Testing of antifungal combinations against yeasts and dermatophytes

Abstract

BACKGROUND: Fungal infections of the nail are a common and chronic problem. The main pathogens responsible for onychomycosis are dermatophytes, yeasts and moulds. Despite significant improvements, approximately 20% of patients with onychomycosis still fail on antifungal therapy. The successful exploitation of drug synergy may provide a useful approach to improve cure rates.

METHODS: The minimum inhibitory concentrations (MIC₈₀) were recorded for pathogens that are most frequently responsible for onychomycosis against combinations of several antifungal agents, namely, fluconazole, itraconazole, terbinafine and amorolfine. Fractional inhibitory concentrations (FICs) were then calculated from the MIC₈₀ results and the FIC values for each drug in the combinations added to determine the degree of synergy. A combined value of <1 was taken to suggest synergy; a value of 1–2 indicated an additive effect or indifference; and a combined FIC value of >2 was taken to suggest antagonism.

RESULTS: Overall, 46% of amorolfine combinations showed results suggestive of synergy, with the most synergistic results seen against dermatophytes (54%) and moulds (52%).

CONCLUSIONS: Some combinations of drugs may have synergistic activity in vitro; however, the importance of this in a clinical setting is yet to be established, and more studies are justified.

• Amorolfine
• Dermatophyte
• Synergy