Exploring the activity of a novel orally bioavailable β-lactam-β-lactamase inhibitor combination, ceftibuten-ledaborbactam, against Enterobacterales-carrying blaOXA-48.

Ledaborbactam is a novel boronic-acid inhibitor of class A, C, and D β-lactamases, including OXA-48, being developed in combination with ceftibuten. Herein, we examined the in vitro activity of this combination vs. other orally bioavailable compounds against 50 Enterobacterales-carrying blaOXA-48. Ranked by MIC90, ceftibuten-ledaborbactam was the most active (0.5 mg/L), followed by levofloxacin and tebipenem (8 mg/L), sulopenem (16 mg/L), and ceftibuten-clavulanic acid, ceftibuten and amoxicillin-clavulanic acid (≥32 mg/L).IMPORTANCECarbapenemase-producing Enterobacterales (CPE) that produce class D OXA-48-like carbapenemases are among the most challenging pathogens to treat. Therefore, new compounds with in vitro activity against these bacteria are crucial due to the limited options available. In this study, we compared the in vitro antimicrobial activity of ceftibuten-ledaborbactam with that of other oral antibiotics, including tebipenem, sulopenem, ceftibuten-clavulanic acid, amoxicillin-clavulanic acid, and levofloxacin, against OXA-48-producing Enterobacterales. Our results show that ceftibuten-ledaborbactam has the most potent activity, with an MIC90 of 0.5 mg/L.