Management of Acinetobacter baumannii Complex Infections in the ICU
Overview and Clinical Significance
Acinetobacter baumannii represents one of the most challenging pathogens in ICU settings, characterized by extraordinary antimicrobial resistance capabilities and environmental persistence. 1 This Gram-negative coccobacillus ranks as the fifth most common ICU pathogen globally, third most common cause of ventilator-associated pneumonia in Europe, and the most frequently identified pathogen in hospital-acquired bloodstream infections across 24 countries. 2
The A. baumannii complex includes A. baumannii, A. nosocomialis, and A. pittii, though routine clinical laboratories need not distinguish between species for treatment purposes. 1 MALDI-TOF MS is the recommended method for accurate phenotypic identification when needed. 1
When to Initiate Empirical Coverage
Empirical coverage for A. baumannii is recommended in severe infections (severe sepsis or septic shock) occurring during an outbreak, in endemic settings, or in previously colonized patients. 1, 2
Key risk factors warranting empirical coverage include: 1
- Active A. baumannii outbreak in the unit
- Previous colonization with A. baumannii (especially carbapenem-resistant strains)
- High colonization pressure in the ICU
- Prolonged ICU stay
- Mechanical ventilation
- Recent broad-spectrum antibiotic exposure
Definitive Treatment Based on Susceptibility
For Carbapenem-Susceptible A. baumannii
Carbapenems (imipenem, meropenem, or doripenem) remain the drugs of choice for carbapenem-susceptible strains. 1, 2, 3, 4 Ertapenem lacks activity against A. baumannii and should not be used. 1
For HAP/VAP specifically, either carbapenems or ampicillin-sulbactam can be used if the isolate is susceptible. 1
For Carbapenem-Resistant A. baumannii (CRAB)
First-Line Options:
For CRAB susceptible to sulbactam causing HAP/VAP, ampicillin-sulbactam is suggested over polymyxins based on superior mortality outcomes. 1 Multiple studies, including RCTs, demonstrate lower mortality with ampicillin-sulbactam compared to colistin (28-day mortality: 5/12 vs 9/11 in one trial). 1 Dosing ranges from 3 to 16 g every 8 hours (for ampicillin-sulbactam 2:1 formulation), with extended infusion of 6 g IV four times daily showing particular benefit. 1
For CRAB resistant to sulbactam or when sulbactam is unavailable, intravenous polymyxins (colistin or polymyxin B) are recommended. 1, 2
- Loading dose: 9 million IU
- Maintenance: 4.5 million IU every 12 hours
- Adjust for renal function
- For continuous renal replacement therapy: at least 9 million IU/day 6
- For intermittent hemodialysis: 2 million IU every 12 hours with normal loading dose 6
Polymyxin B may be preferred due to less nephrotoxicity: 1.5-3 mg/kg/day with a loading dose of 2-2.5 mg/kg. 2, 6 Polymyxin B has potential pharmacokinetic advantages over colistin but lacks robust clinical data in HAP/VAP. 1
Adjunctive Inhaled Therapy:
For CRAB sensitive only to polymyxins causing HAP/VAP, adjunctive inhaled colistin is suggested in addition to intravenous polymyxins. 1 This recommendation addresses the negligible concentrations of intravenous colistin in epithelial lining fluid. 1 Recent data from 2025 shows that combining intravenous and inhaled colistin improved clinical cure rates (57.4% vs 37.0%, p=0.003). 7 Colistin for inhalation must be administered promptly after mixing with sterile water per FDA recommendations. 1
Alternative Agents:
Tigecycline can be considered for skin/soft tissue or intra-abdominal infections (if MIC ≤1 mg/L) but is NOT recommended for HAP/VAP or bacteremia. 1, 2, 6 The IDSA/ATS guidelines strongly recommend against tigecycline for Acinetobacter HAP/VAP. 1 Standard dosing is 100 mg loading, then 50 mg twice daily; high-dose regimens (200 mg loading, then 100 mg twice daily) can be used for severe infections. 6
Cefiderocol is conditionally recommended AGAINST for CRAB treatment. 1
Combination vs. Monotherapy
For definitive therapy when susceptibilities are known, monotherapy with an active agent is recommended over combination therapy. 1 While combination therapy may increase microbiological eradication rates, no clinical studies demonstrate improved mortality or length of stay. 5
Exception: For patients remaining in septic shock or at high risk for death (mortality risk >25%) when susceptibilities are known, combination therapy using two active antibiotics may be considered. 1
Rifampicin should NOT be added to colistin for HAP/VAP - this combination does not improve clinical outcomes despite increased microbiological eradication. 1
Duration of Therapy
For VAP caused by A. baumannii, a 7-day course of antimicrobial therapy is recommended. 1
Special Situations
Meningitis/Ventriculitis
Consider intrathecal or intraventricular administration of antimicrobials for A. baumannii CNS infections. 6
Heteroresistance
Colistin heteroresistance (emergence of resistant subpopulations from susceptible strains) occurs in 18.7-100% of isolates. 1 Previous colistin use is a risk factor. 1 While microdilution cannot detect heteroresistance, colonies within disc diffusion inhibition zones may suggest its presence. 1 The clinical implications remain unclear. 1
Monitoring and Toxicity
Nephrotoxicity is the primary concern with polymyxins, occurring in up to 53.7% of patients receiving colistin. 7 Monitor renal function closely throughout therapy. 6 Polymyxin B appears to cause less nephrotoxicity than colistin. 2, 5
Infection Control Measures
Strict contact precautions are mandatory for all patients with A. baumannii. 2, 6 Additional measures include: 2, 6
- Alert systems to identify colonized/infected patients promptly
- Thorough environmental cleaning with appropriate disinfectants (0.5% sodium hypochlorite recommended)
- Surveillance cultures at least weekly during outbreaks
- Antibiotic stewardship programs to control resistance emergence
Critical Pitfalls to Avoid
- Never use ertapenem - it lacks activity against A. baumannii 1
- Never use aminoglycoside monotherapy for A. baumannii infections 1
- Never use tigecycline for bacteremia or HAP/VAP due to poor serum/lung concentrations 1, 2, 6
- Never omit loading doses of colistin - inadequate initial dosing leads to treatment failure 2, 5
- Never assume carbapenem susceptibility in endemic areas or during outbreaks without testing 1
- Never delay empirical coverage in previously colonized patients with severe sepsis 1