In-vitro activity of SCH39304 in comparison with amphotericin B and flaconazole

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Abstract
The in-vitro activity of SCH39304, a new imidazolc, was compared with that of amphotericin B using two media (Sabouraud dextrose and tissue culture (TC) medium) with or without 25% human serum. At an inoculum of 1·5 × 104 cfu/ml, the IC95% for amphotericin B ranged from 0·08 to 0·3 mg/l irrespective of the medium. At the same inoculum, the IC95% of the two imidazoles ranged from 0·3 to > 80 mg/l. The inoculum effect (from 1·5 × 104 to 1·5 × 105 cfu/ml) was < 1 dilution for the three antifungal agents. Serum increased the inhibitory activity (IC80%) of SCH393O4 and fluconazole but not of amphotericin B. The IC80%, IC95% and minimal fungicidal concentration (MFC) for amphotericin B usually ranged within two dilutions. Using kill curve methodology, the initial killing rate (0–4 h) of amphotericin B correlated with concentration (P < 0·001), and was faster in TC medium than in Sabouraud dextrose (P < 0·0006). SCH393O4 and fluconazole did not produce any significant killing over the range of concentrations tested (0·5–20 mg/l). SCH393O4 was similar to fluconazole.