2012

iMedPub Journals THE INTERNATIONAL ARABIC JOURNAL Vol. 2 No. 1:1

Our Site: http://www.imedpub.com/ OF ANTIMICROBIAL AGENTS doi: 10.3823/705

Najla S.Dar-Odeh1, Mohammad Al-Beyari2,

The role of Osama A. Abu-Hammad1
antifungal 1 Professor, Faculty of dentistry, 2Assistant Professor, Faculty Correspondence:
drugs in the University of Jordan, Amman,
Jordan.
of Dentistry, Um Al Qura
University, Mecca, Saudi
Najla S.Dar-Odeh
najla_dar_odeh@yahoo.com
management of Arabia.

denture-associated Abstract
stomatitis Background: Denture-associated stomatitis is a chronic infection of the oral cav-
ity that may be associated with a number of bacterial and candidal organisms as
well as some predisposing factors. Its management may prove to be difficult if the
treatment plan was not comprehensive in addressing all the factors involved in its
etiology. The aim of this review is to underline the effectiveness of antifungal drugs
in the management of denture-associated stomatitis according to our personal
experience and the recently published literature.

Methods: Articles were obtained from pubmed as well as by a hand search.

Denture stomatitis and antifungal were used as keywords. Only articles written
in English and which were published starting from the year 1990 were included.

Conclusions: Antifungal drugs certainly have a place in the management of

This article is available from:
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denture-associated stomatitis. However, their use should be called upon after the
control of factors known to cause this infection. Denture and oral hygiene, and
management of adverse medical conditions should be the primary goal of treat-
ment. This should go hand in hand with the application of topical antifungal agents
particularly those in the cream or gel form for better patients compliance.
Key words: Denture-associated stomatitis, antifungal drugs.

Introduction environment of lowered pH and anaerobic conditions by de-

Denture-associated stomatitis (DAS) (Candida-associated
denture stomatitis, chronic atrophic candidiasis, denture-sore
mouth) is a chronic infection of the oral mucosa caused solely
by Candida species or in association with bacteria (1). The role
of Candida, and specifically C. albicans, in development of
denture stomatitis is associated with pathogenic overgrowth
of Candida on denture surfaces and the oral mucosa, and is
widely accepted as a leading etiological factor.
It affects 24-60% of denture wearers (2), and it is usually
found on the palatal mucosa beneath the fitting surface of
the upper denture. Dental prostheses may produce a local
creasing the flow of oxygen and saliva to the underlying tissue;
these conditions favor fungal overgrowth (3-5). Furthermore,
biofilms in denture plaque represent a protective reservoir for
oral microbes (6). It has also been demonstrated that Candida
organisms have an affinity for the tissue side of the denture
and although Candida infection is the primary aetiology of
most of these lesions, other factors such as poor denture
hygiene and associated bacterial flora, continuous denture
wearing, ill-fitting and traumatic dentures, carbohydrate-rich
diet and rarely, allergy to denture material are contributory
co-factors (7). It was noticed that the prevalence is associated
with the amount of tissue covered by dentures (2). It was
also found that wearing denture at night and smoking were
associated with the most extensive inflammation (8).

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There is chronic erythema and edema of the mucosa in con-
tact with the fitting surface of the denture which is usually
the maxillary denture. However, mucosa under mandibular
dentures is hardly ever involved being protected by salivary
flow (1). Clinically, there are three subtypes of DAS; type I is
a localized simple inflammation or pinpoint hyperemia, type
II is an erythematous or generalized simple type presenting
as more diffuse erythema involving a part of or the entire
denture-covered mucosa, and type III is a granular or papil-
lary type commonly involving the central part of the hard
palate and alveolar ridge (Inflammatory Papillary hyperplasia).
All three types can be found simultaneously and in varying
combinations. (2) Although the lesion is not painful, it might
cause some unfavorable complications. The affected mucosa
is atrophic providing less support for the dentures. Some pa-
tients complain of burning sensation or tingling sensation be-
neath the denture. Patients may also complain of associated
angular cheilitis (1). Early reports pointed to the carcinogenic
potential of candidal infections (9). In some patients with
HIV infection, oral candidiasis may also lead to secondary
complications such as esophageal candidiasis.(1)
Management of DAS depends upon a compehensive treat-
ment plan. Elimination of predisposing factors is considered
the first and most crucial step. The use of topical and systemic
antifungal drugs is also considered an important measure.
The goals of treatment are to identify and eliminate pos-
sible contributing factors, prevent systemic dissemination and
eliminate any associated discomfort (10).
The aim of this paper is to discuss the management of DAS
with special emphasis on antifungal drugs, a rapidly develop-
ing field for the treatment of this infection as well as other
types of oral candidiasis.
Antifungal therapy of
denture-associated stomatitis
Antifungal agents are either polyenes (nystatin and am-
photericin B) or azoles which are classified into: imidazoles(
clotrimazole, econazole, fenticonazole, isoconazole, ketocon-
azole, miconazole, sulconazole, tioconazole); and triazoles
(fluconazole, itraconazole) (1). Some of these drugs are used
topically, while others are used in a systemic form. Recent re-
search has concentrated upon a number of antifungal drugs
for the treatment of DAS namely, fluconazole, itraconazole,
miconazole and nystatin.
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OF ANTIMICROBIAL AGENTS doi: 10.3823/705
Topical Antifungals
Topical antifungal therapy for oral candidal infections is avail-
able in many forms like pastilles, troches, creams, ointments
and oral suspensions and remains the cornerstone of treat-
ment in mild, localized cases of candidoses in healthy patients
(10).
It was shown that most Candida species are susceptible to
topical antifungal drugs like amphotericin B, (11, 12) nystatin
(13), Miconazole (14-17) and clotrimazole (1). Being recom-
mended as the first choice of treatment, (1) Amphotericin B
is usually in the form of lozenges or oral suspension, while
nystatin can be in the form of cream, pastille and oral sus-
pension. On the other hand, clotrimazole is usually presented
in a cream or solution form; the cream form also has an
antistaphylococcal activity (1). Miconazole can be used as a
lacquer (15, 18), gel (12, 17) or cream. The gel form of mi-
conazole was shown to be more effective than the lacquer
form (17). Chlorhexidine in the form of mouth wash (0.2%)
and 2% suspension for overnight denture disinfection, can
also be used to supplement antifungal drugs (19).
Systemic antifungals
Systemic antifungal agents have been recommended for pa-
tients with poor compliance such as patients with special
needs. They are also recommended for immunocompromised
patients (20). Among systemic antifungal drugs, fluconazole
and itraconazole have been the most extensively studied and
proven as efficient antifungal drugs (21,22). Specifically, flu-
conazole is one of the most effective agents for the treat-
ment of oropharyngeal candidiasis in HIV-infected patients
as well as prophylaxis for fungal infections in neutropenic
patients undergoing bone marrow transplantation (23,24).
It was shown to be effective, especially when administered
with an oral antiseptic such as chlorhexidine.(25) Compared
to miconazole, it was demonstrated that fluconazole is more
effective (16). It is the drug of choice in the management of
HIV-related oral candidiasis and it is superior to other topi-
cally administered or systemic antifungals due to its water-
solubility, oral bioavailability and good safety profile (26).
Fluconazole is usually used in the form of 50 or 100 mg
capsules. However, it should be given with caution in certain
circumstances as it interacts with anticoagulants among other
drugs. It is also contraindicated in pregnancy and liver and
renal disease. Itraconazole also was shown to be effective
in the management of DAS, (22) and even more effective
than fluconazole (21). Martin-Mazuelos et al., (1997) showed
 2012
iMedPub Journals THE INTERNATIONAL ARABIC JOURNAL Vol. 2 No. 1:1
Our Site: http://www.imedpub.com/ OF ANTIMICROBIAL AGENTS doi: 10.3823/705

that itraconazole was effective against 100% of fluconazole- factors against complete recovery, leading to chronic recur-
resistant strains (27). Similar to fluconazole, it is usually used rences of the disease (1). Another factor that would affect
in the form of 100 mg capsules. prognosis of this infection is its severity. Mild and moderate
types are usually more responsive to antimicrobial therapy
than the severe type which usually requires systemic antifun-
Discussion gals and may need additional surgical treatment to achieve
a better prognosis (18).
The field of antifungal therapy is rapidly developing, espe-
Other factors that may complicate treatment is the systemic
cially that there is a better understanding of the pathogen-
condition of the patient that plays an important role in modi-
esis of disease and the worldwide problem of antimicrobial
fying the immune response to different sorts of infections.
resistance. The multifaceted nature of DAS etiology involves
Medical problems can complicate local infections particulary
numerous predisposing factors operating locally and systemi-
in immunocompromised patients (28), Diabetes (34), and HIV
cally. Consequently, treatment plan should address all pos-
infection (35), for instance, present a problem when treating
sible etiological factors before the decision on the antifungal
oral Candidal infections.
drug is made. Denture and oral hygiene were found to be
of primary importance in healing of lesions and preventing
Smoking is considered an important factor in modulating
its recurrence (28).
the response of oral mucosa to the different factors (36),
however, this relationship was not confirmed in the case of
This is to improve prognosis and to prevent the recurrence
DAS (37).
of infection (29,30). Denture cleaning plays an important role
in eliminating the conditions that favor candidal growth. This
Pharmacologic treatment should be tailored to the individual
can be achieved by mechanical means, such as ultrasonic
patient, based on his/her health status and the clinical pre-
cleaners, or chemical cleansers which are particularly of ben-
sentation and severity of infection. Leaving dentures out at
efit for institutionalized elders or patients who are unable
night and improvement of denture hygiene should be the
to maintain a proper level of oral hygiene due to mental or
primary therapeutic approach, prior to instituting antifungal
physical disability.
therapy.
Antifungal drugs should be used alongside denture care.
Antifungal drugs certainly have a place in treating DAS. In
However, and despite the availability of a number of antifun-
healthy patients, the antifungal drugs of choice would be
gal drugs, therapeutic failure is not uncommon. This is in part
a topical polyene drug. However, if the patient is immuno-
due to the diluent effect of saliva and cleansing action of the
compromised, the need to a systemic antifungal drug like
oral musculature which often tend to reduce the availability
fluconazole may arise. It was shown that fluconazole inhibits
of the antifungal drug below the effective therapeutic con-
biofilm formation by both fluconazole-susceptible and fluco-
centration. Another cause of failure is the presence of Can-
nazole-resistant Candida albicans strains (38). Patient educa-
dida biofilms on mucosal and inert surfaces like prostheses
tion regarding denture hygiene, the number of daily doses
and implants. In response to attachment to a surface, fungal
and duration of therapy is important. Another important
cells produce biofilms, three-dimensional structures made up
aspect is the follow-up of patients condition to determine
of cells surrounded by exo-polymeric, mostly polysaccharide
the response to treatment. Failure of treatment may neces-
matrices that contribute to the infectious process and anti-
sitate culture and susceptibility testing together with further
biotic resistance (31). Biofilms are difficult to eliminate and
investigating the patients medical condition. Some studies
are a source of many refractory infections (28). It was shown
have shown that some C. glabrata strains are developing re-
that development of antifungal resistance was associated
sistance to fluconzole and were detected in association with
with increased pathogenicity in systemic infection as well as
denture-related stomatitis and among patients treated in in-
increased propensity for biofilm formation (32). Furthermore,
tensive care units (12, 39). Previous fluconazole use has also
the use of topical antifungals may be associated with lower
been identified as a significant risk factor for development of
patient compliance because it is required from the patient to
fluconazole-resistant among non-albicans Candida species,
use multiple daily doses for a relatively long period of time
especially Candida glabrata and Candida krusei ( 39 ). There-
that may extend to three or four weeks (33). Poor patient
fore, there is a need to identify patients at risk of developing
compliance coupled with possible underlying immunodefi-
candidasis caused by species resistant to fluconazole in order
ciency and emergence of drug resistance are all additional
to initiate adequate empirical antifungal therapy.

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References
1. Samaranayake, LP, Cheung, LK, Samaranayake, YH. Candidiasis and
other fungal diseases of the mouth. Dermatologic Therapy 2002; 15:
251-269.
2. Webb, BC, Cyril, J, Whittle,T, Whittle, T. A 2- year study of Candida-
associated denture stomatitis treatment in aged care subjects.
Gerodontology 2005; 22: 168-176.
3. Shulman, JD, Rivera-Hidalgo, F, Beach, MM. Risk factors associated
with denture stomatitis in the United States. Journal of Oral Pathology
and Medicine 2005; 34: 340-6.
4. Muzyka, BC, Glick, M. A review of oral fungal infections and
appropriate therapy. Journal of the American Dental Association 1995;
126:63-72.
5. Shay, K, Truhlar, MR, Renner, RP. Oropharyngeal candidosis in the
older patient. Journal of the American Geriatric Society 1997; 45:863-
870.
6. Chandra, J, Mukherjee, PK, Leidich, SD, Faddoul, FF, Hoyer, LL,
Douglas, LJ, et al. Antifungal resistance of candidal biofilms formed on
denture acrylic in vitro. Journal of Dental Restorations 2001; 80: 903-
8.
7. Samaranayake, LP, Fidel, PL, Naglik, JR, Sweet, SP, Teanpaisan, R,
Coogan, MM, et al. Fungal infections associated with HIV infection.
Oral Disease 2002; 8(Suppl. 2):151-160.
8. Barbeau, J, Sguin, J, Goulet, JP, de Koninck, L, Avon, SL, La londe, B,
et al. Reassessing the presence of Candida albicans in denture-related
stomatitis. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology
and Endodontics 2003;95:51-9
9. Krogh, P. The role of yeasts in oral cancer by means of endogenous
nitrosation. Acta Odontologica Scandinavica 1990; 48(1):85-8.
10. Sherman, RG, Prusinski, L, Ravenel, MC, Joralmon, RA. Oral
candidosis. Quintessence International 2002; 33(7):521-32.
11. Dorocka-Babkowska, B, Konopka, K, Dungunes, N. Influence of
antifungal polyenes on the adhesion of Candida albicans and Candida
glabrata to human epithelial cells in vitro. Archives of Oral Biology
2003; 48(12)805-14.
12. Dar-Odeh, NS, Shehabi, AA. Oral candidosis in patients with
removable dentures. Mycoses 2003; 46(5-6):187-91.
13. Webb, BC, Thomas, CJ, Willcox, MD, Harty, DW, Knox, KW. Candida-
associated denture stomatitis. Aetiology and management: a review.
Part 3. Treatment of oral candidosis. Australian Dental Journal 1998;
43(4):244-9.
4 Under License of Creative Commons Attribution 3.0 License
2012
Vol. 2 No. 1:1
OF ANTIMICROBIAL AGENTS doi: 10.3823/705
14. Vasconcelos, LC, Sampaio, MC, Sampaio, FC, Higino, JS. Use of Punica
granatum as an antifungal agent against candidosis associated with
denture stomatitis. Mycoses 2003; 46(5-6):192-6.
15. Dias AP, Samaranayake LP, Lee MT. Miconazole lacquer in the
treatment of denture stomatitis: clinical and microbiological findings in
Chinese patients. Clinical Oral Investigations 1997; 1(1):47-52.
16. Salonen, MA, Raustia, AM, Oikarinen, KS. Effect of treatment of
palatal inflammatory papillary hyperplasia with local and systemic
antifungal agents accompanied by renewal of complete dentures.
Acta Odontologica Scandinavica 1996; 54(2):87-91.
17. Parvinen, T, Kokko, J, Yli-Urpo, A. Miconazole lacquer compared with
gel in treatment of denture stomatitis. Scandinavian Journal of Dental
Restorations 1994; 102(6):361-6.
18. Konsberg, R, Axell, T. Treatment of Candida-infected denture
stomatitis with a miconazole lacquer. Oral Surgery, Oral Medicine,
Oral Pathology, Oral Radiology and Endodontics 1994; 78:306-11.
19. Ellepola, AN, Samaranayake, LP. Adjunctive use of chlorhexidine in oral
candidoses: a review.Oral Disease 2001; 7(1):11-7
20. McIntyre GT. Oral candidosis. Dental Update 2001; 28(3):132-9
21. Cross, LJ, Bagg, J, Wray, D, Aitchison, TA. comparison of fluconazole
and itraconazole in the management of denture stomatitis: a pilot
study. Journal of Dentistry 1998; 26(8):657-64.
22. Cross, LJ, Bagg, J, Aitchison, TC. Efficacy of the Cyclodextrin Liquid
Preparation of Itraconazole in Treatment of Denture Stomatitis:
Comparison with Itraconazole Capsules. Antimicrobial Agents and
Chemotherapy 2000; 44(2):425-427
23. White, TC, Holleman, S, Dy, F, Mirels, LF, Stevens, DA. Resistance
mechanisms in clinical isolates of Candida albicans. Antimicrobial
Agents and Chemotherapy 2002; 46: 1704-13.
24. Andriole, VT. The 1998 Garrod lecture. Current and future antifungal
therapy: new targets for antifungal agents. Journal of Antimicrobials
and Chemotherapy 1999; 44:151-62
25. Kulak, Y, Arikan, A, Delibalta, N. Comparison of three different
treatment methods for generalized denture stomatitis. Journal of
Prosthetic Dentistry 1994; 72(3):283-8.
26. Reents, S, Goodwin, SD, Singh, V. Antifungal prophylaxis in
immunocompromised hosts. Annals of Pharmacotherapy 1993; 27:53-
60.
27. Martin-Mazuelos, E, Aller, AI, Romero, MJ, Rodriguez Armijo, A,
Gutierrez MJ, Bernal, S, Montero, O. Response to fluconazole and
itraconazole of Candida spp. in denture stomatitis. Mycoses 1997;
40(7-8):283-9.

iMedPub Journals THE INTERNATIONAL ARABIC JOURNAL
Our Site: http://www.imedpub.com/
28. Pires, FR, Santos, EB, Bonan, PR, De Almeida, OP, Lopes, MA. Denture
stomatitis and salivary Candida in Brazilian edentulous patients.
Journal of Oral Rehabilitaion 2002; 29(11):1115-9.
29. Kulak-Ozkan, Y, Kazazoglu, E, Arikan, A. Oral hygiene habits, denture
cleanliness, presence of yeasts and stomatitis in elderly people. Journal
of Oral Rehabilitation 2002; 29(3):300-4.
30. Perezous, LF, Flaitz, CM, Goldschmidt, ME, Engelmeier, RL.
Colonization of Candida species in denture wearers with emphasis on
HIV infection: A literature review. Journal of Prosthetic Dentistry 2005;
93:288-93.
31. Kumamoto, C. A. Candida biofilms. Curr. Opin. Microbiol 2002.
5:608611.
32. Angiolella L, Stringaro AR, De Bernardis F, Posteraro B, Bonito M,
Toccacieli L, Torosantucci A, Colone M, Sanguinetti M, Cassone A,
Palamara AT. Increase of virulence and its phenotypic traits in drug-
resistant strains of Candida albicans. Antimicrob Agents Chemother.
2008;52(3):927-36.
33. Haberland-Carrodeguas, C, Allen, CM, Beck, FM, Buesching, WJ,
Koletar, SL, Sundstrom, P. Prevalence of fluconazole-resistant strains
of Candida albicans in otherwise healthy outpatients. Journal of Oral
Pathology and Medicine 2002; 31:99-105.
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2012
Vol. 2 No. 1:1
OF ANTIMICROBIAL AGENTS doi: 10.3823/705
34. Dorocka- Babkowska, B,Budtz-Jorgensen, E, Welch, S. Non-insulin-
dependent diabetes mellitus as a risk factor for denture stomatitis.
Journal of Oral Pathology and Medicine 1996; 25:411-16.
35. Patton, LL, Phelan, JA, Ramos-Gomez, FJ, Nittayananta, W, Shiboski,
CH, Mbuguye, TL. Prevalence and classification of HIV-associated oral
lesions. Oral Disease 2002;8 Suppl 2:98-109
36. Sakki, TK, Knuuttila, ML, Laara, E, Anttila, SS. The association of
yeasts and denture stomatitis with behavioral and biologic factors.
Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and
Endodontics 1997;84(6):624-9.
37. Fenlon, MR, Sherriff, M, Walter, JD. Factors associated with the
presence of denture related stomatitis in complete denture wearers:
a preliminary investigation. European Journal of Prosthodontics and
Restorative Dentistry 1998; 6(4):145-7.
38. Bruzual I, Riggle P, Hadley S, Kumamoto CA. Biofilm formation
by fluconazole-resistant Candida albicans strains is inhibited by
fluconazole. J Antimicrob Chemother. 2007;59(3):441-50.
39. Ruan, SY, Lee NL, Jerng SJ, Yu JC, Hsueh RP. Candida glabrata
fungaemia in intensive care units. Clin Microbiol Infect 2008;14:136-
140
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