Experimental pulmonary aspergillosis due to Aspergillus terreus: Pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B

Thomas J. Walsh, Vidmantas Petraitis, Ruta Petraitiene, Aida Field-Ridley, Deanna Sutton, Mahmoud Ghannoum, Tin Sein, Robert Schaufele, Joanne Peter, John Bacher, Heather Casler, Derek Armstrong, Anna Espinel-Ingroff, Michael G. Rinaldi, Caron A. Lyman

Research output: Contribution to journalArticle

180 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)305-319
Number of pages15
JournalJournal of Infectious Diseases
Volume188
Issue number2
DOIs
StatePublished - Jul 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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    Walsh, T. J., Petraitis, V., Petraitiene, R., Field-Ridley, A., Sutton, D., Ghannoum, M., Sein, T., Schaufele, R., Peter, J., Bacher, J., Casler, H., Armstrong, D., Espinel-Ingroff, A., Rinaldi, M. G., & Lyman, C. A. (2003). Experimental pulmonary aspergillosis due to Aspergillus terreus: Pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B. Journal of Infectious Diseases, 188(2), 305-319. https://doi.org/10.1086/377210