The role of new β-lactamase inhibitors in gram-negative infections

Purpose of review In recent years, traditional beta-lactams have dramatically reduced their effectiveness against gram-negative bacteria mainly because of their ability to express multiple beta-lactamase or carabapenemases that are not hydrolyzed by the old beta-lactam inhibitors (BLIs) such as clavulanic acid, tazobactam, and sulbactam. New BLIs molecules have been developed to face the need of compounds that are active against multidrug or pandrug resistant gram-negative pathogens. The aim of this review is to summarize the new generation of BLIs and beta-lactams combinations. Recent findings A number of new molecules with activity against Ambler class A (e.g., extended-spectrum beta-lactamases, serine carbapenemases), class C (e.g., AmpC), or class D (e.g., oxacillinase-48) have been recently approved in combination with old beta-lactams for the treatment of multidrug-resistant bacteria, and other agents are under investigation. These new compounds include diazabicyclooctanones non-beta-lactam inhibitors (e.g., avibactam, relebactam, nacubactam) and boronic acid inhibitors (e.g., vaborbactam). Summary Newly approved and investigational new BLIs are expected to offer many advantages for the management of patients with multidrug-resistant gram-negative pathogens. Promising characteristics of new compounds include high activity against multi drug resistance gram-negative bacteria and a favorable safety profile.