The investigational agent E1210 is effective in treatment of experimental invasive candidiasis caused by resistant Candida albicans

Abstract

The in vitro and in vivo activity of the inositol acyltransferase inhibitor E1210 was evaluated against echinocandin-resistant Candida albicans. E1210 demonstrated potent in vitro activity, and in mice with invasive candidiasis caused by echinocandin-resistant C. albicans, oral doses of 10 and 40 mg E1210/kg of body weight twice daily significantly improved survival and reduced fungal burden compared to those of controls and mice treated with caspofungin (10 mg/kg/day). These results demonstrate the potential use of E1210 against resistant C. albicans infections.

FIG 1

Survival curves in mice infected with C. albicans 43001 and treated with placebo by oral gavage twice daily (5% glucose twice daily by oral gavage), E1210 at doses of 2.5 mg/kg, 10 mg/kg, or 40 mg/kg by oral gavage twice daily, fluconazole (FLU) at 20 mg/kg by oral gavage twice daily, or caspofungin (CAS) at 10 mg/kg by intraperitoneal injection once daily. Treatment began 1 day postinoculation and continued for 7 days. Mice were then monitored off therapy until day 21. n = 20 mice per group. Survival was plotted by Kaplan-Meier analysis, and differences in median survival time and the percent survival among groups were analyzed by the log-rank test and Fischer's exact test, respectively. *, P < 0.05 versus control; §, P < 0.05 versus the caspofungin group.

FIG 2

Kidney fungal burden (CFU/g of tissue) on day 8 in mice infected with C. albicans 43001 and treated with placebo (5% glucose twice daily by oral gavage), E1210 (2.5, 10, or 40 mg/kg by oral gavage twice daily), fluconazole (FLU; 20 mg/kg by oral gavage twice daily), or caspofungin (CAS; 10 mg/kg by intraperitoneal injection once daily) beginning 1 day postinoculation and continuing for 7 days. n = 20 mice per group. Differences in kidney fungal burden (reported as mean CFU/g ± standard deviation) among the groups were assessed for significance by analysis of variance (ANOVA) with Tukey's posttest for multiple comparisons. *, P < 0.05 versus control; §, P < 0.05 versus caspofungin.