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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, Combination Therapy in Treatment of Experimental Pulmonary Aspergillosis: Synergistic Interaction between an Antifungal Triazole and an Echinocandin, The Journal of Infectious Diseases, Volume 187, Issue 12, 15 June 2003, Pages 1834–1843, https://doi.org/10.1086/375420
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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
- computed tomography
- antifungal agents
- bronchopulmonary aspergillosis
- neutropenia
- aspergillus fumigatus
- cell membrane
- cell wall
- combined modality therapy
- oryctolagus cuniculus
- triazoles
- morbidity
- mortality
- lung infiltration
- ravuconazole
- echinocandins
- aspergillosis, invasive pulmonary
- toxic effect
- lung injuries
- micafungin
- galactomannan
- biosynthesis