What is the treatment for carbapenem-resistant Acinetobacter baumannii infections?

Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections

For carbapenem-resistant Acinetobacter baumannii (CRAB) infections, polymyxins (colistin) are the primary treatment option, with combination therapy recommended for severe infections using two in vitro active agents among polymyxin, sulbactam, tigecycline, or aminoglycosides. 1

First-Line Treatment Options Based on Susceptibility

• For CRAB susceptible to sulbactam, ampicillin-sulbactam is the preferred treatment, especially for hospital-acquired/ventilator-associated pneumonia (HAP/VAP) 1
• For CRAB resistant to sulbactam, a polymyxin (colistin) should be used if the isolate is susceptible in vitro 1, 2
• High-dose tigecycline can be considered if the isolate shows in vitro activity 1, 3
• For severe infections, combination therapy with two active agents is recommended to improve outcomes and prevent resistance development 1, 4

Specific Dosing Recommendations

• Ampicillin-sulbactam: Administer as a 4-hour infusion of 3g sulbactam every 8 hours (9-12g/day total) for isolates with MIC ≤4 mg/L 2, 1
• Colistin: Dosing should be weight-based and adjusted for renal function according to institutional protocols 1, 5
• Tigecycline: Higher than standard dosing may be needed for CRAB infections, though resistance can develop during treatment 3

Combination Therapy Considerations

• Combination therapy is recommended for severe CRAB infections to improve clinical outcomes and prevent resistance 1, 4
• Important combinations to AVOID:
  • Polymyxin-meropenem combination is NOT recommended based on high-quality evidence 1
  • Polymyxin-rifampin combination is NOT recommended 1, 5
  • Colistin plus glycopeptides (vancomycin) is discouraged due to increased nephrotoxicity 2, 1
• Potentially beneficial combinations:
  • Colistin plus carbapenem may reduce 7-day mortality in certain scenarios 4
  • Sulbactam-containing regimens may reduce 28-day mortality 4
  • Minocycline-containing regimens show good microbiological response 4

Special Considerations

• For CRAB with meropenem MIC <8 mg/L, high-dose extended-infusion carbapenem as part of combination therapy may be considered 1
• Colistin monotherapy should be avoided as it's associated with increased mortality and resistance development 4, 5
• The novel combination sulbactam-durlobactam has shown non-inferiority to colistin with significantly lower nephrotoxicity (13% vs 38%) in a recent phase 3 trial 6
• Duration of therapy should be individualized but generally maintained for 2 weeks in severe infections such as VAP or bacteremia 2

Monitoring and Adverse Effects

• Monitor renal function in patients receiving colistin, as nephrotoxicity occurs in up to 33% of patients 2, 6
• Watch for hepatotoxicity in patients receiving tigecycline 4
• Monitor for emergence of resistance during therapy, particularly with colistin, as heteroresistance has been reported 2, 5

Treatment Algorithm

1. Obtain cultures and susceptibility testing before initiating therapy 2
2. Start empiric therapy based on local resistance patterns and patient risk factors 2
3. For confirmed CRAB infection:
   • If susceptible to sulbactam: Use ampicillin-sulbactam (9-12g/day) 2, 1
   • If resistant to sulbactam: Use colistin (with appropriate weight-based dosing) 1
   • For severe infections: Consider combination therapy with two active agents 1, 4
4. Avoid colistin monotherapy due to increased mortality risk 4
5. Continue treatment for approximately 2 weeks for severe infections 2
6. Monitor for clinical response and development of toxicity 2, 6