In vitro pharmacodynamic characteristics of flucytosine determined by time-kill methods.
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 Cryptococcusisolates, flucytosine at concentrations > 1 x 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 x 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.
Lewis
R E
RE
University of Iowa Colleges of Pharmacy, S-412 Pharmacy Bldg., Iowa City, IA, USA.
Klepser
M E
ME
Pfaller
M A
MA
D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D015169:Colony Count, Microbial; D003454:Cryptococcus / Q000187:drug effects* / Q000254:growth & development; D005437:Flucytosine / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D005437:Flucytosine