Cefiderocol

How it works

It binds ferric iron and is actively transported into the bacterial periplasm via iron-uptake systems (a Trojan-horse mechanism), then inhibits cell-wall synthesis by binding penicillin-binding proteins; this entry route and its stability confer activity against many carbapenemase-producing organisms.

Prescribing in practice

• Reserve for confirmed or strongly suspected multidrug-resistant Gram-negative infection with limited options, used under specialist microbiology advice, as some trial data showed higher mortality in certain critically ill subgroups.
• Contraindicated in patients with hypersensitivity to cefiderocol or other cephalosporins, with caution in broader beta-lactam allergy.
• Renally cleared, so dose adjustment is required across the range of renal function, including augmented renal clearance.

Monitoring

Monitor renal function, clinical and microbiological response, and consider susceptibility testing as activity is organism-specific.

Counselling the patient

• This is a last-line hospital antibiotic for highly resistant infections.
• Report any rash, diarrhoea, or breathing difficulty to the team.

Evidence & guidelines

The APEKS-NP and CREDIBLE-CR trials informed its use against carbapenem-resistant Gram-negative infections, the latter prompting caution in some critically ill patients.