Antifungal susceptibilities and genetic relatedness of serial Trichophytonrubrum isolates from patients with onychomycosis of the toenail

Onychomycosis is a common fungal disease infecting up to 20 % of the popula tion over age 40. The major causative agent of onychomycosis is Trichophyto n rubrum. Uncontrolled infection may eventually lead to penetration of the newly forming nail plate. In spite of the encouraging cure rate with recent antifungal agents such as the allylamines (terbinafine) and azoles (itraco nazole and fluconazole) some patients inevitably fail therapy. In this inve stigation, a group of patients from a multi-center study designed to assess the efficacy of terbinafine with known cases of onychomycosis were selecte d for evaluation. Nail samples from this patient group were colonized with I: rubrum throughout the terbinafine therapy. Antifungal susceptibility tes ting was performed on these T. rubrum isolates to detect change in MIC valu es. Strain relatedness was examined using random amplified polymorphic DNA (RAPD) technique. Our results revealed failure of patients to clear I: rubr um is not related to the development of resistance to the drug. While speci es determination was possible, we were not able to identify differences tha t would indicate reinfection with a new strain. Analysis of patient demogra phic data revealed that 70% of patients were over 45 years old, 56.6% were previously treated with antifungals, 60 % came from family history with ony chomycosis and 13 % were diabetic. In conclusion, our data indicate that pa tients' failure to clear onychomycosis was not associated with resistant de velopment. Failure of terbinafine therapy may be dependent on host-related factors.