Fungicidal versus fungistatic activity of terbinafine and itraconazole: An in vitro comparison

Abstract

Background: The ratio of fungicidal to fungistatic activity of two new antifungal agents, itraconazole and terbinafine, against the causative organisms in onychomycosis may have clinical relevance. Objective: This study compared the fungistatic and fungicidal activity of terbinafine and itraconazole against clinical isolates of dermatophytes and Candida species causing onychomycosis. Methods: The antifungal agent was added to suspensions of dermatophyte conidia and hyphal fragments (5 × 10 3 to 5 × 10 4 fungal elements/ml) that had been preincubated to allow hyphal formation. Cell suspensions of Candida species (1 to 5 × 10 3 cells/ml) were not preincubated before drug exposure. Macrobroth and macrobroth dilution assays were used to test antifungal susceptibility of dermatophytes and yeasts, respectively. An agent was considered fungicidal if the minimal fungicidal concentration (MFC) to minimal inhibitory concentration (MIC) ratio was ≤ 4 and fungistatic if the ratio was > 4. Cell death was also visualized by a vital stain. Results: For both itraconazole and terbinafine, the MIC for dermatophytes was low. The MFCs and MFC/MIC ratios for terbinafine against dermatophytes were lower than for itraconazole; the fungicidal activity of terbinafine was excellent and initiated rapidly (by 7 hours) and that of itraconazole was poor (fungicidal activity was not evident until 10 to 12 hours). For yeasts, the MICs were higher than for dermatophytes, and the differences between itraconazole and terbinafine were less pronounced. Conclusion: Both itraconazole and terbinafine inhibit growth of dermatophytes. The more rapid fungicidal activity of terbinafine may have clinical relevance in the treatment of onychomycosis. (J Am Acad Dermatol 1998;38:S37-41.)