Activity of MK-3118, a New Oral Glucan Synthase Inhibitor, Tested Against Candida and Aspergillus spp. using Two Reference Broth Microdilution (BMD) Methods

Ref ID: 18704

Author:

M. A. Pfaller, MD – Cons 1, S. A. Messer, MS – MT 1, M. R. Motyl, PhD – Lead Sci 2, R. N. Jones, MD – CEO 1, M. Castanheira, PhD – Dir1;

Author address:

1JMI Lab., N Liberty, IA, 2Merck Sharp & Dohme Corp, Kenilworth, NJ.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: MK-3118 is a potent inhibitor of fungal glucan synthase that is derived from enfumafungin. We compared the activity of MK-3118 against Aspergillus spp. (ASP) and Candida spp. (CSP) using CLSI and EUCAST (BMD) methods.
Methods: 71 ASP (23 A. flavus [AFL], 21 A. fumigatus [AFU], 9 A. niger [ANG], and 18 A. terreus [ATR]) and 113 CSP (29 C. albicans [CA], 29 C. glabrata [CGLA], 15 C. parapsilosis [CPRP], 21 C. tropicalis [CTRO] and 18 C. krusei [CKRU]) were tested against MK-3118, amphotericin B (AMB; ASP) and fluconazole (FLC; CSP) and caspofungin (CAS) by CLSI and EUCAST methods. MK-3118 was read at 24-h, 48-h, 50% and 100% inhibition. ASP included 8 itraconazole (ITR)-resistant (R; MIC, ≥ 4 µg/ml) and CSP included 31 CAS-R fks hot spot (HS) mutants (16 also FLC-R) and 19 FLC-R.
Results: Activities of MK-3118, CAS, FLC and AMB are displayed in the Table. MK-3118 demonstrated good activity against ASP and CSP. MK-3118 showed excellent activity against ITR-R strains of AFU (MEC range, 0.03 to 0.5 µg/ml), ANG and ATR (MEC, 0.06 and 0.12 µg/ml, respectively). MK-3118 was very active against FLC-R CA (MIC range, 0.06-2 µg/ml), CGLA (0.5-2 µg/ml), CTRO (0.25-1 µg/ml), and CPRP (0.25-0.5 µg/ml) and was most potent against CAS-R CA (MIC range, 0.12-2 µg/ml), CGLA (0.5-2 µg/ml), CTRO (0.25-2 µg/ml) and CKRU (0.5-2 µg/ml). Overall essential agreement (±2 log2 dilution steps) was 94.3% for ASP and 97.1% for CSP.

Conclusions: MK-3118 was shown to be a potent and broad-spectrum antifungal agent regardless of the BMD method applied, with excellent activity against challenging R strains of ASP and CSP.

Abstract Number: M-1714

Conference Poster: y

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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