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

Krisztina M Papp-Wallace, Sarah M McLeod, Alita A Miller
Author Information
  1. Krisztina M Papp-Wallace: Research Service, Veterans Affairs Northeast Ohio Healthcare System, USA.
  2. Sarah M McLeod: Entasis Therapeutics, Waltham, MA, USA.
  3. Alita A Miller: Entasis Therapeutics, Waltham, MA, USA.

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

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MeSH Term

Humans
Sulbactam
beta-Lactamase Inhibitors
Acinetobacter Infections
Acinetobacter baumannii
Anti-Bacterial Agents
beta-Lactamases
Microbial Sensitivity Tests

Chemicals

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

Word Cloud

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