Cefiderocol matches best available therapy for carbapenem-resistant Gram-negative infections

  • Bassetti M & al
  • Lancet Infect Dis
  • 13 Oct 2020

  • curated by Liz Scherer
  • Clinical Essentials
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Takeaway

  • Cefiderocol intravenous (IV) infusion is noninferior to best available therapy for carbapenem-resistant Gram-negative infections.
  • Acinetobacter infections are linked to higher mortality rates.
  • Related study.

Why this matters

  • Editorial: cefiderocol could be a salvage option for treating most multidrug-resistant Gram-negative infections, except those caused by metallo-β-lactam-producing Enterobacterales.

Key results

  • Patients: 118 (cefiderocol, 80; best available therapy, 38) in intention-to-treat microbiological population.
  • Pathogens: 46% (54) Acinetobacter baumannii, 33% (39) Klebsiella pneumoniae, 19% (22) Pseudomonas aeruginosa.
  • Clinical cure rates (95% CIs) at test of cure, cefiderocol vs best available therapy:
    • Nosocomial pneumonia:
      • 50% (33.8%-66.2%; n=20/40) vs
      • 53% (28.9%-75.6%; n=10/19). 
    • Bloodstream infection/sepsis:
      • 43% (23.2%-65.5%; n=10/23) vs
      • 43% (17.7%-71.1%; n=6/14).
  • Microbiological eradication at test of cure, cefiderocol vs best available therapy (95% CIs):
    • Complicated UTI:
      • 53% (27.8%-77.0%; n=9/17) vs
      • 20% (0.5%-71.6%; n=1/5).
  • Survival (without therapy change):
    • 63% (50/80) with cefiderocol vs 61% (23/38) with best available therapy.
    • Treatment difference, 1.1% (95% CI, −17.7 to 20.0).
  • All-cause mortality (Acinetobacter spp) infections:
    • Cefiderocol 50% (21/42) vs best available therapy 18% (3/17).

Study design

  • Randomized, multicenter, parallel-group, pathogen-focused, open-label, phase 3 study of hospitalized patients with carbapenem-resistant, Gram-negative infections requiring IV antibiotics.
  • Funding: Shionogi.

Limitations

  • Small sample size.
  • Open label.
  • Confounded composite endpoint.