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.

对于与社区和医院获得性感染相关的细菌以及潜在的生物防御威胁，抗菌素耐药性 (AMR) 已成为越来越难以克服的问题。需要确定新类别和/或具有独特机制的新疗法对于在未来几年对抗 AMR 至关重要。GT-1 (LCB10-0200)，一种铁载体连接的头孢菌素，就是这样一种新颖的选择，其配方可单独使用或与新型广谱 β-内酰胺酶抑制剂 GT-055 (LCB18-055) 联合使用. 本研究评估了 GT-1 和 GT-055 对多种多重耐药和生物威胁病原体的体外和体内功效。在这里，我们展示了低于 4 µg ml ⁻¹在体外对多种病原体有效。我们进一步确定，在通过气溶胶途径感染鼠疫耶尔森氏菌的小鼠中，GT-1/GT-055 治疗的疗效至少相当于比较抗生素环丙沙星。