What are the treatment options for Acinetobacter (A. baumannii) infections resistant to meropenem?

Treatment of Meropenem-Resistant Acinetobacter baumannii

For carbapenem-resistant A. baumannii (CRAB) infections, high-dose ampicillin-sulbactam (9-12g sulbactam/day) is the preferred first-line agent when the isolate has a sulbactam MIC ≤4 mg/L, with colistin-based therapy reserved for sulbactam-resistant strains. 1

Primary Treatment Selection Algorithm

Step 1: Obtain Susceptibility Testing

• Determine sulbactam MIC and colistin susceptibility immediately 1
• Check meropenem MIC even though resistant (if MIC <8 mg/L, may influence combination therapy decisions) 1

Step 2: Choose Initial Regimen Based on Susceptibilities

If Sulbactam MIC ≤4 mg/L (Preferred Option):

• Ampicillin-sulbactam: 3g sulbactam every 8 hours as a 4-hour infusion (total 9-12g/day) 2, 1
• This provides superior safety compared to colistin, with lower nephrotoxicity rates (15.3% vs 33%) 2
• Clinical and microbiological cure rates are comparable to colistin but with better tolerability 2

If Sulbactam-Resistant or MIC >4 mg/L:

• Colistin: 9 million IU/day in 2-3 divided doses (after loading dose of 6-9 million IU) 2
• Weight-based dosing adjusted for renal function per institutional protocols 1
• Expect nephrotoxicity in up to 33% of patients; monitor renal function closely 2, 1

Combination Therapy Considerations

Evidence for Combination vs Monotherapy

The evidence on combination therapy is contradictory and nuanced:

• For bloodstream infections: Colistin-carbapenem combination had the highest ranking for clinical cure (SUCRA 83.6%) and microbiological cure (SUCRA 87.1%) in network meta-analysis 2

• For pneumonia and severe infections: Two large RCTs (AIDA and OVERCOME trials) showed no mortality benefit of colistin-meropenem combination over colistin monotherapy 2

  • AIDA trial (312 CRAB patients): No difference in clinical failure or 14-day mortality 2
  • OVERCOME trial: 28-day mortality was 46% for monotherapy vs 42% for combination (p=0.5) 2

Practical Combination Therapy Recommendations

For severe infections (septic shock, high bacterial burden):

• Consider colistin plus high-dose meropenem (2g every 8 hours as extended infusion) for bloodstream infections 2
• Rationale: Potential synergy despite carbapenem resistance, higher microbiological eradication rates 2

For clinical failures or high MIC isolates:

• Add rifampin (600 mg/day or every 12 hours) to sulbactam or colistin 2
• However, routine colistin-rifampin is NOT recommended due to lack of mortality benefit and increased hepatotoxicity 2

Avoid these combinations:

• Colistin plus vancomycin or glycopeptides: Significantly increased nephrotoxicity without clinical benefit 2
• Tigecycline monotherapy: Higher treatment failure rates compared to colistin-based regimens 2

Specific Clinical Scenarios

For Pneumonia (HAP/VAP):

• First choice: Ampicillin-sulbactam 9-12g/day if susceptible 1
• Second choice: Colistin monotherapy (combination not proven superior) 2
• Avoid tigecycline monotherapy (associated with excess mortality when MIC >2 mg/L) 2

For Bloodstream Infections:

• Weak recommendation for colistin-carbapenem combination over monotherapy 2
• Despite RCT evidence showing no benefit, retrospective studies suggest higher microbiological eradication 2

For Colistin-Resistant CRAB:

• Post-hoc analysis showed no benefit to adding meropenem when isolate is also colistin-resistant 2
• Consider minocycline (60-80% susceptibility rates reported) as alternative option 2
• Colistin-rifampin combination showed synergy in 100% of colistin-resistant strains in vitro 3

Treatment Duration

• Minimum 14 days for severe infections including VAP and bacteremia 1
• Extended courses may be needed for non-fermenting gram-negative bacilli 2

Critical Monitoring Parameters

• Renal function: Check every 2-3 days on colistin (nephrotoxicity occurs in 33% of patients) 2, 1
• Hepatic function: Monitor if using rifampin (increased hepatotoxicity risk) 2
• Microbiological surveillance: Repeat cultures to assess for emergence of resistance, particularly with colistin 1

Common Pitfalls to Avoid

• Do not use tigecycline as monotherapy for CRAB pneumonia 2
• Do not routinely combine colistin with glycopeptides (vancomycin/teicoplanin) due to additive nephrotoxicity 2
• Do not assume combination therapy is always superior—high-quality RCTs show no mortality benefit for most combinations 2
• Do not use standard carbapenem doses in combinations; use high-dose extended infusions if combining 2, 1