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Resistance of yeasts to azole-derivative antifungals
1Department of Bacteriology and Mycology, Janssen Research Foundation, Beerse, Belgium.
Abstract:
There are relatively few antifungal agents available for the treatment of systemic mycoses. The incidence of these infections, particularly among the immunocompromised, has increased significantly in recent years. Amphotericin B, flucytosine and the azole-derivatives--fluconazole, itraconazole and ketoconazole--are the only drugs of value in the treatment of systemic yeast infections currently available. To date resistance among individual yeast species or strains has only been a serious problem with flucytosine. However, resistance among Candida spp. to orally administered azole-derivatives has been observed. The frequency with which resistance has been described in clinical practice among yeasts differs considerably between the three azole antifungal agents. Fluconazole has been implicated in emergent resistance more frequently than ketoconazole, and ketoconazole more often than itraconazole. It must be a matter for concern that, by analogy with the known emergence of antibiotic-resistance among bacteria, that the widespread use of a drug inactive against a particular species may lead to an increased incidence of such infections. An international epidemiological survey is required to establish the extent and degree of resistance to the azole antifungals.
Insights
Limited antifungal drugs exist for systemic mycoses. Azole antifungal resistance in yeasts is emerging, with fluconazole showing higher resistance rates than ketoconazole and itraconazole, necessitating further study.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Systemic mycoses are increasing, especially in immunocompromised individuals.
- Available antifungal agents for systemic yeast infections are limited, including amphotericin B, flucytosine, and azole derivatives (fluconazole, itraconazole, ketoconazole).
- Antifungal resistance is a growing concern, particularly with azole-derivatives in Candida species.
Purpose of the Study:
- To review the current landscape of antifungal agents for systemic mycoses.
- To highlight the emerging issue of azole antifungal resistance in yeasts.
- To emphasize the need for epidemiological surveillance of azole resistance.
Main Methods:
- Literature review of available antifungal agents and resistance patterns.
- Analysis of reported resistance frequencies for fluconazole, itraconazole, and ketoconazole.
- Discussion of the implications of antifungal resistance.
Main Results:
- Resistance to flucytosine has been a significant problem, but resistance among Candida spp. to oral azole-derivatives is now observed.
- Resistance emergence varies among azole antifungals: fluconazole > ketoconazole > itraconazole.
- Widespread use of ineffective antifungal drugs may increase the incidence of resistant infections.
Conclusions:
- There is a critical need for more antifungal agents to treat systemic mycoses.
- Emerging resistance to azole antifungals, particularly fluconazole, is a significant clinical concern.
- An international epidemiological survey is required to determine the extent of azole antifungal resistance.