Pharmacodynamics of the Novel Metallo-β-Lactamase Inhibitor ANT2681 in Combination with Meropenem for the Treatment of Infections Caused by NDM-Producing <i>Enterobacteriaceae</i>
Shampa Das, Adam Johnson, Laura McEntee, Nicola Farrington, Adam Kirby, Jennifer Unsworth, Ana Jimenez‐Valverde, Ruwanthi Kolamunnage‐Dona, Justine Bousquet, Laethitia Alibaud, Carole A. Sable, Magdalena Zalacaín, Martin Everett, William Hope
Abstract
Enterobacteriaceae that produce metallo-β-lactamases (MBLs) are an emerging threat to public health. The metallo-β-lactamase inhibitor (MBLi) ANT2681 inhibits the enzymatic activity of MBLs through interaction with the dinuclear zinc ion cluster present in the active site that is common to these enzymes. ANT2681 is being codeveloped, with meropenem as the partner β-lactam, as a novel combination therapy for infections caused by MBL-producing bacteria. The pharmacokinetics/pharmacodynamics of meropenem-ANT2681 were studied in a murine neutropenic thigh model of NDM-producing Enterobacteriaceae .