Innovative Antibiotics: The Experience of Cefiderocol in Carbapenem-Resistant Gram-Negative Infections

Carbapenem-resistant and multidrug-resistant (MDR) Gram-negative infections are rapidly increasing worldwide and represent one of the greatest current challenges in infectious diseases. The introduction of novel beta-lactam agents, including cefiderocol, a siderophore cephalosporin with a unique mechanism of cell entry, has significantly reshaped the therapeutic approach to these difficult-to-treat infections. Six years after its first FDA approval in November 2019, real-world data have provided valuable insights into the use of cefiderocol across diverse clinical scenarios. Overall, evidence confirms its role as an effective therapeutic option able to overcome multiple resistance mechanisms and improve outcomes in infections caused by resistant Gram-negative bacteria, with, however, notable differences among pathogens. Several unsolved issues remain: the emergence of resistance to cefiderocol is an ongoing phenomenon that warrants continuous surveillance; moreover, the benefit of combination therapy over monotherapy remains uncertain, as current real-life data do not demonstrate clear advantages, and randomized controlled trials are lacking. The aim of this review is to provide an updated overview of real-life evidence on cefiderocol, outlining its role, limitations, and future perspectives in the management of carbapenem-resistant and MDR Gram-negative infections.