In-vitro activity of dicationic aromatic compounds and fluconazole againstCryptococcus neoformans and Candida spp.

We investigated the in-vitro activity of three selected dicationic aromatic compounds for nine clinical isolates of Cryptococcus neoformans and 93 cli nical isolates of Candida spp,, representing 12 different species, using a broth macrodilution method following NCCLS recommendations. All the clinica l isolates were also tested for fluconazole susceptibility. The in-vitro da ta demonstrate that compounds 39 and 57 have excellent in-vitro activity fo r all tested strains (MIC 0.19-1.56 mg/L) except Candida pelliculosa. Moreo ver, compound 39 showed excellent in-vitro fungicidal activity against Cand ida krusei, Candida glabrata, Candida lusitaniae and Cryptococcus neoforman s with MFCs in the range 0.39-6.25 mg/L. Both compounds 39 and 57 showed ex cellent in-vitro activity against fluconatole-resistant Candida albicans is olates, including a C. albicans strain that contains all known fluconazole- resistant mechanisms. Comparing MIC data from compounds 21, 39 and 57 with fluconazole, we found a statistically significant difference only with comp ound 39 (P = 0.043). However, comparing MFC data from compounds 21, 39 and 57 with fluconazole, we found statistically significant differences with al l three compounds (P < 0.00001). These data indicate the potential antifung al breadth of two bis-benzimidazoles (compounds 39 and 57) as antifungal ag ents against yeasts. if it can be determined that compounds 39 and 57 are e ffective and non-toxic in vivo, the prospect of these compounds as clinical ly useful antifungal agents will be enhanced.