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Clinical Therapeutics

Efficacy of the Cyclodextrin Liquid Preparation of Itraconazole in Treatment of Denture Stomatitis: Comparison with Itraconazole Capsules

L. J. Cross, J. Bagg, T. C. Aitchison
L. J. Cross
University of Glasgow Dental School, Glasgow G2 3JZ, and
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J. Bagg
University of Glasgow Dental School, Glasgow G2 3JZ, and
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T. C. Aitchison
Department of Statistics, University of Glasgow, Glasgow G12 8QW, Scotland
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DOI: 10.1128/AAC.44.2.425-427.2000
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ABSTRACT

This study investigated the efficacy of a cyclodextrin solution of itraconazole in the treatment of Candida-associated denture stomatitis. It was found that the liquid and capsule preparations of itraconazole were equally effective adjuncts in the treatment of this condition. However, the side effect profile indicates that capsules are the preferred formulation.

The systemic antifungal agent itraconazole is dispensed as a lactose bead-encapsulated preparation and, more recently, as a liquid formulation based on hydroxy-β-cyclodextrin. This new cyclodextrin solution of itraconazole may provide a major therapeutic advantage over traditional treatment of oral candidosis as it combines the effect of topical application to the oral mucosa and systemic activity after absorption (5).

Forty edentulous patients whose palatal and tongue swab specimens were culture positive for yeasts were enrolled in a parallel-design, single-blind clinical trial. Demographic details and a full medical and dental history were obtained from each participant. An oral examination was performed, and denture stomatitis was classified according to the method of Newton (13). Palatal erythema was assessed visually (7) and measured objectively by using an electro-optical instrument known as an erythema meter (9). Denture-fitting surfaces were given a visual denture cleanliness score (4). Imprint cultures (4) of the palate, tongue, and upper denture, an oral rinse specimen, and a denture disc specimen were collected for microbiological examination. Blood was taken for routine hematological and biochemical analyses. All participants were given both verbal and written denture hygiene instructions.

The patients were randomized to receive either a cyclodextrin solution of itraconazole (Sporanox Liquid; Janssen-Cilag Ltd., High Wycombe, United Kingdom) or itraconazole capsules (Sporanox; Janssen-Cilag Ltd.), both at a dose of 100 mg twice daily for 15 days. Patients were reviewed on completion of the antifungal treatment and at 4 weeks and 6 months after treatment commenced. To assess compliance to the protocol and to record side effects, patients completed a questionnaire following treatment. Differences in the effects of the two formulations of itraconazole and any effects through time were analyzed by repeated-measures analysis of variance.

Nine male and 31 female patients whose ages ranged from 29 to 81 years (mean, 62 years) entered the study. Eighteen patients in each group completed the course of itraconazole and were evaluated. There was a general reduction in erythema with both forms of itraconazole. Patients in the cyclodextrin liquid group had a higher mean level of erythema at baseline than those in the capsule group, and incorporation of the baseline erythema meter index as a covariate in the repeated-measures analysis eliminated any significant treatment difference (P = 0.38).

The proportion of patients who removed their dentures for sleeping improved from 25% at baseline to 70% 6 months after treatment commenced. However, analysis of clinical visual denture cleanliness scores recorded throughout the study revealed little overall change between the initial and subsequent visits.

Eight patients (three receiving cyclodextrin and five who were administered capsules) were iron deficient (serum ferritin, <25 ng/ml) at baseline, and 12 (four in the cyclodextrin group and eight in the capsule group) had hyperglycemia (random blood glucose level, >6.0 mmol/liter) at the time of enrollment. Despite this, all demonstrated reduced erythema and yeast counts after antifungal treatment. There were no significant changes in hematologic indices, liver function test results, urea and electrolyte measurements, or C-reactive protein levels throughout the trial.

A wide range of yeast species were isolated from the mouths of the denture stomatitis patients before treatment (Table1). Following antifungal therapy, patients were classified as having responded to treatment if they were mycologically cured or if the yeast count was reduced. The mycological response to treatment in each patient group is shown in Table2. None of these results indicates any significant difference between the efficacies of the two preparations of itraconazole. Denture cleanliness in both treatment groups improved very slightly, but significantly (P = 0.01), by an average value of 0.3 (95% confidence interval, 0.1 to 0.5).

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Table 1.

The species of yeast isolated from patients with denture stomatitis before treatment

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Table 2.

The mycological response to treatment in each patient group

Completed questionnaires from 18 patients in each treatment group who had the entire course of itraconazole were available. In general, patients found their particular formulation of itraconazole pleasant and convenient to take. However, 12 patients in the cyclodextrin liquid group complained of gastrointestinal side effects such as diarrhea and stomach cramps. None of the patients who were administered itraconazole capsules reported any side effects. Subjectively, 15 of the patients on the liquid preparation and 9 of those taking capsules said that their mouths felt more comfortable following the course of antimycotic treatment.

Denture stomatitis is a multifactorial disease (6). Although treatment should be directed primarily toward reducing levels of denture plaque (1), most patients do not follow denture hygiene advice, as seen in this clinical trial. Overall, the results of this study show that administration of an antifungal medication as an adjunct to other measures is significantly beneficial. Antifungal treatment should also be considered for patients who have other risk factors, such as diabetes mellitus, since beneficial effects were evident for 12 such patients in this study.

The two groups in the present investigation were well matched for age and sex, though there was an overall predominance of females, as might be expected because of the epidemiology of this condition (6). However, there was no difference between the sexes with regard to compliance with the two antifungal agent protocols or denture hygiene advice.

Itraconazole is clearly a very effective drug for use in the treatment of denture stomatitis. Both forms of itraconazole produced similar mycological responses, with 17 patients in the cyclodextrin liquid group and 18 in the capsule group being mycologically cured or having reduced yeast counts at the end of each treatment course. Although one patient in the cyclodextrin group had no change in yeast count on completion of the antifungal therapy, all patients in each treatment group had improved clinically by this stage in the trial, and it could be concluded that both preparations of itraconazole reduced the inflammation associated with denture stomatitis.

Some workers have reported that although fluconazole has a relatively narrow spectrum of activity (14), itraconazole shows a high potency against all of the commonly encountered pathogenicCandida species (10, 12, 16-18). Other studies, however, have indicated that neither fluconazole nor itraconazole is active against Candida glabrata, Candida krusei, or Fusarium species (11, 15). In all but three cases, when C. glabrata was one of the yeasts isolated at baseline in the present study, it persisted after antimycotic therapy.

Progressive recolonization of the mucosa and the denture-fitting surface by yeasts and the consequent recurrence of denture stomatitis after completion of antifungal treatment have been reported (2, 3, 8). In the present study, eight patients (22%) were free of yeasts at the 6-month review appointment. However, 50% of the patients who were mycologically cured at 2 or 4 weeks after treatment commenced were found to be recolonized by yeasts at 6 months.

The relationship between denture cleanliness and inflammation in denture stomatitis is well established (19). Although 70% of the patients followed the advice to remove their dentures at night, denture cleanliness did not improve substantially, as evidenced by both the clinical and the microbiological scores. This suggests that educating patients to improve their denture hygiene without providing adjunctive antifungal therapy is an unrealistic form of denture stomatitis treatment.

The triazoles are generally well tolerated (11, 14, 16). Routine hematological and biochemical investigations indicated no significant changes attributable to the itraconazole in this study. The two forms of itraconazole were similar with regard to ease of use and patient compliance, with only two patients from each treatment group failing to complete the 2-week course. However, an important difference between the two forms of itraconazole was seen in the incidence of gastrointestinal side effects. Two-thirds of the patients using the cyclodextrin liquid preparation complained of diarrhea, stomach cramps, or nausea during the course of itraconazole treatment. These symptoms were transient, resolved on completion of the course of itraconazole, and did not result in failure to complete the study. No gastrointestinal side effects were experienced by those taking capsules. Therefore, since the clinical and mycological responses to treatment were similar for the two preparations, the itraconazole capsules would be preferred over the cyclodextrin solution of itraconazole for outpatient management of denture stomatitis.

ACKNOWLEDGMENTS

Grant Carnegie and Nigel Blatchford of Janssen-Cilag Ltd. are thanked for support and helpful comments. David Wray and Mervyn Lyons are thanked for assistance with recruitment of patients for the study.

FOOTNOTES

    • Received 10 August 1999.
    • Returned for modification 16 August 1999.
    • Accepted 3 November 1999.
  • Copyright © 2000 American Society for Microbiology

REFERENCES

  1. 1.↵
    1. Arendorf T. M.,
    2. Walker D. M.
    Oral candidal populations in health and disease. Br. Dent. J. 147 1979 267 272
    OpenUrlCrossRefPubMedWeb of Science
  2. 2.↵
    1. Bergendal T.,
    2. Holmberg K.,
    3. Nord C. E.
    Yeast colonisation in the oral cavity and faeces in patients with denture stomatitis. Acta Odontol. Scand. 37 1979 37 45
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Bissell V.,
    2. Felix D. H.,
    3. Wray D.
    Comparative trial of fluconazole and amphotericin in the treatment of denture stomatitis. Oral Surg. Oral Med. Oral Pathol. 76 1993 35 39
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Blair Y.,
    2. Bagg J.,
    3. MacFarlane T. W.,
    4. Chestnutt I.
    Microbiological assessment of denture hygiene among patients in longstay and daycare community places. Community Dent. Oral Epidemiol. 23 1995 100 103
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Blatchford N. R.
    Treatment of oral candidosis with itraconazole: a review. J. Am. Acad. Dermatol. 23 1990 565 567
    OpenUrlCrossRefPubMedWeb of Science
  6. 6.↵
    1. Budtz-Jörgensen E.
    The significance of Candida albicans in denture stomatitis. Scand. J. Dent. Res. 82 1974 151 190
    OpenUrlPubMedWeb of Science
  7. 7.↵
    1. Budtz-Jörgensen E.,
    2. Bertram U.
    Denture stomatitis. I. The etiology in relation to trauma and infection. Acta Odontol. Scand. 28 1970 71 92
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    1. Budtz-Jörgensen E.,
    2. Theilade E.,
    3. Theilade J.
    Quantitative relationship between yeasts and bacteria in denture-induced stomatitis. Scand. J. Dent. Res. 91 1983 134 142
    OpenUrlPubMed
  9. 9.↵
    Cross, L. J., J. Bagg, and H. Moseley.Evaluation of an optical instrument for objective assessment of oral mucosal erythema. J. Oral Rehab. 25:496–501.
  10. 10.↵
    1. Espinel-Ingroff A.,
    2. Shadomy S.,
    3. Gebhart R. J.
    In vitro studies with R51,211 (itraconazole). Antimicrob. Agents Chemother. 25 1984 5 9
    OpenUrl
  11. 11.↵
    1. Karyotakis N. C.,
    2. Anaissie E. J.
    The new antifungal azoles: fluconazole and itraconazole. Curr. Opin. Infect. Dis. 7 1994 658 666
    OpenUrlCrossRef
  12. 12.↵
    1. Lombardi G.,
    2. Gramegna G.,
    3. Cavanna C.,
    4. Poma G.,
    5. Marangoni E.,
    6. Michelone G.
    Itraconazole vs. amphotericin B: in vitro comparative evaluation of the minimum inhibitory concentration (MIC) against clinically isolated yeasts. Mycopathologia 106 1989 31 34
    OpenUrlCrossRefPubMedWeb of Science
  13. 13.↵
    1. Newton A. V.
    Denture sore mouth. A possible aetiology. Br. Dent. J. 112 1962 357 360
    OpenUrl
  14. 14.↵
    1. Odds F. C.
    Itraconazole—a new oral antifungal agent with a very broad spectrum of activity in superficial and systemic mycoses. J. Dermatol. Sci. 5 1993 65 72
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Odds F. C.
    Resistance of yeasts to azole-derivative antifungals. J. Antimicrob. Chemother. 31 1993 463 471
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    1. Osterloh I. H.
    Safety Antifungal agents Powderly W. B., van t'Wout J. W. 1. Fluconazole 1992 40 60 Marius Press Carnforth, United Kingdom
    OpenUrl
  17. 17.↵
    1. van Cutsem J.
    The in vitro antifungal spectrum of itraconazole. Mycoses 32 (Suppl. 1) 1989 7 13
    OpenUrl
  18. 18.↵
    1. van Cutsem J.,
    2. van Gerven F.,
    3. Janssen P. A. J.
    Activity of orally, topically and parenterally administered itraconazole in the treatment of superficial and deep mycoses: animal models. Rev. Infect. Dis. 9 1987 15 32
    OpenUrl
  19. 19.↵
    1. Walker D. M.,
    2. Stafford G. D.,
    3. Huggett R.,
    4. Newcombe R. G.
    The treatment of denture-induced stomatitis. Evaluation of two agents. Br. Dent. J. 151 1981 416 419
    OpenUrlCrossRefPubMed
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Efficacy of the Cyclodextrin Liquid Preparation of Itraconazole in Treatment of Denture Stomatitis: Comparison with Itraconazole Capsules
L. J. Cross, J. Bagg, T. C. Aitchison
Antimicrobial Agents and Chemotherapy Feb 2000, 44 (2) 425-427; DOI: 10.1128/AAC.44.2.425-427.2000

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Efficacy of the Cyclodextrin Liquid Preparation of Itraconazole in Treatment of Denture Stomatitis: Comparison with Itraconazole Capsules
L. J. Cross, J. Bagg, T. C. Aitchison
Antimicrobial Agents and Chemotherapy Feb 2000, 44 (2) 425-427; DOI: 10.1128/AAC.44.2.425-427.2000
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KEYWORDS

antifungal agents
Cyclodextrins
itraconazole
Stomatitis, Denture

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