title: Pathogenic Dermatophytes Survive in Nail Lesions During Oral Terbinafine Treatment for Tinea Unguium.
abstract: Tinea unguium caused by dermatophyte species are usually treated with oral antimycotic, terbinafine (TBF). To understand the mechanisms of improvement and recalcitrance of tinea unguium by oral TBF treatment, a method of quantifying dermatophyte viability in the nail was developed, and the viability of dermatophytes was analyzed in toenail lesions of 14 patients with KOH-positive tinea unguium treated with oral TBF 125 mg/day for up to 16 weeks. Mycological tests, including KOH examination and fungal culture, and targeted quantitative real-time PCR for internal transcribed spacer (ITS) region, including rRNA, were demonstrated at the initial visit and after 8 and 16 weeks of treatment. Assays in eight patients showed that average ITS DNA amount significantly decreased, to 44% at 8 weeks and 36% at 16 weeks compared with 100% at initial visit. No significant difference was observed between at 8 and 16 weeks, despite the TBF concentration in the nail supposedly more than 10-fold higher than the minimum fungicidal concentration for dermatophytes. This finding suggests the pathogenic dermatophytes in nail lesions could survive in a dormant form, such as arthroconidia, during oral TBF treatment. Both antimycotic activity and nail growth are important factors in treatment of tinea unguium.
authors.affiliation: Department of Dermatology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. t-iwanag@kanazawa-med.ac.jp.|R&D Laboratories, POLA PHARMA INC., 560 Kashio-cho, Totsuka-ku, Yokohama, Kanagawa, 244-0812, Japan. t-iwanag@kanazawa-med.ac.jp.
authors.forename: Tomoyuki
authors.identifier: http://orcid.org/0000-0003-1158-4403
authors.initials: T
authors.lastname: Iwanaga
authors.affiliation: Department of Dermatology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ushigami
authors.affiliation: Department of Dermatology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Anzawa
authors.affiliation: Department of Dermatology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mochizuki
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage*; D003883:Arthrodermataceae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D021903:DNA, Ribosomal Spacer / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D050296:Microbial Viability / Q000187:drug effects*; D008828:Microbiological Techniques; D008875:Middle Aged; D009262:Nails / Q000382:microbiology*; D009281:Naphthalenes / Q000008:administration & dosage*; D014009:Onychomycosis / Q000188:drug therapy*; D060888:Real-Time Polymerase Chain Reaction; D000077291:Terbinafine; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D004271:DNA, Fungal; D021903:DNA, Ribosomal Spacer; D009281:Naphthalenes; D000077291:Terbinafine
keywords: Dermatophyte; Onychomycosis; Quantitative real-time PCR; Terbinafine; Tinea unguium; Trichophyton; Viability