Relative inhibition factors--a novel approach to the assessment of antifungal antibiotics in vitro

Abstract

A system is described for measurement of relative inhibition factors (RIFs) for antifungal agents--that is, the area under a fixed portion of the antifungal dose-response curve, expressed as a percentage of the area under the dose-response curve for a theoretical noninhibitory substance. The RIFs for two polyenes, 5-fluorocytosine (5FC) and griseofulvin correlated with the known inhibitory activity of these compounds against pathogenic yeasts, Aspergillus spp. and dermatophytes in vitro and in vivo, but revealed wholly new relative inhibitory properties among five imidazole antifungals: ketoconazole and tioconazole emerged as the most active imidazole antifungals against yeasts and clotrimazole and econazole against Aspergillus spp. Because of the high reproducibility of the assay, and because tests were done in a tissue culture medium in the presence of serum, it is considered that measurement of RIFs could give better predictions of likely antifungal activity in vivo than is at present afforded by tests for minimal inhibitory concentrations.