Treatment Options for Multidrug-Resistant (MDR) Acinetobacter Infections
For MDR Acinetobacter infections, colistin-based combination therapy is the recommended treatment option, with specific regimens depending on the infection site and local susceptibility patterns. 1
First-line Treatment Options by Infection Site
Pneumonia
- Recommended regimen: Colistin (5 mg CBA/kg IV loading dose, then 2.5 mg CBA per formula IV q12h) with or without a carbapenem (imipenem/cilastatin 500 mg IV q6h or meropenem 2 g IV q8h) plus adjunctive inhaled colistin (1.25-15 MIU/day in 2-3 divided doses) 1
- Duration: At least 7 days 1
- Carbapenem addition may provide synergistic benefit if the carbapenem MIC is ≤32 mg/L, with extended infusion time (>3 hours) recommended 1
Bloodstream Infections
- Recommended regimen: Colistin (5 mg CBA/kg IV loading dose, then 2.5 mg CBA per formula IV q12h) with or without a carbapenem (imipenem/cilastatin 500 mg IV q6h or meropenem 2 g IV q8h) 1
- Duration: 10-14 days 1
- Colistin-carbapenem combination therapy has shown the highest clinical cure rates in network meta-analyses 1
Alternative Treatment Options
For Pneumonia
- Sulbactam 6-9 g/day IV in 3-4 divided doses 1
- Colistin + tigecycline (100 mg IV loading dose, then 50 mg IV q12h) + sulbactam (6-9 g/day IV in 3-4 divided doses) 1
For Bloodstream Infections
- Colistin + tigecycline (100 mg IV loading dose, then 50 mg IV q12h) 1
- Colistin + sulbactam (6-9 g/day IV in 3-4 divided doses) 1
Important Considerations for Specific Agents
Colistin (Polymyxin E)
- Considered the backbone of treatment for MDR Acinetobacter infections 1
- Dosing requires careful calculation based on colistin base activity (CBA) and renal function 1
- Main adverse effect is nephrotoxicity, which requires close monitoring 1, 2
Sulbactam
- Has intrinsic activity against Acinetobacter species 1
- Recommended dose for severe infections: 9-12 g/day in 3 daily doses 1
- May be preferable to colistin for strains with MIC ≤4 mg/L due to better safety profile 1
- Often administered as ampicillin-sulbactam combination 1
Tigecycline
- Not recommended as monotherapy for pneumonia due to poor outcomes 1
- May be used for approved indications (cSSSIs and cIAIs) if MIC ≤1 mg/L 1
- For severe infections, high-dose regimen (200 mg loading dose, then 100 mg q12h) is suggested 1
- Always use in combination with another active agent for non-approved indications 1
- Limited efficacy for bloodstream infections due to low serum concentrations 1
Carbapenems
- First choice for Acinetobacter infections in areas with low carbapenem resistance 1
- In high resistance areas, should only be used in combination therapy if synergy is expected (MIC ≤32 mg/L) 1
- Extended infusion recommended for meropenem (>3 hours) 1
Combination vs. Monotherapy
- Combination therapy is generally preferred over monotherapy for severe MDR Acinetobacter infections 1
- Meta-analyses show higher clinical cure rates with combination therapy compared to monotherapy 1
- Colistin-carbapenem combinations have shown the best outcomes in network meta-analyses 1
Emerging Options
- Minocycline has shown in vitro activity against MDR Acinetobacter (60-80% susceptibility) and may be considered when other options are limited 1
- Newer agents like eravacycline and cefiderocol show promising in vitro activity but clinical data was limited at the time of guideline development 1
Pitfalls and Caveats
- Tigecycline monotherapy should be avoided for pneumonia and bloodstream infections 1
- Aminoglycoside monotherapy is not recommended due to PK/PD limitations in lungs, abscesses, and CNS 1
- Susceptibility testing is essential before initiating therapy, as resistance patterns vary widely 1
- There have been reports of developing tigecycline resistance during standard treatment due to MDR efflux pump mechanisms 3
- Infectious disease consultation is highly recommended for management of all MDR Acinetobacter infections 1