Terbinafine Resistance in Dermatophytes: A French Multicenter Prospective Study
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Alicia Moreno-Sabater1,2, Anne-Cécile Normand3, Anne-Laure Bidaud4
1Service de Parasitologie-Mycologie, Hôpital Saint-Antoine, AP-HP, 75012 Paris, France.
Abstract:
In recent years, we have moved from the sporadic description of terbinafine-resistant (TerR) Trichophyton spp. isolates to the Indian outbreak due to T. indotineae. Population flows have spread TerR worldwide, altering local epidemiology. We conducted a prospective multicentric study to determine the relative frequency of TerR isolates in France (Paris area) and of the newly introduced T. indotineae species. TerR isolates were screened by the terbinafine-containing-agar-medium (TCAM) method and confirmed by EUCAST. Sequencing methods were used to identify isolates to the species/genotype level and to analyze substitutions in the squalene epoxidase gene (SQLE). In total, 3 isolates out of 580 (T. rubrumn = 1; T. interdigitalen = 1; T. indotineaen = 1) grew on TCAM, showed terbinafine resistance by EUCAST and harbored the Phe397Leu (n = 2) or Leu393Ser (n = 1) substitution in the SQLE. ITS-sequencing of isolates of the T. mentagrophytes/interdigitale complex (n = 125) revealed a relative frequency of 4.8% for T. indotineae and the presence of T. mentagrophytes genotype VII. Despite the detection of terbinafine resistance, isolates from this complex remained susceptible to itraconazole, voriconazole and amorolfine. Terbinafine resistance is present in France and the dermatophyte epidemiology is changing. Efficient systems must be implemented to survey the evolution of newly introduced species and to identify TerR isolates.
Insights
Terbinafine-resistant Trichophyton species are emerging globally. This study found terbinafine resistance in France, with the new T. indotineae species present, highlighting changing dermatophyte epidemiology.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Sporadic reports of terbinafine-resistant (TerR) Trichophyton spp. have escalated to a significant outbreak in India caused by T. indotineae.
- Global population movements are contributing to the worldwide spread of TerR isolates, consequently altering local dermatophyte epidemiology.
Purpose of the Study:
- To ascertain the prevalence of TerR isolates in France (Paris area).
- To determine the presence and frequency of the newly introduced T. indotineae species in France.
Main Methods:
- Prospective multicentric study design.
- Screening of TerR isolates using terbinafine-containing-agar-medium (TCAM) and confirmation via EUCAST standards.
- Species/genotype identification and analysis of squalene epoxidase gene (SQLE) substitutions using sequencing methods.
Main Results:
- Three out of 580 isolates (T. rubrum, T. interdigitale, T. indotineae) exhibited terbinafine resistance, confirmed by EUCAST, and carried SQLE substitutions (Phe397Leu or Leu393Ser).
- ITS-sequencing identified T. indotineae at a relative frequency of 4.8% within the T. mentagrophytes/interdigitale complex (n=125), along with T. mentagrophytes genotype VII.
- Despite terbinafine resistance, isolates remained susceptible to itraconazole, voriconazole, and amorolfine.
Conclusions:
- Terbinafine resistance has been confirmed in France, indicating a shift in dermatophyte epidemiology.
- The emergence and spread of T. indotineae necessitate efficient surveillance systems to monitor evolving species and identify TerR isolates.
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