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Ketoconazole resistance in Torulopsis glabrata
G Nobre1, E Mendes, M J Charrua
1Instituto Bacteriológico Câmara Pestana, University of Lisbon, Portugal.
Mycopathologia
|July 1, 1989
Summary
Agar dilution tests may overestimate ketoconazole effectiveness against Candida glabrata, a yeast prone to mutation. Broth dilution and animal studies indicate resistance, suggesting agar tests are unreliable for this species.
Area of Science:
- Mycology
- Antimicrobial Resistance
- Pharmacology
Background:
- Candida glabrata is a significant opportunistic fungal pathogen.
- Clinical isolates of C. glabrata exhibit variable susceptibility to ketoconazole.
- High mutation rates in C. glabrata's haploid state may influence drug response.
Purpose of the Study:
- To investigate the discrepancy in ketoconazole susceptibility testing for Candida glabrata.
- To evaluate the in vivo efficacy of ketoconazole against C. glabrata infections.
- To determine the reliability of agar dilution versus broth dilution methods for C. glabrata.
Main Methods:
- Agar dilution and broth microdilution methods were used to assess ketoconazole susceptibility.
- Experimental C. glabrata infections were established in immunocompetent and immunocompromised mice.
- Mice were treated with oral ketoconazole, and treatment response was evaluated.
Main Results:
- Clinical isolates showed sensitivity to ketoconazole via agar dilution but resistance via broth dilution.
- Experimental C. glabrata infections did not respond to oral ketoconazole treatment.
- In vivo results correlated with broth dilution findings, not agar dilution results.
Conclusions:
- Agar dilution sensitivity testing may be inadequate for yeasts with high mutation rates, such as C. glabrata.
- Broth dilution methods and in vivo models provide a more accurate assessment of ketoconazole efficacy against C. glabrata.
- Ketoconazole's clinical effectiveness against C. glabrata may be limited due to intrinsic resistance mechanisms and high mutation rates.