title: The effect of antifungal agents and human monocytes on in vitro galactomannan release by Aspergillus spp. in liquid culture medium.
abstract: Invasive pulmonary aspergillosis is increasing in incidence in immunosuppressed patients. Diagnosis of this infection is problematic, relying on clinical suspicion and computerized tomography of the thorax and sinuses. An assay capable of detecting the fungal cell wall component galactomannan (GM) as a sign of Aspergillus infection is in use in patients with hematological malignancies. The aim of this study was to investigate the release of GM during growth of two medically important species, Aspergillus fumigatus and Aspergillus terreus, in liquid medium, including interaction with fluconazole, amphotericin B, liposomal amphotericin B and itraconazole, as well as human monocytes. Our results showed that for both species, amphotericin B deoxycholate, liposomal amphotericin B and itraconazole reduced the concentrations of GM to very low levels at the lowest doses tested (1, 3 and 4 microg/L, respectively). High doses of fluconazole had negligible effect on GM release by A. terreus, as expected. However, fluconazole at 128 microg/L increased GM concentrations released by A. fumigatus without reduction in visible growth. Co-incubation with human monocytes had no significant effect on GM release. The effects of antifungal agents on GM release may have diagnostic implications.
authors.affiliation: Department of Microbiology, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. richard.winn@tst.nhs.uk
authors.forename: Richard M
authors.initials: RM
authors.lastname: Winn
authors.forename: Adilia
authors.initials: A
authors.lastname: Warris
authors.forename: Peter
authors.initials: P
authors.lastname: Gaustad
authors.forename: Tore G
authors.initials: TG
authors.lastname: Abrahamsen
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003470:Culture Media; D015725:Fluconazole / Q000494:pharmacology; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D008351:Mannans / Q000378:metabolism*; D009000:Monocytes
chemical_list: D000935:Antifungal Agents; D003470:Culture Media; D008351:Mannans; C068538:liposomal amphotericin B; C012990:galactomannan; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole; D005690:Galactose