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Otomycosis is a common mycotic infection of the external auditory canal, and Aspergillus species are one of the most frequent causative agents worldwide. The limited antifungal arsenal, the high toxicity and side effects of antifungal agents, and the growing resistance to the currently available antifungals underscore the need for new therapeutic strategies. The present study aimed to evaluate the combined in vitro efficacy of terbinafine and ketoconazole against Aspergillus species with terbinafine high MIC values isolated from patients with otomycosis.84 Aspergillus species with high MIC values to terbinafine (≥ 4 µg/ml), consisting of A. flavus, A. tubingensis, A. niger, and A. terreus, were included in this study. The checkerboard microdilution method evaluated the in vitro interactions using the CLSI reference technique. Synergistic effects were observed for 66.67% (56/84) of all isolates (FICI ranging from 0.19 to 0.5). However, the interactions of terbinafine and ketoconazole exhibited indifference in 33.33% (28/84) of the isolates, and no antagonism was observed for any combination. The interaction of terbinafine and ketoconazole showed synergistic activity against Aspergillus species with high MIC values, suggesting that this is an alternative and promising approach for treating otomycosis.

Fungal otitis externa, an infection of the external auditory canal caused by molds and yeasts, accounts for approximately 10-20% of ear canal infections accompanying high recurrence. The purpose of the current study was to assess the pattern of etiological agents of otomycosis and resistance profile as well as the rate of tympanic membrane perforation. A total of 1040 patients with symptoms of fungal otitis externa, in a period of two years, were investigated. The mycological tests revealed the presence of different fungi in 237 ears (22.8%). Fungal otitis was more related to filamentous fungi of the species Aspergillus flavus (54.43%), A. tubingensis (10.97%), and A. niger (8.86%), followed by yeasts, Candida orthopsilosis (7.59%), C. albicans (6.75%), and C. parapsilosis (5.06%). Tympanic membrane perforation rate was found to be 6.75% and was more common with otomycosis caused by A. flavus, A. tubingensis and C. albicans. In antifungal susceptibility tests, all tested drugs showed generally good activity against most isolates of molds and yeasts, while tolnaftate, clotrimazole, nystatin, and terbinafine had lowest effects. We found that among Aspergillus isolates, one A. niger isolate was resistant to voriconazole, and one A. flavus isolate was resistant to amphotericin B. Furthermore, among Candida species, three isolates of C. orthopsilosis showed high MIC values to fluconazole, two C. albicans isolates were considered fluconazole resistant and one isolate of C. parapsilosis was resistant to caspofungin and 3 isolates were resistant to fluconazole. Regarding the existence of the cases with perforated tympanic membrane and emerging species causing fungal otitis in the current report, the importance of the early physical examination, precise molecular identification, and the antifungal susceptibility evaluation is highlighted.

Trichophyton benhamiae is a zoophilic dermatophyte mainly transmitted to humans from guinea pigs. This zoophilic species can also cause dermatophytosis as reported by human contact with other animals, such as rabbit, cat, and fox. Here, we report the tinea faciei and tinea corporis cases: a 12-year-old girl and her 53-year-old father, with no history of immunodeficiency and underlying disease, caused by T. benhamiae transmitted from a guinea pig in Iran. Dermatological examination revealed several erythematous, round, scaly, and approximately 1-4-cm-diameter lesions in both patients. The girl had seven skin lesions, and her father presented two skin lesions on the front side of his neck. The girl's lesions had started 3 weeks before and her father's lesions appeared 7 days after the first clinical appearance of the lesions in the daughter. The girl had daily close contact with a guinea pig, while her father did not have any direct exposure to the pet. Examination of the lesions scraping with 10% potassium hydroxide (KOH 10%) revealed hyaline septate hyphae and arthroconidia. The dermatophyte isolated in culture was identified as T. benhamiae using molecular analysis. The patients were successfully treated using topical sertaconazole nitrate 2% cream twice a day for 4 weeks.

The data on the epidemiological and antifungal susceptibility profile of tinea capitis (TC) in Iran has not been updated in recent decades. This report presents the Iranian epidemiological and drug susceptibility data regarding the distribution of dermatophytes species isolated by six national mycology centers for a period of one year (2020-2021).A total of 2100 clinical samples from individuals suspeted to TC were subjected to mycological analysis of direct microscopy and culture. For definite species identification, the culture isolates were additionally subjected to PCR-RFLP and PCR-sequencing of the ITS ribosomal DNA (ITS-rDNA) region. Antifungal susceptibility profiles for eight common antifungal drugs were determined by CLSI M38-A3 guidelines. The SQLE gene was partially amplified and sequenced in two terbinafine-resistant and two susceptible T. mentagrophytes isolates to elucidate probable substitutions involved in resistance.TC (n = 94) was diagnosed in 75 children (79.8%) and 19 adults (20.2%) by direct microscopy and culture. Frequency of TC was significantly more among males (66 males = 70.2% vs 28 females = 29.8%). The prevalent age group affected was 5-9 years (39.36%). Thirty-two (34.04%) T. mentagrophytes, 27 (28.7%) T. tonsurans, 14 (14.9%) M. canis, 13 (13.8%) T. violaceum, 5 (5.32%) T. indotineae, 2 (2.1%) T. benhamiae, and 1 (1.1%) T. schoenleinii were identified as the causative agents. MIC values of isolates showed susceptibility to all antifungal agents, except for fluconazole and griseofulvin with GM MIC of 11.91 μg/ml and 2.01 μg/ml, respectively. Terbinafine exhibited more activity against isolates, with GM MIC 0.084 μg/ml followed by ketoconazole (0.100 μg/ml), econazole (0.107 μg/ml), itraconazole (0.133 μg/ml), butenafine (0.142 μg/ml), and miconazole (0.325 μg/ml). Two resistant T. mentagrophytes isolates harbored missense mutations in SQLE gene, corresponding to amino acid substitution F397L. Remarkably, one unique mutation, C1255T, in the SQLE sequence of two terbinafine-susceptible T. mentagrophytes strains leading to a change of leucine at the 419th position to phenylalanine (L419F) was detected.T. mentagrophytes, T. tonsurans, and M. canis remained the main agents of TC in Iran, however less known species such as T. indotinea and T. benhamiae are emerging as new ones. Terbinafine could still be the appropriate choice for the treatment of diverse forms of TC.

Otomycosis is a superficial infection of the external ear caused by fungal pathogens. The genera Aspergillus and Candida are considered the main fungal causative agents, with the predominance of Aspergillus section Nigri. The present study aimed to evaluate the clinical symptoms of patients with otomycosis and predisposing factors and to identify fungal etiological agents using molecular approaches. We also present an overview of published papers on tympanic membrane perforation (TMP) secondary to otomycosis.An otorhinolaryngologist collected specimens from external ear canals of patients with suspected otomycosis based on the patient's history and clinical examinations. The specimens were collected using sterile swabs. Fungal isolates were confirmed in clinical specimens by direct microscopy and culture methods. Fungal isolates were identified based on molecular approaches.In total, specimens from 211 patients with suspected otomycosis were examined. The presence of fungi was confirmed in about 51% of patients based on fungal elements in direct microscopy and culture-positive fungi. Aspergillus tubingensis was the most commonly isolated species (52.77%), followed by Aspergillus niger (25.92%). Otomycosis due to infection with Candida species was observed in 16% of cases. Of note, in 36.11% of cases, otomycosis was associated with TMP.A mycological examination is indispensable for a correct diagnosis in patients with otitis extern. TMP should be considered in patients with otomycosis, as it appears to be relatively common in this population.

Management of superficial aspergillosis is a major challenge owing to the frequent relapses and treatment failure, which may pose a potential risk, thereby gradually developing resistant species. Therefore, necessitating the development of new antifungals with higher potency should be considered as alternative strategies for efficient management of infections. We aimed to investigate the susceptibility of Aspergillus isolates toward a novel triazole, efinaconazole, in comparison with various classes of antifungal drugs. Antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute M38-A2 guidelines. Efinaconazole exhibited poor activity against mutant A. fumigatus strains, A. niger sensu stricto, and A. tubingensis with GM MIC values of 3.62, 1.62, and 2 μg/ml, respectively; however, surprisingly, it efficiently inhibited the growth of A. terreus sensu stricto, followed by wild-type A. fumigatus and A. flavus with GM MIC values of 0.29, 0.42, and 0.52 μg/ml, respectively. Presumably, efinaconazole is inefficient in aspergillosis treatment due to the low susceptibility of A. niger sensu stricto, A. tubingensis, and mutant A. fumigatus; however, it may be effective in treating superficial aspergillosis caused by wild-type A. fumigatus, A. terreus sensu stricto, and A. flavus. Further studies are needed to determine how these findings may translate into in vivo efficacy.