1887

Abstract

Infections caused by species other than are increasingly common, and decreased susceptibility to azoles has made them more difficult to treat. Since phagocytic killing is important in elimination of infections, intracellular killing of fluconazole-resistant , and (four strains each) by voriconazole was investigated in human monocyte-derived macrophages (MDMs). MDMs were infected with , and voriconazole was then added. MDMs were lysed at 0, 24 or 48 h after infection, and viable in the lysates enumerated. Compared to the starting inoculum, the number of viable intracellular and in untreated MDMs increased to 28 121 and 351 %, respectively, in 48 h. In contrast, the number of decreased to 42 %. In MDMs treated with voriconazole, the decrease in viable count was dependent upon drug concentration. At 48 h, was killed only at 5× MIC (<0.05), was killed at all voriconazole concentrations, while was inhibited at 0.5 and 1× MIC and killed at ⩾2.5× MIC (<0.05). The data show that intracellular growth and survival of these species in the absence or presence of voriconazole vary markedly. The activity of voriconazole depends on the concentration of the drug and the time of exposure. For the 12 strains studied, regression curves show that the maximum intracellular anticandidal activity of voriconazole was reached at 3.5–5× MIC.

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2006-07-01
2019-11-12
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