Ceftolozane-Tazobactam (Zerbaxa) vs Ceftazidime-Avibactam (Avycaz) for Pseudomonas aeruginosa Infections
For severe infections due to multidrug-resistant Pseudomonas aeruginosa, ceftolozane-tazobactam (Zerbaxa) is suggested as the preferred treatment over ceftazidime-avibactam (Avycaz) based on higher clinical success rates, particularly for respiratory infections. 1, 2
Comparative Effectiveness
- Ceftolozane-tazobactam demonstrates superior clinical success rates (61% vs 52%) compared to ceftazidime-avibactam for invasive multidrug-resistant P. aeruginosa infections 1
- The advantage of ceftolozane-tazobactam is most pronounced in pneumonia cases (63% vs 51% clinical success) 1
- The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) specifically suggests ceftolozane-tazobactam for difficult-to-treat CRPA (carbapenem-resistant Pseudomonas aeruginosa) infections when active in vitro 2
- For bacteremia, both agents show similar efficacy (51% for ceftolozane-tazobactam vs 57% for ceftazidime-avibactam) 1
Treatment Algorithm Based on Infection Type
For Respiratory Infections (Pneumonia):
- First choice: Ceftolozane-tazobactam (adjusted odds ratio for success 2.34 compared to ceftazidime-avibactam) 1
- Alternative: Ceftazidime-avibactam if resistance to ceftolozane-tazobactam is present 2, 3
For Bloodstream Infections:
- Either agent is appropriate as they show comparable efficacy for bacteremia 1
- Consider local resistance patterns and specific susceptibility testing 3
Dosing Considerations
- For ceftolozane-tazobactam: Consider continuous infusion rather than intermittent bolus administration for isolates with MICs ≥4 mg/L to achieve better pharmacodynamic targets 4
- Standard dosing of ceftolozane-tazobactam (2g/1g every 8 hours as 1-hour infusion) may be inadequate for P. aeruginosa strains with MICs ≥4 mg/L 4
- Both agents require dose adjustment in patients with renal impairment 5
Resistance Considerations
- Development of resistance is a concern with both agents (22% for ceftolozane-tazobactam and 23% for ceftazidime-avibactam) 1
- For severe infections, combination therapy may be considered to prevent resistance development 6, 3
- Regular monitoring of susceptibility patterns is essential as resistance patterns can evolve 1
Special Patient Populations
- For immunocompromised patients with severe Pseudomonas infections, combination therapy is strongly recommended regardless of which agent is chosen 6
- In patients with renal impairment, ceftolozane-tazobactam has been used successfully without worsening renal function 5
Important Caveats
- Selection between these agents should ultimately be guided by in vitro susceptibility testing whenever possible 6, 3
- Local resistance patterns should influence the choice between these agents 3
- For non-severe or low-risk CRPA infections, older antibiotics that show in vitro activity may be considered for antibiotic stewardship purposes 2
- Neither agent should be used as monotherapy for metallo-β-lactamase-producing strains, as these enzymes confer resistance to both drugs 2