Bactericidal and inhibitory effects of azole antifungal compounds on Mycobacterium smegmatis

Azole antifungals are central to therapy and act by inhibiting a cytochrome P450, sterol 14-demethylase and blocking normal sterol synthesis. Our rece nt identification of a mycobacterial sterol biosynthetic pathway led us to probe the efficacy of a range of these compounds against Mycobacterium smeg matis. Several showed equivalent or greater inhibitory effects to those aga inst Candida albicans, and bactericidal activity was demonstrated for four compounds, clotrimazole, econazole, miconazole and tebuconazole. The major drug used clinically, fluconazole, was ineffective. The results are discuss ed in the light of the world-wide spread of tuberculosis, including drug re sistant Forms and the requirement For new drugs. (C) 2000 Federation of Eur opean Microbiological Societies. Published by Elsevier Science B.V. All rig hts reserved.