2024 IDSA MDR/DTR P. aeruginosa治療策略

1. Definitions and Characteristics

• MDR P. aeruginosa: Non-susceptibility to at least one antibiotic in three or more classes, including:
  • Penicillins.
  • Cephalosporins.
  • Fluoroquinolones.
  • Aminoglycosides.
  • Carbapenems.
• DTR P. aeruginosa: Non-susceptibility to all of the following:
  • Piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, meropenem, imipenem-cilastatin, ciprofloxacin, and levofloxacin.
• Resistance Mechanisms:
  • Decreased porin expression (OprD).
  • Upregulated efflux pumps (MexAB-OprM).
  • Pseudomonal AmpC mutations (PDC enzymes).
  • Rare carbapenemases (e.g., blaKPC, blaVIM, blaNDM).

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2. General Treatment Recommendations

2.1. MDR P. aeruginosa

• Preferred approach:
  • Use traditional β-lactams (e.g., piperacillin-tazobactam, ceftazidime, cefepime) if susceptible.
  • Avoid carbapenems unless traditional agents are ineffective.
• Alternative approach:
  • High-dose, extended-infusion traditional β-lactams.
  • Newer β-lactams (ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam) in critically ill patients or those with poor source control.

2.2. DTR P. aeruginosa

• Newer β-lactams:
  • Ceftolozane-tazobactam.
  • Ceftazidime-avibactam.
  • Imipenem-cilastatin-relebactam.
  • Cefiderocol (alternative for metallo-β-lactamase [MBL] producers or if others fail).

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3. Treatment by Infection Type

3.1. Uncomplicated Cystitis

• Preferred agents:
  • Ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam, cefiderocol.
• Alternative agents:
  • Single-dose aminoglycosides (e.g., tobramycin, amikacin).
  • Colistin (with caution due to nephrotoxicity).

3.2. Pyelonephritis or Complicated UTI

• Preferred agents:
  • Same as uncomplicated cystitis.
• Alternative agents:
  • Once-daily aminoglycosides (tobramycin or amikacin).

3.3. Non-Urinary Tract Infections

• Preferred agents:
  • Ceftolozane-tazobactam.
  • Ceftazidime-avibactam.
  • Imipenem-cilastatin-relebactam.
• Alternative agents:
  • Cefiderocol (when others are ineffective or unavailable).

3.4. MBL-Producing P. aeruginosa

• Preferred agent:
  • Cefiderocol.
• Rationale:
  • MBL producers are generally resistant to other β-lactam-β-lactamase inhibitors (e.g., ceftazidime-avibactam).

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4. Additional Considerations

4.1. Resistance Emergence

• Highest risk:
  • Ceftolozane-tazobactam and ceftazidime-avibactam due to PDC mutations.
• Other agents:
  • Imipenem-cilastatin-relebactam and cefiderocol show lower resistance rates but should still be monitored.

4.2. Combination Therapy

• Not recommended:
  • Combination therapy with aminoglycosides or polymyxins offers no clear benefit over monotherapy with newer β-lactams.
• Exceptions:
  • Last-resort scenarios where no β-lactam is effective.

4.3. Nebulized Antibiotics

• Not suggested:
  • No significant clinical benefit observed in trials for gram-negative pneumonia, including P. aeruginosa.

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5. Clinical Monitoring

• Repeat susceptibility testing is essential for:
  • Relapsed infections.
  • Recurrent sepsis-like presentations in patients previously treated for MDR/DTR P. aeruginosa.
• Consider switching to alternative agents (e.g., imipenem-cilastatin-relebactam, cefiderocol) if prior therapies fail or resistance emerges.