A New Hope Against Antimicrobial-Resistance Wars: Cefiderocol

The increasing diffusion of antimicrobial resistance represents one of the major public health problems worldwide. In the last years, novel antimicrobial molecules have been developed to contrast the emergence of antimicrobial resistance and to provide a valuable therapeutic options against multi drug-resistant (MDR) GNB microorganisms. A new siderophore cephalosporin, Cefiderocol, represents a novel valuable antimicrobial drug for the treatment of infections caused by MDR-GNB. The mechanism of cefiderocol to penetrate trough the outer membrane of bacterial cell with a particular mechanism defined at “Trojan horse” render this molecule unique and immune against the different strategies adopted by GNB to counteract the activity of antimicrobial molecules. The broad spectrum of activity against different GNB species, the potent antibacterial activity, the pharmacokinetics properties, safety, and tolerability render cefiderocol a fundamental drug for the treatment of infections due MDR strains. Although this novel antimicrobial molecule has revolutionized the therapeutic antimicrobial armamentarium against MDR-GNB, the recent emergence of cefiderocol resistant strains have redefined its role in clinical practice and requested novel strategies to preserve its antibacterial activity. In this review, we discuss the mechanism of action of Cefiderocol, emerging resistance mechanisms, pharmacokinetic/pharmacodynamic (PK/PD) properties, efficacy data against the main Gram-negative bacteria, and future prospectives.