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Journal of Antimicrobial Chemotherapy (1986) 17, 423-432
© 1986 The British Society for Antimicrobial Chemotherapy

research-article

Effect of miconazole and clotrimazole on K+ release and inhibition of ergosterol biosynthesis in Trichophyton mentagrophytes and related ultrastructural observations

E. M. Scott, S. P. Gorman, J. S. Millership and L. R. Wright

Department of Pharmacy, The Queen's University of Belfast Belfast BT9 7BL, Northern Ireland

accepted 29 November 1985

Measurement of K+ ions in extracellular fluids was used to provide evidence of direct membrane damage induced by miconazole and clotrimazole in Trichophyton mentagrophytes mycelium. K+ release from mycelium treated with high concentrations of drug was extensive, although leakage occurred more rapidly and to a greater extent with miconazole than with clotrimazole. Cells treated with fungicidal concentrations of drug were completely necrotic. The effect of miconazole was concentration dependent.

A reduction in ergosterol levels was evident after 5 h treatment with miconazole. Further reduction in ergosterol concentration was demonstrated after 24 h with fungistatic concentrations of drug and was a concentration dependent effect. Fungistatic concentrations of miconazole also induced ultrastrictural changes in mycelium, which were apparent within 5 h of treatment and became more pronounced after 24 h. Clotrimazole also reduced ergosterol levels and affected ultra-structure of mycelium. The plasma membrane in particular was affected by both these drugs.


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