title: Experimental pulmonary aspergillosis due to Aspergillus terreus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B.
abstract: Aspergillus terreus is an uncommon but emerging fungal pathogen, which causes lethal infections that are often refractory to amphotericin B (AmB). In comparison to Aspergillus fumigatus, A. terreus was resistant to the in vitro fungicidal effects of safely achievable concentrations of AmB. These in vitro findings correlated directly with resistance of A. terreus to AmB in experimental invasive pulmonary aspergillosis. Residual fungal pulmonary burden and galactomannan antigenemia demonstrated persistent infection, despite therapy with deoxycholate AmB or liposomal AmB. By comparison, posaconazole and itraconazole resolved GM antigenemia, reduced residual fungal burden, and improved survival. There were no differences in phagocytic host response to A. terreus versus A. fumigatus; however, the rate of conidial germination of A. terreus was slower. The strain of A. terreus with the highest minimum inhibitory and minimum lethal concentration of AmB also had the lowest membrane ergosterol content. The hyphae of A. terreus in vivo displayed distinctive aleurioconidia, which may be a practical microscopic feature for rapid preliminary diagnosis.
authors.affiliation: Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, NIH Building 10, Room 13N240, Bethesda, MD 20892, USA. walsht@mail.nih.gov
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
authors.forename: Vidmantas
authors.initials: V
authors.lastname: Petraitis
authors.forename: Ruta
authors.initials: R
authors.lastname: Petraitiene
authors.forename: Aida
authors.initials: A
authors.lastname: Field-Ridley
authors.forename: Deanna
authors.initials: D
authors.lastname: Sutton
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ghannoum
authors.forename: Tin
authors.initials: T
authors.lastname: Sein
authors.forename: Robert
authors.initials: R
authors.lastname: Schaufele
authors.forename: Joanne
authors.initials: J
authors.lastname: Peter
authors.forename: John
authors.initials: J
authors.lastname: Bacher
authors.forename: Heather
authors.initials: H
authors.lastname: Casler
authors.forename: Derek
authors.initials: D
authors.lastname: Armstrong
authors.forename: Anna
authors.initials: A
authors.lastname: Espinel-Ingroff
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rinaldi
authors.forename: Caron A
authors.initials: CA
authors.lastname: Lyman
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001230:Aspergillus / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D021821:Communicable Diseases, Emerging / Q000188:drug therapy / Q000382:microbiology*; D025141:Drug Resistance, Fungal; D005260:Female; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008172:Lung Diseases, Fungal / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013045:Species Specificity
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B