Fluconazole resistance in Candida glabrata.
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.
Hitchcock
C A
CA
Department of Discovery Biology, Pfizer Central Research, Sandwick, Kent, United Kingdom.
Pye
G W
GW
Troke
P F
PF
Johnson
E M
EM
Warnock
D W
DW
D000368:Aged; D001393:Azoles / Q000494:pharmacology; D002175:Candida / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004352:Drug Resistance, Microbial; D005260:Female; D015725:Fluconazole / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D010539:Permeability; D058886:Sterol 14-Demethylase; D013261:Sterols / Q000096:biosynthesis
D001393:Azoles; C548418:CYP51A1 protein, human; D065607:Cytochrome P-450 Enzyme Inhibitors; D013261:Sterols; D015725:Fluconazole; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase