Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton indotineae

Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton indotineae

July 2024 | Avrom S. Caplan, MD; Gabrielle C. Todd, PhD; YanChun Zhu, MS; Michelle Sikora, BS; Christine C. Akoh, MD, PhD; Jeannette Jakus, MD, MBA; Shari R. Lipner, MD, PhD; Kayla Babbush Graber, MD; Karen P. Acker, MD; Ayana E. Morales, MD; Rebecca M. Marrero Rolón, MD; Lars F. Westblade, PhD; Maira Fonseca, MD; Abigail Cline, MD, PhD; Jeremy A. W. Gold, MD, MS; Shawn R. Lockhart, PhD; Dallas J. Smith, PharmD, MAS; Tom Chiller, MD; William G. Greendyke, PhD; Swati R. Manjari; Nilesh K. Banavali; Sudha Chaturvedi, PhD
A case series of 11 patients with Trichophyton indotineae infections in New York City (2022-2023) highlights the clinical features, antifungal susceptibility, and genomic characteristics of this emerging dermatophyte. The infections, often extensive and unresponsive to standard antifungal treatments like terbinafine, were associated with delayed diagnosis and travel history to Bangladesh. Most patients had widespread skin lesions, and topical antifungal therapy failed. Terbinafine treatment failed in 7 patients due to amino acid substitutions (L393S and F397L) in the squalene epoxidase gene, leading to elevated minimum inhibitory concentrations (MICs). Fluconazole and griseofulvin showed partial effectiveness, while itraconazole was generally effective, with 5 of 7 patients showing improvement. Whole-genome sequencing revealed US isolates formed a distinct cluster from Indian isolates, suggesting a probable origin in Bangladesh. The study emphasizes the need for molecular testing for accurate diagnosis and highlights the importance of prolonged itraconazole treatment for effective management. The findings underscore the global spread of T. indotineae and the need for international collaboration to address its emergence and resistance patterns.A case series of 11 patients with Trichophyton indotineae infections in New York City (2022-2023) highlights the clinical features, antifungal susceptibility, and genomic characteristics of this emerging dermatophyte. The infections, often extensive and unresponsive to standard antifungal treatments like terbinafine, were associated with delayed diagnosis and travel history to Bangladesh. Most patients had widespread skin lesions, and topical antifungal therapy failed. Terbinafine treatment failed in 7 patients due to amino acid substitutions (L393S and F397L) in the squalene epoxidase gene, leading to elevated minimum inhibitory concentrations (MICs). Fluconazole and griseofulvin showed partial effectiveness, while itraconazole was generally effective, with 5 of 7 patients showing improvement. Whole-genome sequencing revealed US isolates formed a distinct cluster from Indian isolates, suggesting a probable origin in Bangladesh. The study emphasizes the need for molecular testing for accurate diagnosis and highlights the importance of prolonged itraconazole treatment for effective management. The findings underscore the global spread of T. indotineae and the need for international collaboration to address its emergence and resistance patterns.
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