Evaluation of in vitro Resistance in Patients with Onychomycosis Who Fail Antifungal Therapy

Abstract

Background: With the increased awareness of onychomycosis and the increasing use of antifungals for this indication, it is prudent to be concerned about the possible emergence of resistant strains. There has been substantial work on the development of standardized methods for testing the in vitro resistance of various fungi and yeasts to the currently available antifungal agents. However, relatively little research has been published concerning the resistance of dermatophyte species. Objective: We report the results of a retrospective study analyzing the relationship between in vitro and clinical resistance in strains of Trichophyton rubrum cultured from patients with recalcitrant dermatophyte toe onychomycosis. Materials and Methods: We analyzed the in vitro resistance of dermatophyte strains obtained from 18 patients with chronic onychomycosis who failed antifungal therapy with itraconazole or terbinafine. Multiple-sequential strains from 11 patients were included in the study. Susceptibility testing of these strains was performed against 4 antifungals, itraconazole, ketoconazole, terbinafine and ciclopirox, using the broth microdilution method as per the NCCLS M27-A guidelines. A record of clinical characteristics that may relate to patient treatment and therapy was maintained. Results: All of the strains were susceptible to 3 of the 4 antifungal agents tested. Although there was no direct correlation between clinical resistance and in vitro resistance, increased minimum inhibitory concentration values for ketoconazole were observed in strains obtained after treatment from 3 of 18 patients evaluated in the study. In all but 1 patient, we were able to identify other factors that may have been responsible for treatment failure. Conclusions: With the more common use of antifungals to treat various fungal infections, development of increased resistance in the causative organisms remains a possibility. However, factors other than fungal resistance may also be implicated in treatment failure.