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.

Biological, Biochemical, and Molecular Characterization of a New Clinical Trichophyton rubrum Isolate Resistant to Terbinafine

“…Nevertheless, the occurrence of terbinafineresistant clinical isolates is rare, and only one case has been documented and thoroughly investigated (7,14,17); the resistance mechanism was identified as a single amino acid substitution in SE. Except for this one case, terbinafine failure in patients suffering from nail infections due to Trichophyton rubrum has been shown not to be related to high MICs or resistance development during therapy (1,9). The same conclusion was drawn by Hofbauer et al (11) in a veterinary study.…”

In Vitro Activities of Miltefosine and Two Novel Antifungal Biscationic Salts against a Panel of 77 Dermatophytes

“…Despite therapy, relapse is frequent and disease persists in up to 25% of cases (5,26). Furthermore, resistance to and clinical failures with itraconazole (ITC) and terbinafine (TRB), the two oral agents commonly used to treat chronic and severe disease, have been reported previously (11,16).…”

Rationale for selection of a topical antimycotic agent

“…Хорошо известно о развитии резистент-ности к флуконазолу среди Candida spp., опублико-ваны данные о развитии резистентности нитчатых грибов к итраконазолу [32]. Кроме того, А. Gupta и Y. Kohli [33] сообщили об увеличении МПК у штам-мов T. rubrum после лечения кетоконазолом. Разви-тие лекарственной устойчивости у всех патогенных микроорганизмов является эволюционным процес-сом, который инициируется путем воздействия про-тивомикробных средств.…”