1. Academic Validation
  2. In vitro activity of the novel antibacterial agent ibezapolstat (ACX-362E) against Clostridioides difficile

In vitro activity of the novel antibacterial agent ibezapolstat (ACX-362E) against Clostridioides difficile

  • J Antimicrob Chemother. 2020 Aug 1;75(8):2149-2155. doi: 10.1093/jac/dkaa134.
Beverly Murray 1 Cindy Wolfe Andrea Marra 1 Chris Pillar 1 Dean Shinabarger 1
Affiliations

Affiliation

  • 1 Micromyx, Inc, 4717 Campus Drive, Kalamazoo, MI 49008, USA.
Abstract

Background: Ibezapolstat (ACX-362E) is the first DNA polymerase IIIC inhibitor undergoing clinical development for the oral treatment of Clostridioides difficile Infection (CDI).

Methods: In this study, the in vitro activity of ibezapolstat was evaluated against a panel of 104 isolates of C. difficile, including those with characterized ribotypes (e.g. 027 and 078) and those producing toxin A or B and was shown to have similar activity to those of comparators against these strains.

Results: The overall MIC50/90 (mg/L) for ibezapolstat against evaluated C. difficile was 2/4, compared with 0.5/4 for metronidazole, 1/4 for vancomycin and 0.5/2 for fidaxomicin. In addition, the bactericidal activity of ibezapolstat was evaluated against actively growing C. difficile by determining the MBC against three C. difficile isolates. Time-kill kinetic assays were additionally performed against the three C. difficile isolates, with metronidazole and vancomycin as comparators.

Conclusions: The killing of C. difficile by ibezapolstat was observed to occur at concentrations similar to its MIC, as demonstrated by MBC:MIC ratios and reflected in time-kill kinetic assays. This activity highlights the therapeutic potential of ibezapolstat for the treatment of CDI.

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