Publications

In Vitro Activity of a Novel Siderophore-Cephalosporin, GT-1 and Serine-Type β-Lactamase Inhibitor, GT-055, against Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. Panel Strains

Nguyen LP, Pinto NA, Vu TN, Lee H, Cho YL, Byun JH, D'Souza R, Yong D

PMID: 32443875

Abstract

This study investigates GT-1 (also known as LCB10-0200), a novel-siderophore cephalosporin, inhibited multidrug-resistant (MDR) Gram-negative pathogen, via a Trojan horse strategy exploiting iron-uptake systems. We investigated GT-1 activity and the role of siderophore uptake systems, and the combination of GT-1 and a non-β-lactam β-lactamase inhibitor (BLI) of diazabicyclooctane, GT-055, (also referred to as LCB18-055) against molecularly characterised resistant , and spp. isolates. GT-1 and GT-1/GT-055 were tested in vitro against comparators among three different characterised panel strain sets. Bacterial resistome and siderophore uptake systems were characterised to elucidate the genetic basis for GT-1 minimum inhibitory concentrations (MICs). GT-1 exhibited in vitro activity (≤2 μg/mL MICs) against many MDR isolates, including extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing and and oxacillinase (OXA)-producing spp GT-1 also inhibited strains with mutated siderophore transporters and porins. Although BLI GT-055 exhibited intrinsic activity (MIC 2-8 μg/mL) against most and isolates, GT-055 enhanced the activity of GT-1 against many GT-1-resistant strains Compared with CAZ-AVI, GT-1/GT-055 exhibited lower MICs against and isolates. GT-1 demonstrated potent in vitro activity against clinical panel strains of , and spp. GT-055 enhanced the in vitro activity of GT-1 against many GT-1-resistant strains.