IN-VITRO ACTIVITIES OF VORICONAZOLE (UK-109,496) AGAINST FLUCONAZOLE-SUSCEPTIBLE AND FLUCONAZOLE-RESISTANT CANDIDA-ALBICANS ISOLATES FROM ORAL CAVITIES OF PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

The susceptibility of Candida albicans to a new antifungal triazole, v oriconazole (UK-109,496), was investigated in 105 isolates obtained fr om the oral cavities of patients with human immunodeficiency virus (HI V) infection to study this drug's activity against fluconazole-suscept ible and -resistant isolates, MICs were determined by a broth microdil ution technique according to document M27-T from the National Committe e for Clinical Laboratory Standards and by using a broth microdilution technique and a synthetic high-resolution medium, These antifungal su sceptibility testing methods showed high levels of agreement (93% for fluconazole and 86% for voriconazole), Data from in vitro studies show ed that voriconazole has good activity against fluconazole-susceptible and -resistant C, albicans isolates; the MICs at which 90% of all iso lates were inhibited were 0.19 to 0.39 mu g/ml. We found that for isol ates for which fluconazole MICs were high, voriconazole MICs were prop ortionally higher than those for fluconazole-susceptible C, albicans ( P < 0.001), Pretreatment isolates from six patients with fluconazole-r efractory esophageal candidiasis were included in the study. For these isolates the MICs were less than or equal to 0.39 mu g/ml, and all pa tients responded to voriconazole. These results suggest that voriconaz ole is effective even in the treatment of fluconazole refractory esoph ageal candidiasis and should be studied further to determine its clini cal relevance in patients with HIV infection.