Study of the effects of antifungal agents upon fungi of medical importance

Ball, Eleanor Hazel (1980) Study of the effects of antifungal agents upon fungi of medical importance. MSc(R) thesis, University of Glasgow.

Abstract

A cellophane square technique has been used to determine Minimum Inhibitory Concentrations and morphological changes induced by exposure of various medically important fungi to antifungal agents. The procedure allows earlier assessment of fungistatic and fungicidal activity than can be achieved by conventional techniques. Fungistatic activity of the imidazoles has been shown not to be affected by the phase of growth of the fungi, but fungicidal activity of miconazole and econazole was found to be more pronounced against the actively growing phases of both yeasts and filamentous fungi. Ketoconazole differed by having significantly higher M. I. C. levels against the test fungi, but was more effective in killing stationary phase cells of Trichophyton mentagrophytes. However, fungicidal activity of ketoconazole against both actively growing and stationary phase cells of Candida albicans was low compared to the other two imidazoles. A feature which was peculiar to the yeasts C. guilliermondii and C. tropicalis was observed on sub-fungi static concentrations of miconazole, econazole and ketoconazole. These yeasts were particularly sensitive to low concentrations of the imidazoles, but at higher concentrations there was some relief of toxicity resulting in partial recovery before growth was finally inhibited by fungistatic concentrations. Since these two yeasts also differed from others in their response to thiamin, the presence of trace amounts of this vitamin in the medium may account for the phenomenon. Alternatively the imidazoles may affect a number of different metabolic pathways within the fungal cell. Resistance to the antifungal agents did not arise spontaneously in any of the fungi during the course of this study. However, physiological adaptation which resulted in an approximate two-fold increase in the amount of growth of C. guilliermondii on econazole was observed although M. I. C. levels remained unaltered, and increased resistance to the imidazoles was induced in Aspergillus nidulans with U. V. light as the mutagenic agent. The potential for resistance to the imidazoles to arise spontaneously in these fungi therefore exists. Selected antifungals were also examined for their in vivo activity. When administered orally, ketoconazole was found to be highly effective in curing ringworm infections in guinea pigs. Topical application of miconazole was shown to be as effective as an established treatment for ringworm, (tolnaftate), against experimentally induced dermatophytosis in guinea pigs.

• Item Type: Thesis (MSc(R))
• Qualification Level: Masters
• Additional Information: Adviser: J C Gentles
• Keywords: Pharmacology
• Date of Award: 1980
• Depositing User: Enlighten Team
• Unique ID: glathesis:1980-72878
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 11 Jun 2019 11:06
• Last Modified: 11 Jun 2019 11:06
• URI: https://theses.gla.ac.uk/id/eprint/72878