Ceftolozane-tazobactam

From IDWiki

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
    • Not active against carbapenemase-producing organisms
    • Limited activity against Oxa-48
    • Limited activity against Acinetobacter 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

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