BioPathogenix Digest Vol.8
BioPathogenix
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Welcome to volume 8 of the Biopathogenix Digest! This April issue tackles the escalating challenge of terbinafine resistance, a once-reliable antifungal medication.
We'll explore the growing prevalence of this resistance, the science behind it, and the impact on treatment and patient outcomes.
Expert insights and potential solutions will be featured, keeping you informed on how to navigate this evolving threat in the field of mycology.
Emerging Concerns: The Escalating Challenge of Terbinafine Resistance
Dermatophytosis, commonly known as ringworm or tinea, is a prevalent fungal infection of the skin, hair, and nails caused by dermatophytes, including Trichophyton, Microsporum, and Epidermophyton species. While dermatophyte infections can occur worldwide, the prevalence and distribution of specific dermatophyte species may vary depending on geographic regions and populations.
Antifungal agents like terbinafine are one of the widely used antifungal agents in the treatment of dermatophyte infections due to their effectiveness and relatively low incidence of resistance. This antifungal medication, listed in the World Health Organization's List of Essential Medicines as a topical treatment, works by inhibiting squalene epoxidase (SQLE). The SQLE is an enzyme crucial in the initial stages of ergosterol biosynthesis, a vital and species-specific element of the fungal cell membrane.
Figure 1. The mode of action of Terbinafine
Nonetheless, there have been numerous reports of terbinafine resistance specifically within certain species of Trichophyton. The United States witnessed its first documented case of terbinafine-resistant dermatophyte in 2003. This case involved a patient with a toenail infection caused by a Trichophyton rubrum isolate.
Resistance mechanisms may involve single point mutations in the gene encoding SQLE.
Currently, substitutions at five specific amino acid positions within the encoded protein have been documented: L393, F397, Q409, F415, and H440. These substitutions have been observed in Trichophyton rubrum and Trichophyton indotineae, which was newly designated as a distinct species in 2020, separate from the Trichophyton mentagrophytes genotype VIII or Trichophyton interdigitale complex. SQLE gene mutations can reduce terbinafine's effectiveness by altering the enzyme's structure or function, impairing its inhibition. This resistance mechanism can lead to treatment failure in dermatophyte infections.
Figure. Diagram of geographical locations in which terbinafine resistance of isolates has been described with minimum inhibitory concentration (MICs) and substitutions in the squalene epoxidase enzyme. (?agowski A. et al. Infection 48, 889–897 (2020)).
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Understanding how mutations in the SQLE gene impact susceptibility to terbinafine is crucial for identifying and managing cases of drug-resistant dermatophyte infections effectively. Molecular assays targeting SQLE gene mutations offer rapid, sensitive, and specific detection of terbinafine resistance in fungal infections. They enable direct testing on infected samples, bypassing the need for culture-based methods. With potential for point-of-care use, these assays hold promise for revolutionizing diagnostics and guiding personalized treatment approaches.
Federal agencies in the USA employ a comprehensive approach to prevent terbinafine resistance and fungal infections. This includes surveillance to track resistance patterns, funding research for new treatments, issuing guidelines for appropriate medication use, promoting public awareness, implementing infection control practices, and collaborating internationally.
It's essential for ongoing surveillance and research to monitor the prevalence and mechanisms of antifungal resistance to ensure effective management of dermatophyte infections. Healthcare providers should stay updated on current recommendations for diagnosis and treatment based on the latest research and guidelines.
References:
?agowski, D., Gnat, S., Nowakiewicz, A. et al. Intrinsic resistance to terbinafine among human and animal isolates of Trichophyton mentagrophytes related to amino acid substitution in the squalene epoxidase. Infection 48, 889–897 (2020). https://doi.org/10.1007/s15010-020-01498-1
BioPathogenix, a leading provider of innovative diagnostic solutions, is excited to announce its participation in the upcoming Cola Laboratory Enhancement Forum, taking place on May 7th-9th at the Destin-Fort Walton Beach Convention Center (Booth 3).
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