Journal
EXPERT OPINION ON INVESTIGATIONAL DRUGS
Volume 27, Issue 2, Pages 193-197Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/13543784.2018.1426745
Keywords
Siderophore; carbapenemase; resistance; Gram negative; urinary tract infection
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Funding
- Shionogi
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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 beta-lactam- and carbapenem-resistant organisms. Areas covered: This paper provides an overview of the mutational and plasmid-mediated mechanisms of beta-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.
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