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Interactions in vitro between polyenes and imidazoles against yeasts
1Department of Medical Microbiology, Charing Cross and Westminster Medical School, London, UK.
The Journal of Antimicrobial Chemotherapy
|April 1, 1991
Summary
This study investigated antifungal drug combinations. Polyenes showed immediate yeast-killing effects, while imidazoles were slow-acting. Combinations revealed complex interactions, with polyenes enhancing imidazoles but being antagonized by them.
Area of Science:
- Mycology
- Pharmacology
- Antimicrobial Chemotherapy
Background:
- Clinical yeast infections pose significant treatment challenges.
- Polyene and imidazole antifungals are commonly used, but their combined efficacy requires further elucidation.
- Understanding drug interactions is crucial for optimizing antifungal therapy.
Purpose of the Study:
- To evaluate the in vitro activity of polyenes (amphotericin B, mepartricin) and imidazoles (miconazole, ketoconazole, itraconazole, fluconazole) alone and in combination against clinical yeast isolates.
- To characterize the nature of interactions between polyenes and imidazoles under various experimental conditions.
- To assess the impact of pooled human plasma on drug activity and interactions.
Main Methods:
- In vitro susceptibility testing of antifungals using shaken and standing liquid cultures.
- Continuous culture methods to simulate dynamic growth conditions.
- Chequerboard titrations to determine drug synergy or antagonism, with and without pooled human plasma.
- Assessment of cidal (killing) and fungistatic (growth-inhibiting) activities.
Main Results:
- Polyenes exhibited rapid, immediate cidal activity, effective even against high yeast cell populations.
- Imidazoles displayed time-dependent fungistatic activity, with a slow increase in efficacy as drug concentration rose.
- Paired polyene-imidazole combinations showed consistent, anomalous interactions across all tested methods.
- Polyene antifungals enhanced the activity of imidazoles.
- Conversely, imidazoles significantly antagonized the activity of polyenes.
Conclusions:
- Polyene and imidazole antifungals possess distinct mechanisms of action and activity profiles.
- Polyene-imidazole combinations result in complex, often antagonistic interactions, contrary to simple additive effects.
- The observed antagonism of polyenes by imidazoles suggests careful consideration is needed when co-administering these drug classes.
- Further research is warranted to understand the clinical implications of these in vitro findings for treating yeast infections.