What is the treatment for Multi-Drug Resistant (MDR) Carbapenem-Resistant Acinetobacter baumannii (CRAB) infections?

Treatment of Multi-Drug Resistant Carbapenem-Resistant Acinetobacter baumannii (CRAB) Infections

For CRAB infections, combination therapy with colistin (polymyxin E) plus carbapenem is recommended as the primary treatment strategy, especially for severe infections such as bloodstream infections and pneumonia. 1

First-Line Treatment Options

For CRAB Pneumonia:

• Colistin with or without carbapenems, plus adjunctive inhaled colistin therapy 1
• Avoid tigecycline monotherapy (strong recommendation) 1
• For CRAB susceptible to sulbactam: ampicillin-sulbactam (conditional recommendation) 1

For CRAB Bloodstream Infections:

• Colistin-carbapenem based combination therapy 1
• For severe infections: combination of two in vitro active antibiotics (polymyxin, aminoglycoside, tigecycline, sulbactam combinations) 1

For CRAB with Lower MIC to Carbapenems:

• For CRAB with meropenem MIC ≤8 mg/L: consider high-dose extended-infusion carbapenem as part of combination therapy 1
• Prolonged infusion of β-lactams is recommended for pathogens with high MICs 1

Treatment Algorithm

1. Obtain antimicrobial susceptibility testing - Essential for guiding definitive therapy 1

2. Consult infectious disease specialist - Strongly recommended for management of CRAB infections 1

3. Select treatment based on infection site and severity:

   • Severe infections/BSI/Pneumonia: Combination therapy with two in vitro active agents
   • Non-severe infections: Consider monotherapy with the most active in vitro agent

4. For sulbactam-susceptible CRAB:

   • Use ampicillin-sulbactam as preferred agent 1

5. For sulbactam-resistant CRAB:

   • Use polymyxin (colistin) or high-dose tigecycline if active in vitro 1
   • Consider combination with carbapenem for synergistic effect 1

6. For pan-resistant CRAB:

   • Treatment with least resistant antibiotic(s) based on MICs relative to breakpoints 1

Specific Antimicrobial Options

Colistin (Polymyxin E):

• Dosing: 5 mg CBA/kg IV loading dose, followed by 2.5 mg CBA maintenance dose 2
• Most active agent against CRAB (97% susceptibility) 3
• Significant nephrotoxicity risk - monitor renal function closely 2

Tigecycline:

• Dosing: 100 mg IV loading dose, then 50 mg IV q12h 1
• Second most active agent against CRAB (88% susceptibility by FDA breakpoints) 3
• Not recommended as monotherapy for pneumonia or bloodstream infections 2
• Hepatotoxicity risk - monitor liver function 4

Ampicillin-Sulbactam:

• For sulbactam-susceptible CRAB
• High-dose regimen recommended for serious infections 5
• Sulbactam-containing regimens associated with reduced 28-day mortality 4

Minocycline:

• Good in vitro activity (66% susceptibility) 3
• Associated with best microbiological responses at 7 days, 28 days, and end of treatment 4

Important Clinical Considerations

• Mortality rates up to 86.1% have been reported in CRAB-infected patients receiving inappropriate empirical antimicrobial therapy 1

• Combination therapy is superior to monotherapy for severe CRAB infections:

  • Colistin monotherapy significantly associated with increased 7-day and 28-day mortality 4
  • Colistin-carbapenem combination significantly reduced 7-day mortality 4
  • Sulbactam-containing regimens significantly reduced 28-day mortality 4

• Antimicrobial synergism between imipenem and combined agents may not be present among CRAB isolates with imipenem MIC ≥32 mg/L 3

• Avoid cefiderocol for CRAB infections (conditional recommendation against) 1

• Strongly avoid polymyxin-meropenem or polymyxin-rifampin combination therapy for CRAB infections 1

Treatment Duration

Based on infection type:

• Complicated urinary tract infections: 5-10 days
• Complicated intra-abdominal infections: 5-10 days
• Ventilator-associated or hospital-acquired pneumonia: 10-14 days
• Bloodstream infections: 10-14 days 2

Monitoring and Adverse Effects

• Monitor renal function closely when using colistin due to significant nephrotoxicity risk
• Monitor liver function when using tigecycline due to hepatotoxicity risk 4
• For combination therapy, monitor for cumulative toxicity of multiple agents