What is the preferred treatment regimen for Acinetobacter infections, colistin or sulbactam-based therapy?

Treatment of Acinetobacter Infections: Sulbactam vs Colistin-Based Regimens

For Acinetobacter baumannii infections, sulbactam-based regimens are preferred over colistin due to comparable efficacy with significantly better safety profile, particularly lower nephrotoxicity rates. 1

First-Line Treatment Options

• For susceptible strains (MIC ≤4 mg/L), sulbactam is the preferred treatment option due to its intrinsic activity against A. baumannii and better safety profile compared to colistin 1
• In areas with low carbapenem resistance, carbapenems remain the drugs of choice for A. baumannii infections 1
• For carbapenem-resistant A. baumannii (CRAB) susceptible to sulbactam, ampicillin-sulbactam should be used as first-line therapy 2
• Colistin should be reserved for strains resistant to both carbapenems and sulbactam to preserve its effectiveness and avoid unnecessary toxicity 1

Comparative Efficacy and Safety

• Clinical studies comparing sulbactam and colistin for MDR A. baumannii ventilator-associated pneumonia (VAP) have shown comparable clinical and microbiological response rates 1
• Nephrotoxicity rates are significantly higher with colistin (33%) compared to sulbactam (15.3%) 1
• A retrospective study of 98 patients with carbapenem-resistant A. baumannii VAP found similar clinical cure rates between sulbactam and colistin groups, but microbiological cure rates at day 7 were significantly lower in the colistin group 1
• Impairment of renal function and 30-day mortality were significantly higher in patients treated with colistin compared to sulbactam 1
• A recent randomized clinical trial demonstrated that levofloxacin plus high-dose ampicillin/sulbactam as continuous infusion was more effective than levofloxacin plus colistin in MDR Acinetobacter VAP patients, with significantly lower risk of nephrotoxicity 3

Dosing Recommendations

• For severe A. baumannii infections, high-dose sulbactam therapy at 9-12 g/day divided into 3 daily doses (3-4 g every 8 hours) is recommended 1, 4
• A 4-hour infusion is suggested for each sulbactam dose to optimize pharmacokinetic/pharmacodynamic properties 1, 4
• 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 1

Combination Therapy Considerations

• There are no convincing data to recommend combination therapy over monotherapy for directed treatment of A. baumannii infections 1
• The routine combination of colistin plus rifampin is not recommended 1
• Combination of colistin with anti-Gram-positive agents (e.g., glycopeptides) is discouraged due to increased nephrotoxicity 1, 2
• For clinical failures or infections with isolates having MICs at the upper limit of susceptibility, combination of sulbactam or polymyxin with a second agent (tigecycline, rifampicin, or fosfomycin) may be considered 1
• Recent in vitro studies have shown enhanced bacterial killing with colistin/sulbactam combinations against carbapenem-resistant A. baumannii 5

Clinical Algorithm for Treatment Selection

1. Obtain cultures and susceptibility testing before initiating therapy 2
2. For empiric therapy in patients with risk factors for A. baumannii infection:
   • In areas with low carbapenem resistance: use a carbapenem 1
   • In areas with high carbapenem resistance: consider a polymyxin 1
3. For directed therapy based on susceptibility results:
   • If susceptible to sulbactam (MIC ≤4 mg/L): Use ampicillin-sulbactam 9-12 g/day 1, 4
   • If resistant to sulbactam but susceptible to colistin: Use colistin with appropriate dosing 1, 2
   • For severe infections with isolates having MICs at the upper limit of susceptibility: Consider combination therapy 1

Common Pitfalls and Considerations

• Underdosing sulbactam (doses <9 g/day) may be insufficient for severe infections 4
• Not considering local resistance patterns and MIC values when selecting therapy 4, 2
• Heteroresistance to colistin is a concern, with rates varying from 18.7% to 100% in clinical isolates 1
• Previous use of colistin might be a risk factor for higher rates of heteroresistance 1
• Monitor renal function closely in patients receiving colistin, as nephrotoxicity occurs in up to 33% of patients 1, 2