Isolation and characterization of fluconazole- and amphotericin B-resistant Candida albicans from blood of two patients with leukemia

Infections with fluconazole-resistant Candida albicans isolates have rarely been described in clinical settings other than oropharyngeal candidiasis in patients with late-stage AIDS. We report on two patients with leukemia who developed fungemia caused by fluconazole-resistant C. albicans after receiving fluconazole prophylaxis (400 mg/day) and empiric amphotericin B therapy (0.5 mg/kg of body weight per day). The fluconazole MICs for the isolates were greater than or equal to 64 mu g/ml, and the isolates were resistant to other azoles and had membrane sterol changes consistent with a mutation in the Delta(5,6)-sterol desaturase gene, The lack of ergosterol in the cytoplasmic membrane of the fluconazole-resistant strains also imparted resistance to amphotericin B. Both patients were successfully treated with high-dose amphotericin B (1 to 1.25 mg/kg/day) and flucytosine (150 mg/kg/day).