What Gram-negative organisms is cefiderocol effective against?

Organisms Covered by Cefiderocol

Cefiderocol is effective against a broad spectrum of multidrug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. 1

Specific Organisms and Resistance Patterns

Enterobacterales

• Highly active against Enterobacterales (99.8% susceptibility) 2
• Effective against:
  • ESBL-producing strains (TEM, SHV, CTX-M, OXA) 1
  • AmpC-producing strains 1
  • Serine-carbapenemase producers (KPC, OXA-48) 1
  • Metallo-carbapenemase producers (NDM, VIM) 1
  • Carbapenem-resistant Enterobacterales (CRE) with 98.2% susceptibility 2
  • Colistin-resistant E. coli containing mcr-1 1

Non-fermentative Gram-negative Bacilli

• Pseudomonas aeruginosa:

  • 99.6% susceptibility across all isolates 2
  • Active against carbapenem-resistant and multidrug-resistant strains 1
  • Maintains activity against strains with porin channel deletions (OprD) and efflux pump up-regulation 1
  • Effective against isolates with VIM, IMP, and GES resistance mechanisms 1

• Acinetobacter baumannii complex:

  • 97.7% susceptibility 2
  • Active against carbapenem-resistant strains 1
  • Effective against isolates with OXA-23, OXA-24/40, OXA-51, OXA-58, and AmpC resistance mechanisms 1

• Stenotrophomonas maltophilia:

  • 100% susceptibility (CLSI 2021 criteria) 2
  • Active against strains containing metallo-carbapenemase (L1) and serine beta-lactamases (L2) 1

• Other non-fermenters:

  • Shows activity against Burkholderia cepacia 1

Mechanism of Action and Resistance Considerations

Cefiderocol has a unique mechanism of action that contributes to its broad spectrum:

1. Functions as a siderophore that binds to extracellular free iron 1
2. Actively transported across bacterial outer membrane using bacterial siderophore iron uptake mechanism 1
3. Exerts bactericidal action by inhibiting cell wall biosynthesis through binding to penicillin-binding proteins 1

Important Clinical Considerations

• Maintains activity against bacteria resistant to other antibiotics, including those resistant to carbapenems, fluoroquinolones, and aminoglycosides 1
• Particularly valuable for treating infections caused by metallo-β-lactamase (MBL) producing organisms, where options are limited 3
• Clinical cure rates of 75% have been observed in patients with MBL-producing CRE treated with cefiderocol compared to 29% with best available therapy 3

Potential Limitations

• Resistance development frequency ranges from 10^-6 to <10^-8 1
• Some isolates with high MICs (2-256 mcg/mL) have been observed 1
• No clinically relevant activity against most Gram-positive bacteria and anaerobic bacteria 1

Synergy with Other Antimicrobials

In vitro studies show no antagonism between cefiderocol and:

• Amikacin
• Ceftazidime/avibactam
• Ceftolozane/tazobactam
• Ciprofloxacin
• Colistin
• Meropenem
• Other commonly used antibiotics 1

Cefiderocol represents an important therapeutic option for infections caused by multidrug-resistant Gram-negative pathogens, particularly for those with limited treatment alternatives due to extensive resistance patterns.