Abstract
Two Candida albicans isolates, three non- albicans Candida isolates ( Candida glabrata, Candida krusei, and Candida tropicalis), and one Cryptococcus neoformans isolate were evaluated by time-kill methods to characterize the relationship of flucytosine concentrations to antifungal activity and the duration of the post-antifungal effect (PAE). Against Candida and Cryptococcus isolates, flucytosine at concentrations > 1 × MIC exhibited fungistatic (≤99% reduction in CFU) activity over a 24-h time-period. The rate and extent of fungistatic activity of flucytosine against all isolates was generally not increased when 5-FC concentrations exceeded 4 × MIC. A notable PAE was detected for flucytosine against both Candida and Cryptococcus species that persisted 2 to 4 h. These in vitro data suggest that flucytosine is predominately a concentration-independent fungistatic agent at clinically achieved serum concentrations. This pharmacodynamic characteristic coupled with the persistent PAE and the relatively long half-life of flucytosine in humans (>5 h), suggests lower daily dosing may possible without loss of antifungal efficacy.
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