Ceftolozane-tazobactam

Background

• Novel antipseudomonal antibiotic

Mechanism of Action

• Structure is similar to ceftazidime, but with C3 substitution
• Ceftolozane is stable against AmpC β-lactamases and is somewhat resistant to efflux pumps and
• Tazobactam is active against most class A and some class C β-lactamases
• Bactericidal

Acitivity

• GNB:
  • MDRPsA with less affinity for pseudomonal AmpC and less affected by efflux and porins
  • Enterobacterales, including many ESBLs
    • Activity against AmpC organisms is variable (50% for Enterobacter vs 97% for Escherichia coli)
  • Not active against carbapenemase-producing organisms
  • Limited activity against Oxa-48
  • Limited activity against Acinetobacter species and Stenotrophomonas maltophilia
• GPC: possibly active against Strep pneumo and pyogenes, but none against Staph and Enterococcus
• Variable against anaerobes

Pharmacokinetics and Pharmacodynamics

• Half-life about 2.5 hours
• Protein binding 20%
• Good penetration into lung
• Renally cleared
• No significant drug-drug interactions

Dosing

• Urinary tract and intraabdominal infection: ceftolozane-tazobactam 1.5 g (1 g / 0.5 g) IV q8h
• Pneumonia: ceftolozane-tazobactam 3 g IV q8h
• Multi-drug-resistant Pseudomonas aeruginosa:
  • Cystitis: 1.5 g IV q8h infused over 1 h
  • Other infections: 3 g IV q8h infused over 3 hours

Safety

• Adverse events similar to other cephalosporins
• GI effects, Clostridioides difficile, liver enzymes

Evidence

• ASPECT-cIAI: complicated intraabdo infections with metronidazole
  • Solomkin CID 2015;60:1462-1471
  • Compared to meropenem
• ASPECT-cUTI: complicated UTI
  • Wagenlehner Lancet 2015;385:1949-1956
  • Compared to levofloxacin
• ASPECT-NP: nosocomial pneumonia
  • Kolleff Lancet ID 2019;19:1299
  • Compared to meropenem