Cefiderocol: a novel siderophore cephalosporin

Expert Opin Investig Drugs. 2018 Feb;27(2):193-197. doi: 10.1080/13543784.2018.1426745. Epub 2018 Jan 24.

Abstract

Introduction: The emergence of multidrug-resistant bacterial pathogens has led to a global public health emergency and novel therapeutic options and drug-delivery systems are urgently needed. Cefiderocol is a siderophore cephalosporin antibiotic that has recently been developed to combat a variety of bacterial pathogens, including β-lactam- and carbapenem-resistant organisms.

Areas covered: This paper provides an overview of the mutational and plasmid-mediated mechanisms of β-lactam and carbapenem resistance, the biochemical pathways of siderophores in bacterial iron metabolism, and how cefiderocol may be able to provide better targeted antimicrobial therapy that escape these drug-resistant mechanisms. We also explore the pharmacokinetics of this new compound as well as results from preclinical and clinical studies.

Expert opinion: There is an urgent need for novel antimicrobial agents to address the emergence of multidrug-resistant pathogens, which are an increasing cause of morbidity and mortality worldwide. Our understanding of multidrug-resistance and bacterial biochemical pathways continues to expand, and the development of cefiderocol specifically targeting siderophore-mediated iron transport shows potential in escaping mechanisms of drug resistance. Cefiderocol, which demonstrates a favorable side effect profile, has the potential to become first-line therapy for our most aggressive and lethal multidrug-resistant Gram-negative pathogens.

Keywords: Gram negative; Siderophore; carbapenemase; resistance; urinary tract infection.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacology*
  • Cefiderocol
  • Cephalosporins / administration & dosage
  • Cephalosporins / adverse effects
  • Cephalosporins / pharmacology*
  • Drug Delivery Systems
  • Drug Design
  • Drug Resistance, Multiple, Bacterial
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Siderophores / administration & dosage
  • Siderophores / adverse effects
  • Siderophores / pharmacology

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Siderophores