What is the recommended antimicrobial regimen and duration for a patient with a confirmed non‑bacteremic carbapenem‑resistant Acinetobacter baumannii infection?

Treatment of Non-Bacteremic Carbapenem-Resistant Acinetobacter baumannii (CRAB) Infections

For non-bacteremic CRAB infections, high-dose ampicillin-sulbactam (3g sulbactam every 8 hours as a 4-hour infusion) is the preferred first-line therapy when the sulbactam MIC is ≤4 mg/L, due to superior safety compared to polymyxins with comparable efficacy. 1

Treatment Selection Algorithm

Step 1: Verify Susceptibility Testing

• Confirm sulbactam MIC using E-test or broth microdilution; automated methods are unreliable for sulbactam susceptibility determination 1
• Check colistin susceptibility if sulbactam MIC >4 mg/L 1, 2

Step 2: Choose Monotherapy vs. Combination Based on Severity

For non-severe infections (no septic shock, stable hemodynamics):

• If sulbactam MIC ≤4 mg/L: Use ampicillin-sulbactam monotherapy at 3g sulbactam every 8 hours as a 4-hour infusion (total 9g/day sulbactam, equivalent to 18g/day ampicillin-sulbactam) 1, 3
• If sulbactam MIC >4 mg/L or resistant: Use colistin with loading dose 6-9 million IU, then 9 million IU/day in 2-3 divided doses, adjusted for renal function 3

For severe infections (pneumonia with respiratory failure, complicated UTI with systemic symptoms, or predicted mortality >25%):

• Use combination therapy with two in-vitro active agents 1, 2
• Preferred combinations: colistin + sulbactam + tigecycline (triple therapy) 1 OR sulbactam + tigecycline (dual therapy) 1
• Alternative: colistin + high-dose carbapenem if carbapenem MIC ≤32 mg/L 1

Step 3: Avoid Ineffective or Toxic Combinations

Never use these combinations:

• Colistin + rifampicin (lacks clinical benefit, increases hepatotoxicity) 4, 1, 2
• Colistin + vancomycin or other glycopeptides (increases nephrotoxicity without added benefit) 4, 1, 2
• Polymyxin-meropenem when carbapenem MIC >16 mg/L (no synergy at high-level resistance) 1, 2
• Tigecycline monotherapy for any bloodstream component (suboptimal serum concentrations) 1

Site-Specific Considerations

Pneumonia (Non-Bacteremic)

• Ampicillin-sulbactam is preferred over polymyxins when sulbactam MIC ≤4 mg/L 1, 2
• Consider adding inhaled colistin 2-6 million IU daily as adjunctive therapy for severe cases 1
• Colistin monotherapy significantly increases 7-day and 28-day mortality and should be avoided 5
• Combination of colistin and carbapenem significantly reduces 7-day mortality 5

Urinary Tract Infections

• Treatment duration: 7 days for uncomplicated UTI, up to 14 days for complicated UTI with systemic symptoms 3
• Remove or replace urinary catheter when possible 3
• Monotherapy is generally sufficient for uncomplicated UTI with susceptible isolates 3

Skin/Soft Tissue Infections

• Ampicillin-sulbactam monotherapy is typically adequate when sulbactam MIC ≤4 mg/L 1
• Duration guided by clinical response, typically 7-14 days 1

Treatment Duration

Minimum durations based on infection type:

• Severe pneumonia or complicated infections: 14 days minimum 1, 3
• Uncomplicated UTI: 7 days 3
• Less severe infections: 7-10 days, guided by clinical response 1

Monitoring Requirements

Nephrotoxicity Surveillance

• Monitor renal function closely in all patients receiving colistin; nephrotoxicity occurs in up to 33% of patients 1, 3
• Ampicillin-sulbactam causes significantly less nephrotoxicity (15.3%) compared to colistin (33%) 1
• Adjust colistin dosing based on creatinine clearance 1, 3

Hepatotoxicity Monitoring

• Weekly liver function tests if rifampicin is used (though this combination is not recommended) 1
• Tigecycline is associated with increased hepatotoxicity 5

Clinical Response Assessment

• Assess clinical improvement at 7 days 5
• Consider repeat cultures to document microbiological clearance 1

Critical Pitfalls to Avoid

1. Do not use standard-dose sulbactam (6g/day) for severe infections—this is inadequate; use 9-12g/day 1

2. Do not use sulbactam empirically—reserve for directed therapy after susceptibility confirmation 1

3. Do not use newer beta-lactam/beta-lactamase inhibitors (ceftazidime-avibactam, ceftolozane-tazobactam)—these have no activity against CRAB 1

4. Do not use cefiderocol—conditionally recommended against for CRAB infections 1, 2

5. Do not use ertapenem—it lacks activity against Acinetobacter species 1

Dosing Summary

Ampicillin-Sulbactam (Preferred when MIC ≤4 mg/L)

• 3g sulbactam every 8 hours as 4-hour infusion 1, 3
• Total daily dose: 9-12g sulbactam (18-24g ampicillin-sulbactam) 1
• Adjust for creatinine clearance <50 mL/min 1

Colistin (When Sulbactam Resistant or MIC >4 mg/L)

• Loading dose: 6-9 million IU 3
• Maintenance: 9 million IU/day in 2-3 divided doses 3
• Weight-based dosing with renal adjustment required 1, 2

Tigecycline (In Combination Only)

• Loading dose: 100mg 1
• Maintenance: 50mg every 12 hours 1

Evidence Quality Notes

The recommendation for ampicillin-sulbactam over polymyxins is based on multiple high-quality guidelines from 2025-2026 1, 3, 2. The 2022 guideline supports colistin-carbapenem combination for severe infections 4, while the most recent 2025-2026 guidelines specifically recommend against polymyxin-carbapenem combinations when carbapenem MIC >16 mg/L 1, 2. A 2021 multicentre Korean study demonstrated that sulbactam-containing regimens significantly reduced 28-day mortality, while colistin monotherapy increased mortality 5.