title: The effects of antifungal agents to conidial and hyphal forms of Aspergillus fumigatus.
abstract: Susceptibility testing for Aspergillus fumigatus is usually performed using a fungal conidial suspension. However, assessment of the susceptibility of fungal hyphae may be more relevant in attempting to mimic the fungal status in infected tissues. In the present study of 12 A. fumigatus clinical isolates and 1 ATCC strain, the antifungal susceptibilities of conidial suspensions, suspensions of hyphal fragments and of hyphal clumps were determined by the XTT-based broth susceptibility assay measuring decrease in fungal metabolic activity. Amphotericin B inhibited A. fumigatus conidia and hyphal fragments in a sharp concentration-dependent manner, with inhibitory concentrations (ICs) of 1 microg/ml for both fungal structures, whereas, hyphal clumps were inhibited at 8 microg/ml. Conidia and hyphal fragments were inhibited by the azoles itraconazole and voriconazole in a more gradual concentration-dependent manner, with ICs of 0.5 microg/ml for both structures with both agents. Hyphal clumps were not inhibited by the azoles at all. Caspofungin inhibited A. fumigatus in a moderate, neither sharp nor gradual, concentration-dependent manner. ICs for conidia were 128 microg/ml and inhibition in metabolic activity was not obtained for both hyphal growth forms. Antifungal susceptibility of conidia was also determined using the E-test in which it was found that the XTT assaygave comparable ICs for amphotericin B, itraconazole and voriconazole but not for caspofungin.
authors.affiliation: Department of Medical Microbiology & Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. w.vandesande@erasmusmc.nl
authors.forename: Wendy W J
authors.initials: WW
authors.lastname: van de Sande
authors.forename: Mehri
authors.initials: M
authors.lastname: Tavakol
authors.forename: Wim
authors.initials: W
authors.lastname: van Vianen
authors.forename: Irma A J M
authors.initials: IA
authors.lastname: Bakker-Woudenberg
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000302:isolation & purification; D000077336:Caspofungin; D054714:Echinocandins / Q000494:pharmacology; D006801:Humans; D025301:Hyphae / Q000187:drug effects; D017964:Itraconazole / Q000494:pharmacology; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests / Q000379:methods; D050296:Microbial Viability / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D013172:Spores, Fungal / Q000187:drug effects; D013778:Tetrazolium Salts / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D011743:Pyrimidines; D013778:Tetrazolium Salts; D014230:Triazoles; C059087:2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; D017964:Itraconazole; D000666:Amphotericin B; D000077336:Caspofungin; D065819:Voriconazole