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. Epub 2021 Sep 14.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Biological Warfare Agents*
  • Cephalosporins / pharmacology*
  • Cephalosporins / therapeutic use
  • Ciprofloxacin / pharmacology
  • Drug Resistance, Multiple, Bacterial
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Plague / drug therapy
  • Plague / microbiology
  • Siderophores / pharmacology
  • Yersinia pestis / drug effects*
  • beta-Lactamase Inhibitors / pharmacology*
  • beta-Lactamase Inhibitors / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Biological Warfare Agents
  • Cephalosporins
  • GT-1 siderophore cephalosporin
  • Siderophores
  • beta-Lactamase Inhibitors
  • Ciprofloxacin