What is the recommended treatment for Carbapenem-Resistant Acinetobacter baumannii (CRAB) using Ceftazidime (Ceftazidime) + Avibactam (Avibactam)?

Ceftazidime-Avibactam Is Not Recommended for CRAB Infections

Ceftazidime-avibactam is not recommended for the treatment of Carbapenem-Resistant Acinetobacter baumannii (CRAB) infections, as current guidelines recommend colistin-based combination therapy as the primary treatment approach. 1

Current Treatment Recommendations for CRAB

CRAB Pneumonia

• Colistin with or without carbapenems, plus adjunctive inhaled colistin therapy is recommended (Weak recommendation, low quality of evidence) 1
• Tigecycline monotherapy is specifically not recommended (Strong recommendation, low quality of evidence) 1

CRAB Bloodstream Infections

• Colistin-carbapenem based combination therapy is recommended (Weak recommendation, low quality of evidence) 1
• Both tigecycline-based and polymyxin-based combination therapies are considered equally preferable, with the choice depending on patient condition 1

Why Ceftazidime-Avibactam Is Not Effective for CRAB

Recent in vitro evaluation shows that CRAB is resistant to ceftazidime-avibactam with MIC values of 32/4 mg/L 2. While increasing avibactam concentrations can reduce ceftazidime MIC in laboratory settings, the concentrations required exceed what is clinically achievable, particularly in epithelial lining fluid 2.

The key reasons ceftazidime-avibactam is not recommended for CRAB include:

1. Lack of clinical evidence supporting its efficacy against CRAB
2. In vitro resistance of CRAB to ceftazidime-avibactam at standard dosing
3. Established guidelines recommending alternative regimens

Important Distinction: CRAB vs. CRE

It's crucial to distinguish between CRAB and Carbapenem-Resistant Enterobacterales (CRE):

• For CRE infections: Ceftazidime-avibactam 2.5g IV q8h is recommended for:

  • CRE bloodstream infections (Weak recommendation, low quality evidence) 1
  • Complicated urinary tract infections caused by CRE (Weak recommendation, very low quality evidence) 1
  • Complicated intra-abdominal infections caused by CRE when combined with metronidazole (Weak recommendation, very low quality evidence) 1

• For CRE with metallo-β-lactamases: Ceftazidime-avibactam combined with aztreonam shows synergy and is associated with lower mortality rates 1, 3

Recommended Treatment Approach for CRAB

Based on current guidelines, the treatment algorithm for CRAB should be:

1. First-line therapy: Colistin-based combination therapy

   • For pneumonia: Colistin ± carbapenems + adjunctive inhaled colistin 1
   • For bloodstream infections: Colistin + carbapenem 1

2. Alternative options:

   • Tigecycline-based combination therapy (except as monotherapy for pneumonia) 1
   • Consider MIC values before initiating tigecycline (better outcomes when MIC ≤2 mg/L) 1

3. Special considerations:

   • Use polymyxins cautiously in patients with renal insufficiency 1
   • Use tigecycline cautiously in patients with liver insufficiency 1

Clinical Pearls and Pitfalls

• Pitfall: Confusing treatment recommendations for CRAB with those for CRE

  • While ceftazidime-avibactam is effective against many CRE infections, it lacks activity against CRAB

• Pitfall: Relying on standard susceptibility testing alone

  • Antimicrobial susceptibility testing or genotypic characterization of resistance should guide selection of antimicrobial agents 1

• Pearl: Combination therapy is generally preferred over monotherapy for CRAB infections to reduce the risk of treatment failure and emergence of resistance 1

• Pearl: Infectious disease consultation is highly recommended for management of infections caused by multidrug-resistant organisms 1