The study was a descriptive, retrospective cross-sectional in nature conducted at SQUH, an academic tertiary care hospital in Oman. It covered one year (January 2013 to December 2013) and data outside this period were excluded. Inpatients and outpatients of all ages and both genders attending SQUH and receiving antifungal medications during the study period were included. Patients’ information (age, gender, body mass index, status, diagnosis and treating department) and drugs information (name, route of administration, treatment duration) were collected from computerized hospital database and analysed thereafter. The study was approved by the Medical Ethics Committee of SQUH.

Data was analysed using descriptive statistics. Frequencies and percentages were reported for categorical variables, while the mean and standard deviation (or median and interquartile range, wherever appropriate) were used to summarize the data for continuous variables. The Statistical Package for the Social Sciences (SPSS), Version 19.0 (IBM Corp., Chicago, Illinois, USA) was used to analyse the data.

The study included 244 patients (56.1% males and 43.9% females). The average age of the patients was 37.5±20.2 years (ranged from 0.1 to 97 years). A total of 1353 antifungal drug were prescribed for the 244 patients. Of these, 40.5% were for inpatients and 59.5 % were for outpatients. The range of episodes per patient was 1 to 37. The baseline characteristics of the patients are shown in [Table/Fig-1].

More than half of all antifungal drug prescriptions were prescribed by haematology, infectious disease and family medicine departments [Table/Fig-2]. The majority of patients prescribed these drugs were diagnosed to have infectious diseases followed by prophylactic use in leukaemia and immunocompromised conditions [Table/Fig-3].

The average number of antifungal drugs prescribed per patient was 5.6 with male patients receiving higher average number of prescriptions compared to the female patients (6.1 vs. 5.1, p=0.175). There was no significant difference in the average number of prescriptions between adults (>18 years) compared to children (≤18 years) (5.7 vs. 5.4, p=0.929).

The majority of drugs were administered by the oral route (n=992; 73.4%) followed by the parenteral route (n=320; 23.7%), topical route (n=27; 2.0%), and then vaginal route (n=13; 1.0%).

Fluconazole was the most commonly prescribed antifungal drug (n=715, 52.8%) followed by nystatin and voriconazole (n=233; 17.2% and n=152; 11.2%, respectively) [Table/Fig-4]. Fluconazole was the most common antifungal drug prescribed in adult patients irrespective to their gender or inpatients and outpatients status. It was the most common drug prescribed by the majority of the departments [Table/Fig-2] and across different diagnosis except solid tumours [Table/Fig-3]. However, amphotericin was the most common prescribed drug in patients ≤ 18 years of age (36.3%) [Table/Fig-4]. It was the most common (61.2%) antifungal drug prescribed in paediatric department [Table/Fig-2]. Several departments prescribed antifungal drugs for different diagnoses [Table/Fig-2,3]. Fluconazole was the most commonly prescribed antifungal agent prescribed by haematology, infectious disease and family medicine departments while nystatin was the most commonly prescribed antifungal agent by oncology department [Table/Fig-2].

Superficial fungal infections (e.g., tinea pedis, sporotrichosis, vulvovaginal candidiasis) are the common form of fungal infections [4,5]. However, the last three decades showed an increase in the incidence and mortality of invasive fungal infections (e.g., aspergillosis, candidiasis, histoplasmosis, cryptococcosis) especially in patients with impaired immunity [2,3,7]. Contrary to superficial infections which are easily treatable, systemic fungal infections are a clinical challenge [2,3]. They often occur in patients with impaired immunity and with several comorbidities and it is uncommon for their causative species to show resistance to several antifungal agents [2,3]. This has led to the development of many antifungal drugs to combat these infections and to provide more options for physicians by using drugs with better toxicity profiles. For example, conventional amphotericin B was the standard treatment for invasive fungal infection for about four decades since its initial approval in 1958 [16]. However, its liposomal formulation and newer drugs such as echinocandins (e.g., anidulafungin, caspofungin) and voriconazole became available alternatives to conventional amphotericin [16].

Limited pharmacoeconomic analyses exist in the antifungal therapeutic area. One study reported that, in 2004, two billion US $ in annual hospital costs in the United States could be attributable to invasive fungal infections [17]. In terms of the total cost of treatment, more expensive antifungal agents may be more cost-effective than lower-cost agents that are less effective and/or more toxic [18]. Pharmaco-epidemiological studies from developing countries detailing antifungal drug prescribing patterns of physicians are very few.

In this study, only 35.2% (n=86) of the patients prescribed with antifungal agents were diagnosed with fungal infections. These infections ranged from superficial to systemic infections including Tinea unugium, Tinea corporis, Tinea pedis, recurrent candidiasis, vaginitis and mucormyosis. The clinical diagnosis was not being able to trace in the electronic system for many cases of the study cohort and most of the patients with multiple prescriptions were prescribed the drugs consecutively on different visits despite the lack of a definite diagnosis. The reason that they have been receiving antifungal therapy could be as prophylaxis or empiric therapy for their underlying conditions which makes them susceptible to invasive fungal infections. These conditions included leukaemias (28.3%, n=69) and immunocompromised status (11.9%, n=29) [Table/Fig-3]. Most of the patients were treated in haematology department (30.3%, n=74) [Table/Fig-2] followed by infectious disease and family medicine departments (12.7%, n=31 and 10.2%, n=25, respectively). In one study, the most common underlying condition was malignancy (42%), followed by hematologic/immunologic deficiency (16%), and cardiovascular condition (15%) [19]. The high rate of antifungal drugs use in haematology department is understandable as it is known that fungal infections are a major cause of death in many hospitalization wards [20].

While Aspergillus, Candida and Cryptococcus species account for the majority of infections, recent epidemiological trends indicate a shift towards Aspergillus and non-albicans Candida species that often have diminished susceptibility to current antifungal agents such as fluconazole [21]. Clinically, candidiasis and aspergillosis account for between 80% and 90% of systemic fungal infections in immunocompromised patients [19]. In this study, it was not possible to retrieve data about the isolated species that caused the infections due to unavailability in the records.

A large retrospective cohort study in paediatric inpatients showed that fluconazole was the most commonly prescribed antifungal agent (76%) [16]. The same study showed an increase in the utilization of both voriconazole and the echinocandins between 2000-2006, while there was a significant decrease in the utilization of conventional amphotericin, itraconazole and flucytosine. Another study showed that fluconazole was the most commonly prescribed antifungal drug in 13 intensive care units in Germany [22]. Fluconazole is a widely used azole because of its long half-life, good patient tolerability and minimal associated toxicity. It is commonly used for the treatment of oropharyngeal and oesophageal candidiasis and as prophylactic agent in patients undergoing bone marrow transplantation or on cytotoxic chemotherapy [20].

Amphotericin B is very effective agent in treatment of several systemic fungal infections such as Cryptococcus, Aspergillus and Candida. It is also used as prophylaxis in suspected fungal infections in patients with febrile neutropenia. However, it is associated with several side effects limiting its use especially nephrotoxicity even with liposomal formulations [1,4,5]. In paediatrics, amphotericin is commonly used in treatment of candidemia and cryptococcal meningitis mainly in patients with immunocomprised status. Similar to previous studies amphotericin B in our cohort was mainly used for paediatrics. We also noticed that some of amphotericin prescription originated from Emergency department and almost one third were for outpatients. This observation require further exploration as this drug should have limited prescriber and patients on this drug should be monitored closely for possible nephrotoxicity.

Nystatin is a widely used antifungal medication for superficial fungal infections and of bacterial origin [23]. Cutaneous, vaginal, mucosal, and oesophageal Candida are sensitive to nystatin [24]. Voriconazole, a second-generation azole, is a broad-spectrum antifungal drug that has activity against some filamentous fungi (e.g. Aspergillus spp.) and also against Fusarium and Scedosporium species [5,7,24]. It is used commonly in clinical practice. However, it has many drug-drug interactions such as with digoxin and prednisolone [5,7,24]. The new agents, echinocandins, are active against some amphotericin B-resistant fungi, may have a role in the management of febrile neutropenia and exciting good option for combination antifungal therapy [5,24]. In our study, anidulafungin was prescribed in 7.1% of the patients [Table/Fig-4] majority of which are adult inpatients. Pulmonology specialty and surgery department were the most common departments/specialties prescribing this drug (61.5% and 52.9%, respectively) [Table/Fig-2]. This could be due to its efficacy against invasive aspergillosis, oesophageal candidiasis and peritonitis and intraabdominal abscess caused by candida species. Ketoconazole and clotrimazole were the least used antifungal agents in our study (0.5% and 1.5%, respectively). As elsewhere these two agents are mainly indicated for topical applications [1].

SQUH is a referral hospital in Oman and the results might not be generalizable to the whole country. It is possible that the results in other hospitals might be different. Data of this study were obtained from the electronic records and this limited our ability to gather information about the nature of the isolated microorganisms, the prevalence of antifungal resistance and patient’s clinical outcome.

The pattern of use of antifungal drugs in our study cohort was similar to the trend elsewhere in the world. Fluconazole was the most common antifungal drug prescribed in our study cohort. The use of newer antifungal agents is also increasing. Due to limited data in our region, the results of this study will help in understanding antifungal prescription practices and help in directing future studies and in developing local policies for appropriate use of antifungal drugs. Such policies will have an impact on many economic parameters such as length of stay and costs of hospitalization.