Effects of Voriconazole, GM-CSF, and Interferon-g on Intracellular Fluconazole-Resistant Candida glabrata and Candida krusei in Human Monocytes.

A. BALTCH, L. BOPP, R. SMITH, W. RITZ, C. CARLYN, P. MICHELSEN

Author address: 

Stratton VA Med. Ctr., Albany, NY, Albany Med. Coll., Albany, NY

Abstract: 

Background: Infections caused by fluconazole-resistant (FluR) Candida glabrata (Cgl) and C. krusei (Ckr) are increasingly common causes of morbidity and mortality. Since cytokine-activated phagocytes are important in host defense, we investigated intracellular killing of FluR Cgl and Ckr by voriconazole (Vor), +/- GM-CSF and IFN-g, in human monocyte-derived macrophages (MDM). Methods: Three strains each of Cgl and Ckr (Vor MICs: 0.25 to 2 µg/ml) were used. Yeast were grown for 18 h, opsonized and resuspended in RPMI 1640 + 15% FBS (RPMI+). Monolayers of MDM from the blood of healthy volunteers were incubated for 18 h +/- GM-CSF or IFN-g, infected for 1 h, washed, and RPMI+ (+/- cytokines and Vor at 2.5xMIC), was then added. MDM were lysed at 0, 24 or 48 h and viable yeast in lysates enumerated. Results: 1] In MDM preincubated (18 h) with GM-CSF or IFN-g and treated after infection with the same cytokine, GM-CSF markedly increased antifungal activity against all Cgl strains; addition of Vor increased this effect (P
2003

abstract No: 

M-378

Full conference title: 

43rd Interscience Conference on Antimicrobial Agents
    • ICAAC 43rd