Efficacy of T-2307, a novel arylamidine, against ocular complications of disseminated candidiasis in mice

Abstract

Objectives\nT-2307, a novel arylamidine, shows broad-spectrum activity against pathogenic fungi, including Candida albicans. Ocular candidiasis is one of the serious complications associated with Candida bloodstream infection and is known to be refractory to conventional antifungal agents. The aim of the present study was to clarify the effectiveness of T-2307 against ocular candidiasis using a mouse model.\n\n\nMethods\nWe evaluated ocular fungal burden in mice infected with C. albicans that received treatment with antifungal agents [T-2307, liposomal amphotericin B (LAMB) or fluconazole] for 3\u2009consecutive days. We also assessed survival rates of mice after C. albicans infection followed by treatment for 7\u2009consecutive days. In addition, ocular T-2307 concentrations and in vitro effectiveness against C. albicans biofilm formation were evaluated.\n\n\nResults\nThe ocular fungal burdens were significantly reduced after T-2307 treatment compared with the control group (no treatment received) and were comparable with those observed following treatment with LAMB or fluconazole in both early- and late-phase treatment experiments. In addition, all of the mice treated with antifungal agents survived for 3\u2009weeks after infection, whereas mice in the control group died within 3\u2009days. The ocular T-2307 trough concentration was maintained above the MIC in the infected mice. An in vitro biofilm inhibition experiment showed that T-2307 suppressed C. albicans biofilm formation at the sub-MIC level, which was comparable with amphotericin B.\n\n\nConclusions\nGiven these results in experimental disseminated candidiasis, T-2307 may be an effective treatment against the complication of ocular candidiasis.