What antibiotics are effective for treating Acinetobacter baumannii infections?

Antibiotic Treatment for Acinetobacter baumannii

For carbapenem-susceptible A. baumannii, use carbapenems (imipenem, meropenem, or doripenem) as first-line therapy; for carbapenem-resistant A. baumannii (CRAB), ampicillin-sulbactam is the preferred agent when sulbactam MIC ≤4 mg/L due to superior safety and comparable efficacy to polymyxins. 1

Treatment Algorithm Based on Susceptibility

Step 1: Obtain Cultures and Determine Resistance Pattern

• Carbapenem-susceptible A. baumannii (in areas with <25% carbapenem resistance):

  • Use carbapenems as first-line monotherapy 1, 2
  • Imipenem: 0.5–1 g every 6 hours (extended infusion not possible due to drug instability) 3, 1
  • Meropenem: 2 g every 8 hours (caution: high doses associated with seizure risk) 3, 1
  • Doripenem is also acceptable 1, 2

• Carbapenem-resistant A. baumannii (CRAB):

  • Proceed to Step 2 for directed therapy based on sulbactam susceptibility 1

Step 2: Directed Therapy for CRAB

When sulbactam MIC ≤4 mg/L (preferred option):

• Ampicillin-sulbactam: 9–12 g/day of sulbactam in 3 daily doses 3, 1
• Administer as 4-hour infusions (3 g sulbactam every 8 hours) 3, 1
• Clinical outcomes comparable to imipenem for severe infections 3, 1
• Significantly lower nephrotoxicity than colistin (15.3% vs 33%) 3, 1
• Higher microbiologic cure rates at day 7 compared to colistin 1

When sulbactam-resistant or MIC >4 mg/L:

• Colistin (Polymyxin E) as alternative therapy 1
• Loading dose: 6–9 million IU 3, 1
• Maintenance: 9 million IU/day in 2–3 divided doses (4.5 million IU every 12 hours in critically ill patients with CrCl >50 mL/min) 3, 1
• Monitor renal function closely (nephrotoxicity occurs in up to 33% of patients) 1, 2

Polymyxin B as colistin alternative:

• Loading dose: 2–2.5 mg/kg 3, 1
• Maintenance: 1.5–3 mg/kg/day in 2 divided doses 3, 1
• Associated with less nephrotoxicity than colistin 1

Step 3: Consider Combination Therapy for Severe Infections

Indications for combination therapy (use two in vitro active agents):

• Severe sepsis or septic shock 1, 2
• Bacteremia with hemodynamic instability 2
• Ventilator-associated pneumonia (VAP) 1

Recommended combinations:

• Colistin + high-dose carbapenem 1
• Colistin + sulbactam + tigecycline 1
• Sulbactam or polymyxin + second agent (tigecycline, rifampicin, or fosfomycin) 2

Combinations to AVOID:

• Colistin + rifampin (lacks proven benefit) 2
• Colistin + glycopeptides like vancomycin (increased nephrotoxicity without added benefit) 2
• Polymyxin-meropenem for CRAB with high-level carbapenem resistance (MICs >16 mg/L) 2

Site-Specific Considerations

Pneumonia/VAP

• Never use tigecycline as monotherapy for pneumonia due to poor lung penetration and suboptimal serum concentrations 1, 2
• Consider nebulized colistin as adjunctive therapy for MDR A. baumannii pneumonia 1, 2
• Standard dose tigecycline (100 mg loading, then 50 mg every 12 hours) may be adequate only for secondary bacteremia from approved indications (abdominal infections, skin/soft tissue infections) 3
• High-dose tigecycline (200 mg loading, then 100 mg every 12 hours) may be used for severe infections as part of combination therapy, though not FDA-approved 1

Bacteremia/Bloodstream Infections

• Never use tigecycline as monotherapy due to suboptimal serum concentrations and higher treatment failure rates 2
• Maintain antimicrobial therapy for 2 weeks, especially in cases of severe sepsis or septic shock 1, 2
• Consider repeat blood cultures to document clearance 2

Urinary Tract Infections

• For sulbactam-susceptible isolates (MIC ≤4 mg/L): Ampicillin-sulbactam 3 g sulbactam every 8 hours 4
• For sulbactam-resistant isolates: Colistin (6–9 million IU loading, then 9 million IU/day) 4
• Remove or replace urinary catheter when possible 4
• Treatment duration: 7 days for uncomplicated UTIs, up to 14 days for complicated UTIs 4

Treatment Duration

• Severe infections (VAP, bacteremia with severe sepsis/septic shock): 2 weeks 1, 2
• Less severe infections: Shorter durations may be acceptable based on clinical response 1
• Uncomplicated UTIs: 7 days 4
• Complicated UTIs: Up to 14 days 4

Critical Pitfalls to Avoid

• Do not use carbapenems as monotherapy for severe infections in areas with high CRAB prevalence (>25% resistance rates) 2
• Do not delay appropriate therapy while awaiting susceptibility results in critically ill patients with known CRAB colonization or during outbreaks 2
• Do not use ertapenem for A. baumannii infections—it lacks activity against this pathogen 2
• Monitor for resistance development during tigecycline treatment, as resistance can emerge during standard therapy via MDR efflux pump mechanisms 5
• Adjust colistin dosing for renal function to minimize toxicity—dosing is complex and requires careful calculation 4
• Sulbactam susceptibility testing using semi-automated methods is unreliable; MIC ≤4 mg/L by Etest is the accepted susceptibility threshold 3

Monitoring Requirements

• Renal function: Monitor closely in all patients receiving colistin or polymyxin B 1, 2, 4
• Clinical response: Assess for improvement in signs/symptoms of infection 4
• Microbiologic clearance: Consider repeat cultures, especially for bacteremia 2
• Resistance surveillance: More frequent monitoring for relapse in patients treated with tigecycline for Acinetobacter infections 5