Feb 16, 2010 - for scedosporiosis in Australia: epidemiology, disease manifestations and emergence of Scedosporium aurantiacum infection. Clin. Microbiol.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Aug. 2010, p. 3233–3240 0066-4804/10/$12.00 doi:10.1128/AAC.00231-10 Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Vol. 54, No. 8
In Vitro Antifungal Activities of Bis(Alkylpyridinium)Alkane Compounds against Pathogenic Yeasts and Molds䌤 Sharon C.-A. Chen,1†* Chayanika Biswas,1† Robyn Bartley,2 Fred Widmer,1 Namfon Pantarat,3 Daniel Obando,4 Julianne T. Djordjevic,1 David H. Ellis,2 Katrina A. Jolliffe,4 and Tania C. Sorrell1 Centre for Infectious Diseases and Microbiology, Westmead Millenium Institute, University of Sydney, Westmead, New South Wales, Australia1; Mycology Unit, South Australia Pathology, South Australia, Australia2; and School of Medicine3 and School of Chemistry,4 University of Sydney, New South Wales, Australia Received 16 February 2010/Returned for modification 1 May 2010/Accepted 31 May 2010
Ten bis(alkylpyridinium)alkane compounds were tested for antifungal activity against 19 species (26 isolates) of yeasts and molds. We then determined the MICs and minimum fungicidal concentrations (MFCs) of four of the most active compounds (compounds 1, 4, 5, and 8) against 80 Candida and 20 cryptococcal isolates, in comparison with the MICs of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and caspofungin, using Clinical Laboratory and Standards Institutes broth microdulition M27-A3 (yeasts) or M38-A2 (filamentous fungi) susceptibility protocols. The compounds were more potent against Candida and Cryptococcus spp. (MIC range, 0.74 to 27.9 g/ml) than molds (0.74 to 59.7 g/ml). MICs against Exophiala were 0.37 to 5.9 g/ml and as low as 1.48 g/ml for Scedosporium but >25 g/ml for zygomycetes, Aspergillus, and Fusarium spp. Compounds 1, 4, 5, and 8 exhibited good fungicidal activity against Candida and Cryptococcus, except for Candida parapsilosis (MICs of >44 g/ml). Geometric mean (GM) MICs were similar to those of amphotericin B and lower than or comparable to fluconazole GM MICs but 10- to 100-fold greater than those for the other azoles. GM MICs against Candida glabrata were
