Antifungal Triazoles and Polymorphonuclear Leukocytes Synergize To Cause Increased Hyphal Damage toScedosporium prolificansandScedosporium apiospermum

Abstract

Scedosporium prolificans and Scedosporium apiospermum (Pseudallescheria boydii) cause pulmonary and disseminated infections refractory to most currently used antifungal agents in immunocompromised patients. We therefore investigated the potential antifungal activities of the triazoles itraconazole (ITC), voriconazole (VRC), and posaconazole (PSC) in combination with human polymorphonuclear leukocytes (PMNs) against the hyphae of these fungal pathogens. A colorimetric assay with (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5-carboxanilide) sodium salt was used for the measurement of hyphal damage as an indicator of antifungal activity. We found that the newer triazoles VRC and PSC displayed synergistic effects with PMNs against S. prolificans hyphae after 24 h (P < 0.05), whereas the effect of ITC in combination with PMNs was additive (P < 0.01). All three triazoles displayed additive antifungal activities in combination with PMNs against S. apiospermum hyphae (P < 0.05). The synergistic or additive effects that these triazoles exhibited, combined with the antifungal activities of human PMNs, may have important therapeutic implications for the management of infections due to S. prolificans and S. apiospermum.