Hdepda: An acyclic adjuvant potentiates meropenem activity in vitro against metallo-β-lactamase-producing enterobacterales.

Metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE) pose an emerging threat to public health worldwide. An effective inhibitor of MBLs is therefore urgently needed for clinical use. In this study, two acyclic pyridine-containing ligands, Hdedpa and compound 8, were discovered with excellent activities when combined with meropenem (MEM) against MBL (bla and bla)-producing clinical isolates, including Escherichia coli, Citrobacter freundii, Proteus mirabilis, Enterobacter cloacae and Klebsiella pneumoniae.

NOTA analogue: A first dithiocarbamate inhibitor of metallo-β-lactamases.

The emergence of antibiotic drug (like carbapenem) resistance is being a global crisis. Among those resistance factors of the β-lactam antibiotics, the metallo-β-lactamases (MBLs) is one of the most important reasons. In this paper, a series of cyclic dithiocarbamate compounds were synthesized and their inhibition activities against MBLs were initially tested combined with meropenem (MEM) by in vitro antibacterial efficacy tests.