We performed Etest and broth microdilution (BMD) susceptibility testing of caspofungin, micafungin and anidulafungin against 67 clinical isolates of Aspergillus spp. and 10 Fusarium spp. Minimal effective concentrations (MECs) by BMD were read after 24 h of incubation at 35 degrees C and Etest MICs were read at 24 and 48 h. MECs < or =0.25 mg/l were obtained with caspofungin for all Aspergillus spp. tested but Etest MICs were < or =1 mg/l at 24 h. The agreement between caspofungin Etest and broth microdilution was good for all Aspergillus species tested (range 82.4-100%) except for A. niger and A. glaucus at 24 h of incubation. Micafungin and anidulafungin MEC and MIC results were lower than those of caspofungin (< or =0.015 mg/l) at 24 and 48 h for all Aspergillus tested. The agreement between the methods was excellent (100%) for micafungin and anidulafungin for all Aspergillus species tested. The three echinocandins were inactive against all isolates of Fusarium spp. showing MECs and MICs >8 mg/l. The Etest method could be a suitable procedure to test the susceptibility of most Aspergillus species to caspofungin, micafungin and anidulafungin; the best agreement was at 24 h.
In this study, we have synthesized several perylene bisimide derivatives and evaluated the antifungal activity against human pathogenic yeasts (Candida spp.) and filamentous fungi (Aspergillus spp., Fusarium spp., and Trichophyton spp.). Three compounds (2-4) from the nine compounds tested presented relevant activity against Candida albicans, C. parapsilosis and C. tropicalis with minimum inhibitory concentrations (MIC 90) values of 3.1-25.0 µg/mL. These three compounds also showed activity against filamentous fungi, F. oxysporum, T. rubrum and T. mentagrophytes at a concentration of 50 µg/mL. The resultant data indicates that perylene bisimides (2-4) display wide spectrum and relevant antifungal activity. Compound 4 represents a new scaffold for the development of antifungal agents and warrant further structure activity relationship studies.
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