A case of double-mutant resistant tinea indotineae

R. Koncan, A. Benini, G. Lo Cascio, N. Di Meo, V. Lepera, G. Palladino, L. Clemente, F. Barbone, I. Zalaudek
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Abstract

In recent years, there has been a concerning increase in a challenging-to-treat dermatophyte lineage of the Trichophyton mentagrophytes complex, known as Trichophyton indotineae. We report the first case of resistant T. indotineae bearing a double mutation in the squalene epoxidase gene (SQLE), isolated in Italy from a 26 -year-old Nepali woman affected by a persistent tinea corporis. Topical terbinafine yielded minimal to no improvement while itraconazole provided partial relief but failed to eradicate the infection. Molecular identification through Sanger sequencing of the internal transcribed spacer region confirmed T. indotineae and sequencing of the SQLE gene revealed the presence of a double mutation (Phe397Leu/Ala448Thr) associated with antifungal resistance. Broth microdilution susceptibility testing demonstrated resistance to fluconazole, but susceptibility to itraconazole. Ultimately complete cure was achieved with prolonged high-dose itraconazole therapy.

Abstract Image

近年来,曼陀罗毛癣菌(Trichophyton mentagrophytes complex)中一种难以治疗的皮癣菌--吲哚毛癣菌(Trichophyton indotineae)出现了令人担忧的增长。我们报告了第一例在角鲨烯环氧化物酶基因(SQLE)发生双重突变的抗药性靛毛癣菌,该病例在意大利从一名患有顽固性体癣的 26 岁尼泊尔妇女身上分离出来。外用特比萘芬的疗效甚微,甚至没有任何改善,而伊曲康唑虽能缓解部分症状,但未能根除感染。通过对内转录间隔区的 Sanger 测序进行分子鉴定,确认了 T. indotineae,而对 SQLE 基因的测序则发现了与抗真菌耐药性相关的双突变(Phe397Leu/Ala448Thr)。肉汤微量稀释药敏试验显示,患者对氟康唑产生抗药性,但对伊曲康唑敏感。通过长期大剂量伊曲康唑治疗,最终完全治愈了该病。
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