What treatment options are available for a patient with meropenem-resistant Pseudomonas infection?

Treatment of Meropenem-Resistant Pseudomonas aeruginosa

For meropenem-resistant Pseudomonas aeruginosa infections, ceftolozane/tazobactam or ceftazidime/avibactam are the first-line treatment options if the organism is susceptible to these agents. 1

First-Line Novel β-Lactam Agents

The most recent international guidelines strongly recommend novel β-lactam/β-lactamase inhibitor combinations as first-line therapy for difficult-to-treat resistant Pseudomonas (DTR-PA), which includes meropenem-resistant strains 1:

• Ceftolozane/tazobactam: 3 grams IV every 8 hours (infused over 1 hour) for hospital-acquired or ventilator-associated pneumonia; 1.5 grams IV every 8 hours for other infections 1
• Ceftazidime/avibactam: 2.5 grams IV every 8 hours 1

These agents have demonstrated >90% in vitro activity against MDR/XDR Pseudomonas collections in multiple studies, second only to colistin, but with significantly better safety profiles consistent with the β-lactam class 1. The 2022 Italian guidelines (endorsed by multiple infectious disease societies) provide moderate-certainty evidence supporting these as first-line options 1.

Alternative Treatment Options

If the novel β-lactams above are unavailable or the organism is resistant to them 1:

• Imipenem/cilastatin-relebactam: 1.25 grams IV every 6 hours 1
• Cefiderocol: Consider for metallo-β-lactamase producers (70.8% clinical cure rate in recent trials) 2
• Colistin-based therapy: 5 mg CBA/kg IV loading dose, then 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours 1

Combination Therapy Considerations

Combination therapy should not be routine but may be considered on a case-by-case basis, especially with infectious disease consultation. 1 The 2022 guidelines provide a conditional recommendation (low certainty evidence) for combination therapy in specific scenarios 1:

• Critically ill or septic shock patients 1
• Severe infections with high bacterial burden 1
• Fosfomycin as a companion agent may be particularly useful in combination regimens 1

For colistin-based regimens specifically, the combination of colistin plus an aminoglycoside or tigecycline may be considered for severe infections when other options are unavailable 1. However, avoid colistin-meropenem combinations, as high-quality RCT evidence shows no benefit over colistin monotherapy for carbapenem-resistant organisms 1.

Treatment Duration

Standard duration is 5-14 days depending on infection site 1:

• Complicated urinary tract infections: 5-10 days 1
• Complicated intra-abdominal infections: 5-10 days 1
• Hospital-acquired or ventilator-associated pneumonia: 10-14 days 1
• Bloodstream infections: 10-14 days 1

Critical Pitfalls to Avoid

• Never assume traditional antipseudomonal agents will work: Meropenem-resistant Pseudomonas is by definition resistant to all carbapenems, and often resistant to ceftazidime, cefepime, and piperacillin/tazobactam as well 1
• Do not use colistin-carbapenem combinations: Two large RCTs (AIDA and OVERCOME) demonstrated no benefit of adding meropenem to colistin for carbapenem-resistant organisms 1
• Verify susceptibility testing: Always confirm MIC values for the novel β-lactams, as resistance patterns vary 1
• Obtain infectious disease consultation: This is highly recommended for all multidrug-resistant Pseudomonas infections 1

When Novel Agents Are Not Available

If ceftolozane/tazobactam, ceftazidime/avibactam, and imipenem/relebactam are all unavailable or the organism is resistant 1:

• Colistin monotherapy or combination therapy becomes the primary option 1
• Consider adding fosfomycin to colistin if available 1
• For respiratory infections, adjunctive inhaled colistin (1.25-15 MIU/day in 2-3 divided doses) may be added to systemic therapy 1