Recommended Antibiotics for Carbapenem-Resistant Pseudomonas aeruginosa
For carbapenem-resistant Pseudomonas aeruginosa infections, ceftolozane-tazobactam is the first-line treatment option when active in vitro, with ceftazidime-avibactam as an alternative, particularly for respiratory infections. 1
First-Line Treatment Options
- Ceftolozane-tazobactam should be used as first-line therapy for carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections when susceptibility testing shows activity 1, 2
- Ceftazidime-avibactam is an alternative first-line option, particularly for respiratory infections when ceftolozane-tazobactam resistance is present 1, 2
- Imipenem-relebactam is another viable option for CRPA infections based on susceptibility testing 2
Treatment Based on Resistance Mechanism
For Non-Metallo-β-lactamase (Non-MBL) Producing CRPA:
- Newer β-lactam/β-lactamase inhibitor combinations (ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam) are preferred when susceptible 3, 1
- For severe infections caused by CRPA resistant to carbapenems and quinolones, combination therapy with intravenous amikacin/tobramycin or colistin plus a carbapenem/ceftazidime may be necessary (even with resistance to provide synergy) 3
For Metallo-β-lactamase (MBL) Producing CRPA:
- Cefiderocol may be considered as a treatment option for MBL-producing strains 4, 2
- Colistin-based therapy is an alternative when newer agents are unavailable or when resistance to newer agents is present 4, 5
- Neither ceftazidime-avibactam nor ceftolozane-tazobactam should be used as monotherapy for MBL-producing strains, as these enzymes confer resistance to both drugs 1, 4
Combination Therapy Considerations
- For severe CRPA infections, combination therapy may be considered to prevent resistance development and improve outcomes 1, 4
- For MBL-producing P. aeruginosa, combination of two in vitro active drugs such as polymyxins (colistin), aminoglycosides, or fosfomycin may be beneficial 4
- Colistin-carbapenem combinations have shown high success rates in network meta-analyses for difficult-to-treat resistant strains 4
Dosing Recommendations
- Colistin: Loading dose of 9 MU of colistin methanesulfonate (CMS) followed by 4.5 MU CMS twice daily as maintenance, with dose adjustments based on renal function 4, 5
- Serum levels of aminoglycosides must be monitored closely in patients with cirrhosis to decrease the risk of renal failure 3
- For non-severe or low-risk CRPA infections that show susceptibility to fluoroquinolones, ciprofloxacin 400mg every 8 hours (IV) or levofloxacin 750mg once daily may be considered 6
Important Monitoring and Caveats
- Antibiotic susceptibility testing should always guide treatment selection 6, 7
- Renal function should be closely monitored during colistin and aminoglycoside therapy due to high nephrotoxicity risk 3, 4
- Colistin has a narrow therapeutic window requiring careful monitoring and dosage adjustment 4, 5
- For patients with limited treatment options (co-resistant to carbapenems, aminoglycosides, polymyxins, and tigecycline), synergistic combinations of older agents may represent a last resort option 8
- Local resistance patterns should influence the choice between agents 1
Special Considerations
- For severe infections (sepsis, pneumonia), initial intravenous treatment is necessary with possible switch to oral treatment once clinically stable 6
- Treatment duration should be adjusted according to the site of infection, severity, and underlying patient conditions (generally 5-10 days for urinary tract infections, 10-14 days for pneumonia or sepsis) 6
- In patients with cirrhosis and CRPA infections, the risk of renal failure with nephrotoxic antibiotics must be carefully weighed against the benefits 3