1625. Activity of a Long-Acting Echinocandin (CD101) and Comparator Antifungal Agents Tested Against Contemporary Worldwide Invasive Fungal Isolates
Session: Poster Abstract Session: Mycology - There's a Fungus Among Us: Treatment
Friday, October 28, 2016
Room: Poster Hall
Posters
  • IDWeek16 CD101 1625-final.pdf (316.2 kB)
  • Background: CD101 is a novel echinocandin displaying exceptional chemical stability and a long-acting pharmacokinetics. This compound has being developed for once-weekly IV administration for the treatment of invasive candidiasis and candidemia. We evaluated the activity of CD101 and comparators against 713 invasive fungal isolates collected worldwide during 2015 using CLSI broth microdilution methods.

     

    Methods: 589 Candida spp. (6 species), 14 C. neoformans (CNEO), 13 A. flavus (ASFL) and 97 A. fumigatus (ASF) were tested for susceptibility (S) to CD101, anidulafungin (ANF), caspofungin (CSF), micafungin (MCF) and azoles. CLSI clinical breakpoint (CBP) and epidemiological cutoff value (ECV) interpretive criteria were applied. Isolates displaying echinocandin MIC>ECV were sequenced for fks hot spot (HS) mutations.

     

    Results: The activity of CD101 was similar to that of other echinocandins (Table). All C. tropicalis (CTRO), C. krusei and C. dubliniensis (CDU; n=12), 99.7% of C. albicans (CA) and 98.3% of C. glabrata (CGLA) were inhibited by ≤0.12 µg/ml of CD101 and were S/wild-type to other echinocandins using CBP/ECV. Two CGLA displayed CD101 MIC >0.12 µg/ml (MIC, 0.25 and 1 µg/ml), elevated CSF (>0.5 µg/ml), ANF (0.25-0.5 µg/ml) and MCF (0.12-0.25 µg/ml) results and possessed HS mutations in fks1/fks2. C. parapsilosis (CPRP) displayed higher MIC values (range 0.25-2 µg/ml), but similar results were observed for other echinocandins. Fluconazole resistance was noted among 6.6% of CGLA, 3.6% CPRP and 0.0% CA, CDU and CTRO. Echinocandins had limited activity against CNEO. CD101 activity against ASF and ASFL (MEC, ≤0.03 µg/ml) was comparable to the other echinocandins (MEC, ≤0.03 µg/ml). These moulds displayed MIC values below ECVs for the mould-active azoles (itraconazole, voriconazole and posaconazole).

     

    Conclusion: CD101 was as active as other echinocandins against common fungal organisms recovered from invasive fungal infections. The extended half-life profile is very desirable since less frequent dosing of this agent should facilitate shorter and cost effective hospital stays, improve compliance for outpatients and provide more convenient outpatient prophylaxis.

     

    Michael Pfaller, MD, FIDSA, Shawn a. Messer, MS-MT, Paul R. Rhomberg, BS, Sarah E. Costello, BS and Mariana Castanheira, PhD, JMI Laboratories, Inc., North Liberty, IA

    Disclosures:

    M. Pfaller, Cidara Pharmaceuticals: Research Contractor , Research grant

    S. A. Messer, Cidara Pharmaceuticals: Research Contractor , Research grant

    P. R. Rhomberg, Cidara Pharmaceuticals: Research Contractor , Research grant

    S. E. Costello, Cidara Pharmaceuticals: Research Contractor , Research grant

    M. Castanheira, Cidara Pharmaceuticals: 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.