JAMA Dermatology

<jats:sec id="ab-doi240012-4"><jats:title>Importance</jats:title><jats:p><jats:italic>Trichophyton indotineae</jats:italic> is an emerging dermatophyte causing outbreaks of extensive tinea infections often unresponsive to terbinafine. This species has been detected worldwide and in multiple US states, yet detailed US data on infections with <jats:italic>T indotineae</jats:italic> are sparse and could improve treatment practices and medical understanding of transmission.</jats:p></jats:sec><jats:sec id="ab-doi240012-5"><jats:title>Objective</jats:title><jats:p>To correlate clinical features of <jats:italic>T indotineae</jats:italic> infections with in vitro antifungal susceptibility testing results, squalene epoxidase gene sequence variations, and isolate relatedness using whole-genome sequencing.</jats:p></jats:sec><jats:sec id="ab-doi240012-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This retrospective cohort study of patients with <jats:italic>T indotineae</jats:italic> infections in New York City spanned May 2022 to May 2023. Patients with confirmed <jats:italic>T indotineae</jats:italic> infections were recruited from 6 New York City medical centers.</jats:p></jats:sec><jats:sec id="ab-doi240012-7"><jats:title>Main Outcome and Measure</jats:title><jats:p>Improvement or resolution at the last follow-up assessment.</jats:p></jats:sec><jats:sec id="ab-doi240012-8"><jats:title>Results</jats:title><jats:p>Among 11 patients with <jats:italic>T indotineae</jats:italic> (6 male and 5 female patients; median [range] age, 39 [10-65] years), 2 were pregnant; 1 had lymphoma; and the remainder were immunocompetent. Nine patients reported previous travel to Bangladesh. All had widespread lesions with variable scale and inflammation, topical antifungal monotherapy failure, and diagnostic delays (range, 3-42 months). Terbinafine treatment failed in 7 patients at standard doses (250 mg daily) for prolonged duration; these patients also had isolates with amino acid substitutions at positions 393 (L393S) or 397 (F397L) in squalene epoxidase that correlated with elevated terbinafine minimum inhibitory concentrations of 0.5 μg/mL or higher. Patients who were treated with fluconazole and griseofulvin improved in 2 of 4 and 2 of 5 instances, respectively, without correlation between outcomes and antifungal minimum inhibitory concentrations. Furthermore, 5 of 7 patients treated with itraconazole cleared or had improvement at the last follow-up, and 2 of 7 were lost to follow-up or stopped treatment. Based on whole-genome sequencing analysis, US isolates formed a cluster distinct from Indian isolates.</jats:p></jats:sec><jats:sec id="ab-doi240012-9"><jats:title>Conclusion and Relevance</jats:title><jats:p>The results of this case series suggest that disease severity, diagnostic delays, and lack of response to typically used doses and durations of antifungals for tinea were common in this primarily immunocompetent patient cohort with <jats:italic>T indotineae</jats:italic>, consistent with published data. Itraconazole was generally effective, and the acquisition of infection was likely in Bangladesh.</jats:p></jats:sec>

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Trichophyton indotineae is an emerging dermatophyte causing outbreaks of extensive tinea infections often unresponsive to terbinafine. This species has been detected worldwide and in multiple US states, yet detailed US data on infections with T indotineae are sparse and could improve treatment practices and medical understanding of transmission.
To correlate clinical features of T indotineae infections with in vitro antifungal susceptibility testing results, squalene epoxidase gene sequence variations, and isolate relatedness using whole-genome sequencing.
This retrospective cohort study of patients with T indotineae infections in New York City spanned May 2022 to May 2023. Patients with confirmed T indotineae infections were recruited from 6 New York City medical centers.
Improvement or resolution at the last follow-up assessment.
Among 11 patients with T indotineae (6 male and 5 female patients; median [range] age, 39 [10-65] years), 2 were pregnant; 1 had lymphoma; and the remainder were immunocompetent. Nine patients reported previous travel to Bangladesh. All had widespread lesions with variable scale and inflammation, topical antifungal monotherapy failure, and diagnostic delays (range, 3-42 months). Terbinafine treatment failed in 7 patients at standard doses (250 mg daily) for prolonged duration; these patients also had isolates with amino acid substitutions at positions 393 (L393S) or 397 (F397L) in squalene epoxidase that correlated with elevated terbinafine minimum inhibitory concentrations of 0.5 μg/mL or higher. Patients who were treated with fluconazole and griseofulvin improved in 2 of 4 and 2 of 5 instances, respectively, without correlation between outcomes and antifungal minimum inhibitory concentrations. Furthermore, 5 of 7 patients treated with itraconazole cleared or had improvement at the last follow-up, and 2 of 7 were lost to follow-up or stopped treatment. Based on whole-genome sequencing analysis, US isolates formed a cluster distinct from Indian isolates.
The results of this case series suggest that disease severity, diagnostic delays, and lack of response to typically used doses and durations of antifungals for tinea were common in this primarily immunocompetent patient cohort with T indotineae, consistent with published data. Itraconazole was generally effective, and the acquisition of infection was likely in Bangladesh.

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

Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of <i>Trichophyton indotineae</i>

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