IN-VITRO ACTIVITY OF AMPHOTERICIN-B, FLUCYTOSINE AND FLUCONAZOLE AGAINST YEASTS CAUSING BLOOD-STREAM INFECTIONS

The in vitro activity of amphotericin B, flucytosine and fluconazole against 95 yeasts causing fungemia in a single institution over the last eight years was determined by a broth macromethod recommended by the National Committee for Clinical Laboratory Standards. All strains were inhibited by amphotericin B concentrations of less than or equal to mu g/ml. With flucytosine in most species the MIC50 was between 0.12 and 0.25 mu g/ml and the MIC90 was between 0.25 and 1 mu g/ml. One exception with flucytosine was Candida krusei, with an MIC50 and MIC90 of 16 mu g/ml and 32 mu g/ml, respectively. Overall, 12% of the isolates needed at least 8 mu g/ml of fluconazole to be inhibited. Fluconazole was very active against Candida albicans, Candida tropicalis and Cryptococcus neoformans, with MIC50 ranging from 0.12 to 0.5 mu g/ml and MIC90 of 1 mu g/ml, and somewhat less active against Candida parapsilosis (MIC50 of 1 mu g/ml and MIC90 of 4 mu g/ml). Fluconazole exhibited poor in vitro activity against Candida krusei (MIC50 and MIC90 of 64 mu g/ml) and Torulopsis glabrata (MIC50 of 4 mu g/ml and MIC90 of 16 mu g/ml). High MICs of fluconazole were found for four strains of Candida albicans, one with an MIC of 4 mu g/ml and three (5.7 %) with MICs of greater than or equal to 16 mu g/ml. Previous exposure to fluconazole could be demonstrated in two of these strains. Further work must be done in order to determine appropriate breakpoints of antifungal agents, to assess the clinical relevance of azole resistance in yeasts causing bloodstream infections and to identify risk factors for infections with azole-resistant yeasts.