Introduction

Candida albicans is common oral inhabitant of healthy population that becomes pathogenic in the presence of any predisposing risk factors(1–3).Risk factors such as diabetes mellitus, broad spectrum antibiotic therapy, and immune deficits disrupt the balance between host and oral microbiology leading to candidiasisinfection(4–6).

Antifungal therapy should consider host and pathogen related factors(1,2,5).Topical medication is selected as the treatment of choice for the healthyindividuals infected with candidiasis, while systemic administration is indicated in recurrent or disseminated infection especially present in immune deficient patients(1,2,4–6).

According to the guidelines of infectious diseases society of America, intensity of the infection is considered in the treatment of oropharyngeal candidiasis. Topical agents such as nystatin suspension or clotrimazole troches are typically used in the treatment of mild infections. For moderate to severe infections, oral fluconazole, itraconazole solution, and posaconazole suspension are recommended.Intravenous echinocandin is limited to those patients with refractory diseases. Combinations of systemic and topical treatments are effective in reduction of dose and duration of treatment(7).

Dentists often do not have the essential pharmacological knowledge and make errors in the prescription of antifungal drugs which leads to drug resistance. The current study aimed to assess the knowledge of antifungal prescription for the treatment of oral candidiasis amongthe seniordental students in Iran.

Materials and Methods

This questionnaire based cross sectional survey was conducted during a month period at the department of prosthodontics, Iran. The initial draft of the study questionnaire was prepared using previous studies and examined for item simplicity, responsiveness, and reading ease with the help from practitioners. Following the initial examination, questionnaire was revised and examined for its test-retestreliabilityin a 10-days period and Kappa statistics was calculated (0.89-0.91).

The final questionnairescontained multiple-choice questions about the desired antifungal therapy and their proper form of administrations. Thequestionnaires and introductory lettersproviding the information about the study objectives and an informed contest were prepared and distributed to 90senior students.

Data were obtained and analyzed by using SPSS statistical package. Descriptive statistics and frequency distributions were performed on the data.

Results

The results of the study are shown in Table 1.76.6%(n=69) of respondentsindicated topical medication as their first choice, whereas 15.5% (n=14) preferred systemic therapy. Nystatin was the most common prescribed antifungal agentin mild candidiasis (62.2%, n=56) followed by Clotrimazole troches (15.5%, n=14).46.6% (n=42) of respondents chose oral amphotericin and 21.1% (n=19) intravenous echinocandin as their first choice treatment of moderate to severe candidiasis.Cholorhexidine mouth rinse was chosen by 25.5% (n=23) of respondents which accompanied other antifungal agents in 51.1 %(n=46). Considering the dosageand timing of drug administration, fluconazole, clotrimazole, and nystatin were prescribed correctly in 28.8% (n=26), 25.5%(n=23),and 37.7% (n=34) of responses respectively.

Table 1: Survey questions and the frequency distribution of responses (n=90).

Discussion

In the current study, questionnaires were distributed among senior dental students and aimed to survey the antifungal prescribing knowledgeof oral candidiasis treatment.Dentists often encounter with the cases of oral candidiasis in their practice and need to be expert in antifungal therapy oninfections with different candida species; however, it is reported that they are reluctant for thetreatment ofchronic oral candidiasis especially if accompanied by immunodeficiency virus infection(8). Oral candidiasis is managed by correct identification, rectification of the predisposing factors and the provision of a proper antifungal medication which eventually mandates sufficient knowledge of the clinicians on the diagnosis and antifungal treatment of the infections(1–3).In the current study, the preferred antifungal agents were nystatin,amphotericin B, intravenous echinocandin, and clotrimazole troches respectively. Nystatin was the most frequently prescribed medication for treating mild infections.Topical agents are the first line treatment for oral candidiasis and do not display the side effects of systemic therapy(5,6). They are often accompanied by systemic therapy in order to reduce the required dose and duration of treatment. Nystatin and amphotericin B have reduced gastrointestinal absorption following oral administration and are suitable for topicalapplication(1–6). However, rapid oral clearance of topical medication decreases the contact time of drug with oral mucosa and makes the therapy ineffective(1,5).Additionally, frequent dosing regimens are problematic and require patient compliance(5).

Amphotericin is as effective as fluconazole in the treatment of denture stomatitis, but is associated with a number of complications and is often poorly tolerated and unsatisfactory(9,10).Miconazoleis a fungicidal derivative, withsimultaneous antifungal and antibacterial effect. A meta-analysis indicated that miconazole is an effective agent for the management of angular cheilitis and denture stomatitis and the recurrence rates of gel are lower than other formulations(11);nonetheless, it is reported that miconazoleaffects warfarin activity causing severe bleeding(12,13).Whenthere is a risk of drug interaction, nystatin is a suitable alternative; although a recent study showed that nystatin suspensionhas strong effect on warfarin either(12). Soif miconazole is required for a patient receiving warfarin therapy, liaison with hishaematologist is essential before any treatment(14).

Invasive and refractory mucocutaneous candidiasis infection is managed by systemic medication. Contrary to previous studies(15,16),the majority of survey respondents choseoral amphotericin as the first choice of systemic therapy followed by intravenous echinocandin and fluconazole.Fluconazole has excellent safety and clinical efficacy in the management of denture stomatitis. It is well absorbed by gastrointestinal tract and reaches the salivary levels similar to the plasma concentration of the drug(1,2). However high rates of partial relapse has been recorded after long term medication(9,17,18).Also, non-albicans species of candidaisolated from HIV-infected patients are less sensitive to fluconazole(2,9,10,17).Itraconazole is a broader spectrum antifungal agent that shows better efficacy and appears to be better tolerated than miconazole and ketoconazole(8,19).Some studies have reported that none of these agents are active against C. glabrata, C. Krusei and Fusarium species(13,17).

Majority of the study participants prescribed chlorhexidine as an adjunct to other antifungal therapies. Chlorhexidine possesses a broad spectrum antimicrobial activity against Candida albicans and other common non-albicans species and is used as antiseptic mouth rinse and denture disinfectant(20).Some investigators applied it as an alternative to antifungal drugs and achieved an acceptable resultsin reducing the risk of oral candidiasis(21–24).In other studies, chlorhexidine rinse is reported as a promising therapy supplementing the effect of antifungal medication(2,20–22).

In summary, the results demonstrated that the pharmacological knowledge of dental students needs to be strengthened. Also, additional attention should be devoted to the appropriate drug dosage and timing alteration in training programs to guarantee the competent prescribing.  Pharmacology which is one of the key preclinical courses in the schools of dentistry is offered to the third year students and constitutes a very small part of the curriculum.Students should acquire the basic knowledge of pharmacology, clinical applicationsand drug administration skillsina relatively short period of time. This prompts the need to review the curriculum for any possible changes andhighlights the importance of problem-based learning method in dental educationto enables dental practitioner to improve the clinical skills of dental students.

Conclusion

The pharmacological knowledge of dental students needs to be strengthened with a special focus on prescribing medications and providing the opportunity to practice more.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

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