Antifungal Activities of a Novel Arylamidine T-2307 against Azole-Resistant Aspergillus Species, A. calidoustus

Ref ID: 18638

Author:

K. Yamashita, MS – Researcher, E. Yamada, MS – Researcher, M. Kaeriyama, MS – Researcher, H. Nishikawa, MS – Researcher, N. Fujino, MS – Researcher, N. Nomura, PhD – General Manager, J. Mitsuyama, PhD – Director;

Author address:

Res. Lab., Toyama Chemical Co.,Ltd., Toyama, Japan.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: Aspergillus calidoustus is a newly identified Aspergillus species that cause invasive aspergillosis (IA). A. calidoustus exhibits reduced susceptibility to several antifungal drugs, especially azoles, and clinical cases of treatment failure have been reported. In this study, we evaluated in vitro and in vivo antifungal activities of T-2307, which is in clinical trials, against clinical isolates of A. calidoustus in comparison with caspofungin (CAS), itraconazole (ITC) and amphotericin B (AMB).
Methods: The in vitro susceptibility of A. calidoustus to T-2307 and other agents was examined in accordance with the CLSI document M38-A2. The minimum fungicidal concentration (MFC) was defined as the lowest concentration of the antifungal agent that produced killing of 99% or more. In murine disseminated infection caused by A. calidoustus CBS 121614, the antifungal agents were subcutaneously administered once daily for 7 days starting at 2 h after infection (n=8/group). The animals were monitored until 14 days for survival and the 50% effective doses (ED50) was calculated by the probit method.
Results:The tested strains showed decreased susceptibility to ITC and the MEC of CAS was variable. T-2307 exhibited potent activity against the tested strains. In murine disseminated infection, the ED50s of T-2307, CAS, ITC and AMB were 1.27, >6, >60 and >3 mg/kg/day, respectively.
Conclusions: T-2307 exhibited potent antifungal activities against A. calidoustus. Our results suggest that T-2307 may be considered a candidate for the treatment of IA caused by azole-resistant Aspergillus species including A. calidoustus.

Abstract Number: F-809

Conference Poster: y

Conference Year: 2012

Link to conference website: NULL

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