What is the recommended treatment for a patient with an Acinetobacter infection?

Treatment of Acinetobacter Infections

For carbapenem-susceptible Acinetobacter, use carbapenems (imipenem or meropenem) as first-line therapy; for carbapenem-resistant strains, ampicillin-sulbactam is preferred when sulbactam MIC ≤4 mg/L, with intravenous polymyxins reserved for isolates resistant to both. 1

Initial Assessment and Susceptibility Testing

• Treatment decisions must be guided by antimicrobial susceptibility testing and local resistance patterns. 1, 2
• Obtain cultures before initiating therapy, but do not delay empiric treatment in critically ill patients with known carbapenem-resistant Acinetobacter baumannii (CRAB) colonization or during outbreaks. 1

Carbapenem-Susceptible Acinetobacter

First-Line Therapy

• Carbapenems are the drugs of choice for carbapenem-susceptible isolates. 3, 1, 2
• Imipenem: 0.5-1 g IV every 6 hours (FDA-approved for lower respiratory tract and skin/soft tissue infections caused by Acinetobacter). 4
• Meropenem: 2 g IV every 8 hours as an extended infusion for optimal outcomes. 1, 2
• Doripenem is an alternative carbapenem option with similar efficacy. 1

Important Considerations

• Extended infusion is recommended for meropenem but not possible for imipenem due to drug instability. 1
• High-dose meropenem may increase seizure risk. 2

Carbapenem-Resistant Acinetobacter baumannii (CRAB)

First-Line Therapy Based on Sulbactam Susceptibility

• Ampicillin-sulbactam is the preferred first-line agent when sulbactam MIC ≤4 mg/L. 1
• Dose: 3 g sulbactam every 8 hours (9-12 g/day total) administered as 4-hour infusions. 1
• Sulbactam demonstrates comparable clinical outcomes to imipenem for severe infections with significantly lower nephrotoxicity than colistin (15.3% vs 33%). 1
• Microbiologic cure rates at day 7 are superior to colistin. 1

Polymyxin-Based Therapy

• For isolates sensitive only to polymyxins, use intravenous polymyxin (colistin or polymyxin B). 3, 2
• This is a strong recommendation when no other options exist. 3
• Regular monitoring of renal function is essential, as nephrotoxicity occurs in up to 33% of patients. 1, 2
• Adjust polymyxin dosing in patients with renal impairment. 2

Adjunctive Inhaled Therapy for Respiratory Infections

• Add adjunctive inhaled colistin for ventilator-associated pneumonia (VAP) caused by CRAB. 3, 1, 2
• Dose: 2 million IU every 8 or 12 hours, with higher doses (5 million IU every 8 hours) for non-resolving cases. 1
• Deliver using ultrasonic or vibrating plate nebulizers. 2
• Colistin for inhalation should be administered promptly after being mixed with sterile water. 3
• Nebulized aminoglycosides (tobramycin or amikacin) are alternatives based on susceptibility. 1

When to Use Adjunctive Nebulized Antibiotics

• Patients nonresponsive to systemic antibiotics. 1
• Recurrent VAP. 1
• Isolates with MICs close to susceptibility breakpoint. 1

Combination Therapy for Severe Infections

• Use combination therapy with two in vitro active agents for severe CRAB infections (septic shock, severe sepsis, or bacteremia). 1, 2, 5
• Recommended combinations include: 1, 5
  • Colistin + high-dose carbapenem (even if resistant, for synergy)
  • Colistin + sulbactam + tigecycline
  • Sulbactam or polymyxin + second agent (tigecycline, rifampicin, or fosfomycin)
• Colistin-carbapenem combinations have shown the best outcomes in network meta-analyses. 5
• For patients whose septic shock resolves when antimicrobial sensitivities are known, continued combination therapy is not recommended. 3

Agents to AVOID

• Never use tigecycline as monotherapy for Acinetobacter infections, particularly pneumonia and bloodstream infections. 3, 1, 2, 5, 6
• Tigecycline has poor outcomes due to very low concentrations in endothelial lining fluids (0.01-0.02 mg/L). 5
• There have been reports of tigecycline resistance developing during standard treatment in Acinetobacter infections. 6
• Never use aminoglycoside monotherapy for Acinetobacter infections. 3, 1, 2
• Never use ertapenem for A. baumannii. 1
• Do not use adjunctive rifampicin with colistin for CRAB. 3

Site-Specific Considerations

Meningitis/Ventriculitis

• Use intravenous antimicrobials plus intrathecal or intraventricular administration of colistin. 2
• Treatment duration: approximately 3 weeks. 1, 2

Ventilator-Associated Pneumonia

• Treatment duration: 7 days for VAP. 3
• For severe infections (VAP, bacteremia with severe sepsis/septic shock): treat for 2 weeks. 1

Less Severe Infections

• Shorter durations may be acceptable for less severe infections. 1

Empiric Therapy Considerations

• Include a polymyxin in empiric therapy when CRAB is suspected in the following scenarios: 2
  • Severe infections during an outbreak
  • Endemic situations
  • Previously colonized patients
• Do not use carbapenems in monotherapy for severe infections in areas with high rates of resistance. 2

Critical Monitoring and Common Pitfalls

• Monitor renal function closely in all patients receiving colistin. 1, 2
• Do not use nebulized antibiotics for colonization without infection. 1
• Do not delay appropriate therapy in critically ill patients with known CRAB colonization or during outbreaks. 1
• More frequent monitoring for relapse is suggested in Acinetobacter infections, as resistance can develop during treatment. 6
• If relapse is suspected, obtain blood and other specimens for culture and susceptibility testing. 6
• Infectious disease consultation is highly recommended for management of all multidrug-resistant Acinetobacter infections. 5