| Autor: |
Baltch, Aldona L., Smith, Raymond P., Ritz, William J., Bopp, Lawrence H., Michelsen, Phyllis B. |
| Předmět: |
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| Zdroj: |
Journal of Applied Research; 2005, Vol. 5 Issue 4, p543-552, 10p, 3 Diagrams, 1 Chart |
| Abstrakt: |
Background: Disseminated infections caused by Candida albicans continue to be associated with high mortality. Monocytes are important host phagocytic cells which, when activated by cytokines, can have increased killing activity. This study compares the intracellular activity of three azoles (fluconazole, voriconazole, and itraconazole) in human monocyte-derived macrophages (MDM) activated or not activated by cytokines. Design and Methods: Human MDM monolayers prepared from heparinized blood of healthy volunteers were infected with C albicans (fluconazole-resistant [fluR] strains 8336-2 and ATCC 64550; fluconazole-susceptible [fluS] strains T=6. ATCC 56882, and ATCC 90028). Antifungal agents (1 x minimal inhibitory concentration) were added following a 1-h phagocytosis time. Numbers of viable C albicans from MDM lysates were determined at 0, 24, and 48 h. Results: For two of the five C albicans strains (ATCC 90028 and T=6), all azoles had similar activity at 24 h. There were slight differences at 48 h. For strains ATCC 64550 and ATCC 56882, the most effective azoles were fluconazole and itraconazole, respectively, and voriconazole was most effective against strain 8336-2. Voriconazole was least effective against strain ATCC 56882, and itraconazole was least effective against strain ATCC 64550. Significant effects of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor α occurred only with voriconazole and were strain-dependent. Activity of voriconazole was enhanced, inhibited, or unaflected by these cytokines. Conclusions: This study clearly indicates that in the presence of different azoles and cytokines, the intracellular anticandidal activity of human VIDM cannot be predicted and may differ for individual C albicans strains. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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