Comparison of in vitro activity of two new triazoles, voriconazole and SCH-56592, and fluconazole against Candida albicans by time-kill methodology

Voriconazole and SCH-56592 are two new investigational triazoles currently under development for the treatment of systemic fungal infections. The purpose of this study was to evaluate the comparative in vitro activity of voriconazole, SCH-56592, and fluconazole against three clinical isolates of Candida albicans. Time-kill studies were conducted utilizing eight drug concentrations ranging from 0.25 to 32 X MIC. Samples were removed at seven predetermined timepoints over 48 hrs and plated onto Sabouraud dextrose agar using a spiral plater. The plates were incubated at 36°C for 24 hrs, and colony counts determined. All concentrations of each antifungal resembled the growth control for C. albicans 98-1262 except voriconazole 32 X MIC. For C. albicans 98-1518, each of the antifungals suppressed growth for the initial 24 hrs. Finally for C. albicans 98-1329, slight inhibition was observed irrespective of antifungal agent or concentration. In summary, voriconazole and SCH-56592 were more potent against C. albicans than fluconazole. However, these newer triazoles did not display any difference in activity compared to fluconazole based on time-kill studies against C. albicans. Investigation of the correlation between time-kill studies and clinical outcomes is warranted.