title: Effect of Lamisil and azole antifungals in experimental nail infection.
abstract: Onychomycosis is primarily caused by dermatophyte fungi but occasionally by yeasts and non-dermatophytic moulds. The aim of this study was to develop an in vitro model of nail invasion by dermatophytes, yeasts and non-dermatophytic moulds, and to provide an alternative system for studying the activity of different classes of antifungal drugs against fungi associated with onychomycosis. In the absence of extraneous nutrients, Trichophyton mentagrophytes was seen in electron microscopy to degrade completely healthy nail plate. Candida albicans germinated on nail fragments, but invasion of the nail plate was not seen. The mould Fusarium formed long channels through the matrix of the nail plate. Aspergillus versicolor appeared to penetrate the outer and intermediate surface of the nail plate only. Acremonium sp. and Scopulariopsis brevicaulis did not invade nail in this model. Exposure of nail fragments to terbinafine (0.25 mg/l for 3 h) inhibited invasion by T. mentagrophytes, C. albicans and the non-dermatophytic moulds. Itraconazole (0.25 mg/l for 3 h) prevented nail plate invasion by T. mentagrophytes, A. versicolor and Fusarium but did not totally inhibit the surface growth of Acremonium or S. brevicaulis. C. albicans grew in the presence of itraconazole. The results indicate that terbinafine is readily absorbed by the nail and that the drug is bio-available in nail keratin. A short exposure of nail to low concentrations of terbinafine acted as a barrier against fungal invasion. Itraconazole appeared to be effective against Trichophyton and some non-dermatophytic moulds.
authors.affiliation: Department of Dermatology, University of Glasgow, UK. M.Richardson@clinmed.gla.ac.uk
authors.forename: M D
authors.initials: MD
authors.lastname: Richardson
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003883:Arthrodermataceae / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D002177:Candidiasis / Q000188:drug therapy / Q000473:pathology; D003881:Dermatomycoses / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005385:Fingers; D006801:Humans; D066298:In Vitro Techniques; D017964:Itraconazole / Q000008:administration & dosage / Q000494:pharmacology*; D008854:Microscopy, Electron; D008962:Models, Theoretical; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D014009:Onychomycosis / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D000077291:Terbinafine; D014005:Tinea / Q000188:drug therapy; D014249:Trichophyton / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure
chemical_list: D000935:Antifungal Agents; D009281:Naphthalenes; D017964:Itraconazole; D000077291:Terbinafine