An Overview of Cefiderocol's Therapeutic Potential and Underlying Resistance Mechanisms

• Published in: Life (Basel, Switzerland) Vol. 13; no. 7; p. 1427
• Main Authors: Domingues, Sara, Lima, Tiago, Saavedra, Maria José, Da Silva, Gabriela Jorge
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.06.2023; MDPI
• Subjects: Antibacterial activity; Antibiotics; Antimicrobial resistance; Bacteria; Bacterial infections; carbapenem-resistant; cefiderocol antibacterial activity; cefiderocol resistance; cephalosporin; Cephalosporins; Clinical medicine; Dithiothreitol; Drug resistance; Drug resistance in microorganisms; Drug therapy; Gram-negative bacteria; Gram-positive bacteria; healthcare infections; Mortality; Nosocomial infections; Pathogens; Patients; Pharmaceutical research; Pneumonia; Review; Siderophores; Staphylococcus infections; Urinary tract diseases; Urinary tract infections; Urogenital system; Ventilators; Portugal; healthcare infections; cefiderocol antibacterial activity; antimicrobial resistance; cefiderocol resistance; carbapenem-resistant; iron transporter; ESKAPE; cephalosporin; siderophore
• ISSN: 2075-1729; 2075-1729
• DOI: 10.3390/life13071427

Antimicrobial resistance continues to increase globally and treatment of difficult-to-treat (DTT) infections, mostly associated with carbapenem-resistant (CR) , CR , and CR- and third-generation-cephalosporins-resistant remains a challenge for the clinician. The recent approval of cefiderocol has broaden the armamentarium for the treatment of patients with DTT infections. Cefiderocol is a siderophore cephalosporin that has shown excellent antibacterial activity, in part due to its innovative way of cell permeation. It is relatively stable compared to most commonly found carbapenamases. However, some resistant mechanisms to cefiderocol have already been identified and reduced susceptibility has developed during patient treatment, highlighting that the clinical use of cefiderocol must be rational. In this review, we summarize the current available treatments against the former resistant bacteria, and we revise and discuss the mechanism of action of cefiderocol, underlying the biological function of siderophores, the therapeutic potential of cefiderocol, and the mechanisms of resistance reported so far.