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 14a-sterol demethylase (P-450DM) in lysates of cells from both susceptible and resistant cultures (50%o inhibitory concentration, 0.2 FM), indicating that resistance was unrelated to changes in P-450DM-Instead, it appeared to arise from a permeability barrier to fluconazole, since resistant celis were unable to take up radiolabelled drug.

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