Antifungal activities of posaconazole and granulocyte-macrophage colony-stimulating factor ex vivo and in mice with disseminated infection due to Scedosporium prolificans

Antimicrobial Agents and Chemotherapy
Maria SimitsopoulouEmmanuel Roilides

Abstract

Invasive infection due to Scedosporium prolificans is characterized by drug resistance and a high rate of mortality. The effects of posaconazole (POS), an investigational antifungal triazole, murine granulocyte-macrophage colony-stimulating factor (GM-CSF), and their combination against S. prolificans were evaluated ex vivo and in a newly developed murine model of disseminated infection due to this organism. When POS was combined with polymorphonuclear leukocytes from untreated or GM-CSF-treated mice (P < 0.01) ex vivo, it had increased activity in terms of the percentage of hyphal damage. Immunocompetent BALB/c mice were infected with 4 x 10(4) conidia of S. prolificans via the lateral tail vein. At 24 h postinfection the mice were treated with GM-CSF (5 microg/kg of body weight/day subcutaneously), POS (50 mg/kg/day by gavage), both agents, or saline only. Half of the brain, lung, liver, and kidney from each animal were cultured; and the other half of each organ was processed for histopathology. The mean survival times were 7.0 +/- 0.3 days for the controls, 7.4 +/- 0.4 days for POS-treated mice, 8.0 +/- 0.3 days for GM-CSF-treated mice (P = 0.08 compared with the results for the controls), and 7.3 +/- 0.3 days for POS-GM-CSF...Continue Reading

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