Evaluation of in vitro resistance in patients with onychomycosis who fail antifungal therapy.
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.


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.
Gupta
Aditya K
AK
Division of Dermatology, Department of Medicine, Sunnybrook and Women's College Health Science Center, Sunnybrook site and the University of Toronto, Toronto, Ontario, Canada. agupta@execulink.com
Kohli
Yatika
Y
D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D025141:Drug Resistance, Fungal / Q000502:physiology*; D005260:Female; D005533:Foot Dermatoses / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D014009:Onychomycosis / Q000188:drug therapy / Q000503:physiopathology*; D012189:Retrospective Studies; D017211:Treatment Failure
D000935:Antifungal Agents