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ORAL CANDIDIASIS
Disusun untuk Memenuhi Syarat Mengikuti Ujian Kepaniteraan Klinik
di Bagian Kulit dan Kelamin
Rumah Sakit Umum Daerah Ambarawa
Diajukan Kepada :
Pembimbing : dr. Hiendarto, Sp.KK
Disusun Oleh :
Ayu Farah Ummamah 1220221145
Kepaniteraan Klinik Departemen Kulit dan Kelamin
FAKULTAS KEDOKTERAN UPN VETERAN JAKARTA
Rumah Sakit Umum Daerah Ambarawa
PERIODE 27 Mei 30 Juni 2013
LEMBAR PENGESAHAN KOORDINATOR KEPANITERAAN
KULIT DAN KELAMIN
Journal reading dengan judul :
ORAL CANDIDIASIS
Diajukan untuk Memenuhi Syarat Mengikuti Ujian Kepaniteraan Klinik
di Departemen Kulit dan Kelamin
Rumah Sakit Umum Daerah Ambarawa
Disusun Oleh:
Ayu Farah Ummamah 1220221145
Telah disetujui oleh Pembimbing:
Nama pembimbing Tanda Tangan Tanggal
dr. Hiendarto, Sp.KK ............................. .............................
Mengesahkan:
Koordinator Kepaniteraan Kulit dan Kelamin
dr. Hiendarto, Sp.KK
NIP. 197308042009091001
ReviewArticle
ORALCANDIDIASIS:AREVIEW
YUVRAJSINGHDANGI
1
,MURARILALSONI
1
,KAMTAPRASADNAMDEO
1
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
management of these conditions is a great challenge.With the widespread adoptionof antifungal prophylaxis,theepidemiology of invasivefungal
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
patients with AIDS. It has a high morbidity amongst the latter group with approximately 85% of patients being infected at some point during the
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,itisimportantthatmeasuresareinstitutedtopreventthespreadofresistantstrainsandthe developmentofcross
resistance.AlthoughtheNCCLShasestablishedareferencemethodtomeasureinvitrosusceptibility,besidesalreadypublishedpapers,moredata
arenecessarytodemonstratethatresistancecorrelateswithclinicalfailure.
Keywords:Candidiasis
INTRODUCTION
Oral candidiasis is one of the most common, treatable oral mucosal
infectionsseen in persons with human immunodeficiency virus (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
candidiasis
2
.TheinfectioniscausedbyCandidaAlbicans,adimorphic
fungal organism that typically is present in the oral cavity in a non
pathogenic state in about onehalf of healthy individuals. Normally
present as a yeast, the organism, under favorable conditions, has the
abilitytotransformintoapathogenic(diseasecausing)hyphaelform.
Conditions that favor this transformation include broadspectrum
antibiotic therapy, xerostomia, immune dysfunction (secondary to
systemic diseases such as diabetes or theuse of immune suppressant
medications), or the presence of removable prostheses. Furthermore,
about onein four patients withlichen planus will havesuperimposed
candidiasis. Unless the patient is severely immunocompromised, the
infection is generally limited to the superficial mucosa and skin.
Invasive candidiasis infection is rare, with disseminated disease even
moreso.Thissuperficialnatureoftheinfectionmakesoralcandidiasis
so amenable to treatment. Several antifungal agents can be used
topically. For topical agents, successful therapy depends on adequate
contact time (2 minutes) between the agent and the oral mucosa.
Treatment duration variesfrom 7 to 14days, withtherapyminimally
continuedfor2to3daysbeyondthelastclinicalsignsandsymptoms.
Topical agents have the benefit of few side effects at normal
therapeutic doses because of their lack ofgastrointestinal absorption.
However, sucrose containing topical agents can be cariogenic when
used over prolonged time periods
3
, such that adjunctive topical
fluoride therapy may be needed. Systemic antifungals have the
advantage of oncedaily dosing and simultaneous treatment of fungal
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. There are many species of Candida (Table 1)
4
but C.
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, dry mouth (xerostomia), diabetes
mellitus, nutritional deficiencies, and immunosuppressive diseases
and therapy
1
. Saliva contains antifungal proteins including histatins
and calprotectin that help protect patients from Candida infections
5
.
Theseprotectiveproteinsareabsentinapatientwhohasxerostomia.
Individuals who use corticosteroid asthma inhalers must rinse their
mouths with water after each use to reduce their chances of
developingoralcandidiasis.Excellentoralhygiene,including brushing
and flossing of the teeth twice daily and maintenance of adequate
intraoral moisture, is critical in the prevention of candidiasis
recurrenceinthesusceptiblepatient.
Fluconazole, a novel bistriazole antifungal agent introduced in 1990,
hassystemiceffectsthatmaybebeneficialforotherfungalinfections.
Subjectsinthefluconazoleprophylacticarmofoneantifungalplacebo
controlled trial showed improvement of dermatophytoses, such as
tinea pedis, onychomycosis, and tinea cruris
6
. In addition, systemic
fluconazole prophylaxis may prevent esophageal and vaginal
candidiasis
7
, cryptococcemia, histoplasmosis, and other deep fungal
infections. Unlike ketoconazole, fluconazole is not altered 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
individuals
8,9,10
.
Causativeorganisms
Candidaspp.
Among the fungal pathogens, Candida spp. are the mostpredominant
causes of invasive infections. The annual incidence of Candida
associated BSIs ranged from 6 to 23 per 100 000 persons in the
USA
11,12
and from 2.53 to 11 per 100 000 persons in European
countries
13
. In various reports, Candida spp. accounted for 810% of
nosocomial BSIs
11
. Rising incidences of candidaemia have been
reported throughout the world in the past two decades
11,13,14
. The
International Journal of Pharmacy and Pharmaceutical Sciences
ISSN- 0975-1491 Vol 2, Issue 4, 2010
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IntJPharmPharmSci,Vol2,Issue4,3641
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38
Table1:SpeciesofOralCandida
SpeciesofOralCandida
C.albicans
C.glabrata
C.guillermondii
C.krusei
C.parapsilosis
C.pseudotropicalis
C.stellatoidea
C.tropicalis
Table2:Topicalantifungalmedications
Topicalantifungalmedications
Dosageform/strength Indication
OTC
Miconazolecream2% Angularcheilitis
Clotrimazolecream1% Angularcheilitis
Prescription
Ketoconazolecream2% Angularcheilitis
Nystatinointment100,000units/gram Angularcheilitis
Nystatintopicalpowder100,000units/gram Denturestomatitis
Nystatinoralsuspension100,000units/gram Intraoralcandidasis
Betamethasonedipropionateclotrimazole
cream
Chloronicangularcheilitis
Clotrimazoletroches10mg Intraoralcandidasis
AmphotericinB100mg/ml Intraoralcandidasis
Table3:Clinicalclassification
Clinicalclassification
Angularchelitis
Chronicatrophic(erythematous)
Denturestomatitis
Endocrinecandidiasissyndrome
Hyperplastic(Candidialleukoplakia)
Inflammatorypapillaryhyperplasia
Medianrhomboidglossitis
Mucocutaneous
Pseudomembranous
Xerostomia
Such patients may require maintenance therapy of twice daily 0.12%
chlorhexidinegluconatemouthrinsesafteranacuteorchronicepisode
oforalcandidiasisisundercontrol.
Recentdevelopments
Formanyyears,amphotericin B deoxycholate remainedthe mainstay
of treatment for IFIs
27
. The major limitations of its usage are the
substantial adverse effects such as fever, chills, nausea and vomiting,
electrolyte abnormalities and, most importantly, nephrotoxicity
45
. 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
problems
46
. 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
ergosterol
47
.This leadsto anaccumulationoftoxic14methylsterols
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
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IntJPharmPharmSci,Vol2,Issue4,3641
39
yetbeencompleted.Voriconazoleisavailablebothinintravenous(i.v.)
andoralformulations.
Thebioavailabilityoftheoralformulationis>90%butisdecreasedto
80% by fatty foods
48
. 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
posaconazolewith a meal,in a suspension rather thana tablet and in
divided doses increases its oral bioavailability
49
. Posaconazole is
excretedmainlyinthefaecesandaminorportionismetabolisedinthe
liver through glucuronidation
49
. Dosage adjustment for oral
voriconazoleandposaconazoleisnotnecessaryinpatientswithrenal
insufciencyorinpatientsreceivingdialysis
50,51
.Theconcentrationsof
voriconazole in cerebrospinal uid (CSF) are ca. 50% of plasma
concentrations, and concentrations in brain tissue are higher than
those in the CSF
52
. Voriconazole and posaconazole are very broad
spectrum antifungal agents. As with other azoles, they appear to be
fungistaticagainstmostyeastsbuthaveafungicidal effectagainstthe
lamentous moulds
53
. Voriconazole and posaconazole are very active
against most Candida spp., including C. krusei, C. glabrata and those
strains that are resistant to uconazole
54,14
. For Aspergillus spp.,
voriconazole and posaconazole are very potent against many species,
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
moulds
56,57,58,59,60
.
Table4:Systemicantifungalmedications
Systemicantifungalmedications
Dosageform/strength Indication
Ketoconazoletablet200mg Intraoralcandidasis
Fluconazoletablet100mg Intraoralcandidasis
Itraconazoletablet100mg Intraoralcandidasis
Table5:Antifungaldrugsfortreatmentoforopharyngealcandidiasis
Genericname Proprietaryname Formulation
AmphotericinB Fungizone 100mg/mloralsuspension
Clotrimazole Mycelex 10mgtroche
Fluconazole Diflucan 100mgtablet
10mg/mloralsuspension
40mg/mloralsuspension
Itraconazole Sporanox 100mgcapsule
10mg/mloralsuspension
Ketoconazole Nizoral 200mgtablet
Nystatin Mycostatin 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 mammals
61
. Inhibition of 1,3d
glucansynthaseinterfereswithfungalcellwallsynthesis,whichleads
to osmotic instability and death of the fungal cell
61
. Until now,
caspofungin, micafungin and anidulafungin are the only echinocandin
agentsapprovedforclinicaluse.Allechinocandinpreparationstodate
are for i.v. use only
62
. The three agents share similar pharmacological
characteristics,withsomevariations
62
.Aoncedailydosingregimenis
optimal based on concentrationdependent pharmacodynamics and
prolongedpostantifungaleffects
53,63,64
.
A loading dose is recommended for caspofungin (75 mg loading on
Day1followedby50mg/day)andanidulafungin(200mgloading on
Day 1 followed by 100 mg/day), but not for micafungin (50150
mg/day)
65,64
. Caspofungin and micafungin are degraded mainly in the
liver
64
whilst anidulafunginuniquelyundergoeschemical degradation
in the blood
65
. All three agents are poor substrates for the hepatic
CYP450 enzyme system. Therefore, unlike triazoles, the CYP450
independent metabolism and degradation of echinocandins reduces
concernaboutdrugdruginteractions
61
.Echinocandinshaveverylow
MICsagainstclinicallysignicantCandidaspp.,includingC.albicans,C.
tropicalis, C. glabrata, C. krusei, C. lusitaniae and Candida
dubliniensis
66,59,67,68
.
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
treating invasive mycoses, but there have been major problems with
systemic toxic reactions associated with its infusion and
nephrotoxicity
69
. 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
toxicity
70,71
.
ThedoseofamphotericinBwassubsequentlyincreasedandresponse
ratestotherapy,withorwithoutflucytosine,improved
72,73
.Atpresent,
we are faced with an increasing incidence of serious invasive fungal
mycoses and a high mortality rate secondary to these
infections
74,75,76,77
.
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