Investigational Antibiotic Shows Broad Activity Against Resistant Gram-Negative Pathogens

A novel antibiotic that targets penicillin-binding proteins (PBPs) without relying on a β-lactam scaffold demonstrated broad in-vitro activity, bactericidal effects, low resistance selection, and encouraging in-vivo efficacy across preclinical studies presented at the inaugural Interdisciplinary Meeting on Antimicrobial Resistance and Innovation (IMARI), in Las Vegas.

A distinct structure

Karen Bush, PhD, a leading authority on β-lactamases, presented data examining FPI-2119’s bactericidal activity and its low propensity to select for resistance in Enterobacterales. Although FPI-2119 targets PBPs, it is structurally distinct from β-lactam antibiotics — a feature that may help it avoid some resistance pathways that undermine existing agents.

We looked at four different persisters, and all of them had essentially the same β-lactamase activity as the wild type. So we’re not selecting for overproduced β-lactamases.Karen Bush, PhD

A clean dose-response

In-vivo data presented by Lynn Miesel, PhD, of Pharmacology Discovery Services, showed FPI-2119 translated its potency into activity in animal models. In a Klebsiella pneumoniae bacteremia model, a single intravenous dose produced dose-responsive reductions across heart, lung, and kidney tissue.

At 40 mg per kg, we saw bacteriostasis. And at 160 mg per kg, there was a two-log kill.Lynn Miesel, PhD

Activity in MDR pathogens

Sameeh Salama, PhD, chief scientific officer at Fedora, reported potent in-vitro activity against carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacterales harboring multiple β-lactamase classes — with activity retained against colistin- and cefiderocol-resistant isolates. Mechanistic studies from St. Jude Children’s Research Hospital showed FPI-2119 binds multiple essential PBPs, supporting a multi-target mechanism.

Adapted from coverage in Infectious Disease Special Edition. The research was supported by Fedora.