What is the recommended treatment for multidrug-resistant (MDR) Acinetobacter infections?

Treatment of Multidrug-Resistant Acinetobacter Infections

For MDR Acinetobacter infections, ampicillin-sulbactam is recommended as first-line therapy for strains susceptible to sulbactam, while colistin-based therapy should be reserved for strains resistant to sulbactam. 1, 2

First-Line Treatment Options

• For carbapenem-resistant Acinetobacter baumannii (CRAB) susceptible to sulbactam, ampicillin-sulbactam is recommended as the preferred treatment due to its intrinsic activity and better safety profile compared to colistin 1, 2
• For CRAB resistant to sulbactam, a polymyxin (colistin) or high-dose tigecycline can be used if active in vitro 1
• Colistin should be considered as therapy for patients with VAP due to carbapenem-resistant Acinetobacter species 1
• The recommended dosing for ampicillin-sulbactam is high-dose therapy at 9-12 g/day divided into 3-4 daily doses, with a 4-hour infusion for each dose 2

Combination Therapy Considerations

• If Acinetobacter species are documented, the most active agents are carbapenems, sulbactam, colistin, and polymyxin, but there are no data documenting improved outcomes with combination regimens 1
• For severe infections, particularly pneumonia and bloodstream infections, combination therapy may be considered, with colistin-based combinations showing the best outcomes 3
• Colistin with or without a carbapenem plus adjunctive inhaled colistin is recommended for pneumonia, with a duration of at least 7 days 3
• For bloodstream infections, colistin with or without a carbapenem is recommended, with a duration of 10-14 days 3

Alternative Treatment Options

• Tigecycline may be considered as part of combination therapy but should not be used as monotherapy for pneumonia or bloodstream infections due to poor outcomes 3, 4
• Minocycline has shown in vitro activity against MDR Acinetobacter and may be considered when other options are limited 3
• Aerosolized antibiotics may have value as adjunctive therapy in patients with VAP due to MDR pathogens 1
• Ceftazidime/avibactam in combination with colistin, tobramycin, or tigecycline has shown synergistic activity against MDR A. baumannii in vitro 5

Comparative Efficacy and Safety

• Clinical studies comparing sulbactam and colistin for MDR A. baumannii ventilator-associated pneumonia have shown comparable clinical response rates 2
• Nephrotoxicity rates are significantly higher with colistin (33%) compared to sulbactam (15.3%), making sulbactam a safer option when susceptibility allows 2
• A retrospective study found that mortality at the end of treatment was significantly higher in patients treated with polymyxins compared to ampicillin-sulbactam 1
• For colistin, when necessary, a loading dose of 6-9 million IU followed by 9 million IU/day in 2-3 doses is recommended, with dose adjustment for renal function 2

Clinical Decision Algorithm

1. Obtain cultures and susceptibility testing before initiating therapy 2
2. For empiric therapy in patients with risk factors for Acinetobacter infection, consider local resistance patterns 2
3. For directed therapy based on susceptibility results:
   • Use ampicillin-sulbactam for strains susceptible to sulbactam (MIC ≤4 mg/L) 1, 2
   • Use colistin for strains resistant to sulbactam but susceptible to colistin 1, 2
   • Consider combination therapy for severe infections, particularly pneumonia and bloodstream infections 3

Common Pitfalls and Considerations

• Underdosing sulbactam may lead to treatment failure; ensure adequate dosing (9-12 g/day) 2
• Tigecycline monotherapy should be avoided for pneumonia and bloodstream infections due to poor outcomes 3, 4
• Monitor renal function closely in patients receiving colistin, as nephrotoxicity occurs in up to 33% of patients 2
• Heteroresistance to colistin is a concern, with rates varying from 18.7% to 100% in clinical isolates 2
• Previous use of colistin might be a risk factor for higher rates of heteroresistance 2
• Resistance to tigecycline in Acinetobacter can develop during treatment due to multidrug-resistant efflux pumps 4