Treatment for Acinetobacter Infections
For carbapenem-susceptible Acinetobacter infections, carbapenems (imipenem, meropenem, or doripenem) are the drugs of choice, while for carbapenem-resistant strains, high-dose ampicillin-sulbactam (9-12g/day) is preferred if the isolate has MIC ≤4 mg/L, or intravenous polymyxins (colistin) if resistant to sulbactam. 1, 2
Initial Assessment and Empirical Therapy
Obtain cultures and susceptibility testing immediately before starting antibiotics. 2, 3
Risk Stratification for Empirical Coverage
Consider empirical coverage for Acinetobacter when patients have: 1
- Prior colonization with Acinetobacter species
- Admission during an active outbreak
- Prolonged ICU stay with multiple invasive procedures
- Recent carbapenem or third-generation cephalosporin exposure
- Mechanical ventilation or central venous catheterization
In areas with high carbapenem resistance rates, include a polymyxin (colistin) in the empirical regimen for suspected Acinetobacter. 1
Definitive Therapy Based on Susceptibility
Carbapenem-Susceptible Isolates
Use carbapenems as monotherapy for non-severe infections: 1, 3
- Imipenem: 0.5-1g every 6 hours (cannot use extended infusion due to drug instability) 1
- Meropenem: 2g every 8 hours as extended infusion 1
- Doripenem: Similar dosing to meropenem 3
Important caveat: Ertapenem lacks activity against Acinetobacter and should never be used. 3, 4
Carbapenem-Resistant Isolates
First-Line: Ampicillin-Sulbactam (if MIC ≤4 mg/L)
Administer 3g sulbactam (9g ampicillin-sulbactam) every 8 hours as a 4-hour infusion for a total of 9-12g sulbactam daily. 1, 2, 3
This regimen is preferred over polymyxins when susceptible because: 1
- Equivalent clinical cure rates to carbapenems (including some carbapenem-resistant isolates)
- Lower nephrotoxicity compared to colistin (15.3% vs 33%)
- Better safety profile overall
Second-Line: Polymyxins (if resistant to sulbactam)
Colistin (polymyxin E) dosing: 2, 3, 5
- Loading dose: 9 million IU (or 6-9 million IU based on institutional protocol)
- Maintenance: 4.5 million IU every 12 hours (total 9 million IU/day)
- Adjust for renal function using weight-based calculations
Monitor renal function closely—nephrotoxicity occurs in up to 33% of patients receiving colistin. 1, 2, 5
For severe pneumonia, add adjunctive inhaled colistin to intravenous therapy. 1, 3 Colistin for inhalation must be administered promptly after mixing with sterile water per FDA guidance. 1
Combination Therapy
When to Use Combination Therapy
Use combination therapy with two active agents for: 2, 3
- Severe infections (septic shock, high mortality risk >25%)
- Ventilator-associated pneumonia
- Bacteremia with severe sepsis
- Clinical failures on monotherapy
- Isolates with MIC at upper limit of susceptibility
Recommended Combinations
For carbapenem-resistant Acinetobacter with meropenem MIC <8 mg/L, consider high-dose extended-infusion meropenem (2g every 8 hours) plus colistin. 2, 3
Alternative combination options: 1, 3
- Colistin + tigecycline
- Colistin + fosfomycin
- Ampicillin-sulbactam + tigecycline
Combinations to AVOID
- Colistin + rifampin (no proven benefit, recommended against by IDSA) 1
- Colistin + vancomycin (increased nephrotoxicity without benefit) 1, 2
- Polymyxin + meropenem for high-level carbapenem resistance (MIC >16 mg/L) 3, 5
Treatment Duration
For severe infections (VAP, bacteremia with sepsis): 2, 3
- Continue therapy for 2 weeks minimum
- Extend duration based on clinical response and source control
For uncomplicated urinary tract infections: 5
- 7 days for uncomplicated cases
- Up to 14 days for complicated UTIs with systemic symptoms
For skin/soft tissue infections and other sites: 3
- Individualize based on infection severity and clinical response
- Generally 10-14 days for most infections
Special Considerations by Infection Site
Respiratory Tract Infections (HAP/VAP)
For documented Acinetobacter VAP, use carbapenem or ampicillin-sulbactam based on susceptibility. 1
Consider aerosolized antibiotics (colistin or aminoglycosides) as adjunctive therapy for highly resistant strains or clinical failures. 1 Aminoglycoside penetration into respiratory tissue is limited, making aerosol delivery potentially advantageous. 1
Urinary Tract Infections
Remove or replace urinary catheters when possible—catheterization is a major risk factor for Acinetobacter UTI. 5
For uncomplicated UTIs with susceptible isolates, monotherapy is sufficient. 5
Meningitis/CNS Infections
Imipenem-cilastatin is NOT indicated for meningitis due to lack of safety and efficacy data. 4 Consider alternative agents with better CNS penetration or consult infectious disease specialists for carbapenem-resistant CNS infections.
Agents NOT Recommended
Tigecycline should NOT be used for Acinetobacter HAP/VAP due to poor outcomes in clinical trials. 1 It may be considered only as part of combination therapy for non-respiratory infections when other options are exhausted. 1, 3
Aminoglycoside monotherapy is NOT recommended due to variable susceptibility and poor tissue penetration. 1
Common Pitfalls to Avoid
- Using ertapenem for Acinetobacter (completely inactive) 3, 4
- Underdosing sulbactam (must use 9-12g/day, not standard ampicillin-sulbactam dosing) 1, 2
- Failing to adjust colistin for renal function (leads to increased toxicity) 2, 5
- Using carbapenems in areas with high resistance rates without susceptibility data 1
- Continuing combination therapy after septic shock resolves when susceptibilities are known 1
- Not monitoring renal function in patients on polymyxins 1, 2, 5
Emerging Resistance Concerns
Heteroresistance to colistin has been reported in 18.7-100% of isolates in some series, potentially leading to rapid resistance development during therapy. 1 While routine detection is not feasible, observe for colonies within inhibition zones on susceptibility testing as an indirect marker. 1
The emergence of carbapenem-resistant clones necessitates using optimal (high) doses of carbapenems when they remain active. 1