Understanding Terbinafine Resistance in Dermatophytosis

Dermatologists worldwide are currently facing a significant clinical hurdle as terbinafine resistance in dermatophytosis becomes a recognized global threat. While terbinafine has long served as the first-line therapy for fungal skin infections, recent reports highlight a rise in resistant strains. Specifically, a prospective laboratory study conducted in Montevideo, Uruguay, from 2023 to 2024, has documented the first local cases of such resistance. Researchers focused on Trichophyton rubrum and the Trichophyton mentagrophytes complex, which remain the primary causes of these infections globally. However, the emergence of resistant isolates suggests that standard treatment protocols may no longer be universally effective.

During the study, the research team processed over 1,200 samples using advanced diagnostic tools like MALDI-TOF mass spectrometry. Among the 171 isolates screened for susceptibility, approximately 2.34% demonstrated resistance to terbinafine. These resistant strains exhibited high minimal inhibitory concentrations (MICs). Consequently, the team performed genetic sequencing on the squalene epoxidase (SQLE) gene. This analysis revealed critical amino acid substitutions at positions 393 and 397. These specific mutations are well-known to confer resistance by altering the enzyme's binding site, thereby rendering the antifungal drug ineffective.

Clinical Implications of SQLE Mutations

The identification of these mutations is particularly relevant for clinicians in India. Historically, India has been the epicenter of a massive tinea epidemic driven by Trichophyton indotineae, a species known for its high level of terbinafine resistance in dermatophytosis. The Uruguayan study underscores that these resistant genotypes are spreading across Latin America and beyond. Therefore, medical practitioners must maintain a high index of suspicion when patients fail to respond to standard terbinafine therapy. Furthermore, the study advocates for the use of the terbinafine-containing agar medium (TCAM) method as a practical screening tool in routine clinical settings.

Moreover, the study highlighted that while T. rubrum was the most common isolate, the T. mentagrophytes complex also showed significant resistance. This finding mirrors the Indian scenario, where multiple species contribute to recalcitrant cases. Additionally, clinicians may need to consider alternative therapies, such as itraconazole, when resistance is suspected. Ultimately, regional surveillance remains vital to track these emerging resistance patterns and to guide effective antifungal stewardship.

Frequently Asked Questions

What is the primary cause of terbinafine resistance in dermatophytes?

Resistance is primarily caused by point mutations in the squalene epoxidase (SQLE) gene. These mutations result in amino acid substitutions at specific positions, such as Phe397Leu and Leu393Phe, which prevent the drug from binding to the target enzyme.

How can clinicians detect resistant fungal infections?

Clinicians can detect resistance through antifungal susceptibility testing (AFST) or by using terbinafine-containing agar medium (TCAM) screening. Genetic sequencing of the SQLE gene provides definitive proof of the resistance mechanism.

Why is this global trend relevant to medical practice in India?

India is already dealing with a widespread epidemic of resistant tinea infections. Understanding global resistance patterns and specific mutations helps Indian doctors refine treatment strategies and underscores the need for strict antifungal stewardship.

Disclaimer: This content is for informational and educational purposes only. It is not intended as medical advice or a substitute for professional clinical judgment. Always seek the advice of a qualified healthcare provider for any medical condition. Refer to the latest local and national guidelines for clinical practice.

References

Puime A et al. First Report of Terbinafine Resistance in Human Dermatophytosis in Uruguay. Med Mycol. 2026 Apr 23. doi: undefined. PMID: 42024427.

Ebert A et al. Terbinafine Resistance in Trichophyton rubrum and Trichophyton indotineae: A Literature Review. J Fungi (Basel). 2025 May 7. doi: 10.3390/jof11050512.

Khurana A et al. Alarming India-wide phenomenon of antifungal resistance in dermatophytes: A multicentre study. Mycoses. 2020;63(7):717-728.