Correlation between In Vitro and In Vivo Activity of Antifungal Agents against Candida Species

Abstract

The correlation between antifungal susceptibility testing and in vivo response to antifungal therapy was examined in experimental murine candidiasis. In vitro susceptibility testing was done using a microbroth dilution method. Twenty-two Candida albicans, 4 Candida lusitaniae, and 2 Candida krusei isolates were tested against fluconazole, flucytosine, and amphotericin B. In vivo antifungal activity was tested in murine hematogenous candidiasis. Normal CFl mice were infected with each of the C. albicans strains; immunosuppressed CF 1 mice were inoculated with C. lusitaniae or C. krusei. Mice received various doses of antifungal agents, and survival was monitored for 21 days. Kidney fungal burden was examined on day 4. Antifungal therapy significantly prolonged survival and reduced tissue counts in animals infected with organisms susceptible to the agent tested (P < .05). In vitro resistance to a drug predicted its lack of in vivo activity. These results appear to correlate well with outcome of murine hematogenous candidiasis.