FLUCONAZOLE RESISTANCE IN CANDIDA-GLABRATA

We report a case of infection with Candida glabrata in which the organ ism became resistant to fluconazole and in which pre- and posttreatmen t isolates were available for comparison. The organism was cross-resis tant to ketoconazole and itraconazole, in common with other azole-resi stant yeasts. Fluconazole was a potent inhibitor of cytochrome P-450-d ependent 14alpha-sterol demethylase (P-450DM) in lysates of cells from both susceptible and resistant cultures (50% inhibitory concentration , 0.2 muM), indicating that resistance was unrelated to changes in P-4 50DM. Instead, it appeared to arise from a permeability barrier to flu conazole, since resistant cells were unable to take up radiolabelled d rug.