Effect of ketoconazole and amphotericin B on encapsulated and non-encapsulated strains of Cryptococcus neoformans.

Growth inhibition studies were done on an encapsulated and non-encapsulated strain of Cryptococcus neoformans at the minimal inhibitory concentration and one-half the minimal inhibitory concentration of ketoconazole and amphotericin B alone and in combination. Growth of both strains was significantly inhibited by ketoconazole, amphotericin B, and the combined drugs at the minimal inhibitory concentration of each drug over a 5-day period. Calculation of the expected inhibition of growth for both strains with both drugs showed antagonism at 24 h followed by an additive effect and synergy for the remaining 4 days of the assay. Although similar results were obtained for both strains with one-half the minimal inhibitory concentration, an additive effect was observed with the drug combination at 24 h for the encapsulated strain, and an antagonistic effect was observed with the non-encapsulated strain.