Meropenem-ANT3310, a unique β-lactam-β-lactamase inhibitor combination with expanded antibacterial spectrum against Gram-negative pathogens including carbapenem-resistant .

ANT3310 is a novel broad-spectrum diazabicyclooctane serine β-lactamase inhibitor being developed in combination with meropenem (MEM) for the treatment of serious infections in hospitalized patients where carbapenem-resistant Gram-negative pathogens are expected. In this study, we evaluated the antibacterial activity of MEM in the presence of ANT3310 at 8 µg/mL against global clinical isolates that included ( = 905), carbapenem-resistant Enterobacterales (CRE), carrying either oxacillinase (OXA) ( = 252) or carbapenemase (KPC) ( = 180) carbapenemases, and ( = 502). MEM was poorly active against as were MEM-vaborbactam, ceftazidime-avibactam, aztreonam-avibactam, cefepime-taniborbactam, cefepime-zidebactam, and imipenem-relebactam (MIC values of ≥32 µg/mL). On the other hand, MEM-ANT3310 displayed an MIC value of 4 µg/mL, similar to that observed with sulbactam-durlobactam, a drug developed to specifically treat infections. ANT3310 (8 µg/mL) additionally restored the activity of MEM against OXA- and KPC-producing CREs decreasing MEM MIC values from >32 µg/mL to 0.25 and 0.5 µg/mL, respectively. The combination of 8 µg/mL of both MEM and ANT3310 prevented growth of 97.5% of and 100% of OXA- and KPC-positive CREs, with ~90% of isolates also displaying MEM MICs ≤8 µg/mL. Furthermore, MEM-ANT3310 was efficacious in both thigh and lung murine infection models with OXA-23 . This study demonstrates the potent activity of the MEM-ANT3310 combination against both carbapenem-resistant and Enterobacterales clinical isolates, a key differentiator to other β-lactam/β-lactamase combinations.