. UHD Journal of Science and Technology | May 2018 | Vol 2 | Issue 2 1 1. INTRODUCTION In the past three decades, invasive life-threatening fungal infections have severely increased due to several reasons including broad-spectrum antibiotics, antagonistic surgery, and the use of immunosuppressive and antineoplastic agents [1]-[5]. Until the 1940s, comparatively few antifungal agents were available for the treatment of fungal infections. In addition, development in the growth of new antifungals agents was lagged behind the antibacterial investigation, from the year 2000 number of agents existing to treat fungal infections has increased by 30%. Nevertheless, still, only 15 agents are approved for clinical use at present [6], [7]. The most common human fungal infection is oral candidiasis (also called oral thrush), which is characterized by an overgrowth of Candida species in the superficial epithelium of the oral mucosa [8], [9]. Treatment for oral thrush varies, polyenes, allylamines, and azoles are three classes of antifungal agents that used most frequently for treatments of oral thrush [10]. Nystatin and amphotericin-B both belong to the polyene’ class of antifungals drug. These class of drugs act by binding to ergosterol in the cell membranes of the fungal; then, this causes in the membrane depolarization and pores formation which increases permeability to proteins and (mono and divalent) cations, disrupting metabolism, and eventually causing cell death [11]. Both antifungal agents are poorly absorbed by the gastrointestinal tract and are widely used for the topical treatment of oral candidal infections [12]. Intravenous forms of amphotericin-B are used in the treatment of systemic fungal infections. Similarly, nystatin has low oral bioavailability profile; therefore, it is generally used in inhibiting colonization with Candida albicans in the gut or as a topical treatment for thrush [13], [14]. Sweetened Current Antifungal Drug Recommendations to Treat Oral Thrush in Sulaimani City-Iraq Hezha O. Rasul Department of Chemistry, College of Science, University of Sulaimani, Iraq A B S T R A C T Oral thrush or oral candidosis is one of the most widespread fungal infections of the mucous membranes in human. This study aims to evaluate the pattern of recommending three antifungal drugs as follows: Nystatin, amphotericin B, fluconazole, and miconazole by the pharmacists and assistant pharmacists, which are used to treat oral thrush. A questionnaire was circulated to a random selection of pharmacies in Sulaimani city of Iraq between March 2017 and June 2017, and responses to the questionnaire were received from 101 pharmacies. The results were analyzed and demonstrated as the absolute and relative frequencies using Statistical Package for the Social Sciences Program version 21. Among the participants, 65.3% were male, and 34.7% were female. The participant’s age range was 21–70 years. The majority (52.3%) holds a postgraduate degree as their highest educational level, and they graduated after 2010. Miconazole and nystatin (70.3%) were the most popular choices of an antifungal agent that pharmacists would use, followed by fluconazole (31.7%) and amphotericin-B (11.9%). Index Terms: Amphotericin B, Antifungal agents, Fluconazole, Nystatin Corresponding author’s e-mail: Hezha O. Rasul, Department of Chemistry, College of Science, University of Sulaimani, Iraq. E-mail: hezha.rasul@univsul.edu.iq Received: 13-11-2017 Accepted: 10-05-2018 Published: 25-07-2018 Access this article online DOI: 10.21928/uhdjst.v2n2y2018.pp1-6 E-ISSN: 2521-4217 P-ISSN: 2521-4209 Copyright © 2018 Rasul. This is an open access article distributed under the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (CC BY-NC-ND 4.0) O R I G I N A L R E S E A R C H A R T I C L E UHD JOURNAL OF SCIENCE AND TECHNOLOGY Hezha O. Rasul: Current Antifungal Drug Recommendations to Treat Oral Thrush in Sulaimani City-Iraq 2 UHD Journal of Science and Technology | May 2018 | Vol 2 | Issue 2 pastille has been developed to overcome the problem of the unpleasant taste of nystatin [15]. The azole antifungals (miconazole and fluconazole) work through inhibiting cytochrome P-450 enzyme in the fungal [16]. Miconazole was the first available azole; fluconazole is a more recently found systemic antifungal agent, which has a long half-life and as a result can be administered in a single daily dose [17]. Chlorhexidine is other antimicrobial agents that available for topical administration in oral candidiasis as mouthwash. It is effective against fungal yeasts, which can be used as an adjunctive therapy or as a primary treatment [18]. The aim of the present study was to examine the current practice of antifungal recommending pattern and attitude toward the treatment of oral candidiasis among pharmacists in Sulaimani City-Iraq during 2017. Hence, this project will commence with the treatment of oral thrush by using different types and form of antifungal agents. 2. MATERIALS AND METHODS A hard copy questionnaire circulated to a random selection of 120 pharmacies. A complete data from 101 participants were returned and integrated into the analysis with 84.1% response rate. Data collection was carried out between March 2017 and June 2017, both males and females pharmacies were involved in the different street of the Sulaimani city. The pharmacies were visited and asked questions based on their interest to take part in the study; each of these pharmacists was given an explanatory letter of a questionnaire (Fig. 1). The questionnaire that was used for data collection in this study was specially created through a search of the relevant literature. The questionnaire was tested initially to estimate approximately the length of the questionnaire in minutes, verify the participant’s interpretation of questions, and develop the questionnaire consequently. These questionnaires were tested in independent data sets; however, these candidate questionnaires were excluded from the concluding analysis. However, the final version of the survey was conducted in Sulaimani city. The final version of the questionnaire included eight questions and required approximately 2 min to complete. Approved by the ethics committee of University of Sulaimani (Sulaimani, Iraq) was obtained. The self- administered questionnaire was composed of two sections. The first section of the questionnaire was comprised of seven questions about sociodemographic data, such as gender, age, university degree and year of the last qualification, workplace (private sector vs. public sector), professional practice, and country of the first-degree qualification. Various antifungal drug options were integrated into the second section of the questionnaire about pharmacists’ recommendation to treat oral candidal infections. Data from the completed questionnaires were entered into a computer database and analyzed using Statistical Package for the Social Sciences Program version 21. Following the statistical evaluation of data and the summarization of frequencies and percentages were produced. 3. RESULTS With the use of the hard copies of the questionnaires, different pharmacies have been participated in Sulaimani city, and 101 questionnaires were returned completed (84.1% response rate), 65.3% were male, and 34.7% were female pharmacist as shown in Table 1. The majority of participants (70.3%) graduated after 2010, while 19.8% graduated between 2000 and 2009. Moreover, the participants, who graduated between 1990 and 1999 recorded 6.9%, with a lower proportion (2%) graduating between 1980 and 1989. Only 1% graduated between 1970 and 1979. There were no respondents from earlier than 1970. The range of the participant’s age was 21–70 years; more than 70% were aged between 21 and 30 years. The majority (47.5%) holds TABLE 1 Sociodemographic data of the participated pharmacists Sociodemographic data Frequency (%) Gender Male 66 (65.3) Female 35 (34.7) Age 21–30 73 (72) 31–40 21 (21) 41–50 3 (3) 51–60 3 (3) 61–70 1 (1) First-degree graduation year After 2010 71 (70.3) 2000–2009 20 (19.8) 1990–1999 7 (6.9) 1980–1989 2 (2) 1970–1979 1 (1) Educational level Diploma 48 (47.5) Undergraduate 30 (29.5) Postgraduate (Msc, PhD) 23 (22.8) Workplace Private sector 60 (59.4) Public sector 3 (3) Both (private and public) 38 (37.6) Professional practice Pharmacist 54 (53.5) Assistant Pharmacist 47 (46.5) Hezha O. Rasul: Current Antifungal Drug Recommendations to Treat Oral Thrush in Sulaimani City-Iraq UHD Journal of Science and Technology | May 2018 | Vol 2 | Issue 2 3 a diploma degree as their highest educational level; while an undergraduate and postgraduate level of education observed as 29.5% and 22.8%, respectively. The participants were questioned about their workplace. Approximately 60% of the respondents have worked in the private sector whereas public sector recorded only 3%. Moreover, 37.6% of the participants were worked in both private and public sectors at the same time. More than half of the participants were pharmacists whereas 46.5% were an assistant pharmacist. The most popular antifungal recommended (Table 2), in any form, was nystatin and miconazole each recorded 70.3%, followed by fluconazole and chlorhexidine as 31.7%. Moreover, the recommendation for amphotericin was recorded 11.9%. The combination of using miconazole and hydrocortisone cream by the respondents were only 7.9%. However, many participants chose more than one type and/or form of an antifungal drug. In addition, the nature of the questionnaire determined the distinction between participants using simultaneous administration of chlorhexidine and participants using different antifungals for different manifestations of oral candidal infection. The participants who recommended chlorhexidine only 19.8% of them were using it as adjunctive therapy. With regard to the results of the questionnaire as mentioned earlier one of the most popular antifungals recommended was nystatin. In addition to that, the oral suspension was the most Fig. 1. The questionnaire. Hezha O. Rasul: Current Antifungal Drug Recommendations to Treat Oral Thrush in Sulaimani City-Iraq 4 UHD Journal of Science and Technology | May 2018 | Vol 2 | Issue 2 popular form with 73% of those recommending nystatin considering this formulation. About 24% of those suggesting nystatin would consider recommending it in the form of an ointment. Only 3% was observed for Pastille form of nystatin suggestion. However, capsules were the most common form of fluconazole considered for recommendation (91%). A lozenge form of amphotericin drug was recommended by the participants more than oral suspension form (as shown in Fig. 2). Only 6% of respondents cited other treatment options, which included clotrimazole, terbinafine, econazole triamcinolone, and anginovag spray. 4. DISCUSSION The present study investigated the currently antifungal drugs recommendation at pharmacies in Sulaimani city, Iraq, in relation to the sociodemographic details as illustrated in a study by Martínez-Beneyto et al. [19]. The previous studies similar to this kind in the United Kingdom and Jordan were conducted; however, they were conducted among the general dental practitioners instead of pharmacists. The first study was undertaken in the UK in 1987 and reported in 1989 [20]. The second study that conducted in the UK reported in 2004 [21].Furthermore, another study was undertaken in Jordan in 2015 [22].In accordance with those studies like the present study, nystatin was the most popular antifungal agent recommended (70.3%). In addition, nystatin oral suspension was selected by 73% of the respondents who suggested nystatin. However, in this study, miconazole was recorded as one of the most frequently recommended antifungal agents also (70.3%). There has also been a visible increase in the proportion of participants recommending miconazole in the present survey compared to the previous studies, and it has now become more popular than amphotericin. In addition, miconazole and nystatin were also the commonly employed antifungals in studies that have been done by other researchers [19], [21], [22]. This is because these drugs may cause less intestinal irritation and other side effects. However, one of the limitations of using topical formulations of nystatin is high sucrose content, which may reduce the amount of practice in diabetes, steroid use, or an immunocompromised state [9]. The triazoles constitute fluconazole being suggested by 31.7% of the participants. Fluconazole in the form of suspension and with different dosages has been used for the treatment of oropharyngeal candidiasis. The theoretical benefit of using topical fluconazole is that a higher concentration of the active drug is delivered to the oral mucosa without the untoward systemic side effects [23], [24]. However, most of the participants recommended capsule form of fluconazole 91% whereas only 9% of the respondents suggested oral suspension form of the drug. Fluconazole oral suspension is Fig. 2. Different form of antifungal recommended by participants. TABLE 2 Choice of antifungal agents. Numbers (%) of pharmacists choosing each antifungal (N=101) Antifungal agentsa Responses % of casesN (%) Nystatin 71 (31.4) 70.3 Amphotericin 12 (5.3) 11.9 Fluconazole 32 (14.2) 31.7 Chlorhexidine 32 (14.2) 31.7 Miconazole oral gel 71 (31.4) 70.3 Miconazole and hydrocortisone cream 8 (3.5) 7.9 Total 226 (100) 223.8 aDichotomy group tabulated at value 1 Hezha O. Rasul: Current Antifungal Drug Recommendations to Treat Oral Thrush in Sulaimani City-Iraq UHD Journal of Science and Technology | May 2018 | Vol 2 | Issue 2 5 administered in a dosage of 10 mg/ml aqueous suspension. Various studies show that fluconazole is a very effective drug, and it has a rapid symptomatic response [25]. Chlorhexidine mouth rinse formulations are widely used for decreasing the microbial burden in the oral cavity. For example, chlorhexidine gluconate with 0.2% concentration is used as an antiseptic oral rinse because of its activity against a broad range of oral microbial species including Candida[26]. Chlorhexidine should not be used simultaneously with nystatin as they interact and render each other ineffective, even though it is suggested as a practical addition to the antifungal agents [27]. In this study also, chlorhexidine was recommended by pharmacists and assistant pharmacist (31.7%) along with other antifungal agents as an adjunctive therapeutic agent. In this study, the result of amphotericin was less frequently recommended (11.9%), and 58% of the participants suggested lozenges form of the drug. This recommendation was very similar to the previous study which demonstrated by Anand et al. [28]. Miconazole in combination with hydrocortisone was recommended by 7.9% of the respondents. However, in general, the diagnosis of oral candidiasis is based on clinical features and symptoms in conjunction with a detailed medical history [29]. Despite the above-mentioned results, this study has several limitations. The small sample size was the main limitation of this questionnaire. Therefore, the future studies with larger sample size covering a wider data may provide better. Furthermore, the possible improvement in the methodology could be the insertion of doctors’ recommendation and compare both results. Differentiation between respondents recommending antifungals based on their knowledge or recommending it based on doctor’s prescription. 5. 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