In vitro and in vivo activity of GT-1, a novel siderophore cephalosporin, and GT-055, a broad-spectrum β-lactamase inhibitor, against biothreat and ESKAPE pathogens

  • J Antibiot (Tokyo). 2021 Dec;74(12):884-892. doi: 10.1038/s41429-021-00472-9.
Stephanie A Halasohoris  1 ,  Jennifer M Scarff  1 ,  Lisa M Pysz  1 ,  Sanae Lembirik  1 ,  Margaret M Lemmon  1 ,  Donald Biek  2 ,  Brendan Hannah  2 ,  Steven D Zumbrun  1 ,  Rekha G Panchal  3
Affiliations
  • 1. US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
  • 2. Geom Therapeutics Inc, San Diego, CA, USA.
  • 3. US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA. [email protected].
PMID: 34522025 DOI: 10.1038/s41429-021-00472-9
Abstract

Antimicrobial-resistance (AMR) has become an increasingly difficult issue to overcome for bacteria associated with both community- and hospital-acquired infections as well as potential biodefense threats. The need to identify new therapeutics of novel classes and/or with unique mechanisms is critical to combatting AMR in the coming years. GT-1 (LCB10-0200), a siderophore-linked cephalosporin, is one such novel option and is formulated to be used either alone or in combination with a novel broad-spectrum β-lactamase inhibitor, GT-055 (LCB18-055). This study assessed the in vitro and in vivo efficacy of GT-1 and GT-055 against a broad array of multi-drug resistant and biothreat pathogens. Here, we demonstrated sub-4 µg ml-1 efficacy against a number of pathogens in vitro. We further determined that in mice infected via aerosol route with Yersinia pestis, efficacy of GT-1/GT-055 treatment is at least equivalent to the comparator Antibiotic, ciprofloxacin.

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