Efficacy of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryptococcosis.
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.
Hata
K
K
Department of Microbiology and Infectious Disease, Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Kimura
J
J
Miki
H
H
Toyosawa
T
T
Moriyama
M
M
Katsu
K
K
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001927:Brain Diseases / Q000188:drug therapy / Q000382:microbiology; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D002180:Candidiasis, Oral / Q000188:drug therapy / Q000382:microbiology; D003453:Cryptococcosis / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use; D008172:Lung Diseases, Fungal / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*
D000935:Antifungal Agents; D013844:Thiazoles; D014230:Triazoles; D015725:Fluconazole; C104066:ER 30346