Durlobactam, a Broad-Spectrum Serine β-lactamase Inhibitor, Restores Sulbactam Activity Against Acinetobacter Species

Clin Infect Dis. 2023 May 1;76(Suppl 2):S194-S201. doi: 10.1093/cid/ciad095.

Abstract

Sulbactam-durlobactam is a pathogen-targeted β-lactam/β-lactamase inhibitor combination in late-stage development for the treatment of Acinetobacter infections, including those caused by multidrug-resistant strains. Durlobactam is a member of the diazabicyclooctane class of β-lactamase inhibitors with broad-spectrum serine β-lactamase activity. Sulbactam is a first-generation, narrow-spectrum β-lactamase inhibitor that also has intrinsic antibacterial activity against Acinetobacter spp. due to its ability to inhibit penicillin-binding proteins 1 and 3. The clinical utility of sulbactam for the treatment of contemporary Acinetobacter infections has been eroded over the last decades due to its susceptibility to cleavage by numerous β-lactamases present in this species. However, when combined with durlobactam, the activity of sulbactam is restored against this problematic pathogen. The following summary describes what is known about the molecular drivers of activity and resistance as well as results from surveillance and in vivo efficacy studies for this novel combination.

Keywords: Acinetobacter; diazabicyclooctane; durlobactam; sulbactam; β-lactamase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acinetobacter Infections* / drug therapy
  • Acinetobacter Infections* / microbiology
  • Acinetobacter baumannii*
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Humans
  • Microbial Sensitivity Tests
  • Sulbactam / chemistry
  • Sulbactam / pharmacology
  • Sulbactam / therapeutic use
  • beta-Lactamase Inhibitors / pharmacology
  • beta-Lactamase Inhibitors / therapeutic use
  • beta-Lactamases / metabolism

Substances

  • Sulbactam
  • beta-Lactamase Inhibitors
  • durlobactam
  • Anti-Bacterial Agents
  • beta-Lactamases