RRC ID 2543
Author Kurita N, Brummer E, Oarada M, Miyaji M.
Title Synergistic antifungal effect of fluconazole and human polymorphonuclear leukocytes on Paracoccidioides brasiliensis: effect of interferon-gamma and granulocyte-macrophage colony-stimulating factor.
Journal Med. Mycol.
Abstract To better understand the in vivo efficacy of fluconazole (FCZ), we investigated the possible synergy of fungistatic FCZ with human polymorphonuclear leukocytes (PMN) against Paracoccidioides brasiliensis (Pb). The effect of interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in this system was also studied. For this purpose, FCZ, PMN, PMN + FCZ, PMN + IFN-gamma, PMN + IFN-gamma + FCZ, PMN + GM-CSF and PMN + GM-CSF + FCZ were co-cultured with Pb and the cfu of Pb was measured. The antifungal effect of FCZ on yeast cells of Pb was concentration-dependent. At 0.1 microg ml(-1), FCZ had no effect on the growth of Pb. At 0.2 microg ml(-1) FCZ showed a growth-inhibitory effect on three isolates of Pb in a long-term (120 h) assay, and at 0.6 microg ml(-1) or higher FCZ was fungicidal. Fungistatic concentration of FCZ (0.4 microg ml(-1)) acted synergistically with fungistatic PMN for killing isolate Bt-4 during the first 24 h of co-culture. Moreover, IFN-gamma and GM-CSF substantially enhanced the synergistic antifungal effect of PMN and FCZ. These findings provide a better understanding of why FCZ is more efficacious in in vivo models of paracoccidioidomycosis than is predicted by in vitro susceptibility tests.
Volume 41(2)
Pages 131-6
Published 2003-4
PMID 12964845
MeSH Antifungal Agents / pharmacology* Drug Synergism Fluconazole / pharmacology* Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology* Humans Interferon-gamma / biosynthesis Interferon-gamma / pharmacology* Neutrophils / immunology* Paracoccidioides / drug effects* Paracoccidioides / immunology Paracoccidioidomycosis / drug therapy* Paracoccidioidomycosis / immunology Paracoccidioidomycosis / microbiology
IF 2.851
Times Cited 0
Pathogenic microorganisms IFM 41621 IFM 41624