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Siderophore Cephalosporin (Pan-Drug Resistant Gram-Negatives) Pregnancy: Avoid — insufficient human data. Beta-lactam class generally preferred over alternatives in pregnancy but cefiderocol has no pregnancy safety data. Use only if no safer alternative available.

Cefiderocol

Brand names: Fetcroja

Adult dose

Dose: 2 g IV every 8 hours infused over 3 hours
Route: Intravenous (3-hour extended infusion)
Frequency: Every 8 hours
Max: 6 g/day
Gram-negative infections including carbapenem-resistant Acinetobacter, Pseudomonas, Enterobacterales (including MBL-producers NDM/VIM/IMP that are NOT covered by ceftazidime-avibactam). Indications: HAP/VAP, bloodstream infections, cUTI due to aerobic Gram-negatives when no other options available. Extended 3-hour infusion mandatory. Source: BNF 90; MHRA SPC Fetcroja; EMA assessment.

Paediatric dose

Dose: Not licensed under 18 years N/A/kg
Route: N/A
Frequency: N/A
Max: N/A
No paediatric licence. Off-label compassionate use in MDR infections in children under specialist ID/microbiology guidance only.

Dose adjustments

Renal

eGFR 30–59 mL/min: 1.5 g every 8h. eGFR 15–29 mL/min: 1 g every 8h. eGFR <15 or haemodialysis: 0.75 g every 8h. Augmented renal clearance (ARC — common in young ICU patients, eGFR >130): increase to 2 g every 6h — underdosing risk with standard dosing in ARC.

Hepatic

No dose adjustment required.

Paediatric weight-based calculator

No paediatric licence. Off-label compassionate use in MDR infections in children under specialist ID/microbiology guidance only.

Clinical pearls

  • Siderophore 'Trojan horse' mechanism: cefiderocol is conjugated to a catecholate siderophore moiety. Gram-negative bacteria actively import iron via siderophore receptors (TonB-dependent transporters) as iron is scarce in tissues. Cefiderocol hijacks this system, bypassing outer membrane resistance. Once inside the periplasm, it inhibits PBP3 — killing the bacterium. Works against all major carbapenem-resistance mechanisms: KPC, NDM, VIM, IMP, OXA-48.
  • MHRA warning — Acinetobacter mortality signal: CREDIBLE-CR trial found higher mortality with cefiderocol vs best available therapy in carbapenem-resistant Acinetobacter baumannii (34% vs 18%). The mechanism is unclear — possibly inadequate comparator in control arm, or Acinetobacter-specific factors. MHRA 2020 warning: use cefiderocol for Acinetobacter infections only when no other options available, with awareness of this signal.
  • APEKS-NP trial (NEJM 2021): cefiderocol non-inferior to meropenem for nosocomial pneumonia caused by Gram-negative pathogens — 12.4% vs 11.6% mortality at day 14. Established cefiderocol as a viable agent in this setting.
  • Pan-drug resistant (PDR) infections — last resort: cefiderocol is a 'last-resort' antibiotic for PDR Gram-negatives where ceftazidime-avibactam, meropenem-vaborbactam, colistin and aminoglycosides have all failed. Prescribe only with ID/microbiology specialist input and after full susceptibility testing.
  • Augmented renal clearance in young ICU patients: patients aged <40 years with preserved cardiac output (often post-trauma, burns) have eGFR >130 mL/min — standard doses of cefiderocol are insufficient. Calculate 24h urine creatinine clearance and adjust dose. PK/PD guided dosing with TDM preferred if available. Source: BNF 90; Wunderink et al. NEJM 2021 (APEKS-NP); MHRA Drug Safety Update 2020; EMA SPC Fetcroja.

Contraindications

  • Hypersensitivity to cephalosporins
  • Iron-deficient states may theoretically reduce efficacy (siderophore mechanism requires iron for cell entry — clinical significance uncertain)

Side effects

  • Diarrhoea, nausea (most common)
  • Elevated liver transaminases
  • Hypokalaemia (reported in trials)
  • Hypersensitivity reactions (beta-lactam class)
  • Clostridioides difficile
  • CREDIBLE-CR trial: cefiderocol had higher all-cause mortality than best available therapy in one subgroup (carbapenem-resistant Acinetobacter — mortality 34% vs 18% — MHRA warning)

Interactions

  • Chloramphenicol: antagonism in vitro — avoid
  • Nephrotoxic agents: monitor renal function closely

Monitoring

  • Cultures and susceptibilities — cefiderocol-specific MIC must be tested (siderophore agar not standard — request specialist laboratory testing)
  • eGFR daily (dose adjustment for every significant change)
  • Clinical response at 48–72h (re-culture if no response)
  • LFTs and renal function
  • Potassium (hypokalaemia monitoring)

Reference: BNFc; BNF 90; Wunderink et al. NEJM 2021 (APEKS-NP); MHRA Drug Safety Update 2020; EMA assessment report Fetcroja. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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