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Journal of Antimicrobial Chemotherapy (1999) 44, 223-228
© 1999 The British Society for Antimicrobial Chemotherapy

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

Maurizio Del Poetaa,,b, Amy S. Bixela, Francesco Barchiesib, Richard R. Tidwellc, David Boykind, Giorgio Scaliseb and John R. Perfecta,*

a Department of Medicine, Division of Infectious Diseases and International Health, Duke University Medical Center, PO Box 3353, Durham, NC 27710, USA; b Institute of Infectious Diseases and Public Health, University of Ancona, Ospedale Umberto I, 60121 Ancona, Italy; c Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; d Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA

We investigated the in-vitro activity of three selected dicationic aromatic compounds for nine clinical isolates of Cryptococcus neoformans and 93 clinical isolates of Candida spp., representing 12 different species, using a broth macrodilution method following NCCLS recommendations. All the clinical isolates were also tested for fluconazole susceptibility. The in-vitro data demonstrate that compounds 39 and 57 have excellent in-vitro activity for all tested strains (MIC 0.19–1.56 mg/L) except Candida pelliculosa. Moreover, compound 39 showed excellent in-vitro fungicidal activity against Candida krusei, Candida glabrata, Candida lusitaniae and Cryptococcus neoformans with MFCs in the range 0.39–6.25 mg/L. Both compounds 39 and 57 showed excellent in-vitro activity against fluconazole-resistant Candida albicans isolates, 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 compound 39 (P= 0.043). However, comparing MFC data from compounds 21, 39 and 57 with fluconazole, we found statistically significant differences with all three compounds (P < 0.00001). These data indicate the potential antifungal breadth of two bis-benzimidazoles (compounds 39 and 57) as antifungal agents against yeasts. If it can be determined that compounds 39 and 57 are effective and non-toxic in vivo, the prospect of these compounds as clinically useful antifungal agents will be enhanced.

* Corresponding author. Tel: +1-919-684-2660; Fax: +1-919-684-8902; E-mail: perfe001{at}mc.duke.edu


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