Antifungal resistance in dermatophytes – review of the epidemiology, diagnostic challenges and treatment strategies for managing <i>trichophyton indotineae</i> infections
Creators: name: Gupta, Aditya K.
name: Wang, Tong
name: Mann, Avantika
name: Ravi, Shruthi Polla
name: Talukder, Mesbah
name: Lincoln, Sara A.
name: Foreman, Hui-Chen
name: Kaplan, Baruch
name: Galily, Eran
name: Piguet, Vincent
name: Shemer, Avner
name: Bakotic, Wayne L.
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Computational Biology

description: There is an increasing number of reports of Trichophyton indotineae infections. This species is usually poorly responsive to terbinafine. A literature search was conducted in May 2024. T. indotineae infections detected outside the Indian subcontinent are generally associated with international travel. Reports of local spread are mounting. As a newly identified dermatophyte species closely related to the <i>T. mentagrophytes</i> complex with limited genetic and phenotypic differences, there is an unmet need to develop molecular diagnosis for <i>T. indotineae</i>. Terbinafine has become less effective as a first-line agent attributed to mutations in the squalene epoxidase gene (Leu393Phe, Phe397Leu). Alternative therapies include itraconazole for a longer time-period or a higher dose (200 mg/day or higher). Generally, fluconazole and griseofulvin are not effective. In some cases, especially when the area of involvement is relatively small, topical non-allylamine antifungals may be an option either as monotherapy or in combination with oral therapy. In instances when the patient relapses after apparent clinical cure then itraconazole may be considered. Good antifungal stewardship should be considered at all times. When both terbinafine and itraconazole are ineffective, options include off-label triazoles (voriconazole and posaconazole). We present four patients responding to these newer triazoles. Ringworm (dermatophytosis, tinea) is a fungal infection of the skin, hair and nails that is commonly seen by primary and secondary healthcare providers. An estimated 20-25% of the global population is affected by this condition. In Europe and the United States, tineas are often treated empirically using over-the-counter medications, which can increase the risk of resistance development. While antifungal resistance is not a new problem, this topic has garnered the attention of physicians and researchers in recent years due to an outbreak from South Asia caused by a new pathogen known as <i>Trichophyton indotineae</i>. In this review, we summarize the global prevalence, diagnosis methods, antifungal resistance profile and treatment options for <i>T. indotineae</i>. While most cases outside of South Asia are linked to international travel, there is evidence suggesting local person-to-person transmission and transmission via animal contact. One hurdle to surveilling the spread of this pathogen is the requirement of complex molecular diagnosis, tackling this challenge will require the development of newer assays. Terbinafine, a widely available antifungal drug, is becoming less effective owing to resistance mutations of the squalene epoxidase gene. Itraconazole has shown effectiveness, especially with a higher dose and a longer treatment duration. There is a significant risk of <i>T. indotineae</i> infections becoming chronic with episodes of relapse. When both terbinafine and itraconazole fail, newer agents such as posaconazole and voriconazole can be considered. Combination therapy using oral and topical medications should also be considered.