Terbinafine resistance in Trichophyton mentagrophytes and Trichophyton rubrum in the Czech Republic: A prospective multicentric study.

BACKGROUND: Terbinafine, an allylamine antifungal, is crucial for treating dermatophytosis by inhibiting squalene epoxidase (SQLE) in the ergosterol biosynthetic pathway. However, resistance is emerging, particularly in India and Southeast Asia, but reports of resistance spread worldwide. Despite this, comprehensive studies on terbinafine resistance in Trichophyton are still limited. OBJECTIVES: This research aimed to determine the prevalence of terbinafine resistance in the Czech Republic, with a focus on Trichophyton rubrum and Trichophyton mentagrophytes, and investigate the underlying molecular mechanisms. PATIENTS/METHODS: A total of 514 clinical strains of T. rubrum and 240 T. mentagrophytes collected from four Czech clinical institutions were screened for terbinafine resistance. Molecular investigations included DNA sequencing, specifically the ITS rDNA region and SQLE gene, as well as antifungal susceptibility testing following EUCAST guidelines. RESULTS: While no resistance was observed in T. rubrum, 2.5% of T. mentagrophytes strains exhibited resistance, marked by the F397L mutation in SQLE. Notably, resistance surged from 1.2% in 2019 to 9.3% in 2020 but reverted to 0% in 2021. All resistant strains were identified as T. mentagrophytes var. indotineae. Resistant strains exhibited high MICs for terbinafine (≥4 mg L-1 ) but low MICs to the other seven antifungals tested except for fluconazole. CONCLUSIONS: This study highlights the emergence of terbinafine-resistant T. mentagrophytes strains in the Czech Republic, with the F397L mutation being pivotal. Due to the relatively low resistance level, the current guidelines for dermatomycosis treatment in the Czech Republic remain effective, but ongoing surveillance is essential for timely adaptations if resistance patterns change.

Defining the relationship between phylogeny, clinical manifestation, and phenotype for Trichophyton mentagrophytes/interdigitale complex; a literature review and taxonomic recommendations.

This study looked for correlations between molecular identification, clinical manifestation, and morphology for Trichophyton interdigitale and Trichophyton mentagrophytes. For this purpose, a total of 110 isolates were obtained from Czech patients with various clinical manifestations of dermatophytosis. Phenotypic characters were analyzed, and the strains were characterized using multilocus sequence typing. Among the 12 measured/scored phenotypic features, statistically significant differences were found only in growth rates at 37 °C and in the production of spiral hyphae, but none of these features is diagnostic. Correlations were found between T. interdigitale and higher age of patients and between clinical manifestations such as tinea pedis or onychomychosis. The MLST approach showed that internal transcribed spacer (ITS) genotyping of T. mentagrophytes isolates has limited practical benefits because of extensive gene flow between sublineages. Based on our results and previous studies, there are few taxonomic arguments for preserving both species names. The species show a lack of monophyly and unique morphology. On the other hand, some genotypes are associated with predominant clinical manifestations and sources of infections, which keep those names alive. This practice is questionable because the use of both names confuses identification, leading to difficulty in comparing epidemiological studies. The current identification method using ITS genotyping is ambiguous for some isolates and is not user-friendly. Additionally, identification tools such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry fail to distinguish these species. To avoid further confusion and to simplify identification in practice, we recommend using the name T. mentagrophytes for the entire complex. When clear differentiation of populations corresponding to T. interdigitale and Trichophyton indotineae is possible based on molecular data, we recommend optionally using a variety rank: T. mentagrophytes var. interdigitale and T. mentagrophytes var. indotineae.

Species in the T. mentagrophytes complex lack support from usual taxonomic methods and simple identification tools are missing or inaccurate. To avoid recurring confusions, we propose naming the entire complex as T. mentagrophytes and optionally use rank variety to classify the observed variability.

Inactivation of dermatophyte infection by nonthermal plasma on animal model.

Superficial fungal infections are a major epidemiological issue with increasing prevalence and are a common global problem. This article describes experimental therapy of superficial fungal skin infection using low-temperature plasma. Groups of guinea pigs were artificially infected with Trichophyton mentagrophytes SK 3286 dermatophyte and treated with plasma produced by a DC cometary discharge with an inserted grid. The course of infection was a week shorter and milder in animals treated by plasma than that in nontreated animals, the significant lowering of dermatophytic germs also occurred in the treated group. The exposure to plasma causes no harm to experimental animals. The results allow for the development of a new dermatophytoses therapy by low temperature plasma treatment.

Inactivation of human pathogenic dermatophytes by non-thermal plasma.

Non-thermal plasma (NTP) was tested as an in vitro deactivation method on four human pathogenic dermatophytes belonging to all ecological groups including anthropophilic Trichophyton rubrum and Trichophyton interdigitale, zoophilic Arthroderma benhamiae, and geophilic Microsporum gypseum. The identification of all strains was confirmed by sequencing of ITS rDNA region (internal transcribed spacer region of ribosomal DNA). Dermatophyte spores were suspended in water or inoculated on agar plates and exposed to NTP generated by a positive or negative corona discharge, or cometary discharge. After 15 min of exposure to NTP a significant decrease in the number of surviving spores in water suspensions was observed in all species. Complete spore inactivation and thus decontamination was observed in anthropophilic species after 25 min of exposure. Similarly, a significant decrease in the number of surviving spores was observed after 10-15 min of exposure to NTP on the surface of agar plates with full inhibition after 25 min in all tested species except of M. gypseum. Although the sensitivity of dermatophytes to the action of NTP appears to be lower than that of bacteria and yeast, our results suggest that NTP has the potential to be used as an alternative treatment strategy for dermatophytosis and could be useful for surface decontamination in clinical practice.

Treatment of a superficial mycosis by low-temperature plasma: a case report.

A case of dermatomycosis caused by zoophilic strain of Trichophyton interdigitale was treated by low-temperature plasma produced by direct current (DC) cometary discharge. The shortening of skin lesion persistence along with suppression of subjective discomfort and etiological agent was observed.