#PBP3 MUTATION SKIN#
These pathogens cause hospital-acquired or ventilator-associated pneumonia (VAP), bacteremia, complicated urinary tract infections and a variety of skin and tissue infections, in both healthy and immuno-compromised individuals ( Lee et al., 2017). Infections caused by multi-drug resistant (MDR) Acinetobacter species are among the most urgent threats to human health.
#PBP3 MUTATION DRIVERS#
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. 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. However, when combined with durlobactam, the activity of sulbactam is effectively restored against these notoriously multidrug-resistant strains. Because sulbactam is also susceptible to cleavage by numerous β-lactamases, its clinical utility for the treatment of contemporary Acinetobacter infections is quite limited. 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.
Sulbactam is a first generation β-lactamase inhibitor with activity limited to a subset of class A enzymes that also has direct-acting antibacterial activity against Acinetobacter spp. Entasis Therapeutics, Waltham, MA, United Statesĭurlobactam is a new member of the diazabicyclooctane class of β-lactamase inhibitors with broad spectrum activity against Ambler class A, C, and D serine β-lactamases.McLeod, Thomas Durand-Réville and Alita A.
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