Durlobactam, a New Diazabicyclooctane beta-Lactamase Inhibitor for the Treatment of Acinetobacter Infections in Combination With Sulbactam.

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Shapiro AB, Moussa SH, McLeod SM, Durand-Reville T, Miller AA

Durlobactam, a New Diazabicyclooctane beta-Lactamase Inhibitor for the Treatment of Acinetobacter Infections in Combination With Sulbactam.

Front Microbiol. 2021 Jul 19;12:709974. doi: 10.3389/fmicb.2021.709974. eCollection 2021.

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34349751 [ View in PubMed
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Abstract

Durlobactam is a new member of the diazabicyclooctane class of beta-lactamase inhibitors with broad spectrum activity against Ambler class A, C, and D serine beta-lactamases. Sulbactam is a first generation beta-lactamase inhibitor with activity limited to a subset of class A enzymes that also has direct-acting antibacterial activity against Acinetobacter spp. The latter feature is due to sulbactam's ability to inhibit certain penicillin-binding proteins, essential enzymes involved in bacterial cell wall synthesis in this pathogen. Because sulbactam is also susceptible to cleavage by numerous beta-lactamases, its clinical utility for the treatment of contemporary Acinetobacter infections is quite limited. However, when combined with durlobactam, the activity of sulbactam is effectively restored against these notoriously multidrug-resistant strains. This sulbactam-durlobactam combination is currently in late-stage development for the treatment of Acinectobacter infections, including those caused by carbapenem-resistant isolates, for which there is a high unmet medical need. The following mini-review summarizes the molecular drivers of efficacy of this combination against this troublesome pathogen, with an emphasis on the biochemical features of each partner.

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