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

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Papp-Wallace KM, McLeod SM, Miller AA

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

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

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37125470 [ View in PubMed
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Abstract

Sulbactam-durlobactam is a pathogen-targeted beta-lactam/beta-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 beta-lactamase inhibitors with broad-spectrum serine beta-lactamase activity. Sulbactam is a first-generation, narrow-spectrum beta-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 beta-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.

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