Recent advances in the development of β-lactamase inhibitors

J Microbiol. 2020 Aug;58(8):633-647. doi: 10.1007/s12275-020-0285-z. Epub 2020 Jul 27.

Abstract

β-Lactam antibiotics are the most commonly prescribed antibiotics worldwide; however, antimicrobial resistance (AMR) is a global challenge. The β-lactam resistance in Gram-negative bacteria is due to the production of β-lactamases, including extended-spectrum β-lactamases, metallo-β-lactamases, and carbapenem-hydrolyzing class D β-lactamases. To restore the efficacy of BLAs, the most successful strategy is to use them in combination with β-lactamase inhibitors (BLI). Here we review the medically relevant β-lactamase families and penicillins, diazabicyclooctanes, boronic acids, and novel chemical scaffold-based BLIs, in particular approved and under clinical development.

Keywords: anti microbial resistance (AMR); boronic acids; diazabicyclooctanes (DBO); serine-β-lactamase, metallo-β-lactamases (MBL); β-lactamase inhibitors.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / genetics
  • Carbapenems / therapeutic use
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / genetics*
  • Humans
  • Penicillins / therapeutic use
  • beta-Lactam Resistance / genetics*
  • beta-Lactamase Inhibitors / therapeutic use*
  • beta-Lactamases / genetics*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • Penicillins
  • beta-Lactamase Inhibitors
  • beta-Lactamases
  • carbapenemase