Roozbeh Yalfani,1,*
1. Department of Nursing, Faculty of Medical Sciences, Islamic Azad University,Varamin-Pishva branch, Tehran, Iran
Introduction: Dermatophytes are the most common cause of fungal infections worldwide, affecting millions of people annually. Dermatophytes are filamentous fungi with the ability to invade keratinised tissue, such as skin, hair, and nails. Classically, they are divided into three genera: Trichophyton, Epidermophyton, and Microsporum. However, this classification is based on the phenotype of the species and led to misclassification of morphological mutants. In 2017, de Hoog et al. constructed a phylogenetic tree using sequences of the nuclear ribosomal internal transcribed spacers (ITS rDNA) and divided the dermatophytes into seven clades: Trichophyton, Epidermophyton, Nannizzia, Paraphyton, Lophophyton, Microsporum, and Arthroderma. Ringworm or tinea is one of the most frequent clinical aspect of dermatophytosis. Among the tinea infections, tinea corporis, tinea cruris, tinea pedis, and onychomycosis are the most predominant types. The dermatophytes T. rubrum, T. interdigitale and T. mentagrophytes, are the main aetiological agents of dermatophytosis of skin and nails in humans.
Methods: Medical treatment of dermatophytosis consists of topical and/or oral antifungal agents. There are many topical agents for treating several less severe forms of tinea. The azole derivatives, such as clotrimazole, miconazole, econazole, and oxiconazole, are the generally used. Agents from the allylamine family, such as terbinafine and naftifine, are also used. Other topical agents, such as ciclopirox or amorolfine, can be effective in the less severe cases of onychomycosis. In the more severe forms of dermatophyte infections, oral treatment is generally employed. Topical (amorolfine, ciclopirox, efinaconazole, tavaborole, and luliconazole) and oral antifungals (terbinafine and itraconazole) are currently used for onychomycosis treatment. Azole antifungals (triazole class: efinaconazole and itraconazole; imidazole class: luliconazole), terbinafine, and amorolfine inhibit lanosterol 14α-demethylase, squalene epoxidase, and ∆14 reductase/∆7-8 isomerase, respectively. These antifungals consequentially block ergosterol biosynthesis in fungal cells. Ciclopirox chelates polyvalent cations, such as Fe3+ and Al3+, resulting in the inhibition of metal-dependent enzymes responsible for degrading peroxides inside fungal cells. Tavaborole inhibits leucyl-tRNA synthetase and consequentially blocks protein synthesis in fungal cells.
Results: Terbinafine therapy of dermatophytosis is usually effective, yet increasing numbers of non-responding cases have been documented. Treatment failures and recurrences can be due to host factors such as poor compliance, drug interactions and in cases of onychomycosis local nail factors. Terbinafine resistance in dermatophytes is typically rare, but reports have been increasing since 2017. It is associated with various point mutations in the squalene epoxidase target gene of T. rubrum and T. interdigitale. However, cases of terbinafine-resistant Trichophyton infections are also seen in other Asian and Middle Eastern countries such as Japan and Iran.
Conclusion: However, clinical resistance does not always correspond to the in vitro resistance and vice versa. This is because several factors influence outcome of an infection including the severity of infection, the host immunity, the timing and dosing of the therapy, compliance and the susceptibility of the infecting organism.
Overall, clinical data would suggest that an antifungal combination regimen might be useful against an infection due to dermatophytes. It is interesting to note that even combining drugs acting against a common fungal target (i.e., ergosterol—azoles, allylamines, and morpholine drugs such as amorolfine), a positive interaction in terms of reduction of the MIC of both drugs is often observed. Also they indicate that an association of antifungal agents (systemic plus topic) is effective, and it might be useful in speeding up the clinical and microbiological healing of a superficial infection.