Treatment of Multi-Drug Resistant Pseudomonas Infections
For multi-drug resistant Pseudomonas aeruginosa infections, the first-line treatment options are novel β-lactam agents such as ceftolozane/tazobactam and ceftazidime/avibactam, with imipenem/cilastatin/relebactam and colistin-based therapy as alternatives. 1
First-Line Treatment Options
Difficult-to-Treat Resistant Pseudomonas aeruginosa (DTR-PA)
- Ceftolozane/tazobactam 1.5-3g IV q8h (use 3g dose for pneumonia) 1
- Ceftazidime/avibactam 2.5g IV q8h 1, 2
- Imipenem/cilastatin/relebactam 1.25g IV q6h 1
Carbapenem-Resistant Pseudomonas aeruginosa (CRPA) with Susceptibility to Other Agents
- Piperacillin/tazobactam 3.375-4.5g IV q6h 1
- Ceftazidime 2g IV q8h 1
- Cefepime 2g IV q8-12h 1
- Ciprofloxacin 400mg IV q8h 1
- Levofloxacin 750mg IV qd 1
- Amikacin 15mg/kg IV qd (for urinary tract infections only) 1
Combination vs. Monotherapy
- For severe infections with DTR-PA, monotherapy with a highly active agent is generally preferred if susceptibility is confirmed 1
- Combination therapy should not be routine but may be considered on a case-by-case basis, especially upon consultation with infectious disease specialists 1
- Combination regimens including fosfomycin as a companion agent could be considered for difficult cases 1
- For polymyxin-based therapy (colistin), combination with another active agent is suggested for severe infections 1
Treatment Duration
- 5-10 days for complicated urinary tract infections and intra-abdominal infections 1
- 10-14 days for hospital-acquired pneumonia, ventilator-associated pneumonia, and bloodstream infections 1
- Treatment duration should be individualized based on infection site, source control, underlying comorbidities, and initial response to therapy 1
Special Considerations for Specific Infections
Pneumonia
- For CRAB pneumonia: Colistin (5 mg CBA/kg IV loading dose, then 2.5 mg CBA per [1.5 CrCl + 30] IV q12h) with or without carbapenems, plus adjunctive inhaled colistin 1
- For DTR-PA pneumonia: Ceftolozane/tazobactam 3g (2g ceftolozane/1g tazobactam) IV q8h 1
Bloodstream Infections
- For DTR-PA bloodstream infections: Novel β-lactams (ceftolozane/tazobactam or ceftazidime/avibactam) are preferred 1
- For CRAB bloodstream infections: Colistin-carbapenem combination therapy is recommended 1
Emerging Therapies
- Cefiderocol shows promising activity against MDR/XDR P. aeruginosa in early studies 1, 3
- Imipenem/cilastatin/relebactam is an emerging option with activity against many resistant strains 3
Pitfalls and Caveats
- Aminoglycoside monotherapy should only be used for urinary tract infections 1
- Tigecycline monotherapy is not recommended for the treatment of Pseudomonas pneumonia 1
- Resistance to novel agents can emerge during therapy; monitoring of susceptibility patterns is crucial 3
- Infectious disease consultation is highly recommended for management of MDR Pseudomonas infections 1
- Prolonged infusion of β-lactams is recommended for pathogens with high minimum inhibitory concentrations (MICs) 1
- For ceftazidime/avibactam, monitor for neurological adverse reactions including encephalopathy, confusion, hallucinations, and seizures 2
Risk Factors for MDR Pseudomonas Infections
- Prolonged hospitalization 4
- Prior antimicrobial therapy, especially within the previous 90 days 1, 4
- Immunocompromised states 4
- Hospital stay of more than 5 days 1
- Renal replacement therapy 1
- Septic shock or ARDS 1
The concept of "difficult-to-treat resistance" (DTR) in P. aeruginosa refers to isolates non-susceptible to all first-line, high-efficacy, low-toxicity agents (ceftazidime, cefepime, piperacillin/tazobactam, aztreonam, imipenem/cilastatin, meropenem, levofloxacin, and ciprofloxacin) 1. This definition helps better identify strains of public health concern compared to the traditional MDR and XDR categories 1.