Treatment of severe infections due to metallo-β-lactamases-producing Gram-negative bacteria

In the last decades, there was an important paucity of agents for adequately treating infections due to metallo-β-lactamases-producing Gram-negative bacteria (MBL-GNB). Cefiderocol, a novel siderophore cephalosporin showing in vitro activity against MBL-GNB, has been recently marketed, and a combination of aztreonam and ceftazidime/avibactam has shown a possible favorable effect on survival of patients with severe MBL-GNB infections in observational studies. Other agents showing in vitro activity against MBL-GNB are currently in clinical development (e.g., cefepime/taniborbactam, LYS228, cefepime/zidebactam) that could be an important addition to our future armamentarium for severe MBL-GNB infections. Nonetheless, we should not discontinue our efforts to optimize the use of non-β-lactams agents, since they could remain an essential last-resort or alternative option in selected cases. Lay abstract Gram-negative bacteria (GNB) are microorganisms that can cause severe infections and may be difficult to treat when they are resistant to commonly used antibiotics. For example, some GNB produce metallo-β-lactamases, which are molecules able to inactivate most β-lactams, a widely used class of antibiotics. Recently, some novel agents or strategies have become available that may allow to treat again infections due to GNB with β-lactams even when they produce metallo-β-lactamases. If confirmed in dedicated studies, these novel agents may help improving survival of patients who develop infection caused by such difficult-to-treat organisms. As for already existing antibiotics, also these (and future) novel agents should be used according to precise medical indications.