Treatment of Carbapenem-Resistant Acinetobacter baumannii (CRAB) Infections
For patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections, combination therapy with two in vitro active antibiotics is recommended for severe infections, while ampicillin-sulbactam should be used for CRAB susceptible to sulbactam. 1
First-Line Treatment Options
Based on Susceptibility Testing
- For CRAB susceptible to sulbactam and hospital-acquired/ventilator-associated pneumonia (HAP/VAP), ampicillin-sulbactam is recommended as the preferred treatment 1
- For CRAB resistant to sulbactam, a polymyxin (colistin) or high-dose tigecycline can be used if active in vitro 1
- For severe and high-risk CRAB infections, combination therapy including two in vitro active antibiotics among polymyxin, aminoglycoside, tigecycline, and sulbactam combinations is suggested 1
Dosing Recommendations
- Ampicillin-sulbactam: 4-hour infusion of 3g of sulbactam every 8 hours for isolates with MIC ≤8 mg/L 1
- Colistin: Dosing based on weight and renal function (specific dosing should follow institutional protocols) 1
- Tigecycline: 100 mg IV loading dose followed by 50 mg IV every 12 hours 2
Important Recommendations Against Specific Combinations
- Do not use polymyxin-meropenem combination therapy for CRAB infections - this strong recommendation is based on high-quality evidence from randomized controlled trials showing no benefit over polymyxin monotherapy 1
- Do not use polymyxin-rifampin combination therapy - strong recommendation based on moderate quality evidence 1
- Conditionally recommend against cefiderocol for CRAB infections based on low-quality evidence 1
Special Considerations
- For CRAB with meropenem MIC <8 mg/L, carbapenem combination therapy using high-dose extended-infusion carbapenem dosing may be considered 1
- For pan-resistant CRAB (resistant also to polymyxins), treatment with the least resistant antibiotic(s) based on MICs relative to breakpoints is recommended 1
- Colistin monotherapy should be avoided for severe CRAB infections due to increased mortality risk 3
Evidence Quality and Treatment Efficacy
- The highest quality evidence (RCTs) shows no benefit to carbapenem-polymyxin combination therapies for CRAB infections with typical high-level carbapenem resistance (MICs >16 mg/L) 1
- Sulbactam-containing regimens have been associated with reduced 28-day mortality in observational studies 3
- Colistin has excellent in vitro activity against CRAB (93-100% susceptibility in most studies) 4
- Tigecycline remains a good therapeutic option for MDR A. baumannii with approximately 89% susceptibility in some studies 4
Monitoring and Adverse Effects
- Monitor for nephrotoxicity with colistin therapy, which occurs in up to 33% of patients 1
- Monitor for hepatotoxicity with tigecycline therapy 3
- For patients on combination therapy, monitor for development of resistance, particularly with colistin, as heteroresistance has been reported 1, 5
- When treating with colistin, surveillance for continued carriage of CRAB should be conducted 1
Treatment Algorithm
- Obtain appropriate cultures and susceptibility testing
- For HAP/VAP with CRAB susceptible to sulbactam: Use ampicillin-sulbactam
- For severe infections with CRAB resistant to sulbactam:
- Use combination therapy with two in vitro active agents
- Avoid polymyxin-meropenem and polymyxin-rifampin combinations
- Consider colistin plus another active agent (aminoglycoside, tigecycline, sulbactam)
- For CRAB with meropenem MIC <8 mg/L: Consider high-dose extended-infusion carbapenem as part of combination therapy
- For pan-resistant CRAB: Use antibiotics with the lowest MICs relative to breakpoints
This approach prioritizes mortality reduction while considering the limited therapeutic options available for this challenging pathogen 6.