1621. Activity of Isavuconazole and Comparator Mould-Active Triazoles Tested against Contemporary Invasive Mould Isolates
Session: Poster Abstract Session: Mycology - There's a Fungus Among Us: Treatment
Friday, October 28, 2016
Room: Poster Hall
Posters
  • IDWeek16 Isavuconazole 1621-final.pdf (308.5 kB)
  • Background: The mould-active triazoles (MAT) are important agents for the treatment of invasive infections due to Aspergillus spp. and other selected rare moulds. We evaluated the in vitro activity of isavuconazole, a new broad-spectrum MAT, and comparators against 665 invasive mould isolates collected worldwide during 2014-2015 using CLSI broth microdilution methods.

     

    Methods: 620 Aspergillus spp. (5 species/species complex [SC]), 18 Fusarium solani SC, 10 Rhizopus microsporus group and 17 Scedosporium apiospermum SC were susceptibility tested against isavuconazole, itraconazole, posaconazole and voriconazole. Species identification was performed by MALDI-TOF and/or DNA sequencing methods. Epidemiological cutoff values (ECVs) were applied to distinguish wild-type (WT) versus non-WT strains where appropriate.

     

    Results: The activity of isavuconazole versus Aspergillus spp. was similar to that of the other MATs. All A. terreus, 98.1% of A. flavus and 98.6% of A. fumigatus were inhibited by ≤1 µg/ml of isavuconazole and were WT (MIC≤ECV) to the other three MATs. Similarly, 100% of A. niger SC were WT to isavuconazole, itraconazole and voriconazole. The MATs had limited in vitro activity (MIC50/90, ≥8 µg/ml) against F. solani SC. Although voriconazole was not active against R. microsporus group, 90% were inhibited by ≤4 µg/ml of isavuconazole and itraconazole and 100% were inhibited by ≤2 µg/ml of posaconazole. Isolates of S. apiospermum SC were most susceptible to voriconazole followed by posaconazole>itraconazole>isavuconazole.

     

    Conclusion: In vitro, isavuconazole was as active as the other MATs against Aspergillus spp. and showed moderate activity against R. microsporus group and S. apiospermum SC. None of the MATs showed in vitro activity against F. solani SC. Considering its in vitro activity and data from recently published phase 3 studies, isavuconazole is a useful agent for the treatment of invasive infections due to a variety of clinically important filamentous fungi.

     

    Michael Pfaller, MD, FIDSA1, Shawn a. Messer, MS-MT1, Rachel D. Dietrich, BA1, Paul R. Rhomberg, BS2 and Mariana Castanheira, PhD1, (1)JMI Laboratories, Inc., North Liberty, IA, (2)Jmi Laboratories, Inc., North Liberty, IA

    Disclosures:

    M. Pfaller, Astellas Pharma Global Development, Inc.: Research Contractor , Research grant

    S. A. Messer, Astellas Pharma Global Development, Inc.: Research Contractor , Research grant

    R. D. Dietrich, Astellas Pharma Global Development, Inc.: Research Contractor , Research grant

    P. R. Rhomberg, Astellas Pharma Global Development, Inc.: Research Contractor , Research grant

    M. Castanheira, Astellas Pharma Global Development, Inc.: Research Contractor , Research grant

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.