International Journal of Pharmacy and Pharmaceutical Sciences

ISSN- 0975-1491

Vol 2, Issue 4, 2010

ReviewArticle

ORALCANDIDIASIS:AREVIEW

YUVRAJSINGHDANGI1,MURARILALSONI1,KAMTAPRASADNAMDEO1
InstituteofPharmaceuticalSciences,GuruGhasidasCentralUniversity,Bilaspur(C.G.)49500Email:yuvi2006@gmail.com
Received:13Jun2010,RevisedandAccepted:16July2010
ABSTRACT
Candidiasis,acommonopportunisticfungalinfectionoftheoralcavity,maybeacauseofdiscomfortindentalpatients.Thearticlereviewscommon
clinical types of candidiasis, its diagnosis current treatment modalities with emphasis on the role of prevention of recurrence in the susceptible
dental patient. The dental hygienist can play an important role in education of patients to prevent recurrence. The frequency of invasive fungal
infections(IFIs)hasincreasedoverthelastdecadewiththeriseinatriskpopulationsofpatients.ThemorbidityandmortalityofIFIsarehighand
managementoftheseconditionsisagreatchallenge.Withthewidespreadadoptionofantifungalprophylaxis,theepidemiologyofinvasivefungal
pathogenshaschanged.NonalbicansCandida,nonfumigatusAspergillusandmouldsotherthanAspergillushavebecomeincreasinglyrecognised
causes of invasive diseases. These emerging fungi are characterised by resistance or lower susceptibility to standard antifungal agents. Oral
candidiasis is a common fungal infection in patients with an impaired immune system, such as those undergoing chemotherapy for cancer and
patientswithAIDS.Ithasahighmorbidityamongstthelattergroupwithapproximately85%ofpatientsbeinginfectedatsomepointduringthe
courseoftheirillness.AmajorpredisposingfactorinHIVinfectedpatientsisadecreasedCD4Tcellcount.ThemajorityofinfectionsareduetoC.
albicans although other species such as C. glabrata, C. tropicalis, C. krusei and C. parapsilosis are increasingly isolated. The systemic azoles,
ketoconazole, fluconazole and itraconazole, have been an important benefit in treatment. To date, resistance has primarily been a problem with
fluconazoleinAIDS.However,itisimportantthatmeasuresareinstitutedtopreventthespreadofresistantstrainsandthedevelopmentofcross
resistance.AlthoughtheNCCLShasestablishedareferencemethodtomeasureinvitrosusceptibility,besidesalreadypublishedpapers,moredata
arenecessarytodemonstratethatresistancecorrelateswithclinicalfailure.
Keywords:Candidiasis

INTRODUCTION
Oral candidiasis is one of the most common, treatable oral mucosal
infectionsseeninpersonswithhumanimmunodeficiencyvirus(HIV)
infection or acquired immune deficiency syndrome (AIDS)1.Oral
candidiasiscanbeafrequentandsignificantsourceoforaldiscomfort,
pain,lossoftaste,andaversiontofood.Candidaalbicanscarriageand
a history of oral candidiasis are other significant risk factors for oral
candidiasis2.TheinfectioniscausedbyCandidaAlbicans,adimorphic
fungal organism that typically is present in the oral cavity in a non
pathogenic state in about onehalf of healthy individuals. Normally
presentasayeast,theorganism,under favorableconditions, hasthe
abilitytotransformintoapathogenic(diseasecausing)hyphaelform.
Conditions that favor this transformation include broadspectrum
antibiotic therapy, xerostomia, immune dysfunction (secondary to
systemicdiseasessuchasdiabetesortheuseofimmunesuppressant
medications),orthepresenceofremovableprostheses.Furthermore,
aboutoneinfourpatientswithlichenplanuswillhavesuperimposed
candidiasis. Unless the patient is severely immunocompromised, the
infection is generally limited to the superficial mucosa and skin.
Invasivecandidiasisinfectionisrare,withdisseminateddiseaseeven
moreso.Thissuperficialnatureoftheinfectionmakesoralcandidiasis
so amenable to treatment. Several antifungal agents can be used
topically.Fortopicalagents,successfultherapy dependsonadequate
contact time (2 minutes) between the agent and the oral mucosa.
Treatmentdurationvariesfrom7to14days,withtherapyminimally
continuedfor2to3daysbeyondthelastclinicalsignsandsymptoms.
Topical agents have the benefit of few side effects at normal
therapeuticdosesbecauseoftheirlackofgastrointestinalabsorption.
However, sucrose containing topical agents can be cariogenic when
used over prolonged time periods3, such that adjunctive topical
fluoride therapy may be needed. Systemic antifungals have the
advantageofoncedailydosingandsimultaneoustreatmentoffungal
infections at multiple body sites. However, these antifungals have
more side effects, and selection requires consideration of important
drug interactions. The present work reviews the common clinical
types of oral candidiasis, its diagnosis, and current treatment
modalities with emphasis on the role of prevention of recurrence in
the susceptible dental patient. The dental hygienist can play an
important role in the education of patients to prevent recurrence.
Candidiasisisacommonoralandperioralopportunisticinfectionthat
usually results from overgrowth of endogenous Candida fungal

microorganisms.TherearemanyspeciesofCandida(Table1)4butC.
albicans is the fungal microorganism most often encountered in the
ambulatory general practice dental patient. Changes in the oral
environment that can predispose or precipitate oral candidiasis
include:antibiotics,corticosteroids,drymouth(xerostomia), diabetes
mellitus, nutritional deficiencies, and immunosuppressive diseases
and therapy1. Saliva contains antifungal proteins including histatins
and calprotectin that help protect patients from Candida infections5.
Theseprotectiveproteinsareabsentinapatientwhohasxerostomia.
Individuals who use corticosteroid asthma inhalers must rinse their
mouths with water after each use to reduce their chances of
developingoralcandidiasis.Excellentoralhygiene,includingbrushing
and flossing of the teeth twice daily and maintenance of adequate
intraoral moisture, is critical in the prevention of candidiasis
recurrenceinthesusceptiblepatient.
Fluconazole,anovelbistriazoleantifungalagentintroducedin1990,
hassystemiceffectsthatmaybebeneficialforotherfungalinfections.
Subjectsinthefluconazoleprophylacticarmofoneantifungalplacebo
controlled trial showed improvement of dermatophytoses, such as
tinea pedis, onychomycosis, and tinea cruris6. In addition, systemic
fluconazole prophylaxis may prevent esophageal and vaginal
candidiasis7, cryptococcemia, histoplasmosis, and other deep fungal
infections.Unlikeketoconazole, fluconazole is notaltered by changes
ingastricacidityandcarrieslessriskofhepatotoxicity;however,many
of the same drug interactions are possible. A newly raised concern
about the wide spread use of fluconazole is the potential for
developmentofazoleresistantCandidaalbicansandselectionofnon
albicans Candida species, which also increase in prevalence with
immune decline and further complicate management of some
individuals8,9,10.
Causativeorganisms
Candidaspp.
Amongthefungalpathogens,Candidaspp.arethemostpredominant
causes of invasive infections. The annual incidence of Candida
associated BSIs ranged from 6 to 23 per 100 000 persons in the
USA11,12 and from 2.53 to 11 per 100 000 persons in European
countries13. In various reports, Candida spp. accounted for 810% of
nosocomial BSIs11. Rising incidences of candidaemia have been
reported throughout the world in the past two decades11,13,14. The

Dangietal.
IntJPharmPharmSci,Vol2,Issue4,3641

major predisposing factors included surgical intervention, intensive

care treatment, solid tumour or haematological malignancies, use of
steroids and premature birth13. Crude mortality rates remain high
despite advances in medical care, ranging from 30% to 50% 11,12,13.
More than 95% of Candidaassociated BSIs are caused by ve major
species: C. albicans, Candida glabrata, Candida parapsilosis, Candida
tropicalisandCandidakrusei12,13,15,16.Candidaparapsilosisoccurswith
high frequency in premature neonates and in patients with vascular
catheters 17,18. Candida glabrata infections are rare in infants and
children butare signicantly more commonin theelderly19. Candida
tropicalis plays an important role as a cause of invasive diseases in
patients with haematological malignancy20. Overall, the nonalbicans
Candidaspp.haveshownanincreasingtrendascausativepathogens
inBSIs21witha1011%incrementovera6.5yearperiodinaglobal
report21.Withthemorewidespreaduseofuconazole,theemergence
ofC.glabrataandC.kruseihasbeenreportedintheUSA22,23.However,
theroleofspecieswithlowersusceptibilitytoazoleshasbeenlimited
inotherareas.Newtriazoles,suchasvoriconazoleandposaconazole,
and the echinocandinsare active against these two species,although
crossresistance was noted within the azoles in some C. glabrata
strains.
Aspergillusspp.
Aspergillus spp. are commonly found in soil, water and decaying
material all over the world. Unlike invasive candidiasis, invasive
aspergillosis(IA)occurspredominantlyinhighlyimmunocompromised
patients24,25,26. The main affected populations are patients with
haematological malignancies and/or those receiving haematopoietic
stem cell transplantation (HSCT)27. IA is also an emerging condition in
patients with other causes of immunosuppression, such as solid organ
transplantation,advancedacquiredimmunodeciencysyndrome(AIDS)
and treatment with newer immunosuppressive agents such as
iniximab28. The usual route of infections for IA is inhalation of
Aspergillusconidia.ThemostfrequentlyinvolvedsitesofIAaresinuses,
lungs, brain and disseminated infection. IA is associated with a high
mortality rate, which exceeds 50% in most reports. Higher mortality
rates were noted in patients receiving HSCT compared with patients
receivingsolidorgantransplants(68%vs.41%;P<0.0001),inpatients
withcentralnervoussystemdisease(88%vs.53%;P=0.0005)andin
nonneutropeniccomparedwithneutropenicpatients(89%vs.60%;P<
0.05)29.
Othermoulds
ZygomycetesarefungibelongingtotheorderMucorales,whichform
broad hyphae and are generally nonseptate. Genera that are able to
cause invasive diseases include Rhizopus, Rhizomucor, Absidia and
Cunninghamella30,31. Infections due to zygomycetes are classically
characterised by vascular invasion, leading to thrombosis and tissue
necrosis.ZygomycetesaresusceptibletoamphotericinBbutgenerally
resistant to most triazoles and the echinocandins. Breakthrough
zygomycosis has been reported in patients receiving voriconazole or
caspofungin prophylaxis, as these agents lack activity against
zygomycetes32,33. Voriconazole and posaconazole have been reported
assuccessfultreatmentsforfusariosis.
Clinicalspectrumofthedisease
InfectionwithCandidaAlbicanspresentsmainlyinanyoffourforms:
pseudomembranous
candidiasis,
hyperplastic
candidiasis,
erythematous candidiasis, or angular cheilitis. Patients may exhibit
oneoracombinationofanyofthesepresentations.Angularcheilitis,
for example, will frequently be seen in combination with
erythematouscandidiasisindenturewearers(Table3).
Pseudomembranouscandidiasis
Pseudomembranouscandidiasis,commonlyknownasthrush,isthe
formoftenseeninneonates.Itcanalso beseeninpatients receiving
topical corticosteroid therapy or in immune suppressed patients. In
fact, the presence of pseudomembranous candidiasis in a seemingly
healthy adult may be an indication of underlying systemic disease,
such as infection with the human immunodeficiency virus (HIV).
Pseudomembranouscandidiasispresentsasmultiplewhiteplaquesof
material resembling cottage cheese that can easily be wiped away.
Theseplaquesconsistoftangledaggregatesofhyphae.Theunderlying

mucosamaybeerythematous,butulcerationwouldnotbeexpected.
Whilesymptomsaretypicallymildforthisformofinfection,patients
may complain of a slight tingling sensation or a foul taste.
Identificationofthe fungalpseudohyphaewithinexfoliative cytologic
preparations,often utilizingperiodicacidSchiffand/or Papanicolaou
stained preparations, is the optimal standard for the diagnosis of all
candidiasis, although the highest yield of positive cytology smears is
withpseudomembranouscandidiasis34.
AtrophicCandidiasis
Atrophiccandidiasisexhibitsadiffuselyreddened,oftenrelativelydry
mucosa.Theredareasareoftenconfinedtomucosaunderlyingdental
appliances such as partial dentures or orthodontic retainers.
Approximately26%ofpatientswithcompletedentureshaveatrophic
candidiasis35.
Hyperplasticcandidiasis
Thisformhasbeenreferredtoascandidalleukoplakia,althoughthis
terminology should probably be avoided. Like leukoplakia,
hyperplasticcandidiasiswillpresentasawhiteplaquethatcannotbe
wiped away by the clinician. Unlike leukoplakia, however, lesions
shouldcompletelyresolvewithroutineantifungaltherapy.
Erythematouscandidiasis
Manyconditionsfallunderthespectrumoferythematouscandidiasis.
As the term implies, lesions clinically appear red or erythematous.
While any mucosal site may be affected, erythematous candidiasis
commonly involves the tongue and palate. A form of erythematous
candidiasis that is especially common involves the hard palate and
gingivabeneathadentureorremovablepartialdenture.
Angularcheilitis
The final clinical presentation of oral candidiasis infection is angular
cheilitis. This form presents as cracking, peeling, or ulceration
involving the corners of the mouth. It will frequently be seen in
combinationwithoneoftheotherformsofcandidiasisinfection,such
astheerythematoustype.Patientswithareducedverticaldimension
of occlusion, secondary to severe attrition or worn dentures, are
particularlysusceptibletothedevelopmentofangularcheilitis.Thisis
duetotheincreasedfoldingofthesofttissuethatisfrequentlyseenat
thecornersofthemouth,creatingahavenfortheorganism.
Several overthecounter (OTC) medications including miconazole
nitrate and clotrimazole creams, and prescription nystatin or
ketoconazole creams are available to topically treat angular cheilitis.
Topicalmiconazolenitrate2%creamisvaluableinthatitiseffective
against both Candida and Staphyolococcus aureus. Dental
professionals should be cautious when recommending OTC topical
antifungalstopatientswhoareusingtheanticoagulantwarfarin.The
combination increases the risk of excessively prolonged coagulation
periods, due to interference with the liver enzymes that aid in the
metabolism of warfarin36. Angular cheilitis is typically clinically
diagnosedbasedontheuniorbilateralpresenceofasymptomaticor
painful red cracks or fissures at the corners of the mouth. Angular
cheilitis may be caused by candidiasis (20%), mixed candidial
bacterialinfections(60%),orbacteriaalone(20%)37.
Treatment
For the normal healthy patient, the treatment of oral candidiasis is
relatively simple and effective. Typically, topical medications are
adequate. A commonly prescribed antifungal agent, nystatin oral
suspension, will usually resolve most infections. However, topical
medicationsmustbeincontactwiththeorganismtoeliminateit.Since
patientsareusuallyunabletoholdliquidsintheirmouthsmorethan
briefly, clotrimazole troches are an effective alternative. These are
dissolvedslowlyintheoralcavity,allowingthedrugtobepresentfor
greaterlengthoftime.
Intraoralcandidiasis
Topical agents include nystatin suspension and clotrimazole troches,
which should be allowed to dissolve slowly in the mouth five times
daily for 14 days. Patients should avoid eating or drinking for 20
minutes after using clotrimazole troches. Intraoral appliances should
37

Dangietal.
IntJPharmPharmSci,Vol2,Issue4,3641

be removed during the treatment as the medication works topically

and must be in contact with the tissue. Systemic prescription
antifungal agents include ketoconazole38, fluconazole39, and
itraconazole40.

applianceshouldbefreeofdebrisandconcretions.Householdchlorine
bleach,althougheffectiveandinexpensive,cancausedamagetodental
metals, acrylic, and tissueconditioning materials42. To avoid damage
to prosthetic appliances, a germicide deodorizer containing sodium
benzoate, citrate, and disodium phosphate (Oral Safe, Great Lakes
Orthodontics, Tonawanda, NY) can beused to soaktheappliance for
sixhours.Thissolutioncanbereusedforoneweekandisharmlessif
ingested43. Another technique utilizes five minutes of microwave
irradiation.Applying60Hzatfullpowertoacompleteacrylicdenture
ineightouncesofwatercaneffectivelysterilizeacrylicand mostsoft
dentureliners44.

Prosthodonticappliances
With any case of oral candidiasis, if the patient utilizes a removable
prosthodontic appliance it is important to disinfect the appliance,
becausetheporousmaterialorsurfacebiofilmcanserveasareservoir
of fungal microorganisms and contribute to relapse or reinfection41.
Disinfection of dental appliances is a twostep process. First, the

Table1:SpeciesofOralCandida
SpeciesofOralCandida
C.albicans
C.glabrata
C.guillermondii
C.krusei
C.parapsilosis
C.pseudotropicalis
C.stellatoidea
C.tropicalis

Table2:Topicalantifungalmedications
Topicalantifungalmedications
Dosageform/strength
OTC
Miconazolecream2%
Clotrimazolecream1%
Prescription
Ketoconazolecream2%
Nystatinointment100,000units/gram
Nystatintopicalpowder100,000units/gram
Nystatinoralsuspension100,000units/gram
Betamethasonedipropionateclotrimazole
cream
Clotrimazoletroches10mg
AmphotericinB100mg/ml

Indication
Angularcheilitis
Angularcheilitis
Angularcheilitis
Angularcheilitis
Denturestomatitis
Intraoralcandidasis
Chloronicangularcheilitis
Intraoralcandidasis
Intraoralcandidasis

Table3:Clinicalclassification
Clinicalclassification
Angularchelitis
Chronicatrophic(erythematous)
Denturestomatitis
Endocrinecandidiasissyndrome
Hyperplastic(Candidialleukoplakia)
Inflammatorypapillaryhyperplasia
Medianrhomboidglossitis
Mucocutaneous
Pseudomembranous

Xerostomia
Suchpatientsmayrequiremaintenancetherapyoftwicedaily0.12%
chlorhexidinegluconatemouthrinsesafteranacuteorchronicepisode
oforalcandidiasisisundercontrol.
Recentdevelopments
Formanyyears,amphotericinBdeoxycholateremainedthemainstay
of treatment for IFIs27. The major limitations of its usage are the
substantialadverse effects suchas fever, chills, nauseaandvomiting,
electrolyte abnormalities and, most importantly, nephrotoxicity45. In
the 1990s, the introduction of the two azoles uconazole and
itraconazole represented a considerable advance in antifungal
therapy. However, the use of uconazole is hampered by its narrow
spectrum, and the use of itraconazole is limited due to absorption

problems46. New therapeutic agents have now been developed that

providebetterantifungalactivitiesandlowertoxicities(Table2,4and
5).
Extendedspectrumtriazoles
Secondgeneration triazoles act predominantly by inhibition of the
cytochrome P450 (CYP450)dependent conversion of lanosterol to
ergosterol47.Thisleadstoanaccumulationoftoxic14methylsterols
andadepletionofmembraneassociatedergosterol.Thischangeincell
membranepropertiesresultsininhibitionofcellgrowthorcelldeath.
Antifungal agents in this class include voriconazole, which was
approved for the treatment of fungal infections in 2002, and
posaconazole,whichreceivedUSFoodandDrugAdministration(FDA)
approval in September 2006. Clinical trials of ravuconazole have not

38

Dangietal.
IntJPharmPharmSci,Vol2,Issue4,3641

yetbeencompleted.Voriconazoleisavailablebothinintravenous(i.v.)
andoralformulations.
Thebioavailabilityoftheoralformulationis>90%butisdecreasedto
80% by fatty foods48. Both i.v. and oral formulations are given as a
twicedaily dosage. A loading dose is needed to achieve steadystate
concentration rapidly (6 mg/kg twice daily on Day 1 followed by 4
mg/kg twice daily)48. Posaconazole is available only in oral
formulation (400800 mg/day in divided doses). Administering
posaconazolewithameal,inasuspensionratherthanatabletandin
divided doses increases its oral bioavailability49. Posaconazole is
excretedmainlyinthefaecesandaminorportionismetabolisedinthe
liver through glucuronidation49. Dosage adjustment for oral
voriconazoleandposaconazoleisnotnecessaryinpatientswithrenal

insufciencyorinpatientsreceivingdialysis50,51.Theconcentrationsof
voriconazole in cerebrospinal uid (CSF) are ca. 50% of plasma
concentrations, and concentrations in brain tissue are higher than
those in the CSF52. Voriconazole and posaconazole are very broad
spectrum antifungal agents. As with other azoles, they appear to be
fungistaticagainstmostyeastsbuthaveafungicidaleffectagainstthe
lamentousmoulds53.Voriconazoleandposaconazoleareveryactive
against most Candida spp., including C. krusei, C. glabrata and those
strains that are resistant to uconazole54,14. For Aspergillus spp.,
voriconazoleandposaconazoleareverypotentagainstmanyspecies,
including A. terreus, which is resistant to amphotericin B, and A.
fumigatus,which is resistant to itraconazole 55,56. They are active
against some but not all strains of opportunistic
moulds56,57,58,59,60 .

Table4:Systemicantifungalmedications
Systemicantifungalmedications
Dosageform/strength
Indication
Ketoconazoletablet200mg Intraoralcandidasis
Fluconazoletablet100mg
Intraoralcandidasis
Itraconazoletablet100mg
Intraoralcandidasis

Table5:Antifungaldrugsfortreatmentoforopharyngealcandidiasis
Genericname
AmphotericinB
Clotrimazole
Fluconazole

Proprietaryname
Fungizone
Mycelex
Diflucan

Itraconazole

Sporanox

Ketoconazole
Nystatin

Nizoral
Mycostatin

Formulation
100mg/mloralsuspension
10mgtroche
100mgtablet
10mg/mloralsuspension
40mg/mloralsuspension
100mgcapsule
10mg/mloralsuspension
200mgtablet
100,000units/mloralsuspension
200,000units/mlpastille
500,000units/mltablet
100,000units/mlvaginaltablet

Echinocandins
The echinocandins are large lipopeptide molecules that inhibit
synthesisof1,3dglucan,whichisanessentialcomponentofthecell
wall of many fungi but is absent in mammals61. Inhibition of 1,3d
glucansynthaseinterfereswithfungalcellwallsynthesis,whichleads
to osmotic instability and death of the fungal cell61. Until now,
caspofungin,micafunginandanidulafunginaretheonlyechinocandin
agentsapprovedforclinicaluse.Allechinocandinpreparationstodate
arefori.v.useonly62.Thethreeagentssharesimilarpharmacological
characteristics,withsomevariations62.Aoncedailydosingregimenis
optimal based on concentrationdependent pharmacodynamics and
prolongedpostantifungaleffects53,63,64.
A loading dose is recommended for caspofungin (75 mg loading on
Day1followedby50mg/day)andanidulafungin(200mgloadingon
Day 1 followed by 100 mg/day), but not for micafungin (50150
mg/day)65,64.Caspofunginandmicafunginaredegradedmainlyinthe
liver64whilstanidulafunginuniquelyundergoeschemicaldegradation
in the blood65. All three agents are poor substrates for the hepatic
CYP450 enzyme system. Therefore, unlike triazoles, the CYP450
independent metabolism and degradation of echinocandins reduces
concernaboutdrugdruginteractions61.Echinocandinshaveverylow
MICsagainstclinicallysignicantCandidaspp.,includingC.albicans,C.
tropicalis, C. glabrata, C. krusei, C. lusitaniae and Candida
dubliniensis66,59,67,68.
Rationaleforandagainstantifungalcombinations
The original use of antifungal combination therapy was in the
treatment of cryptococcal meningitis in patients who did not have
AIDS. Amphotericin B was the first agent available for successfully
treatinginvasive mycoses,but there have beenmajorproblemswith
systemic toxic reactions associated with its infusion and

nephrotoxicity69. Indeed, several trials have demonstrated that when

flucytosine is included in the treatment regimen, the dose of
amphotericin B could be reduced, thereby decreasing somewhat its
toxicity70,71.
ThedoseofamphotericinBwassubsequentlyincreasedandresponse
ratestotherapy,withorwithoutflucytosine,improved72,73.Atpresent,
we are faced with an increasing incidence of serious invasive fungal
mycoses and a high mortality rate secondary to these
infections74,75,76,77.
REFERENCES
1.
2.
3.

4.
5.
6.

7.

Greenspan D. Treatment of oral candidiasis in HIV infection.

OralSurgOralMedOralPathol1994;78:2115.
MacPhailLA,HiltonJF,DoddCL,GreenspanD.Prophylaxiswith
nystatin pastilles for HIVassociated oral candidiasis. J Acquir
ImmuneDeficSyndr1996;12:4706.
Pons V, Greenspan D, LozadaNur F, MacPhail L, Gallant JE,
Tunkel A, et al. Oropharyngeal candidiasis in patients with
AIDS: randomized comparison of fluconazole versus nystatin
oralsuspensions.ClinInfectDis1997;24:12047.
Scully C, el Kabir M, Samaranyake LP. Candida and oral
candidosis: A review. Crit Rev Oral Biol Med 1994;5(2):125
157.
Challacombe SJ. Immunologic aspects of oral candidiasis. Oral
SurgOralMedOralPathol1994;78(2):202210.
Stevens DA, Greene SI, Lang OS. Thrush can be prevented in
patients with acquired immunodeficiency syndrome and the
acquired immunodeficiency syndromerelated complex.
Randomized,doubleblind,placebocontrolledstudyof100mg
oralfluconazoledaily.ArchInternMed1991;151:245864
SchumanP,CappsL,PengG,VazquezJ,ElSadrW,GoldmanAI,
et al. Weekly fluconazole for the prevention of mucosal
39

Dangietal.
IntJPharmPharmSci,Vol2,Issue4,3641

8.

9.
10.

11.
12.
13.
14.

15.

16.

17.
18.

19.
20.

21.

22.

23.

24.
25.
26.

candidiasis in women with HIV infection. A randomized,

doubleblind, placebocontrolled trial.Terry Beirn Community
Programs for Clinical Research on AIDS. Ann Intern Med
1997;126:68996
Hunter KD, Gibson J, Lockhart P, Pithie A, Bagg J.
Fluconazoleresistant Candida species in the oral flora of
fluconazoleexposedHIVpositivepatients.OralSurgOralMed
OralPatholOralRadiolEndod1998;85:55864.
Tumbarello M, Tacconelli E, Caldarola G, Morace G, Cauda R,
OrtonaL.FluconazoleresistantoralcandidiasisinHIVinfected
patients.OralDis1997;3(Suppl1):S1102.
SangeorzanJA,BradleySF,HeX,ZarinsLT,RidenourGL,Tiballi
RN, et al. Epidemiology of oral candidiasis in HIV infected
patients: colonization, infection, treatment, and emergence of
fluconazoleresistance.AmJMed1994;97:33946.
Clark TA, Hajjeh RA. Recent trends in the epidemiology of
invasivemycoses.CurrOpinInfectDis2004;17:5115.
PfallerMA,PappasPG,WingardJR.Invasivefungalpathogens:
currentepidemiologicaltrends.ClinInfectDis2006;43(Suppl.
1):S314.
Tortorano AM, Kibbler C, Peman J, Bernhardt H, Klingspor L,
GrillotR.CandidaemiainEurope:epidemiologyandresistance.
IntJAntimicrobAgents2006;27:35966
Hsueh PR, Teng LJ, Yang PC, Ho SW, Luh KT. Emergence of
nosocomial candidemia at a teaching hospital in Taiwan from
1981 to 2000: increased susceptibility of Candida species to
uconazole.MicrobDrugResist2003;8:3119.
Pfaller MA, Diekema DJ. Rare and emerging opportunistic
fungal pathogens: concern for resistance beyond Candida
albicans and Aspergillus fumigatus. J Clin Microbiol
2004;42:441931.
Hajjeh RA, Sofair AN, Harrison LH, et al. Incidence of
bloodstream infections due to Candida species and in vitro
susceptibilities of isolates collected from 1998 to 2000 in a
populationbasedactivesurveillanceprogram.JClinMicrobiol
2004;42:151927.
Kuhn DM, Mikherjee PK, Clark TA, et al. Candida parapsilosis
characterization in an outbreak setting. Emerg Infect Dis
2004;10:107481.
Sarvikivi E, Lyytikainen O, Soll DR, et al. Emergence of
uconazole resistance in a Candida parapsilosis strain that
caused infections in a neonatal intensive care unit. J Clin
Microbiol2005;43:272935.
MalaniA,HmoudJ,ChiuL,CarverPL,BielaczycA,KauffmanCA.
Candidaglabratafungemia:experienceinatertiarycarecenter.
ClinInfectDis2005;41:97581.
Marr KA, Seidel K, White TC, Bowden RA. Candidemia in
allogeneic blood and marrow transplant recipients: evolution
ofriskfactorsaftertheadoptionofprophylacticuconazole. J
InfectDis2000;181:30916.
Pfaller MA, Diekema DJ, Rinaldi MG, et al. Results from the
ARTEMISDISKglobalantifungalsurveillancestudy:a6.5year
analysis of the worldwide susceptibility of Candida and other
yeasts species to uconazole and voriconazole using
standardized disk diffusion testing. J Clin Microbiol
2005;43:584859.
Trick WE, Fridkin SK, Edwards JR, Hajjeh RA, Gaynes RP.
Seculartrendofhospitalacquiredcandidemiaamongintensive
care unit patients in theUnited tates during 19891999. Clin
InfectDis2002;35:62730.
Hope W, Morton A, Eisen DP. Increase in prevalence of
nosocomial nonCandida albicans candidaemia and the
association of Candida krusei with uconazole use. J Hosp
Infect2002;50:5665.
Baddley JW, Stroud TP, Salzman D, Pappas PG. Invasive mold
infectionsinallogeneicbonemarrowtransplantrecipients.Clin
InfectDis2001;32:131924.
Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology
and outcome of mould infections in hematopoietic stem cell
transplantrecipients.ClinInfectDis2002;34:90917.
Patterson TF, Kirkpatrick WR, White M, et al. Invasive
aspergillosis: disease spectrum, treatment practices, and
outcomes. I3 Aspergillus Study Group. Medicine (Baltimore)

2000;79:25060
27. Patterson TF. Advances and challenges in management of
invasivemycoses.Lancet2005;366:101325.
28. Lin SJ, Schranz J, Teutsch SM. Aspergillosis casefatality rate:
systematic review of the literature. Clin Infect Dis
2001;32:35866.
29. Comillet A, Camus C, Nimubona S, et al. Comparison of
epidemiological, clinical, and biological features of invasive
aspergillosisinneutropenicandnonneutropenicpatients:a6
yearsurvey.ClinInfectDis2006;43:57784.
30. Roden MM, Zaoutis T, Buchanan WL, et al. Epidemiology and
outcome of zygomycosis: a review of 929 reported cases. Clin
InfectDis2005;41:63453.
31. Spellberg B, Edwards Jr J, Ibrahim A. Novel perspectives on
mucormycosis:
pathophysiology,
presentation,
and
management.ClinMicrobiolRev2005;18:55669
32. KontoyiannisDP,LionakisMS,LewisRE,etal.Zygomycosisina
tertiarycare cancer center in the era of Aspergillusactive
antifungal therapy: a casecontrol observational study of 27
recentcases.JInfectDis2005;191:135060.
33. Imhof A, Balajee A, Fredricks D, Englund J, Marr KA.
Breakthrough fungal infections in stem cell transplant
recipients receiving voriconazole. Clin Infect Dis 2004; 39:
7436.
34. Skoglund A, Sunzel B, Lerner UH. Comparison of three test
methodsusedforthediagnosisofcandidiasis.ScandJDentRes
1994;102(5):295298
35. FenlonMR,SherriffM.Prevalenceofdenturerelatedstomatitis
inpatientsattendingadentalteachinghospitalforprovisionof
replacement complete dentures. J Ir Dent ssoc 1998;44(1):9
10.
36. Evans J, Orme DS, Sedgwick ML, Youngs GR. Treating oral
candidiasis:Potentiallyfatal.BrDentJ1997;182(12):452.
37. Ohman SC, Dahln G, Mller A, Ohman A. Angular cheilitis: A
clinicalmicrobialstudy.JOralPathol1986;15(4):213217.
38. Muzyka BC, Glick M. A review of oral fungal infections and
appropriatetherapy.JAmDentAssoc1995;126(1):6372.
39. BlomgrenJ,BerggrenU,JontellM.Fluconazoleversusnystatin
in the treatment of oral candidosis. Acta Odontol Scand
1998;56(4):202205.
40. Eisen D, Lynch DP. The Mouth: Diagnosis and Treatment. St.
Louis,MO:Mosby;1998:128135,286287.
41. Webb BC, Thomas CJ, Willcox MD, et al. Candidaassociated
denturestomatitis.Aetiologyandmanagement:Areview.Part
3. Treatment of oral candidosis. Aust Dent J 1998;43(3):160
166.
42. Chau VB, Saunders TR, Pimsler M, Elfring DR. Indepth
disinfection of acrylic resins. J Prosthet Dent 1995;74(3):309
313.
43. Granata JS, Staffanou RS. Evaluation of a new denture bath
solution.JProsthDent1991;66(6):790791.
44. Dixon DL, Breeding LC, Faler TA. Microwave disinfection of
denture base material colonized with Candida albicans. J
ProsthetDent1999;81(2):207214.
45. BatesDW,SuL,YuDT,etal.Mortalityandcostsofacuterenal
failureassociatedwithamphotericinBtherapy.ClinInfectDis
2001;32:68993
46. Poirier JM, Cheymol G. Optimisation of itraconazole therapy
usingtargetdrugconcentrations.ClinPharmacokinet1998;35:
46173
47. Manavathu EK, Cutright JL, Chandrasekar PH. Organism
dependent fungicidal activities of azoles. Antimicrob Agents
Chemother1998;42:301821
48. Jhonson LB, Kauffman CA. Voriconazole: a new triazole
antifungalagent.ClinInfectDis2003;36:6307.
49. KeatingGM.Posaconazole.Drugs2005;65:155367.
50. Leveque D, Niviox Y, Jehl F, Herbrecht R. Clinical
pharmacokinetics of voriconazole. Int J Antimicrob Agents
2006;27:27484.
51. Torres HA, Hachem RY, Chemaly RF, Kantoyiannis DP, Raad I.
Posaconazole: a broadspectrum triazole antifungal. Lancet
InfectDis2005;5:77585
40

Dangietal.
IntJPharmPharmSci,Vol2,Issue4,3641

52. LutsarI,RoffeyS,TrokeP.Voriconazoleconcentrationsinthe
cerebrospinal fluid and brain tissue of guinea pigs and
immunocompromisedpatients.ClinInfectDis2003;37:72832
53. Groll AH, Kolve H. Antifungal agents: in vitro susceptibility
testing, pharmacodynamics, and prospects for combination
therapy.EurJClinMicrobiolInfectDis2004;23:25670
54. BarchiesiF,ArzeniD,FothergillAW,etal.Invitroactivitiesof
the new antifungal triazole SCH 56592 against common and
emerging yeast pathogens. Antimicrob Agents Chemother
2000;44:2269.
55. HsuehPR,LauYJ,ChuangYC,etal.Antifungalsusceptibilitiesof
clinical isolates of Candida species, Cryptococcus neoformans,
and Aspergillus species from Taiwan: surveillance of
multicenter antimicrobial resistance in Taiwan program data
from2003.AntimicrobAgentsChemother2005;49:5127.
56. EspinelIngroff A. In vitro fungicidal activities of voriconazole,
itraconazole, and amphotericin B against opportunistic
moniliaceous and dematiaceous fungi. J Clin Microbiol
2001;39:9548.
57. Carrillo AJ, Guarro J. In vitro activities of four novel triazoles
against Scedosporium spp. Antimicrob Agents Chemother
2001;45:21513.
58. Safdar A. Progressive cutaneous hyalohyphomycosis due to
Paecilomyces lilacinus: rapid response to treatment with
caspofunginanditraconazole.ClinInfectDis2002;34:14157.
59. PfallerMA,MesserSA,HollisRJ,JonesRN,DiekemaDJ.Invitro
activities of ravuconazole and voriconazole compared with
those of four approved systemic antifungal agents against
6,970 clinical isolates of Candida spp. Antimicrob Agents
Chemother2002;46:17237.
60. Gonzalez GM, Fothergill AW, Sutton DA, Rinaldi MG,
Loebenberg D. In vitro activities of new and established
triazoles against opportunistic filamentous and dimorphic
fungi.MedMycol2005;43:2814.
61. Keating GM, Figgitt DP. Caspofungin: a review of its use in
oesophageal candidiasis, invasive candidiasis and invasive
aspergillosis.Drugs2003;63:223563.
62. DenningDW.Echinocandinantifungaldrugs.Lancet2003;362:
114251
63. GreenLJ, MarderP,Mann LL,ChioLC, Current WL.LY303366
exhibitsrapidandpotentfungicidalactivityinflowcytometric
assays of yeast viability. Antimicrob Agents Chemother
1999;43:8305.

64. Chandrasekar PH, Sobel JD. Micafungin: a new echinocandin.

ClinInfectDis2006;42:11718.,
65. VazquezJA,SobelJD.Anidulafungin:anovelechinocandin.Clin
Infect Dis 2006;43:21522., Denning DW. Echinocandin
antifungaldrugs.Lancet2003;362:114251.
66. PfallerMA,DiekemaDJ,MesserSA,HollisRJ,JonesRN.Invitro
activities of caspofungin compared with those of fluconazole
anditraconazoleagainst3,959clinicalisolatesofCandidaspp.,
including157fluconazoleresistantisolates.AntimicrobAgents
Chemother2003;47:106871.
67. Tawara S, Ikeda F, Maki K, et al. In vitro activities of a new
lipopeptide antifungal agent, FK463, against a variety of
clinicallyimportantfungi.AntimicrobAgentsChemother2000;
44:5762.
68. CarverPL.Micafungin.AnnPharmacother2004;38:170721.
69. GallisHA,DrewRH,PickardWV~.AmphotericinB:30yearsof
clinicalexperience.RevInfectDis1990;12:308329
Bennett JE, DismukesWE, Duma RJ et aI.A comparison of
amphotericin B alone and combined with flucytosine in the
treatment of cryptococcal meningitis. N Engl J Med 1979; 30
I:126131.
70. DismukesWE, Cloud G, Gallis HA et aI.Treatment of
cryptococcalmeningitiswithcombinationamphotericinBand
flucytosinefor4ascomparedwith6weeks.NEnglJMed1987;
317:33434I.
71. Saag MS, PowderlyWG, Cloud GA et al. Comparison of
amphotericinBwithfluconazoleinthetreatmentofacuteAIDS
associated cryptococcal meningitis. N Engl J Med 1992; 326:
8389.
72. Van Der Horst C, Saag M, Cloud Get aI.Treatment of
cryptococcal meningitis associated with the acquired
immunodeficiencysyndrome.NEnglJMed1997;337:1521.
73. JarvisWR. Epidemiology of nosocomial fungal infections, with
emphasis on Candida species. Clin Infect Dis 1995; 20:1526
1530.
74. Anaissie E, Gokaslan A, Hachem R et al. Azole therapy for
trichosporonosis: clinical evaluation of eight patients,
experimental therapy for murine infection, and review. Clin
InfectDis.1992;15(5):781787.
75. Dromer F, Dupont B. The increasing problem of fungal
infections in the immunocompromised host.J Mycologie
Medicale1996;6:I6.
76. SamonisG,BafaloukosD. Fungal infections in cancer patients:
an escalating problem. In Vivo 1992; 6(2): 183193.

41