Meropenem/Vaborbactam, the First Carbapenem/β-Lactamase Inhibitor Combination

Abstract

M/V has a valuable role in the treatment of CRE and should be used judiciously to preserve its use for resistant infections.

19F NMR Monitoring of Reversible Protein Post‐Translational Modifications: Class D β‐Lactamase Carbamylation and Inhibition

“…We appliedt he method to monitort he binding interactions between OXA-48a nd the latest generation of SBL inhibitors, including avibactam andvaborbactam. [3,4] Our resultss how that 19 FNMR may be generally applicable for the study of carbamylation in other proteins.Due to the drawbacks encounteredw hile using protein-observe 13 CNMR to monitor the carbamylations tate of class D Figure 1. Carbapenemase mechanism anddetection of carbamylation with 19 FNMR.…”

“…We appliedt he method to monitort he binding interactions between OXA-48a nd the latest generation of SBL inhibitors, including avibactam andvaborbactam. [3,4] Our resultss how that 19 FNMR may be generally applicable for the study of carbamylation in other proteins.…”

“…We report the application of 19 F NMR spectroscopy to investigate carbamylation of the class D SBL OXA‐48, a major clinical cause of carbapenem resistance. We applied the method to monitor the binding interactions between OXA‐48 and the latest generation of SBL inhibitors, including avibactam and vaborbactam . Our results show that 19 F NMR may be generally applicable for the study of carbamylation in other proteins.…”

“…Cyclic boronates are currently of considerable interest as inhibitors of SBLs, metallo‐β‐lactamases (MBLs), and possibly of penicillin‐binding proteins (PBPs; the bacterial target of the β‐lactam antibiotics) (Figure B) Vaborbactam (formerly RPX‐7009), a (predominantly) monocyclic boronate β‐lactamase inhibitor, was recently FDA approved for use in combination with the carbapenem meropenem . Boronates form covalent complexes with SBLs in which the nucleophilic serine is bonded to the tetrahedral boron, mimicking the tetrahedral complex formed during β‐lactamase catalysis …”

“…RPX-7009), a( predominantly) monocyclic boronate b-lactamase inhibitor, was recently FDA approved for use in combination with the carbapenem meropenem. [4] Boronates form covalent complexes with SBLs in which the nucleophilic serine is bondedt ot he tetrahedral boron, mimicking the tetrahedral complexf ormed during b-lactamase catalysis. [13,15] Following addition of vaborbactam to OXA-48 T213C*, a new 19 Fs ignal appeared, assigned as correspondingt of ormation of the boronate-enzyme complex (Figure 3B,3C).…”