Fluconazole resistance in Candida glabrata.

Antimicrobial agents and chemotherapy ·Vol. 37 ·No. 9 ·1993-09-00 ·Pages 1962-5

Hitchcock CA, Pye GW, Troke PF, Johnson EM, Warnock DW

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.

MeSH Terms

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

Chemicals

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

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Hitchcock C A

Department of Discovery Biology, Pfizer Central Research, Sandwick, Kent, United Kingdom.

Pye G W

Troke P F

Johnson E M

Warnock D W

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Article Info

Journal

Antimicrobial agents and chemotherapy

Abbr.

Antimicrob Agents Chemother

ISSN

0066-4804

DOI

10.1128/AAC.37.9.1962

Published

1993-09-00

Pages

1962-5

Language

English

Region

United States

NLM ID

0315061

PMCID

PMC188100

Subset

External Links

PubMed source DOI: 10.1128/AAC.37.9.1962 PMC Full Text View journal details

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