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

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-beta-lactamases, which are molecules able to inactivate most beta-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 beta-lactams even when they produce metallo-beta-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. In the last decades, there was an important paucity of agents for adequately treating infections due to metallo-beta-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-beta-lactams agents, since they could remain an essential last-resort or alternative option in selected cases.