Treatment of Multidrug-Resistant Acinetobacter baumannii Infections
For multidrug-resistant Acinetobacter baumannii infections, use intravenous colistin-based combination therapy as first-line treatment, with specific regimens determined by infection site and severity. 1, 2
Primary Treatment Algorithm by Infection Site
Pneumonia (HAP/VAP)
- Colistin IV (loading dose 5 mg CBA/kg, then maintenance 2.5 mg CBA × [1.5 × CrCl + 30] q12h) PLUS a carbapenem (meropenem 2g IV q8h or imipenem 500mg IV q6h) PLUS adjunctive inhaled colistin for at least 7 days 3, 1, 2
- Duration: 10-14 days for HAP/VAP 2
- Alternative if MIC to sulbactam ≤4 mg/L: Sulbactam 9-12 g/day IV in 3-4 divided doses as 4-hour infusions 3, 1, 2
Bloodstream Infections
- Colistin IV (same dosing as above) with or without carbapenem for 10-14 days 1, 2
- Alternative: Colistin + tigecycline (loading 100mg IV, then 50mg IV q12h) 1
- Extend to 2 weeks if severe sepsis or septic shock present 2
Complicated Intra-abdominal Infections
- Colistin 5 mg CBA/kg IV loading, then 2.5 mg CBA (1.5 × CrCl + 30) IV q12h PLUS tigecycline 100mg IV loading, then 50mg IV q12h OR meropenem 1g IV q8h by extended infusion for 5-7 days 3
Complicated Urinary Tract Infections
- Aminoglycosides preferred: Gentamicin 5-7 mg/kg/day IV once daily OR amikacin 15 mg/kg/day IV once daily for 5-7 days 3
- Alternative: Colistin-based regimen if aminoglycoside-resistant 3
Critical Dosing Considerations
Colistin Dosing (FDA-Approved)
- Always use loading dose even in renal impairment—skipping it causes 2-3 days of subtherapeutic levels and increases mortality 2, 4
- Standard dose: 2.5-5 mg/kg/day divided into 2-4 doses for normal renal function 4
- Renal adjustment required: See specific formula above for maintenance dosing 2, 4
- Monitor renal function closely: nephrotoxicity risk 33-39% 2
Sulbactam Dosing
- 9-12 g/day in 3-4 divided doses, administered as 4-hour infusions 3, 1, 2
- Only use if MIC ≤4 mg/L by Etest (do not rely on automated testing) 3, 2
- Preferred over colistin when susceptible due to significantly lower nephrotoxicity (15.3% vs 33%) 3, 1, 2
Special Populations
Patients with Renal Impairment
- Sulbactam-based therapy (9-12 g/day) is preferred first-line when MIC ≤4 mg/L to preserve kidney function 2
- If colistin required: adjust maintenance dose using formula 2.5 mg CBA × (1.5 × CrCl + 30) IV q12h, but do NOT skip loading dose 2, 4
- Avoid tigecycline monotherapy due to poor outcomes 1, 2
Patients in Septic Shock
- Mandatory combination therapy with two active agents 2
- Colistin-carbapenem combinations show best outcomes in network meta-analyses 1
Critical Pitfalls to Avoid
What NOT to Do
- Never use tigecycline as monotherapy for pneumonia or bloodstream infections—associated with poor outcomes and very low lung concentrations (0.01-0.02 mg/L) 3, 1
- Do not add rifampicin to colistin—a randomized trial of 210 patients showed no mortality benefit and should not be used routinely 3, 5
- Never use aminoglycoside monotherapy for pneumonia 3
- Do not skip colistin loading dose in any patient, including those with renal failure 2
Susceptibility Testing Requirements
- Obtain susceptibility testing before finalizing therapy—resistance patterns vary widely 1
- For sulbactam: use Etest with MIC ≤4 mg/L cutoff; automated methods are unreliable 3, 2
- Test for colistin susceptibility as resistance rates are increasing, particularly in Asia 6
Emerging Evidence
Newer Agents
- Sulbactam-durlobactam showed non-inferiority to colistin in the ATTACK trial (2023) with significantly lower nephrotoxicity (13% vs 38%, p<0.001) and 28-day mortality of 19% vs 32% 7
- Minocycline demonstrates 60-80% susceptibility against MDR strains and should be used in combination, not as monotherapy 1
- Cefiderocol and eravacycline show promising in vitro activity but limited clinical data 1