Ceftazidime-avibactam

Background

• Brand name Avycaz

Mechanism of Action

• Ceftazidime is a third-generation cephalosporin
• Avibactam
  • Inhibitis class A, C, and some class D beta-lactamases, includign OXA-48
  • No activity against class B
  • Reduces MIC to ceftazidime in most Enterobacterales including Pseudomonas
  • Does not induce AmpC expression
  • Slowly-reversible inhibitor that gets recycled

Spectrum of Activity

• GNBs
  • Active against carbapenem-resistant Enterobaceriaceaea, including KPCs and AmpC beta-lactamases
  • Restores activity with ceftazidime in Pseudomonas and other GNBs
  • Poor activity against Acinetobacter and Stenotrophomonas

Pharmacokinetics and Pharmacodynamics

• Short half-life 2.7 hours
• Low protein binding
• Primarily renally cleared

Dosing

• Ceftazidime-avibactam 2.5 g (2 g / 0.5 g) IV q8h, infused over 3 hours
  • Consider adjunctive aztreonam 2 g IV q8h infused concurrently over 3 hours for metallo-β-lactamase-producing carbapenem-resistant Enterobacterales or Stenotrophomonas maltophilia

Pediatric Dosing

• 3 months to <6 months: ceftazidime 40 mg/kg plus avibactam 10 mg/kg IV q8h, infused over 2 hours
• 6 months to <18 years: ceftazidime 50 mg/kg plus avibactam 12.5 mg/kg IV q8h, infused over 2 hours