2024 IDSA Carbapenem-Resistant Enterobacterales(CRE)治療策略

1. Characteristics of CRE

• Definition: Resistance to at least one carbapenem (ertapenem, meropenem, imipenem, or doripenem) or the presence of carbapenemase enzymes.
• Mechanisms of Resistance:
  1. Non-carbapenemase-producing: Outer membrane porin loss combined with overproduction of non-carbapenemase β-lactamases.
  2. Carbapenemase-producing: Enzymes include:
     • KPC (most common in the U.S.).
     • Metallo-β-lactamases (NDM, VIM, IMP).
     • Oxacillinase (OXA-48-like).
• Epidemiology:
  • Carbapenemase-producing CRE accounts for 35-83% of cases.
  • blaKPC predominates but blaNDM and OXA-48-like are increasing.

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2. Treatment Recommendations for CRE Infections

2.1. Uncomplicated Cystitis

• Preferred agents:
  • Nitrofurantoin.
  • TMP-SMX.
  • Ciprofloxacin or levofloxacin.
• Alternative agents:
  • Single-dose aminoglycosides (e.g., plazomicin preferred).
  • Oral fosfomycin (E. coli only).
  • Colistin (limited to CRE cystitis, avoid in other infections).
  • Ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, or cefiderocol.

2.2. Pyelonephritis or Complicated UTI (cUTI)

• Preferred agents:
  • TMP-SMX.
  • Ciprofloxacin or levofloxacin (if susceptible).
  • Ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, cefiderocol.
• Alternative agents:
  • Aminoglycosides (plazomicin preferred).
• Not recommended:
  • Fosfomycin (limited renal parenchymal concentration).

2.3. Non-Carbapenemase-Producing CRE

• Preferred agents:
  • If meropenem/imipenem susceptible: Extended-infusion meropenem or imipenem.
  • If no carbapenem susceptibility: Ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam.
• Not recommended:
  • Polymyxins (except colistin for uncomplicated cystitis).

2.4. KPC-Producing CRE

• Preferred agents:
  • Meropenem-vaborbactam (first-line).
  • Ceftazidime-avibactam.
  • Imipenem-cilastatin-relebactam.
• Alternative agent:
  • Cefiderocol.
• Considerations:
  • Slightly higher resistance emergence with ceftazidime-avibactam compared to meropenem-vaborbactam.

2.5. MBL-Producing CRE (e.g., NDM, VIM, IMP)

• Preferred agents:
  • Ceftazidime-avibactam plus aztreonam.
  • Cefiderocol.
• Alternative options:
  • Aztreonam in combination with other agents (if ceftazidime-avibactam unavailable).

2.6. OXA-48-Like-Producing CRE

• Preferred agent:
  • Ceftazidime-avibactam.
• Alternative agent:
  • Cefiderocol.

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3. Special Considerations

3.1. Resistance Concerns

• Resistance emergence is a concern for all β-lactam agents:
  • Highest risk with ceftazidime-avibactam (~10-20%).
  • Resistance mechanisms include KPC mutations, porin loss, and efflux pump changes.

3.2. Role of Tetracycline Derivatives

• Agents: Tigecycline, eravacycline (not for bloodstream or urinary infections).
• Alternative uses:
  • Intra-abdominal, skin, soft tissue, or respiratory infections.
• Dosing: High-dose regimens recommended for tigecycline.

3.3. Role of Polymyxins

• Not recommended:
  • Systemic infections due to nephrotoxicity and poor outcomes.
• Exception:
  • Colistin for uncomplicated cystitis.

3.4. Role of Combination Therapy

• Not recommended:
  • Once susceptibility to a single β-lactam agent is confirmed, combination therapy offers no additional benefit and increases toxicity risk.