Antifungal Effect of Macrophages Against Candida krusei-Synergistic Effect with Flucytosine.
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Some antifungal agents are known to work more effectively in vivo than expected by their MIC level measured in vitro. To determine whether this enhanced antifungal effect in vivo is caused by the synergy of these agents with the host defense mechanism, we investigated the synergistic effect of flucytosine against Candida krusei with murine peritoneal macrophages. C. krusei were added to thioglycollate-elicited murine peritoneal macrophages and were incubated with or without flucytosine. After 24 hours macrophages were lysed and the number of viable yeasts was measured by counting CFU to determine the antifungal activity. The results showed that: 1) the macrophages were fungistatic against C. krusei; 2) at the concentration of 0.1-1μg/ml, flucytosine had no effect against C. krusei when given to the yeasts by itself, and showed antifungal activity at 10μg/ml; 3) when added together with macrophages, flucytosine showed antifungal activity at as low as 0.1μg/ml. Thus macrophages can work synergistically with flucytosine against C. krusei. This synergy can also be seen in other antifungal agents, causing the discrepancy between MIC and the clinical efficacy.
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