What is the treatment for Acinetobacter infections?

Treatment of Acinetobacter Infections

For carbapenem-susceptible Acinetobacter baumannii, use carbapenems (imipenem, meropenem, or doripenem) as first-line therapy; for carbapenem-resistant strains, ampicillin-sulbactam is preferred over polymyxins when the sulbactam MIC is ≤4 mg/L due to superior safety and comparable efficacy. 1, 2

Initial Assessment and Susceptibility-Based Treatment

The treatment approach hinges on local resistance patterns and susceptibility testing results. 3

Carbapenem-Susceptible A. baumannii

• Imipenem is FDA-approved for Acinetobacter infections affecting the lower respiratory tract and skin/soft tissue, dosed at 0.5-1 g every 6 hours (extended infusion not possible due to drug instability). 1, 4
• Meropenem should be dosed at 2 g every 8 hours as an extended infusion for optimal outcomes. 1
• Doripenem is an alternative carbapenem option with similar efficacy. 2
• Carbapenems should not be used as monotherapy for severe infections in areas where carbapenem resistance exceeds 25%. 1

Carbapenem-Resistant A. baumannii (CRAB)

Ampicillin-sulbactam is the preferred first-line agent for CRAB when sulbactam MIC ≤4 mg/L:

• Dose: 3 g sulbactam every 8 hours (9-12 g/day total) administered as 4-hour infusions. 1, 2
• Sulbactam demonstrates comparable clinical outcomes to imipenem for severe infections. 1
• Nephrotoxicity is significantly lower than colistin (15.3% vs 33%). 1
• Microbiologic cure rates at day 7 are superior to colistin. 1

Polymyxins (colistin or polymyxin B) are reserved for CRAB resistant to all beta-lactams and sulbactam:

Colistin Dosing

• Loading dose: 6-9 million IU. 5, 1
• Maintenance: 4.5 million IU every 12 hours in critically ill patients with creatinine clearance >50 mL/min. 5, 1
• Adjust maintenance dose based on creatinine clearance. 5
• For continuous renal replacement therapy: at least 9 million IU/day. 5
• For intermittent hemodialysis: 2 million IU every 12 hours with normal loading dose; dialysis should occur toward the end of dosing interval. 5

Polymyxin B Dosing

• Loading dose: 2-2.5 mg/kg. 5, 1
• Maintenance: 1.5-3 mg/kg/day in 2 divided doses. 5, 1
• Polymyxin B has lower nephrotoxicity than colistin and does not require dose adjustment for renal replacement therapy. 5, 1

Combination Therapy for Severe Infections

Use combination therapy with two in vitro active agents for severe CRAB infections (septic shock, severe sepsis, or bacteremia). 1, 2

Recommended combinations include:

• Colistin + high-dose carbapenem (even if resistant, for synergy). 2
• Colistin + sulbactam + tigecycline. 2
• Sulbactam or polymyxin + second agent (tigecycline, rifampicin, or fosfomycin). 2

Avoid these combinations:

• Colistin + rifampin routinely (lacks proven benefit). 2
• Colistin + glycopeptides like vancomycin (increases nephrotoxicity without benefit). 5, 2
• Polymyxin-meropenem for CRAB with high-level carbapenem resistance (MICs >16 mg/L). 2

Site-Specific Considerations

Ventilator-Associated Pneumonia (VAP)

Nebulized antibiotics are recommended as adjunctive therapy in specific situations:

• Patients nonresponsive to systemic antibiotics. 5
• Recurrent VAP. 5
• Isolates with MICs close to susceptibility breakpoint. 5

Nebulized colistin dosing:

• Standard: 2 million IU every 8 or 12 hours. 5
• Higher doses (5 million IU every 8 hours) can be used in non-resolving cases. 5
• Must be delivered using ultrasonic or vibrating plate nebulizers. 5
• Always combine with intravenous antimicrobial therapy for pneumonia. 5

Nebulized aminoglycosides (tobramycin or amikacin) are alternatives based on susceptibility. 5

Meningitis and Ventriculitis

Parenteral therapy alone is insufficient due to poor CNS penetration of colistin. 5

• Combination of intravenous + intrathecal (IT) or intraventricular (IVT) colistin is required. 5
• IT/IVT colistin dose: 125,000 IU once daily (range 20,000-500,000 IU). 5
• Consider loading dose of 500,000 IU. 5
• Alternative: IT/IVT aminoglycoside (10-50 mg amikacin or 5-20 mg tobramycin daily) if susceptible. 5
• Treatment duration: 3 weeks, with CSF sterilization monitoring to tailor duration. 5

Tracheobronchitis

• Use nebulized antibiotics (colistin or aminoglycosides based on susceptibility). 5
• Whether concurrent intravenous therapy is necessary remains unclear. 5

Urinary Tract Infections

• Sulbactam-susceptible: Ampicillin-sulbactam 3 g sulbactam every 8 hours. 1
• Sulbactam-resistant: Colistin (6-9 million IU loading, then 9 million IU/day). 1

Tigecycline Considerations

Tigecycline should NOT be used as monotherapy for A. baumannii infections, particularly bacteremia or primary bloodstream infections, due to suboptimal serum concentrations. 1, 2

• Only consider for approved indications (complicated intra-abdominal infections, complicated skin/soft tissue infections) with secondary bacteremia. 1
• High-dose regimens (200 mg loading, then 100 mg every 12 hours) may be used as part of combination therapy for severe infections, though not FDA-approved. 1
• Avoid for pneumonia/VAP due to poor lung penetration. 3

Treatment Duration

• Severe infections (VAP, bacteremia with severe sepsis/septic shock): 2 weeks. 1, 2
• Less severe infections: Shorter durations may be acceptable. 1
• Meningitis/ventriculitis: 3 weeks. 5

Critical Monitoring and Pitfalls

Monitor renal function closely in all patients receiving colistin, as nephrotoxicity occurs in up to 33% of patients. 1, 2

Common pitfalls to avoid:

• Never use ertapenem for A. baumannii (lacks activity against this pathogen). 2
• Do not use nebulized antibiotics for colonization without infection. 5
• Avoid aminoglycoside monotherapy. 3
• Do not delay appropriate therapy in critically ill patients with known CRAB colonization or during outbreaks. 2
• High-dose meropenem carries seizure risk. 1