Investigational Agents for the Treatment of Gram-Negative Bacterial Infections: A Reality Check

Antibiotic-resistant Gram-negative bacteria are, arguably, the most difficult organisms to treat, with a limited number of new antibiotics in the development pipeline. Currently 24 new agents in phase 1, phase 2, or phase 3 clinical development were identified for the potential treatment of infections caused by Gram-negative bacteria. Of these agents, most are improved iterations of known antibiotic classes, including new aminoglycosides, β-lactams, β-lactamase inhibitors, quinolones, and tetracyclines with greater potency or a broader spectrum of activity. However, novel structures also appear, with host defense peptide mimetics, boronic acid, and bridged diazabicyclooctane β-lactamase inhibitors and unique bacterial topoisomerase inhibitors. Most of the new agents have received a Qualified Infectious Disease Product (QIDP) designation that may help to accelerate FDA drug approvals. Because resistance will inevitably arise to any antibacterial agent, it will be necessary to continue to identify additional new agents in the future.