Combination therapy in treatment of experimental pulmonary aspergillosis: Synergistic interaction between an antifungal triazole and an echinocandin

Vidmantas Petraitis, Ruta Petraitiene, Alia A. Sarafandi, Amy M. Kelaher, Caron A. Lyman, Heather E. Casler, Tin Sein, Andreas H. Groll, John Bacher, Nilo A. Avila, Thomas J. Walsh

Research output: Contribution to journalArticle

Abstract

Invasive pulmonary aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Simultaneous inhibition of fungal cell-wall and cell-membrane biosynthesis may result in synergistic interaction against Aspergillus fumigatus. We studied the antifungal activity of micafungin, a new echinocandin, in combination with ravuconazole, a second-generation triazole, against experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. This combination led to significant reductions in mortality (P ≤ .001 ), residual fungal burden (P ≤ .05), and serum galactomannan antigenemia (P ≤ .01 ), compared with either agent alone. Combination therapy also resulted in reduction (P ≤ .05) of organism-mediated pulmonary injury and of pulmonary infiltrates detected by thoracic computed tomography (P ≤ .001 ). No toxicity was observed with the echinocandin-triazole combination. An MTT hyphal damage assay demonstrated significant in vitro synergistic interaction between the antifungal triazole and the echinocandin. The combination of an antifungal triazole and echinocandin may represent a new strategy for treatment of invasive pulmonary aspergillosis.

Original languageEnglish (US)
Pages (from-to)1834-1843
Number of pages10
JournalJournal of Infectious Diseases
Volume187
Issue number12
DOIs
StatePublished - Jun 15 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Petraitis, V., Petraitiene, R., Sarafandi, A. A., Kelaher, A. M., Lyman, C. A., Casler, H. E., Sein, T., Groll, A. H., Bacher, J., Avila, N. A., & Walsh, T. J. (2003). Combination therapy in treatment of experimental pulmonary aspergillosis: Synergistic interaction between an antifungal triazole and an echinocandin. Journal of Infectious Diseases, 187(12), 1834-1843. https://doi.org/10.1086/375420