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Effects of voriconazole on Cryptococcus neoformans
David van Duin1, Wendy Cleare, Oscar Zaragoza
1Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
Antimicrobial Agents and Chemotherapy
|May 25, 2004
Summary
Voriconazole remains effective against melanized Cryptococcus neoformans, a trait not affected by fungal melanin. This broad-spectrum antifungal may be a valuable treatment for cryptococcosis.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Voriconazole is a broad-spectrum triazole antifungal with activity against various yeasts and molds.
- Melanization in fungi can reduce susceptibility to some antifungal drugs, but its effect on voriconazole is unknown.
- Cryptococcus neoformans is an important fungal pathogen, particularly in immunocompromised individuals.
Purpose of the Study:
- To assess the in vitro activity of voriconazole against melanized and non-melanized Cryptococcus neoformans.
- To investigate the impact of subinhibitory voriconazole concentrations on C. neoformans cell morphology, capsule, and phagocytosis.
Main Methods:
- Minimum Inhibitory Concentration (MIC) analysis and time-kill assays were performed on melanized and non-melanized C. neoformans.
- Cell morphology, capsule size, capsule release, and phagocytosis rates were evaluated in the presence and absence of voriconazole.
Main Results:
- Voriconazole demonstrated fungicidal activity (>Â=8 µg/ml) against C. neoformans, irrespective of melanization.
- Subinhibitory voriconazole concentrations reduced cell and capsule volume but did not affect capsule induction by serum.
- Voriconazole-treated cells were phagocytosed at rates comparable to untreated cells.
Conclusions:
- Melanization does not diminish the in vitro efficacy of voriconazole against C. neoformans.
- Voriconazole's consistent activity against both melanized and non-melanized C. neoformans suggests its potential as a key therapeutic agent for cryptococcosis.