Efficacy of NND-502, a novel imidazole antimycotic agent, in experimental models of Candida albicans and Aspergillus fumigatus infections

Yoshimi Niwano, Naoki Kuzuhara, Yuri Goto, Yukimi Munechika, Hiroki Kodama, Kazuo Kanai, Masanori Yoshida, Tsuneo Miyazaki, Hideyo Yamaguchi

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22 Citations (Scopus)

Abstract

In vitro and in vivo anti-Candida albicans and anti-Aspergillus fumigatus activities of NND-502, a new imidazole-antimycotic, were compared with those of fluconazole (FCZ), itraconazole (ITZ) and/or amphotericin B (AmB). NND-502 exhibited strong in vitro antifungal activity against both fungal species; its MIC against C. albicans was 1-4 times lower than that of FCZ, and its MIC against A. fumigatus was at least 60-2000 times lower than that of ITZ and AmB. In vivo antifungal treatments with each drug were initiated 1 h after inoculation in the experimental models, so that antifungal potential reflected prophylactic activity rather than therapeutic activity. The oral regimen of NND-502 in a murine model of systemic C. albicans infection was much less effective than that of FCZ. In vivo anti-A. fumigatus activity of oral NND-502 in a murine model of systemic infection was apparently superior to that of FCZ and ITZ in terms of prolonging survival. In addition to the murine model of systemic aspergillosis, intravenous NND-502 was shown to be highly effective in a rat model of pulmonary aspergillosis compared with intravenous AmB; 90% of animals survived at a dose of 2.5 mg/kg per day of NND-502 while only 30% of animals escaped death when 5 mg/kg per day of AmB was used. This potent efficacy of NND-502 was also confirmed in a sublethal challenge study in which the administration of the agent at a dose as low as 1.25 mg/kg per day resulted in the significant reduction of organisms in the lung; no comparable effect of AmB was found. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)221-228
Number of pages8
JournalInternational Journal of Antimicrobial Agents
Volume12
Issue number3
DOIs
Publication statusPublished - 1999 Aug

Keywords

  • Aspergillus fumigatus
  • Candida albicans
  • Experimental infection
  • Imidazole antimycotic
  • NND-502

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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