Efficacy of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryptococcosis

Abstract

ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. In the present study, we investigated the therapeutic effects of oral ER-30346 on experimental local infections caused by Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans and compared them with those of itraconazole and fluconazole. In experimental murine models of pulmonary aspergillosis, candidiasis, and cryptococcosis, ER-30346 reduced the numbers of CFU in the lungs significantly compared with the numbers of CFU in the lungs of the controls (P < 0.05). ER-30346 was as effective as or more effective than itraconazole against pulmonary aspergillosis. Against pulmonary candidiasis and cryptococcosis, ER-30346 was more effective than itraconazole and was as effective as fluconazole. ER-30346 was also effective against pulmonary candidiasis caused by fluconazole-resistant C. albicans. In mice with intracranial cryptococcosis, ER-30346 reduced the numbers of CFU in the brains significantly compared with the numbers of CFU in the brains of the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. In an experimental model of oral candidiasis in rats, ER-30346 reduced the numbers of CFU in oral swabs significantly compared with the numbers of CFU in oral swabs from the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. Thus, ER-30346 shows efficacy in murine aspergillosis, candidiasis, and cryptococcosis models. Further studies are needed to determine the potential of ER-30346 for use in the treatment of these infections.

Madurella mycetomatis Is Highly Susceptible to Ravuconazole

“…Moreover, high concentrations were also detected in lung and uterus of rat [27]. Due to these high levels of the drug in tissue, good therapeutic efficacy was obtained in animal models with pulmonary and disseminated aspergillosis, candidiasis, histoplasmosis, intracranial and disseminated cryptococcosis [21], [23], [28], [29]. Based on the in vitro susceptibility generated in this study, the next step will be to study the efficacy of ravuconazole in an animal model of mycetoma.…”

“…Moreover, ravuconazole showed potent in vitro activity against the parasite Trypanosoma cruzi [12]. Several studies have been conducted to evaluate the in vivo efficacy of ravuconazole and E1224 using animal models of aspergillosis, candidiasis, and cryptococcosis, with each demonstrating encouraging activity of the drug [21], [22], [23]. In addition, phase 1/2 clinical trials have shown that ravuconazole and E1224 were well tolerated.…”

Review of Newer Antifungal and Immunomodulatory Strategies for Invasive Aspergillosis

“…One murine study revealed that both ravuconazole and itraconazole led to decreased lung fungal burden in a dose-dependent fashion [234]. Penetration of ravuconazole into healthy rat tissue showed that the concentration of drug in the lungs was 2-6 times higher than the corresponding blood concentration [235].…”

Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization

“…Other immunosuppressive medicines were used, like 5-fluorouracil (Hata et al, 1996a,b, 2011; Wallace et al, 1997; Graybill et al, 1998, 2003a; BitMansour et al, 2005; Stojanovic et al, 2011; Salas et al, 2013), tacrolimus (FK506; High and Washburn, 1997; Herbst et al, 2013, 2015; Shirkhani et al, 2015), cyclosporine A (Polak-Wyss, 1991; High and Washburn, 1997), mitotic poisons (Baisakh et al, 1975; Balloy et al, 2005a,b; Loussert et al, 2010; Hein et al, 2015). Tunicamycin was employed once because of its anti-Natural Killer (NK) cell property (Maheshwari et al, 1988), and liposomal dichloromethylene diphosphonate (DMPD) because it decreases macrophages in liver and spleen (Moonis et al, 1994).…”