What are the guidelines for treating Acinetobacter infections?

Guidelines for Treating Acinetobacter Infections

For patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections, combination therapy including two in vitro active antibiotics among polymyxins, aminoglycosides, tigecycline, or sulbactam combinations is recommended for severe and high-risk infections. 1

First-Line Treatment Options Based on Susceptibility

For Carbapenem-Susceptible Acinetobacter

• Carbapenems: First choice for susceptible isolates
  • Imipenem 0.5-1g every 6 hours 2, 3
  • Meropenem 2g every 8 hours (extended infusion recommended) 2

For Carbapenem-Resistant Acinetobacter (CRAB)

Severe Infections

1. For CRAB susceptible to sulbactam:

   • Ampicillin-sulbactam is recommended (conditional recommendation, low-quality evidence) 1
   • Dosing: 9-12g/day of sulbactam component in 3 doses (4-hour infusion recommended) 2

2. For CRAB resistant to sulbactam:

   • Polymyxins (colistin or polymyxin B) if active in vitro 1
     • Colistin: Loading dose 6-9 million IU, followed by 9 million IU/day in 2-3 doses 2
     • Polymyxin B: Loading dose 2-2.5 mg/kg, followed by 1.5-3 mg/kg/day in 2 doses 2
   • High-dose tigecycline if active in vitro 1
     • Loading dose 200 mg followed by 100 mg every 12h 1
   • For polymyxin-only susceptible CRAB: Intravenous polymyxin with adjunctive inhaled colistin 1

3. Newer option (recently approved):

   • Sulbactam-durlobactam showed non-inferiority to colistin with significantly lower nephrotoxicity (19% vs 32% mortality) 4

Non-Severe or Low-Risk Infections

• Monotherapy chosen from among in vitro active antibiotics, selected on an individual basis according to the source of infection 1

Combination Therapy Recommendations

• For severe and high-risk CRAB infections: Combination therapy with two in vitro active antibiotics is recommended 1

• Specifically NOT recommended combinations:

  • Polymyxin-meropenem combination (strong recommendation against) 1
  • Polymyxin-rifampin combination (strong recommendation against) 1
  • Colistin plus glycopeptides (e.g., vancomycin) is discouraged 1

• For CRAB with meropenem MIC ≤8 mg/L: Consider carbapenem combination therapy using high-dose extended-infusion carbapenem dosing 1

Special Considerations

Site-Specific Treatment

• For pneumonia (HAP/VAP):
  • Standard tigecycline dosing is inadequate for pulmonary infections 1
  • If tigecycline is used for pulmonary infections, high-dose regimen is suggested 1
  • Adjunctive inhaled colistin for polymyxin-only susceptible CRAB pneumonia 1

Duration of Therapy

• For VAP: 7-day course of antimicrobial therapy is recommended rather than longer duration 1
• For other infections: Duration should be individualized based on infection site, clinical response, and microbiological data 1

Monitoring and Pitfalls

Common Pitfalls

1. Inappropriate empiric therapy: Significantly increases mortality - one study found no survivors among patients receiving inappropriate therapy for A. baumannii bacteremia 2

2. Tigecycline issues:

   • Standard dosing inadequate for pneumonia 1
   • Risk of resistance development during therapy 5
   • Not recommended as monotherapy for CRAB pneumonia 1

3. Nephrotoxicity concerns:

   • Polymyxins have high nephrotoxicity rates (19-50%) 6
   • Consider sulbactam-based regimens when possible due to better safety profile 2, 4

4. Resistance development:

   • Monitor for heteroresistance to colistin and carbapenems 2
   • Regular monitoring for relapse of infection is crucial 5

Evidence Quality Assessment

Most recommendations for CRAB treatment are based on low or very low-quality evidence 1. The strongest evidence (high/moderate quality) exists for recommendations against specific combinations (polymyxin-meropenem and polymyxin-rifampin) 1.

Recent clinical trial data for sulbactam-durlobactam shows promising results with lower mortality and significantly reduced nephrotoxicity compared to colistin for CRAB infections 4, potentially representing an important advance in treatment options.