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J Infect Dis. 2003 Jun 15;187(12):1834-43. Epub 2003 Jun 4.

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

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Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.


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.

[Indexed for MEDLINE]

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