Autor(es): Henriques, Camila
Data: 2020
Identificador Persistente: http://hdl.handle.net/10400.18/7706
Origem: Repositório Científico do Instituto Nacional de Saúde
Assunto(s): Dermatophytes; Terbinafine; Resistance; Superficial Mycosis; Infecções Sistémicas e Zoonoses; Portugal
Superficial mycoses caused by Trichophyton rubrum are among the most common infections worldwide. In Portugal, it is estimated that 1,510,391 of Portuguese suffer from dermatophytosis, corresponding to an incidence of 14,300 per 1,000,000 inhabitants. In a retrospective analysis carried out from 2014 to 2016, with data collected from various hospital institutions in the North and Center of the country and in the metropolitan area of Lisbon, with the aim of evaluating the etiological agents of superficial mycoses diagnosed at national level, comparing their geographic distribution as well as analyzing the species distribution in relation to the cutaneous area involved, 15 different species of dermatophytes were found, with T. rubrum being the most frequent species (53.6%) and the main etiological agent of dermatophytosis of glabrous skin and feet onychomycosis. Superficial mycoses caused by Trichophyton rubrum are among the most common infections worldwide. T. rubrum infections are difficult to treat and are often associated with recurrences after interruption of the antifungal therapy. Terbinafine is one of the allylamine antifungal agents whose target is squalene epoxidase (SQLE). This agent has been extensively used in the therapy of dermatophyte infections. The emergence of resistance to terbinafine in Trichophyton species (namely T. rubrum) has been described recently. The incidence of patients with tinea pedis or unguium tolerant to terbinafine treatment prompted us to screen the terbinafine resistance of Trichophyton isolates obtained by culture at the Mycology Reference Laboratory of the National Institute of Health Doctor Ricardo Jorge. We aimed to determine the frequency of terbinafine resistance and to identify which mutations were involved and their associated mechanism of resistance. Dermatophytes were identified by culture and MALDI-TOF and/or ITS sequencing. All isolates were grown onto agar supplemented with terbinafine in order to detect potential resistant isolates. Antifungal susceptibility testing was performed following CLSI M38A2 broth microdilution method. Among 102 T. rubrum and 17 of T. interdigitale isolates that were tested, 1 T. rubrum isolate (≈1%) and 3 T. interdigitale isolates (≈18%) showed reduced susceptibility to terbinafine. Overall, three isolates showed high terbinafine resistance (MICs, 4 to ≥ 8mg/L) and one isolate displayed moderate terbinafine resistance (MIC, 1 to 2 mg/L). After antifungal susceptibility testing, we sequenced SQLE gene and only 1 isolate from each species were found to harbor different single point mutations in the SQLE gene , leading to single amino acid substitutions at one position (Phe^397) of the SQLE protein. Taken together, our results prompt the current knowledge about the necessity of antifungal susceptibility testing to select effective strategies for management of clinical cases of dermatophytosis not only in Portugal but worldwide.
