Fluconazole resistance in Candida glabrata

Antimicrob Agents Chemother. 1993 Sep;37(9):1962-5. doi: 10.1128/AAC.37.9.1962.

Abstract

We report a case of infection with Candida glabrata in which the organism became resistant to fluconazole and in which pre- and posttreatment isolates were available for comparison. The organism was cross-resistant to ketoconazole and itraconazole, in common with other azole-resistant yeasts. Fluconazole was a potent inhibitor of cytochrome P-450-dependent 14 alpha-sterol demethylase (P-450DM) in lysates of cells from both susceptible and resistant cultures (50% inhibitory concentration, 0.2 microM), indicating that resistance was unrelated to changes in P-450DM. Instead, it appeared to arise from a permeability barrier to fluconazole, since resistant cells were unable to take up radiolabelled drug.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Azoles / pharmacology
  • Candida / drug effects*
  • Candida / enzymology
  • Candida / metabolism
  • Candidiasis / drug therapy
  • Candidiasis / microbiology
  • Cytochrome P-450 Enzyme Inhibitors
  • Drug Resistance, Microbial
  • Female
  • Fluconazole / metabolism
  • Fluconazole / pharmacology*
  • Fluconazole / therapeutic use
  • Humans
  • Oxidoreductases / antagonists & inhibitors
  • Permeability
  • Sterol 14-Demethylase
  • Sterols / biosynthesis

Substances

  • Azoles
  • CYP51A1 protein, human
  • Cytochrome P-450 Enzyme Inhibitors
  • Sterols
  • Fluconazole
  • Oxidoreductases
  • Sterol 14-Demethylase