnecessaryfordiagnosisif
microscopyshowsyeast,anditiscostly,delaysthetimetodiagnosisbyseveraldays,andmaybepositivedueto
colonizationratherthaninfection.
Weobtainaculturein:
Womenwithclinicalfeaturesofvulvovaginalcandidiasis,normalvaginalpH,andnopathogens(yeast,cluecells,
trichomonads)visibleonmicroscopy.Apositivecultureinthesepatientsconfirmsthediagnosisandrevealsthe
speciesofCandida,thusavoidingempiric,unindicatedorincorrecttherapy.
Womenwithpersistentorrecurrentsymptomsbecausemanyofthesewomenhavenonalbicansinfectionresistant
toazoles(see'Diagnosisofrecurrentvulvovaginalcandidiasis'below).
Toperformaculture,avaginalsampleisobtainedfromthelateralwallusingacottontippedswabandinoculatedonto
Sabouraudagar,Nickerson'smedium,orMicrostixcandidamediumthesemediaperformequallywell[8].Culturefor
Candidadoesnotrequirequantificationofinvitrocolonycount.SpeciationofCandidaisnotessentialforprimary
diagnostictestingasmostisolatesareCandidaalbicanshowever,speciesidentificationisessentialinrefractoryand
recurrentdisease.LaboratorytechniquesforidentificationofmultipleCandidaspeciesarereviewedseparately.(See
"BiologyofCandidainfections",sectionon'Detectioninthemicrobiologylaboratory'.)
OthertestsTherearenoreliablepointofcaretestsforCandidaavailableintheUnitedStates[5964].ADNAprobe
testperformedinacentralizedlaboratoryoffersresultscomparabletoculturewithresultsavailableinseveralhours,butno
speciation(AffirmVPIII).
Polymerasechainreaction(PCR)methodshavehighsensitivityandspecificityandashorterturnaroundtimethanculture
[6568],butarecostlyandoffernoprovenbenefitovercultureinsymptomaticwomen[65].
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Papsmearispositivein25percentofpatientswithculturepositive,symptomaticvulvovaginalcandidiasis[8].Itis
insensitivebecausethecellsarederivedfromthecervix,whichisnotaffectedbyCandidavaginitis.TreatmentofCandida
onaPapsmearofanasymptomaticwomanisnotindicated(see'Treatment'below).
SelfdiagnosisSelfdiagnosisofvulvovaginalcandidiasisisfrequentlyinaccurateandshouldbediscouraged[69,70].
Inastudythatadministeredaquestionnaireto600womentoassesstheirknowledgeofthesymptomsandsignsof
vulvovaginalcandidiasis(andotherinfections)afterreadingclassiccasescenarios,only11percentofwomenwithouta
previousdiagnosisofvulvovaginalcandidiasiscorrectlydiagnosedthisinfection[69].Womenwhohadhadapriorepisode
weremoreoftencorrect(35percent),butwerelikelytouseoverthecounterdrugsinappropriatelytotreatother,potentially
moreserious,gynecologicdisorders.
Inanotherreport,theactualdiagnosesin95womenwhoselfdiagnosedvulvovaginalcandidiasiswere:vulvovaginal
candidiasis(34percent),bacterialvaginosis(19percent),mixedvaginitis(21percent),normalflora(14percent),
trichomonasvaginitis(2percent),andother(11percent)[70].Womenwithapreviousepisodeofvulvovaginalcandidiasis
andthosewhoreadthepackageinsertfortheiroverthecountermedicationwerenotmoreaccurateinmakingadiagnosis
thanotherwomen.
Someconsequencesofmisdiagnosisandinappropriatetherapyincludeadelayincorrectdiagnosisandtreatment,wasted
monetaryexpenditure,andprecipitationofvulvardermatitis.
DiagnosisofrecurrentvulvovaginalcandidiasisRecurrentvulvovaginalcandidiasisisdefinedasfourormore
episodesofsymptomaticinfectionwithinoneyear[16].Vaginalculturesshouldalwaysbeobtainedtoconfirmthe
diagnosisandidentifylesscommonCandidaspecies,ifpresent.Asdiscussedabove,recurrentdiseaseisusuallydueto
relapsefromapersistentvaginalreservoiroforganismsorendogenousreinfectionwithidenticalstrainsofsusceptibleC.
albicans[19]however,rarely,anewstrainofCandidaisresponsiblefortheinfection.
TestingforHIVinfectionVulvovaginalcandidiasisoccursmorefrequentlyandhasgreaterpersistence,butnot
greaterseverity,inhumanimmunodeficiencyvirus(HIV)infectedwomenwithverylowCD4countsandhighviralload
however,thispopulationislikelytomanifestotheracquiredimmunedeficiencysyndrome(AIDS)relatedsentinel
conditions[34].HIVtestingofwomenonlyfortheindicationofrecurrentvulvovaginalcandidiasisisnotjustified,given
thatrecurrentCandidavaginitisisacommonconditioninwomenwithoutHIVinfectionandthemajorityofcasesoccurin
uninfectedwomen.ThemicrobiologyofvulvovaginalcandidiasisinHIVinfectedwomenissimilartothatinHIVnegative
women[8].
WomenwithriskfactorsforacquisitionofHIVshouldbecounseledandofferedscreening.Theseriskfactorsare
describedindetailseparately.(See"Screeningforsexuallytransmittedinfections".)
DifferentialdiagnosisOtherconditionstobeconsideredinthedifferentialdiagnosisofvulvovaginitiswithnormal
vaginalpHincludehypersensitivityreactions,allergicorchemicalreactions,andcontactdermatitis.Theseconditionsare
discussedindetailelsewhere.Recognizinglocaladversereactionstotopicalagentsisimportantotherwise,additional
topicalagents,includinghighpotencycorticosteroids,areoftenprescribedempiricallyandfurtheraggravatesymptoms.
(See"Vulvardermatitis".)Mechanicalirritationduetoinsufficientlubricationduringcoituscanalsoresultinvaginal
discomfort.
IfvaginalpHexceeds4.5orexcesswhitecellsarepresent,mixedinfectionwithbacterialvaginosisortrichomoniasis
maybepresent.Mixedinfection(2pathogensandallaresymptomatic)isestimatedtooccurin<5percentofpatients
coinfection(2pathogensbutsomearenotsymptomatic)ismorecommon:20to30percentofwomenwithbacterial
vaginosisarecoinfectedwithCandidaspecies[58].(See"Bacterialvaginosis"and"Trichomoniasis".)
TREATMENTTreatmentisindicatedforreliefofsymptoms.Tento20percentofreproductiveagewomenwhoharbor
Candidaspeciesareasymptomaticthesewomendonotrequiretherapy[56].
Thetreatmentregimenisbasedonwhetherthewomanhasanuncomplicatedinfection(90percentofpatients)or
complicatedinfection(10percentofpatients).Criteriaarelistedinthetable(table2).Uncomplicatedinfectionsusually
respondtotreatmentwithinacoupleofdays.Complicatedinfectionsrequirealongercourseoftherapyandmaytaketwo
weekstofullyresolve.
Treatmentofsexualpartnersisunnecessary.Thereisnomedicalcontraindicationtosexualintercourseduringtreatment,
butitmaybeuncomfortableuntilinflammationimproves.
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UncomplicatedinfectionCriteriaforuncomplicatedinfectionincludeallofthefollowing[17]:

Sporadic,infrequentepisodes(3episodes/year)
Mildtomoderatesigns/symptoms
ProbableinfectionwithCandidaalbicans
Healthy,nonpregnantwoman

Avarietyoforalandtopicalpreparations,manyavailableoverthecounterandinsingledoseregimens,isavailableforthe
treatmentofuncomplicatedvulvovaginalcandidiasis(table3)[71].Inrandomizedtrials,oralandtopicalantimycoticdrugs
achievedcomparableclinicalcurerates,whichareinexcessof90percentshorttermmycologiccureisslightlylower(70
to80percent)[7275].Studiesthathaveassessedpatientpreferenceconsistentlyreportedapreferenceforthe
convenienceoforaltreatment[73].However,topicaltreatmentshavefewersideeffects(eg,possiblelocalburningor
irritation),whileoralmedicationmaycausegastrointestinalintolerance,headache,rash,andtransientliverfunction
abnormalities.Inaddition,oralmedicationstakeadayortwolongerthantopicaltherapytorelievesymptoms.The
absenceofsuperiorityofanyformulation,agent,orrouteofadministrationsuggeststhatcost,patientpreference,and
contraindicationsarethemajorconsiderationsinthedecisiontoprescribeanantifungalfororalortopicaladministration
[75].
Wesuggestuseoforalfluconazole,giventhatmostwomenconsideroraldrugsmoreconvenientthanthoseapplied
intravaginally.Fluconazolemaintainstherapeuticconcentrationsinvaginalsecretionsforatleast72hoursafterthe
ingestionofasingle150mgtablet[76].Sideeffectsofsingledosefluconazole(150mg)tendtobemildandinfrequent.
However,fluconazoleinteractswithmultipledrugstherefore,thepotentialfordruginteractionsshouldbeaddressedwhen
prescribingthisagent.Sincefluconazoleisnowavailableinagenericform,asingledoseregimenoffluconazoleisless
expensivethanoverthecountertopicalantifungals.
AzoleresistancehasonlybeenreportedinonecaseofvaginitiscausedbyC.albicans[77].Thus,invitrosusceptibility
testsarerarelyindicatedunlesscompliantpatientswithacultureprovendiagnosishavenoresponsetoadequatetherapy.
ComplicatedinfectionsCharacteristicsofcomplicatedinfectionsincludeoneormoreofthefollowingcriteria[17]:

Severesigns/symptoms
CandidaspeciesotherthanC.albicans,particularlyC.glabrata
Pregnancy,poorlycontrolleddiabetes,immunosuppression,debilitation
Historyofrecurrent(4/year)cultureverifiedvulvovaginalcandidiasis

Thetreatmentofcomplicatedinfectionissummarizedinthetableanddescribedinmoredetailbelow(table4).
SeveresymptomsorcompromisedhostWomenwithsevereinflammationorhostfactorssuggestiveof
complicatedinfectionneedlongercoursesoforalortopicalantimycoticdrugs.Itisunknownwhetheronerouteismore
effectivethantheother,ascomparativetrialsoftopicalversusoraltreatmentofcomplicatedinfectionhavenotbeen
performed.
Giventheconvenienceoforaltherapy,wesuggestfluconazole(150mgorally)fortwotothreesequentialdoses72hours
apartfortreatmentofcomplicatedinfections,dependingontheseverityoftheinfection(table4)[75].Theefficacyofthis
approachwassupportedbyatrialthatrandomlyassigned556womenwithsevereorrecurrentcandidiasistotherapywith
asingledoseoffluconazole(150mg)ortwosequentialdosesgiventhreedaysapart[78].Severityofdiseasewasbased
uponascoringsysteminvolvingdegreeofpruritusandphysicalsigns(erythema,edema,excoriation/fissureformation).
Thetwodoseregimenresultedinsignificantlyhigherclinicalcure/improvementratesatevaluationonday14(94versus85
percent)andday35(80versus67percent)inwomenwithsevere,butnotrecurrent,disease.However,theresponseto
therapywaslowerinthe8percentofwomeninfectedwithnonalbicansCandida.
Ifthepatientpreferstopicaltherapy,observationalseriesreportthatcomplicatedpatientsrequire7to14daysoftopical
azoletherapy(eg,clotrimazole,miconazole,terconazole)ratherthanaonetothreedaycourse[1,75].
ForsevereCandidavulvarinflammation(vulvitis),lowpotencytopicalcorticosteroidscanbeappliedtothevulvafor48
hoursuntiltheantifungalsexerttheireffect.
C.glabrataC.glabratahaslowvaginalvirulenceandrarelycausessymptoms,evenwhenidentifiedbyculture.
EveryeffortshouldbemadetoexcludeothercoexistentcausesofsymptomsandonlythentreatforC.glabratavaginitis.
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Treatmentfailurewithazolesiscommon(around50percent)inpatientswithC.glabratavaginitis[54].Moderatesuccess
(65to70percent)inwomeninfectedwiththisorganismcanbeachievedwithintravaginalboricacid(600mgcapsuleonce
dailyatnightfortwoweeks)[54,79].Betterresults(>90percentcure)havebeenachievedwithintravaginalflucytosine
cream(5gnightlyfortwoweeks)[79].Neitherboricacidcapsulesnorflucytosinecreamisavailablecommerciallyand
mustbemadebyacompoundingpharmacy.Boricacidcapsulescanbefatalifswallowed.
TherearenogooddataregardinguseoforalvoriconazoleforC.glabratavaginitis.Anecdotalreportssuggestpoor
responseandrarecures,andthepotentialfortoxicity.
Therearealsonogooddataontheefficacyofnystatin,whichisavailableasapessaryinsomepartsoftheworld.Oneor
twopessariesof100,000unitsnystatinareinsertedintothevaginanightlyfor14days[80].Alternatively,asuppository
canbepreparedbyacompoundingpharmacy.Potentialsideeffectsincludeburning,redness,andirritation.
C.kruseiCandidakruseiisusuallyresistanttofluconazole,butishighlysusceptibletotopicalazolecreamsand
suppositories,suchasclotrimazole,miconazole,andterconazole.Wetreatfor7to14days.Itisalsolikelytorespondto
oralitraconazoleorketoconazole,buttheseoralagentshavevariabletoxicitysotopicaltherapyisadvisedforfirstline
therapy.Idiosyncratichepatotoxicitysecondarytoketoconazoletherapyisaconcern,butrareinthissetting.Invitro
susceptibilitytestingisindicatedincompliantpatientswithcultureprovendiagnosisofC.kruseiandnoresponsetoa
conventionalcourseofoneofthesenonfluconazoletherapies.
PregnancyForpregnantwomenwithsymptomaticCandidavulvovaginitis,wesuggestapplicationofatopical
imidazole(clotrimazoleormiconazole)vaginallyforsevendaysratherthantreatmentwithanoralazolebecauseof
potentialriskswithoralazoletherapyinpregnancy.Treatmentofpregnantwomenisprimarilyindicatedforreliefof
symptomsvaginalcandidiasisisnotassociatedwithadversepregnancyoutcomes[81].Thisapproachisconsistentwith
statementsfromtheUnitedStatesCentersforDiseaseControlandPreventionandUSFoodandDrugAdministration
[1,82,83].
Duringpregnancy,weavoidoralazoletherapy,particularlyduringthefirsttrimester,becauseitsimpactonmiscarriagerisk
isunclearandhighdosesappeartoincreasetheriskofbirthdefects.Sincetopicaltherapyisaneffectivealternativeto
oraldosing,weprefervaginaltreatmentuntilmoredataareavailabletosupportthesafetyoflowdoseoraltreatment.
Miscarriage:Acohortstudyofover3300womenwhoreceived150to300mgoralfluconazolebetween7and22
weeksofpregnancyreportedanapproximately50percentincreasedriskofmiscarriageinexposedwomen
comparedwitheitherunexposedwomenorwomentreatedwithvaginalazoletherapy[84].Stillbirthriskdidnotdiffer
amongthegroups,althoughstillbirthwasarelativelyrareoutcome.Thisstudycontrastswithtwopriorcohortstudies
totalingjustover1500womenthatdidnotreportanassociationbetweenoralfluconazoleandmiscarriage[85,86].As
thelargerstudymayhavehadgreaterpowertodetectanincreaseinmiscarriagerisk,weprefertoavoidoralazole
therapyuntilmoredataareavailable.
Birthdefects:Casereportshavedescribedapatternofbirthdefects(abnormalitiesofcranium,face,bones,and
heart)afterfirsttrimesterexposuretohighdosefluconazoletherapy(400to800mg/day)[87,88].Themagnitudeof
theteratogenicriskisunknown.Further,theimpactoflowdosefluconazoleexposureisunclear.AUnitedStates
casecontrolstudyincludingover31,000mothersofchildrenwithbirthdefectsreportedanassociationwithfirst
trimesterfluconazoleuseandcleftlipwithcleftpalateanddtranspositionofthegreatarteries[89].Limitationsof
thisstudyincludedthatfluconazoleusewasassessedbyselfreportandthetotalnumberofcasesforeach
abnormalityweresmall(sixcleftlipwithpalateandthreedtranspositionofthegreatarteries),whichmakesthe
findinglesscertain.Multiplesmallerepidemiologicstudieshavenotreportedanincreasedriskofbirthdefectsafter
firsttrimesteruseofasingle,lowdoseoffluconazole150mgtotreatvaginalyeastinfection[85,86,9094].Inthe
largeststudy,whichincluded7352pregnancies,therewasnooverallriskofembryopathyassociatedwithexposure
tocumulativefluconazoledosesof150,300,or350to6000mgduringthefirsttrimesternorwithexposuretooral
itraconazoleorketoconazole[90].Overall,thesedataappearreassuringforwomenwhotooklowdosefluconazole
beforerealizingthattheywerepregnant[95],althoughanincreasedriskofspecificanomaliescannotbedefinitively
excluded.
AlthoughtreatmentofvaginalCandidacolonizationinhealthypregnantwomenisunnecessary,inGermanytreatmentis
recommendedinthethirdtrimesterbecausetherateoforalthrushanddiaperdermatitisinmaturehealthynewbornsis
significantlyreducedbymaternaltreatment[55].
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Thereislessinformationaboutthepregnancysafetyprofileofterconazole,atriazole,thanforimidazoles.Vaginalnystatin
isanotheroptionfortreatment.Asdiscussedabove,apessaryisavailableinsomepartsoftheworld.Oneortwo
pessariesof100,000unitsnystatinareinsertedintothevaginanightlyfor14days[80].Alternatively,asuppositorycanbe
preparedbyacompoundingpharmacy.Potentialsideeffectsincludeburning,redness,andirritation.
RecurrentinfectionThetreatmentofwomenwithrecurrentinfectionscanbedifficultandfrustrating[96].Recurrent
vulvovaginalcandidiasisisdefinedasfourormoreepisodesofsymptomaticcandidalvaginitisina12monthperiod[1,96].
Attemptsshouldbemadetoeliminateorreduceriskfactorsforinfectionifpresent(eg,improveglycemiccontrol,switch
tolowerestrogendoseoralcontraceptive).Althoughnotbasedupondatafromrandomizedtrials,implementingachange
inoneormorebehavioralfactors(eg,avoidanceofpantyliners,pantyhose,cranberryjuice,sexuallubricants)toseeif
thereisimprovementmaybebeneficialinrarewomen[38].Managementofsexualdysfunctionandthemaritaldiscord
thatfrequentlyaccompanychronicvaginitisshouldalsobeaddressed.
DecreasinggastrointestinalCandidacolonizationbyoraladministrationofnystatindoesnotpreventrecurrentsymptomatic
vaginalinfection[16].
AzolesRandomizedtrialscomparingdifferenttherapeuticregimenshavenotbeenperformed.Basedonthedata
citedbelowandpersonalexperience,webelievethattheoptimaltherapyforrecurrentvulvovaginalcandidiasisin
nonpregnantwomenconsistsofinitialinductiontherapywithfluconazole150mgevery72hoursforthreedoses,followed
bymaintenancefluconazoletherapyonceperweekforsixmonths[97].Therapyisthendiscontinued,atwhichpointsome
patientsachieveaprolongedremission,whileothersrelapse.Ashorttermrelapse,withcultureconfirmationofthe
diagnosis,meritsreinductiontherapywiththreedosesoffluconazole,followedbyrepeatweeklymaintenancefluconazole
therapy,thistimeforoneyear.Aminorityofwomenpersistinrelapsingassoonasfluconazolemaintenanceiswithdrawn
(fluconazoledependentrecurrentvulvovaginalcandidiasis).Symptomsinthesepatientscanbecontrolledbymonthsor
yearsofweeklyfluconazole.
Giventhesafetyprofileoflowdosefluconazole,mostexpertsdonotsuggestanylaboratorymonitoringhowever,ifother
oralimidazoles(ketoconazole,itraconazole)areused,particularlyiftakendaily,thenmonitoringliverfunctiontestsis
recommended.Idiosyncratichepatotoxicitysecondarytoketoconazoletherapyisaconcern,butrareinthissetting.
Althoughdruginteractionsarereportedwithfluconazoleandseveraloralagents(eg,warfarin,rifampin),suchinteractions
areextremelyunlikelywithmaintenancefluconazoleduetothelowplasmaconcentrationsaccompanyingtheonceweekly
150mgdosingregimen.Accordingly,noadditionaltestingneeded.
Alternativeapproachesthathavebeensuggestedinclude:
Treateachrecurrentepisodeasanepisodeofuncomplicatedinfection(table3)[1]
Treateachrecurrentepisodewithlongerdurationoftherapy(eg,topicalazolefor7to14daysorfluconazole150mg
orallyonday1,day4,andday7)[1]
TheInfectiousDiseasesSocietyofAmerica(IDSA)recommends10to14daysofinductiontherapywithatopicalor
oralazole,followedbyfluconazole150mgonceperweekforsixmonths(clotrimazole200mgvaginalcreamtwice
weeklyisanonoralalternative)[75].
EvidenceforsuppressivetherapyMultipleobservationalstudiesofnonpregnantwomenwithrecurrent
vulvovaginalcandidiasishaveshownthatantifungalmaintenancesuppressivetherapytakenforsixmonthsafteraninitial
inductionregimenresultedinnegativecultures[72,98].Thebestavailableoptioninnonpregnantwomenisfluconazole150
mgorallyonceperweekforsixmonths[75].However,maintenancetherapyisonlyeffectiveforpreventingrecurrent
infectionaslongasthemedicationisbeingtaken.Thiswasillustratedinatrialof387womenwithrecurrentvulvovaginal
candidiasistreatedwithopenlabelfluconazole(150mgorallyat72hourintervalsforthreedoses)andthenrandomly
assignedtoweeklydosesoffluconazole(150mg)orplaceboforsixmonths[97].Themaintenancetherapyphasewas
beguntwoweeksafterinitiationoftreatmentinpatientswhowereclinicallycured.Studydrugswerediscontinuedin
patientsdiagnosedwithrecurrentcandidalinfectionduringfollowupvisits.
Theproportionofwomenwhoremaineddiseasefreewassignificantlyhigherinthefluconazolegroup(91versus36
percentat6months,73versus28percentat9months,and43versus22percentat12months).
Themeantimetorecurrenceinthefluconazoleandplacebogroupswas10.2and4.0months,respectively.
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ResistantisolatesofC.albicansorsuperinfectionwithC.glabratawerenotobserved.
Althoughthisregimenofmaintenancefluconazolewasconvenient,safe,andaseffectiveasothertherapies,longterm
cureofrecurrentvulvovaginalcandidiasiswasnotachievedinonehalfofthewomenstudied.Episodesofrecurrent
candidiasisresumedwhenmaintenancetherapywasdiscontinued.
FluconazoleresistanceInwomenwithrecurrentvulvovaginalcandidiasis,thereissomeevidencethat
frequentandprolongeduseoffluconazolecaninfrequentlyselectforfluconazoleresistanceinC.albicansstrains
previouslysusceptibletofluconazole,whichlimitstheoptionsavailablefortreatingthesewomen.Inastudyof25women
withrefractoryCandidavaginitisandaC.albicansisolatewithfluconazoleminimuminhibitoryconcentration(MIC)2
micrograms/mL,thosewithfluconazoleMICvaluesof2or4micrograms/mLweretreatedsuccessfullybyincreasing
fluconazoledosageto200mgtwiceweekly[99].Intheauthorsexperience,ahigherdoseoffluconazolewasnot
effectiveforwomenwithMIC8micrograms/mL.Thesewomenshouldbeevaluatedforcrossresistancetoitraconazole
andketoconazole,assomepatientscanbetreatedeffectivelywithlongtermmaintenancedailyimidazoletherapy.
However,useofitraconazoleorketoconazolerequiresintermittenthepaticfunctiontesting.Idiosyncratichepatotoxicity
secondarytoketoconazoletherapyisaconcern,butrareinthissetting.
Womenwithsevererecurrentvulvovaginalcandidiasisinfectionandhighlevelpanazoleresistancedonothaveoptions
otherthantopicalboricacid(see'Boricacid'below)ornystatinsuppositories[100].
InwomenwithrefractoryvulvovaginalcandidiasiswithpersistentlypositiveC.albicanscultures,MICstovarious
antifungalscanbetestedbyusingthebrothmicrodilutionmethodconductedinaccordancewithClinicalandLaboratory
StandardsInstitution(CLSI)criteriaandbreakpoints[101].(See"Antifungalsusceptibilitytesting".)
ProbioticsThereisnoevidencethatwomenwithrecurrentvulvovaginalcandidiasishavevaginalfloradeficient
inlactobacilli,andthereforewedonotrecommenduseofprobioticlactobacilli[11,12].Althoughthereisapopularbelief
thatingestionorvaginaladministrationofyogurtorotheragentscontaininglivelactobacillidecreasestherateofcandidal
colonizationandsymptomaticrelapse,thefewstudiesinthisareahaveanumberofmethodologicflaws(eg,nocontrol
group,shortfollowup)andsmallnumbersofsubjects[102106].Thevalueofadministeringlivelactobacillitowomenwith
recurrentinfectionhasbeenrefutedinotherstudies[38,107]andthisapproachshouldbeconsideredunproven.Thequality
ofprobioticsvariesworldwideintheUnitedStatestheseproductsarenotstandardizedandoftenofpoorquality.TheUS
FoodandDrugAdministrationhascautionedagainstusingprobioticswithbacteriaoryeastinimmunocompromised
patients[108].
GentianvioletTopicalgentianvioletwaswidelyusedpriortotheavailabilityofthetopicalazoleintravaginal
antifungalcreamsandsuppositories.Useofthisagenthaslargelybeenabandonedbecauseazoleantimycoticsaremore
effective(potent)andbecauseitismessyandinconvenient(eg,itpermanentlystainsclothes).However,itisusefulasa
vulvarantipruriticandforoccasionalrefractorycasesofvulvovaginalcandidiasis,especiallythosedemonstratingazole
resistance[109].Thedrugisappliedtoaffectedareasofthevulvaandvaginadailyfor10to14days.
BoricacidWebelieveboricacidhasnoroleintreatmentofrecurrentvulvovaginitisduetoC.albicans,unless
azoleresistanceisdemonstratedbyinvitrotests[110].Therearenosafetydataonlongtermuseofboricacid,which
causessignificantlocalirritationandhasthepotentialfortoxicity(includingdeath)ifingestedbyaccident.Acourseof
boricacid(600mgintravaginalboricacidvaginalsuppositoriesdailyfortwoweeks)shouldbeconsideredonlyincasesof
provenazoleresistantinfectionthesecasesarerare.
ImmunotherapyLocalvaginalhypersensitivitytoC.albicanshasbeenproposedasthecauseofrecurrent
infectioninsomewomen[111].Immunotherapyofcandidalvaginitisforbothpreventionandtreatmentisatherapeutic
approachunderinvestigation[112].Aprophylacticvaccinewouldneedtoinduceahostimmuneresponseagainstfungal
virulencetraitswithoutalteringthetolerance/inflammationbalanceofthevaginalenvironment,whereasatherapeutic
vaccineindicatedforwomenwithrecurrentvulvovaginalcandidiasiscouldenhanceorrectifytolerance/inflammation
imbalanceinthevagina[113].Twovaccinesareindevelopment.
AllergytofluconazoleTheincidenceoffluconazoleallergyinwomenwithacuteCandidavaginitisisunknown,but
uncommon.Theauthorhasseenpatientswithallergicsymptoms,varyingfromrashto,occasionally,angioedema.Itis
importanttorecognizethatfluconazoleisonememberoftheazoleclassofdrugsanditisdifficulttodistinguishbetween
patientswithallergytofluconazolealoneversusthosewithallergytotheentireazoleclass.Therefore,otheroralazoles
suchasketoconazole(Nizoral)oritraconazole(Sporanox)shouldnotbeprescribedtopatientswithtruefluconazole
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allergy.However,patientswithfluconazoleallergycanreceivetopicalazoles,suchasmiconazoleorclotrimazole.For
thosepatientswithfluconazoleallergymanifestedbyangioedemaorsevererash,theauthorhasresortedtouseoftopical
agentsinsteadofweeklyfluconazole150mg.Bothmiconazoleandclotrimazolecanbeprescribedonaonceweeklyhigh
doseregimen,500to1500mg,dependingonthedosecommerciallyavailablelocally.Otheroptionsincludenystatinper
vagina100,000unitsdailyfor7daysforacutevaginitisorboricacidpervaginafor7days.Discussionwithanallergistis
recommended.Therearenodataontheefficacyoffluconazoledesensitization,whichistheoreticallypossible.
TreatmentofpartnersAlthoughsexualtransmissionofCandidaspeciescanoccur,mostexpertsdonotrecommend
treatmentofsexualpartnerssincesexualactivityisnotasignificantcauseofinfectionorreinfection.Althoughthebulkof
evidencefromrandomizedtrialsdoesnotsupporttreatmentofsexualpartners[4750],inwomanwithrecurrent
vulvovaginitis,thisissueremainscontroversial.
Treatmentofsymptomaticmenisreviewedseparately.(See"Balanitisandbalanoposthitisinadults".)
BreastfeedingwomenNystatindoesnotenterbreastmilkandiscompatiblewithbreastfeeding.Fluconazoleis
excretedinhumanmilk,buttheAmericanAcademyofPediatrics(AAP)considerstheuseoffluconazolecompatiblewith
breastfeeding[114],asnoadverseeffectshavebeenreportedinbreastfedinfantsorinfantstreatedwithparenteral
fluconazole[115].Thereisnoinformationontheeffectofmiconazole,butoconazole,clotrimazole,tioconazole,or
terconazoleonnursinginfants,butsystemicabsorptionaftermaternalvaginaladministrationisminimal,hencetopicaluse
innursingmothersisreasonable.
PostcoitalhypersensitivityreactioninmalepartnerInavariantsyndrome,malepartnersofwomenwithvaginal
Candidacolonizationdevelopimmediatepostcoitalitchingandburningwithrednessandarashofthepenis.This
postcoitalsyndromeprobablyrepresentsanacutehypersensitivityreactiontoCandidaorganismsorantigensinthe
partner'svagina,evenintheabsenceofsymptomaticvulvovaginitis.
Maleswithrecurrentpostcoitalsymptomsdonotbenefitfromtopicalantimycotictherapysincethekeytoeradicating
symptomsliesineliminatingCandidaorganismsfromthelowergenitaltractofthefemalesexualpartner.Thisoften
requiresthefemalepartnertofollowalongtermmaintenanceantimycoticregimen.
Apostcoitalshowerandapplicationofatopicallowpotencycorticosteroidtothepenismayprovidesymptomaticrelief
within12to24hours.PenileculturesmayremainpositiveforCandidadespitenormalphysicalfindings.
PREVENTIONAsdiscussedabove,oralnystatindoesnotpreventvaginalcandidiasisandlactobacillus(oralor
vaginal)doesnotpreventpostantibioticvulvovaginitis.Inwomensusceptibletosymptomaticyeastinfectionswhentaking
antibiotictherapy,adoseoffluconazole(150mgorally)atthestartandendofantibiotictherapymaypreventpostantibiotic
vulvovaginitis[8].
COMPLEMENTARYANDALTERNATIVEMEDICINEThereisnoevidencefromrandomizedtrialsthatgarlic,tea
treeoil,yogurt(orotherproductscontainingliveLactobacillusspecies),ordouchingiseffectivefortreatmentorprevention
ofvulvovaginalcandidiasisduetoCandidaalbicans[116].
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsandBeyond
theBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgradereadinglevel,and
theyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.Thesearticlesarebestfor
patientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatienteducation
piecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10thto12thgradereadinglevel
andarebestforpatientswhowantindepthinformationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicsto
yourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingonpatientinfoandthe
keyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Vulvovaginalyeastinfection(TheBasics)"and"Patientinformation:Vulvar
itching(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Vaginalyeastinfection(BeyondtheBasics)")
SUMMARYANDRECOMMENDATIONS
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Candidaisconsideredpartofthenormalvaginalflora,butovergrowthoftheorganismandpenetrationofsuperficial
epithelialcellscanresultinvulvovaginitis.Candidaalbicansaccountsfor80to92percentofepisodesof
vulvovaginalcandidiasisCandidaglabrataisthenextmostcommonspecies.(See'Prevalence'aboveand
'Microbiology'aboveand'Pathogenesis'above.)
Vulvarpruritusisthedominantsymptom.Vulvarburning,soreness,andirritationarecommonandmayresultin
dysuriaanddyspareunia.Thevulvaandvaginaappearerythematous,andvulvarexcoriationandfissuresmaybe
present.Thereisoftenlittleornodischargewhenpresent,itisclassicallywhite,thick,adherent,andclumpy(curd
likeorcottagecheeselike)withnoorminimalodor.(See'Clinicalfeatures'above.)
ThediagnosisofvulvovaginalcandidiasisisbasedonthepresenceofCandidaonwetmount,Gramsstain,or
cultureofvaginaldischargeinawomanwithcharacteristicclinicalfindings.(See'Officediagnosis'above.)
Cultureisnotnecessaryfordiagnosisifmicroscopyshowsyeast,butshouldbeobtainedin(see'Roleofculture'
above):
Womenwithclinicalfeaturesofvulvovaginalcandidiasis,normalvaginalpH,andnegativemicroscopy.
Womenwithpersistentorrecurrentsymptomsbecausemanyofthesewomenhavenonalbicansinfection
resistanttoazoles.
Treatment
Treatmentisindicatedtorelievesymptoms.Asymptomaticwomenandsexualpartnersdonotrequiretreatment.
(See'Treatment'aboveand'Treatmentofpartners'above.)
Thetreatmentregimenisbasedonwhetherthewomanhasanuncomplicatedinfection(90percentofpatients)or
complicatedinfection(10percentofpatients).Criteriaarelistedinthetable(table2).(See'Treatment'above.)
UncomplicatedinfectionsOralandtopicalantimycoticdrugsachievecomparableclinicalcurerates,whicharein
excessof80percentinuncomplicatedinfection(table3).(See'Uncomplicatedinfection'above.)
Wesuggestasingledoseoforalfluconazole(150mg)fortreatmentofuncomplicatedinfectionsratherthan
multidoseandtopicalregimens(Grade2C).(See'Uncomplicatedinfection'above.)
ComplicatedinfectionsWomenwithcomplicatedinfectionrequirelongercoursesoftherapythanwomenwith
uncomplicatedinfection.(See'Complicatedinfections'above.)
Forwomenwithseveresymptoms,wesuggestfluconazole(150mg)intwosequentialdosesgiventhreedaysapart
ratherthantopicalantimycoticagents(Grade2C).(See'Severesymptomsorcompromisedhost'above.)
FortreatmentofC.glabrata,wesuggestintravaginalboricacid(600mgcapsuleoncedailyatnightfortwoweeks)
ratherthananazole,boricacid,orflucytosinecream(Grade2C).(See'C.glabrata'above.)
Forpregnantwomen,wesuggestatopicalimidazole(clotrimazole,miconazole)vaginallyforsevendaysratherthan
anystatinpessaryoranoralazole(Grade2C).Casereportshavedescribedapatternofbirthdefects(abnormalities
ofcranium,face,bones,andheart)afterfirsttrimesterexposuretohighdoseoralazoletherapy(400to800mg/day)
andcohortstudieshavereportedconflictingdataonriskofmiscarriage.(See'Pregnancy'above.)
Forwomenwithrecurrentvulvovaginitis(4episodes/year),wesuggestsuppressivemaintenancetherapyrather
thantreatmentofindividualepisodes(Grade2B).Weprescribeinitialinductiontherapywithfluconazole150mg
every72hoursforthreedoses,thenmaintenancefluconazole150mgonceperweekforsixmonths.Womenwith
recurrentinfectionshouldtrytoeliminateorreduceriskfactorsforinfection.(See'Recurrentinfection'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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GRAPHICS
Clinicalfindingsinwomenwithvaginitis
Normal
findings

Parameter

Vulovaginal
candidiasis

Bacterial
vaginosis

Trichomoniasis

Symptoms

Noneormild,
transient

Pruritus,soreness,
dyspareunia

Malodorous
discharge,no
dyspareunia

Malodorous
discharge,burning,
postcoitalbleeding,
dyspareunia,dysuria

Signs

Normalvaginal
dischargeconsists
of1to4mLfluid
(per24hours),
whichiswhiteor
transparent,thin
orthick,and
mostlyodorless

Vulvarerythema
and/oredema.
Dischargemaybe
whiteandclumpy
andmayormay
notadhereto
vagina.

Offwhite/graythin
dischargethat
coatsthevagina

Thingreenyellow
discharge,
vulvovaginal
erythema

VaginalpH

4.0to4.5

4.0to4.5

>4.5

5.0to6.0

Aminetest

Negative

Negative

Positive(in7080
percentof
patients)

Oftenpositive

Salinemicroscopy

PMN:ECratio<1
rodsdominate
squames+++

PMN:ECratio<1
rodsdominate
squames+++
pseudohyphae
(presentinabout
40percentof
patients)budding
yeastfor
nonalbicans
Candida

PMN:EC<1loss
ofrodsincreased
coccobacilliclue
cellscompriseat
least20percentof
epithelialcells
(presentin>90
percentof
patients)

PMN++++mixed
floramotile
trichomonads
(presentinabout60
percentofpatients)

10percent

Negative

Pseudohyphae(in
about70percent
ofpatients)

Negative

Negative

Ifmicroscopy
nondiagnostic:

QuantitativeGram
stain(eg,Nugent
criteria,Hay/Ison
criteria)

Ifmicroscopy
nondiagnostic:

DNAHybridization
probe(eg,Affirm
VPIII)

Rapidantigentest
(eg,OSOM
TrichomonasRapid
Test)

potassium
hydroxide
microscopy
Othertests

Culture
DNAhybridization
probe(eg,Affirm
VPIII)

Cultureofno
value

Culture(eg,InPouch
TVculturesystem)

Nucleicacid
amplificationtest
(eg,APTIMA

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Trichomonas
vaginalistest)
DNAHybridization
probe(eg,AffirmVP
III)
Differential
diagnosis

Physiologic
leukorrhea

Contactirritantor
allergicvulvar
dermatitis,
chemicalirritation,
focalvulvitis
(vulvodynia)

ElevatedpHin
trichomoniasis,
atrophicvaginitis,
anddesquamative
inflammatory
vaginitis

Purulentvaginitis,
desquamative
inflammatory
vaginitis,atrophic
vaginitis,erosive
lichenplanus

PMN:polymorphonuclearleukocytesEC:vaginalepithelialcells.
Graphic68759Version10.0

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Candidaalbicansvaginitis

Lowpowermicrographofhyphalelementsseenon10%potassium
hydroxideexaminationofapatientwithC.albicansvaginitis.
CourtesyofJackDSobel,MD.
Graphic59030Version4.0

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Buddingyeast

BuddingyeastrepresentingC.glabrata.
Graphic61326Version2.0

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BuddingcellsofCandidaspecies

Candidaalbicans,C.krusei,C.parapsilosisandC.tropicalisallform
ellipticalbuddingcellsthattypicallyarelargerinsizethanthoseofC.
glabrata.Elaboratemulticellularfilaments,particularlywhenin
contactwithasolidsubstratesuchasmucosalmembranesoragar
culturemedia.
CourtesyofWileySchell,MS.
Graphic53369Version3.0

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Candidapseudohyphae

Pseudohyphae(asopposedtotruehyphae)areformedwhenbuds
elongatewithdifferentialratesofwallsynthesisatvariouspoints
alongthecellwall.Elongationthenstops,andthecellproducesanew
apicalbudwhichelongates.Thisrepeatedprocessofbuddingand
elongationcanresultinextensivefilamentation.Sidebranches
initiateasbudsanddevelopinthesamemanner.Inmostcases,a
constrictionremainsandcanbeseenattheoriginofeachbud.
CourtesyofWileySchell,MS.
Graphic80723Version2.0

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TruehyphaeofCandidaalbicans

Truehyphae(asopposedtopseudohyphae)elongatethrougha
processofapicalsynthesisthatdoesnotinvolvebudding.Sincebuds
arenotpresentatthehyphaltips,thehyphaedonotexibitperiodic
constrictionsassociatedwiththebuddingprocess.
CourtesyofWileySchell,MS.
Graphic76924Version1.0

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Candidaglabrata

Candidaglabratagrowsasasmall,elliptical,budding,unicellular
yeast.Budsrarelyadheretooneanotherinrudimentarychains,but
filamentousgrowthdoesnotoccur.
CourtesyofWileySchell,MS.
Graphic61641Version3.0

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Classificationofcandidalvaginitis
Variable

Uncomplicated
disease*

Complicateddisease

Symptomseverity

Mildormoderate

Severe

Frequency

Sporadic

Recurrent

Organism

Candidaalbicans

Nonalbicansspecies

Host

Normal

Abnormal(eg,uncontrolleddiabetesmellitus,
recurrentinfections,immunosuppression)

*PatientsmusthaveALLofthesefeatures.
PatientsmayhaveANYofthesefeatures.
Graphic62038Version3.0

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Treatmentofuncomplicatedvaginalcandidiasis
Drugandtrade
name(s)

Requiresa
prescriptioninUS

Preparation

Intravaginal*
doseforadult

Clotrimazole
GyneLotrimin

No

1percentcream

1applicatorful(~5g)
dailyfor7days

GyneLotrimin3

No

2percentcream

1applicatorful(~5g)
dailyfor3days

GyneLotrimin

Notapplicable(not
availableinUS)

100mgvaginaltablet

Insert1vaginaltablet
dailyfor7daysor2
tabletsdailyfor3days

No

2percentcream

1applicatorful(~5g)
dailyfor7days

Miconazole
Monistat7

(combinationkitmay
include2percent
miconazolecreamfor
externaluse)
Monistat3

No

4percentcream

1applicatorful(~5g)
dailyfor3days

Monistat7

No

100mgvaginal
suppository

1suppositorydailyfor7
days

Monistat3 ,Vagistat
3

No(combinationkit)

200mgvaginal
suppository
(combinationkitmay
include2percent
miconazolecreamfor
externaluse)

1suppositorydailyfor3
days

Monistat1

No

1200mgvaginal
suppository
(combinationkitmay
include2percent
miconazolecreamfor
externaluse)

1suppositoryfor1day

Notapplicable(not
availableinUS)

100,000unitvaginal
tablet

Insert1vaginaltablet
dailyfor14days

Terazole7,Zazole

Yes

0.4percentcream

1applicatorful(~5g)
dailyatbedtimefor7
days

Terazole3,Zazole

Yes

0.8percentcream

1applicatorful(~5g)
dailyatbedtimefor3
days

Yes(genericsuppository)

Nystatin
Nystatinvaginal
(formerUStrade
nameMycostatin)
Terconazole

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Terazole3,Zazole

Yes

80mgvaginal

1suppositorydailyat

suppository

bedtimefor3days

No

6.5percentointment

1applicatorful(~5g)at
bedtimeasasingledose

Yes

2percentcream

1applicatorful(~5g)as
asingledose

150mgoraltablet

Singledosebymouth

Tioconazole
Vagistat1,1Day
(fromMonistat)
Butoconazole
Gynazole1

FluconazoleORALADMINISTRATION
Diflucan

Yes

Therearenosignificantdifferencesinefficacyamongtopicalandsystemicazoles(curerates>80
percentforuncomplicatedvulvovaginalcandidiasis).
g:grams.
*Exceptfluconazole(oraladministration).
Genericequivalentpreparation(s)areavailableinUS.
NotavailableinUS.
Cureratewithnystatinis70to80percent.
Itraconazoleisanotheroralantifungalthatappearstobeeffective.PitsouniE,etal.AmJObstetGynecol
2008198:153.
Rarecasesofanaphylaxisandtoxicepidermalnecrolysishavebeenreportedduringterconazoletherapy.
Datafrom:LexicompOnline.Copyright19782016Lexicomp,Inc.AllRightsReserved.
Graphic71686Version14.0

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Treatmentofcomplicatedvaginalcandidiasis
Severevaginitissymptoms
Oralfluconazole150mgevery72hoursfor2or3doses(dependingonseverity)
OR
Topicalazoleantifungaltherapydailyfor7to14days.Alowpotencytopicalcorticosteroidcanbeappliedto
thevulvafor48hourstorelievesymptomsuntiltheantifungaldrugexertsitseffect.

Recurrentvulvovaginalcandidiasis
Inductionwithfluconazole150mgevery72hoursfor3doses,followedbymaintenancefluconazole150
mgonceperweekfor6months.
Iffluconazoleisnotfeasible,optionsinclude10to14daysofatopicalazoleoralternateoralazole(eg,
itraconazole)followedbytopicalmaintenancetherapyfor6months(eg,clotrimazole200mg[eg,10
gramsof2percent]vaginalcreamtwiceweeklyor500mgvaginalsuppositoryonceweekly).

NonalbicansCandidavaginitis
Therapydependsuponspeciesidentified:
C.glabrata:Intravaginalboricacid*600mgdailyfor14days
Iffailureoccurs:17percenttopicalflucytosinecream,5gramsnightlyfor14days
C.krusei:Intravaginalclotrimazole,miconazole,orterconazolefor7to14days
Allotherspecies:Conventionaldosefluconazole

Compromisedhost(eg,poorlycontrolleddiabetes,immunosuppression,
debilitation)andCandidaisolatesusceptibletoazoles
Oralortopicaltherapyfor7to14days

Pregnancy
Topicalclotrimazoleormiconazolefor7days

Boricacidcapsulesandflucytosinecreamarenotcommerciallyavailable,butcanbemadebya
compoundingpharmacy.
*Boricacidcapsulescanbefatalifswallowed.
Reference:
1.PappasPG,KauffmanCA,AndesD,etal.Clinicalpracticeguidelinesforthemanagementofcandidiasis:
2009updatebytheInfectiousDiseasesSocityofAmerica.ClinInfectDis200948:503.
Graphic50932Version8.0

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Candidavulvovaginitis

ContributorDisclosures
JackDSobel,MDNothingtodisclose.RobertLBarbieri,MDNothingtodisclose.CarolAKauffman,MDNothingto
disclose.KristenEckler,MD,FACOGNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedby
vettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.
AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
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