Siderophorecephalosporin

Siderophorecephalosporin, or siderophore cephalosporin, is a class of beta-lactam antibiotics in which a cephalosporin core is linked to a siderophore moiety. The siderophore binds ferric iron and hijacks bacterial iron transport systems, enabling active uptake of the antibiotic into Gram-negative bacteria.

Cefiderocol is a prominent member. It uses a catechol-type siderophore to chelate Fe3+ and gain entry via iron transport receptors. Inside, the cephalosporin portion inhibits penicillin-binding proteins and shows stability to many beta-lactamases, including many carbapenemases.

Activity is mainly against Gram-negative organisms, including ESBL and resistant strains; activity against Gram-positives is limited. Notable targets include Pseudomonas aeruginosa and Acinetobacter species, with efficacy influenced by the expression of iron-uptake systems.

Administration is intravenous; renal excretion requires dose adjustment in renal impairment. Pharmacokinetics are influenced by iron availability and transporter activity.

Resistance can arise from loss or alteration of siderophore receptors, changes in iron transport, or enhanced beta-lactamase production. Clinically, siderophorecephalosporins have been approved for complicated urinary tract infections and certain nosocomial pneumonias in several countries.

Safety considerations include hypersensitivity and gastrointestinal effects, as with many beta-lactam antibiotics. Cefiderocol remains the best-known example and serves as a reference point for the therapeutic potential of the siderophore delivery strategy.