Treatment of Carbapenem-Resistant Acinetobacter baumannii (CRAB) Infections

First-Line Treatment Options

For patients with CRAB susceptible to sulbactam and hospital-acquired/ventilator-associated pneumonia (HAP/VAP), ampicillin-sulbactam is recommended as the preferred treatment, according to the Clinical Microbiology and Infection guidelines 1, 3
For CRAB resistant to sulbactam, a polymyxin (colistin) or high-dose tigecycline can be used if active in vitro, as suggested by the Clinical Microbiology and Infection guidelines 1, 4
For severe and high-risk CRAB infections, combination therapy including two in vitro active antibiotics among polymyxin, aminoglycoside, tigecycline, and sulbactam combinations is suggested, based on the Clinical Microbiology and Infection guidelines 1, 2

Ampicillin-sulbactam should be administered as a 4-hour infusion of 3g of sulbactam every 8 hours for isolates with MIC ≤8 mg/L, as recommended by the Intensive Care Medicine guidelines 5
Colistin dosing should be based on weight and renal function, following institutional protocols, according to the Intensive Care Medicine guidelines 5

The Clinical Microbiology and Infection guidelines strongly recommend against using polymyxin-meropenem combination therapy for CRAB infections, based on high-quality evidence from randomized controlled trials 1, 2
The Clinical Microbiology and Infection guidelines strongly recommend against using polymyxin-rifampin combination therapy, based on moderate quality evidence 1, 2
The Clinical Microbiology and Infection guidelines conditionally recommend against using cefiderocol for CRAB infections, based on low-quality evidence 1, 2

For CRAB with meropenem MIC <8 mg/L, carbapenem combination therapy using high-dose extended-infusion carbapenem dosing may be considered, as suggested by the Clinical Microbiology and Infection guidelines 1, 2
For pan-resistant CRAB, treatment with the least resistant antibiotic(s) based on MICs relative to breakpoints is recommended, according to the Clinical Microbiology and Infection guidelines 1, 4

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), as reported by the Clinical Microbiology and Infection guidelines 6

Patients on colistin therapy should be monitored for nephrotoxicity, which occurs in up to 33% of patients, as recommended by the Intensive Care Medicine guidelines 5
Patients on combination therapy should be monitored for development of resistance, particularly with colistin, as heteroresistance has been reported, according to the Intensive Care Medicine guidelines 7, 6

For HAP/VAP with CRAB susceptible to sulbactam, ampicillin-sulbactam is recommended, as suggested by the Clinical Microbiology and Infection guidelines 4
For severe infections with CRAB resistant to sulbactam, combination therapy with two in vitro active agents is recommended, avoiding polymyxin-meropenem and polymyxin-rifampin combinations, according to the Clinical Microbiology and Infection guidelines 4, 2, 3
For CRAB with meropenem MIC <8 mg/L, high-dose extended-infusion carbapenem as part of combination therapy may be considered, as suggested by the Clinical Microbiology and Infection guidelines 1
For pan-resistant CRAB, antibiotics with the lowest MICs relative to breakpoints should be used, according to the Clinical Microbiology and Infection guidelines 4