Treatment of Carbapenem-Resistant Acinetobacter baumannii (CRAB) Infections
Polymyxin (colistin) combination therapy is strongly recommended as the preferential choice over monotherapy for treating CRAB infections in patients who require polymyxin treatment. 1
First-Line Treatment Options
- For CRAB infections requiring polymyxin treatment, combination therapy is recommended over monotherapy based on moderate-quality evidence showing reduced treatment failure rates and improved pathogen eradication 1
- For CRAB susceptible to sulbactam, ampicillin-sulbactam is recommended as the preferred treatment, particularly for hospital-acquired/ventilator-associated pneumonia (HAP/VAP) 2
- For CRAB bloodstream infections (BSI), colistin-carbapenem based combination therapy is recommended, though this is a weak recommendation based on low-quality evidence 1
Specific Combination Regimens
- Colistin-carbapenem combinations may be suggested for CRAB infections if meropenem MIC is ≤32 mg/L, using extended-infusion of meropenem for 3 hours 1
- For CRAB pneumonia, colistin-carbapenem combinations ranked highest for clinical cure (SUCRA 91.7%) and second for microbiological cure (SUCRA 68.7%) in network meta-analyses 1
- Colistin-tigecycline combinations have shown the lowest mortality rates (SUCRA 93.4%) in some analyses 1
- Colistin-sulbactam combinations have demonstrated efficacy, with high-dose sulbactam (6-9g per day) recommended 1, 3
Important Recommendations Against Specific Combinations
- Strong recommendation against polymyxin-meropenem combination therapy for CRAB infections with high-level carbapenem resistance (MICs >16 mg/L) based on high-quality evidence from randomized controlled trials 1, 2
- Strong recommendation against polymyxin-rifampin combination therapy based on moderate quality evidence 1, 2
Dosing Considerations
- Colistin dosing requires careful attention to unit conversion: 1 million U = 80 mg mass CMS = 33 mg colistin base activity (CBA) 1
- A loading dose of colistin followed by high, extended-interval maintenance doses is recommended 4
- For sulbactam, doses of 6-9g per day are recommended, typically administered as fixed-dose combinations (e.g., cefoperazone 1.5g/sulbactam 1.5g every 6h or ampicillin 18g/sulbactam 9g per day) 1
- Ampicillin-sulbactam should be administered as a 4-hour infusion of 3g of sulbactam every 8 hours for isolates with MIC ≤8 mg/L 2
Special Considerations for Respiratory Infections
- Aerosolized polymyxin in addition to intravenous polymyxin is suggested for CRAB respiratory tract infections, though this is a weak recommendation based on low-quality evidence 1
- Colistin methanesulfonate (CMS) is preferred for inhalation therapy 1
Monitoring and Adverse Effects
- Renal function should be monitored during polymyxin treatment, with therapeutic drug monitoring (TDM) encouraged when possible 1
- Ototoxic and nephrotoxic drugs should be avoided in combination with polymyxin 1
- Nephrotoxicity is a significant concern with colistin therapy, occurring in up to 33% of patients 2
Alternative Options for Resistant Strains
- Tigecycline has activity against many CRAB isolates, but monotherapy is not recommended for CRAB pneumonia due to higher treatment failure rates 1, 5
- For pan-resistant CRAB, treatment with antibiotics having the lowest MICs relative to breakpoints is recommended 2
- Combination therapy using colistin with either sulbactam (≥6 g/day) or fosfomycin (≥18 g/day) has shown efficacy even against some colistin-resistant A. baumannii isolates 3
Clinical Pearls and Pitfalls
- In vitro synergy testing may help guide therapy but does not always translate to clinical benefit 1, 6
- Resistance to tigecycline can develop during treatment due to MDR efflux pump mechanisms, requiring close monitoring for relapse 5
- The optimal treatment for CRAB infections remains challenging, with limited high-quality evidence to guide therapy 7, 4
- Colistin combination therapy appears to reduce treatment failure rates by approximately 119 cases per 1000 patients compared to monotherapy 1