title: Isolation and characterization of fluconazole- and amphotericin B-resistant Candida albicans from blood of two patients with leukemia.
abstract: Infections with fluconazole-resistant Candida albicans isolate 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 > or = 64 micrograms/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).
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. fnolte@emory.edu
authors.forename: F S
authors.initials: FS
authors.lastname: Nolte
authors.forename: T
authors.initials: T
authors.lastname: Parkinson
authors.forename: D J
authors.initials: DJ
authors.lastname: Falconer
authors.forename: S
authors.initials: S
authors.lastname: Dix
authors.forename: J
authors.initials: J
authors.lastname: Williams
authors.forename: C
authors.initials: C
authors.lastname: Gilmore
authors.forename: R
authors.initials: R
authors.lastname: Geller
authors.forename: J R
authors.initials: JR
authors.lastname: Wingard
mesh_terms: D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects* / Q000472:pathogenicity; D002177:Candidiasis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D018432:Drug Resistance, Multiple; D005260:Female; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use*; D005437:Flucytosine / Q000627:therapeutic use; D016469:Fungemia / Q000150:complications / Q000188:drug therapy; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications*; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications*; D014774:Virulence
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine