What is the main treatment for Acinetobacter baumannii infections?

Treatment of Acinetobacter baumannii Infections

For Acinetobacter baumannii infections, the main treatment depends on antimicrobial susceptibility patterns, with carbapenems being the drugs of choice for susceptible isolates, while polymyxins (colistin) are recommended for carbapenem-resistant strains, often in combination with another active agent. 1, 2, 3

First-Line Treatment Options Based on Susceptibility

Carbapenem-Susceptible A. baumannii

• Carbapenems (imipenem, meropenem, doripenem) are the drugs of choice for infections caused by A. baumannii in areas with low rates of carbapenem resistance 1
• These should not be used in monotherapy for severe infections in areas with high rates of resistance to carbapenems 1

Carbapenem-Resistant A. baumannii (CRAB)

• For CRAB susceptible to sulbactam, ampicillin-sulbactam is the preferred treatment, especially for hospital-acquired/ventilator-associated pneumonia (HAP/VAP) 2, 3
• For CRAB resistant to sulbactam, a polymyxin (colistin) should be used if the isolate is susceptible in vitro 2, 3
• Combination therapy is recommended for severe CRAB infections to improve clinical outcomes and prevent resistance 4

Specific Dosing Recommendations

• Ampicillin-sulbactam: Administer as a 4-hour infusion of 3g sulbactam every 8 hours (9-12g/day total) for isolates with MIC ≤4 mg/L 1, 2
• Colistin: Dosing should be weight-based and adjusted for renal function according to institutional protocols, with a loading dose of 9 million IU followed by maintenance doses of 4.5 million IU every 12 hours 2, 5
• For tigecycline, when used for non-approved indications (especially pulmonary infections), high-dose regimen (loading dose 200 mg followed by 100 mg every 12 hours) is suggested 1

Combination Therapy Considerations

• For severe infections caused by CRAB, combination therapy with two in vitro active agents is recommended 3, 4
• The Infectious Diseases Society of America recommends combination therapy over monotherapy for CRAB infections requiring polymyxin treatment 4
• Important combinations to avoid:
  • Polymyxin-meropenem combination therapy is not recommended for CRAB infections with high-level carbapenem resistance (MICs >16 mg/L) 3, 4
  • Polymyxin-rifampin combination therapy is strongly discouraged 3, 4
  • Colistin plus glycopeptides (vancomycin) is discouraged due to increased nephrotoxicity 2, 4

Special Considerations

• For CRAB with meropenem MIC <8 mg/L, high-dose extended-infusion carbapenem as part of combination therapy may be considered 2, 3
• For respiratory tract infections, aerosolized polymyxin in addition to intravenous polymyxin may be beneficial 4
• Tigecycline may be an option for directed therapy of infections caused by A. baumannii if the tigecycline MIC is ≤1 mg/L and the isolate is resistant to other agents 1, 6
• Due to uncertainties about efficacy, tigecycline should be used in combination with another active agent when possible 1

Monitoring and Adverse Effects

• Monitor renal function in patients receiving colistin, as nephrotoxicity occurs in up to 33% of patients 2, 4
• Watch for emergence of resistance during therapy, particularly with colistin, as heteroresistance has been reported 2
• For patients on tigecycline, monitor for potential development of resistance, as there have been reports of resistance development during standard treatment 6

Treatment Algorithm

1. Obtain cultures and susceptibility testing before initiating therapy 2
2. Start empiric therapy based on local resistance patterns and patient risk factors 1
3. For confirmed A. baumannii infection:
   • If carbapenem-susceptible: Use carbapenem (imipenem, meropenem, doripenem) 1, 7
   • If carbapenem-resistant but sulbactam-susceptible: Use ampicillin-sulbactam (9-12g/day) 2, 3
   • If resistant to both carbapenems and sulbactam: Use colistin with appropriate weight-based dosing 2, 5
   • For severe infections: Consider combination therapy with two active agents 3, 4
4. Continue treatment for approximately 2 weeks for severe infections such as VAP or bacteremia 2

Common Pitfalls and Caveats

• Indiscriminate use of polymyxins may contribute to selection of further resistance and expose patients to unnecessary toxicity 1
• Heteroresistance detection requires special methods and equipment that most laboratories cannot routinely perform 1
• Tigecycline has limitations for pulmonary infections due to higher treatment failure rates 4, 8
• Emergence of resistance during treatment is a significant concern, particularly with A. baumannii infections 6