Exploring the activity of a novel orally bioavailable β-lactam-β-lactamase inhibitor combination, ceftibuten-ledaborbactam, against Enterobacterales-carrying <i>bla</i> _OXA-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 <i>in vitro</i> activity of this combination vs. other orally bioavailable compounds against 50 Enterobacterales-carrying <i>bla</i>_OXA-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 <i>in vitro</i> activity against these bacteria are crucial due to the limited options available. In this study, we compared the <i>in vitro</i> 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.