Correlation of in vitro susceptibility test results with in vivo response: flucytosine therapy in a systemic candidiasis model

Abstract

The in vitro susceptibility of Candida albicans isolates to flucytosine was compared to therapeutic effect in experimental murine candidiasis (candidosis). Four groups of 10 isolates were chosen, based upon their broth dilution minimal inhibitory concentrations (MICs), from a group of 402 isolates from patients without prior flucytosine therapy. Group I MICs were less than 12.5 micrograms/ml after seven days, whereas group II, III, and IV MICs exceeded 12.5 micrograms/ml on days 7, 2, and 1, respectively. Pilot experiments selected challenge inocula of similar virulence. Mice were infected intravenously and given various flucytosine doses. Significant prolongation of survival correlated with MICs and with agar disk-diffusion zone diameters (P less than 0.05). In vivo response to therapy was more favorable for group I isolates compared with group IV isolates (P less than 0.01). The present study demonstrates in this animal model that in vitro susceptibility does correlate with in vivo response to therapy, although exceptions occur with individual isolates.