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- Title
Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton indotineae.
- Authors
Caplan, Avrom S.; Todd, Gabrielle C.; Zhu, YanChun; Sikora, Michelle; Akoh, Christine C.; Jakus, Jeannette; Lipner, Shari R.; Graber, Kayla Babbush; Acker, Karen P.; Morales, Ayana E.; Rolón, Rebecca M. Marrero; Westblade, Lars F.; Fonseca, Maira; Cline, Abigail; Gold, Jeremy A. W.; Lockhart, Shawn R.; Smith, Dallas J.; Chiller, Tom; Greendyke, William G.; Manjari, Swati R.
- Abstract
Key Points: Question: What are the clinical features, antifungal susceptibility, and genome sequencing of Trichophyton indotineae? Findings: In this case series of 11 patients in New York City, severe disease, ineffective standard antifungal treatments, and diagnostic delays were common. Squalene epoxidase sequence variations L393S and F397L, and terbinafine minimum inhibitory concentration values of 0.5 μg/mL or higher were associated with terbinafine therapy failure, with US isolates showing differences from known Indian isolates. Meaning: The manifestation of T indotineae involves extensive and recalcitrant infections, often resistant to standard terbinafine therapy, while analysis of travel history and isolate relatedness suggests a probable origin of these infections in Bangladesh. Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Main Outcome and Measure: Improvement or resolution at the last follow-up assessment. Results: 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. Conclusion and Relevance: 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. This case series describes the clinical features, antifungal susceptibility, and genome sequencing of Trichophyton indotineae in 11 patients in New York City.
- Publication
JAMA Dermatology, 2024, Vol 160, Issue 7, p701
- ISSN
2168-6068
- Publication type
Article
- DOI
10.1001/jamadermatol.2024.1126