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

1986; Oxford University Press; Volume: 17; Issue: 4 Linguagem: Inglês

10.1093/jac/17.4.423

1460-2091

Elizabeth Scott, Shelley Gorman, Jeffrey S. Millership, Lacey Wright,

Antifungal resistance and susceptibility

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.