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

Area of Science:

• Infectious Diseases
• Microbiology
• Pharmacology

Background:

• Rising global antimicrobial resistance poses a significant clinical challenge.
• Difficult-to-treat (DTT) infections are often caused by carbapenem-resistant (CR) bacteria like *Pseudomonas aeruginosa* and *Acinetobacter baumannii*, and resistant *Enterobacterales*.
• Limited treatment options exist for these DTT infections.

Purpose of the Study:

• To review current treatments for infections caused by CR *Pseudomonas aeruginosa*, CR *Acinetobacter baumannii*, and CR *Enterobacterales*.
• To discuss the mechanism of action, therapeutic potential, and resistance mechanisms of cefiderocol.
• To highlight the importance of rational clinical use of cefiderocol.

Main Methods:

• Literature review of current treatments for DTT infections.
• Analysis of cefiderocol's mechanism of action, including its siderophore cephalosporin class and cell permeation.
• Review of identified resistance mechanisms to cefiderocol.

Main Results:

• Cefiderocol is a novel siderophore cephalosporin with broad-spectrum activity against many DTT pathogens.
• Its unique mechanism of iron uptake facilitates bacterial cell entry.
• Cefiderocol demonstrates stability against common carbapenemases.
• Emerging resistance mechanisms and reduced susceptibility during treatment have been reported.

Conclusions:

• Cefiderocol expands treatment options for DTT infections.
• Understanding cefiderocol's mechanism and resistance is crucial for effective clinical application.
• Rational use is essential to preserve the efficacy of this important antibiotic.