Journal Article

A comparative study of fungicidal activities of voriconazole and amphotericin B against hyphae of <i>Aspergillus fumigatus</i>

Suganthini Krishnan, Elias K. Manavathu and Pranatharthi H. Chandrasekar

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 55, issue 6, pages 914-920
Published in print June 2005 | ISSN: 0305-7453
Published online April 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki100
A comparative study of fungicidal activities of voriconazole and amphotericin B against hyphae of Aspergillus fumigatus

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Objectives: To study the in vitro fungicidal activity of voriconazole against hyphae of Aspergillus fumigatus and compare the results with those obtained for the known fungicidal drug amphotericin B.

Methods: A. fumigatus mycelia were grown on Sabouraud dextrose agar and in peptone yeast extract glucose broth until the cultures reached a mid-logarithmic growth phase. The fungicidal activities of voriconazole and amphotericin B against actively growing hyphae of A. fumigatus were examined by a kill-curve experiment and a fungal cell viability test. For the kill-curve study, the drug-treated hyphae were washed, homogenized and resuspended in 1 mL of sterile water, diluted 10–1000 fold and aliquots of 0.1 mL were spread on Sabouraud dextrose agar and allowed to grow for 48 h at 35°C. The cfu were determined and plotted against drug concentrations for each time of exposure to obtain the kill curve. The viability of drug-treated A. fumigatus hyphae was determined by their ability to reduce tetrazolium compound 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide.

Results: Exposure of A. fumigatus hyphae to several concentrations (1–16 mg/L) of voriconazole or amphotericin B for various time intervals killed the hyphae in a time- and drug concentration-dependent manner. Voriconazole at 1 mg/L killed >95% of the hyphae grown on Sabouraud dextrose agar after 48 h of exposure, whereas amphotericin B at the same concentration killed ∼70% of the hyphae after exposure for the same duration. Approximately 99% killing of hyphae grown in peptone yeast extract glucose broth was obtained for voriconazole at 1 mg/L after 48 h of exposure, whereas amphotericin B at 1 mg/L yielded ∼82% killing after 48 h. The fungal cell viability test by tetrazolium reduction assay showed that mycelia exposed to ≥1 mg/L (Sabouraud dextrose agar blocks) and ≥2 mg/L (broth cultures) of voriconazole for 48 h completely failed to reduce 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide. At low concentrations (1–2 mg/L) amphotericin B had no detectable effect on 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction by drug-treated mycelia, whereas mycelia treated with 16 mg/L for 48 h showed ∼50% inhibition of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction compared with the control.

Conclusions: Voriconazole possesses excellent fungicidal activity against actively growing hyphae of A. fumigatus. A comparison of results with those obtained for the known fungicidal drug amphotericin B shows that, in peptone yeast extract glucose broth, voriconazole has superior fungicidal activity against A. fumigatus hyphae compared with that of amphotericin B.

Keywords: voriconazole; fungicidal activity; Aspergillus fumigatus; fungal hyphae; kill curve; viability test

Journal Article.  4325 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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