Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections
For carbapenem-resistant Acinetobacter baumannii (CRAB) infections, the recommended first-line treatment is colistin (polymyxin E) with or without a carbapenem (imipenem/cilastatin or meropenem), with ampicillin-sulbactam as an alternative for sulbactam-susceptible isolates. 1, 2
First-Line Treatment Options
- For CRAB susceptible to sulbactam, ampicillin-sulbactam is the preferred treatment, especially for hospital-acquired/ventilator-associated pneumonia (HAP/VAP) 3, 2
- For CRAB resistant to sulbactam, colistin (polymyxin E) should be used if the isolate is susceptible in vitro 1, 2
- For pneumonia, colistin can be administered both intravenously and as adjunctive inhaled therapy 1
- For severe infections, combination therapy with two in vitro active agents is recommended to improve clinical outcomes and prevent resistance 3, 2
Specific Dosing Recommendations
- Colistin: 5 mg colistin base activity (CBA)/kg IV loading dose, then 2.5 mg CBA (1.5 CrCl + 30) IV q12h 1
- Ampicillin-sulbactam: 6-9 g/day IV in 3-4 divided doses as a 4-hour infusion for isolates with MIC ≤4 mg/L 3, 2
- Carbapenems (if used in combination): Imipenem/cilastatin 500 mg IV q6h or meropenem 2 g IV q8h with extended infusion time >3 hours 1
- Tigecycline (as part of combination therapy): 100 mg IV loading dose, then 50 mg IV q12h 1
Important Combinations and Contraindications
- Colistin plus a carbapenem may be beneficial if the carbapenem MIC is ≤32 mg/L 1
- Colistin plus tigecycline is an alternative combination for bloodstream infections 1
- Avoid polymyxin-meropenem combination therapy for CRAB infections with high-level carbapenem resistance (MICs >16 mg/L) 2
- Avoid polymyxin-rifampin combination therapy based on evidence showing no benefit 2
- Avoid colistin plus glycopeptides (e.g., vancomycin) due to increased nephrotoxicity 3
Treatment Duration
- For pneumonia: at least 7 days 1
- For bloodstream infections: 10-14 days 1
- For severe infections, maintain antimicrobial therapy for approximately 2 weeks, especially in cases of severe sepsis or septic shock 4
Special Considerations
- For CRAB with meropenem MIC <8 mg/L, high-dose extended-infusion carbapenem as part of combination therapy may be considered 3, 2
- Tigecycline monotherapy is not recommended for pneumonia 1
- Tigecycline resistance can develop in Acinetobacter through multi-drug resistant (MDR) efflux pumps 5
- For pan-resistant CRAB, treatment with the least resistant antibiotic(s) based on MICs relative to breakpoints is recommended 2
Monitoring and Adverse Effects
- Monitor renal function in patients receiving colistin, as nephrotoxicity occurs in up to 33% of patients 3, 2
- Monitor for emergence of resistance during therapy, particularly with colistin, as heteroresistance has been reported 3
- Tigecycline may have limited efficacy for pulmonary infections due to pharmacokinetic limitations 6
Emerging Treatment Options
- Sulbactam-durlobactam in combination with background carbapenem therapy has shown promising results in reducing mortality for CRAB pulmonary infections 6
- Cefiderocol has shown mixed results and is not currently recommended as first-line therapy for CRAB infections 2, 6
Treatment Algorithm for CRAB Infections
- Obtain cultures and susceptibility testing before initiating therapy 2
- Start empiric therapy based on local resistance patterns and patient risk factors 4
- For confirmed CRAB infection:
- For pneumonia, consider adding inhaled colistin to systemic therapy 1
- Continue treatment for the appropriate duration based on infection site (7 days for pneumonia, 10-14 days for bloodstream infections) 1