What is the recommended treatment for carbapenem‑resistant Acinetobacter infection when ampicillin‑sulbactam is not available?

Treatment of Carbapenem-Resistant Acinetobacter (CRAB) When Ampicillin-Sulbactam Is Not Available

When ampicillin-sulbactam is unavailable for carbapenem-resistant Acinetobacter baumannii (CRAB) infection, use a polymyxin (colistin or polymyxin B) combined with high-dose tigecycline for severe infections, or polymyxin monotherapy for less severe cases if the isolate is susceptible in vitro. 1

Primary Treatment Algorithm

Step 1: Verify Susceptibility Testing

• Confirm CRAB resistance pattern using broth microdilution, as automated methods are unreliable for sulbactam and tigecycline 1
• Check polymyxin (colistin/polymyxin B) susceptibility status 1
• Verify tigecycline MIC if available; efficacy is reduced when MIC >2 mg/L 1

Step 2: Choose Regimen Based on Infection Severity

For severe infections (septic shock, VAP, bacteremia):

• Combination therapy with two active agents is strongly recommended 1
• Primary regimen: Polymyxin + high-dose tigecycline 2, 3
  • Polymyxin B: 2.5 mg/kg IV loading dose, then maintenance adjusted for renal function 4
  • Tigecycline: 100 mg IV loading dose, then 50 mg IV every 12 hours 2
• Alternative combination: Polymyxin + carbapenem (if carbapenem MIC ≤32 mg/L) 1
  • This exploits potential synergy even against "resistant" isolates 1
  • Do NOT use if carbapenem MIC >16 mg/L 1, 4

For less severe infections:

• Polymyxin monotherapy may be acceptable if active in vitro 1
• High-dose tigecycline monotherapy is NOT recommended due to suboptimal serum concentrations and higher failure rates 1, 2, 4

Step 3: Consider Additional Combination Partners

If polymyxin + tigecycline is insufficient or contraindicated:

• Add fosfomycin (12-24 g/day in 3-4 divided doses) 1, 5
• Consider minocycline (IV) if available; 60-80% of CRAB isolates remain susceptible 1
• Aminoglycosides (amikacin 25-30 mg/kg/day once daily) can be added 2

Critical Combinations to AVOID

These combinations increase toxicity without improving outcomes:

• Polymyxin + rifampin: No proven clinical benefit, increases hepatotoxicity 1, 2, 4
• Polymyxin + glycopeptides (vancomycin): Increases nephrotoxicity without added antimicrobial effect 1, 2
• Polymyxin + carbapenem when carbapenem MIC >16 mg/L: No synergy at high-level resistance 1, 4

Dosing Specifications

Polymyxin B

• Loading dose: 2.5 mg/kg IV 4
• Maintenance: Adjust for renal function and therapeutic drug monitoring when available 4
• Monitor serum creatinine daily; nephrotoxicity occurs in 20-57% of patients 6

Colistin

• Loading dose: 9 million IU IV 6
• Maintenance: 4.5 million IU IV every 12 hours, adjusted for renal function 6
• Nephrotoxicity rate approximately 33% vs 15% with ampicillin-sulbactam 1, 6

High-Dose Tigecycline

• Loading: 100 mg IV 2
• Maintenance: 50 mg IV every 12 hours 2
• Never use as monotherapy for bacteremia or severe infections 2, 4

Adjunctive Inhaled Colistin (for pneumonia)

• 2-6 million IU daily via nebulization to improve pulmonary penetration 6
• Use in addition to IV polymyxin, not as replacement 6

Treatment Duration

• Severe infections (septic shock, bacteremia, VAP): Minimum 14 days 1, 6
• Less severe infections: 7-10 days if good clinical response 4
• Obtain repeat cultures at days 3-5 to assess microbiological response 2

Monitoring Requirements

Daily assessments:

• Serum creatinine and creatinine clearance calculation for nephrotoxicity 4
• Clinical signs: fever resolution, decreased oxygen requirements, improved imaging 2

Weekly assessments (if using rifampin):

• Hepatic enzymes due to hepatotoxicity risk 6

Common Pitfalls and How to Avoid Them

1. Using tigecycline monotherapy for bacteremia: This leads to treatment failure due to inadequate serum levels 1, 2, 4. Always combine with polymyxin for bloodstream infections.

2. Delaying combination therapy in severe infections: Monotherapy has higher mortality in septic shock 1. Start combination immediately when CRAB is suspected in critically ill patients.

3. Adding carbapenem to polymyxin when MIC >16 mg/L: This wastes resources without benefit 2, 4. Check carbapenem MIC before adding to regimen.

4. Empiric use without considering local resistance patterns: In ICUs where ≥25% of Acinetobacter isolates are CRAB, empiric coverage is warranted 6. Otherwise, wait for susceptibility results.

5. Inadequate polymyxin dosing: Use weight-based loading doses and adjust maintenance for renal function 6, 4. Underdosing leads to treatment failure.

Special Considerations for Pneumonia

• Intravenous colistin achieves negligible concentrations in epithelial lining fluid 1
• Add inhaled colistin (2-6 million IU daily) to IV therapy for VAP 6
• Combination therapy is particularly important for pneumonia given poor lung penetration of IV polymyxins 1

Emerging Alternatives (Limited Clinical Data)

• Cefiderocol: Conditionally recommended AGAINST for CRAB due to increased mortality signal 1
• Eravacycline: Insufficient clinical data at present 1, 7
• Durlobactam: May have therapeutic potential but not yet widely available 3