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
- 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 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
