Treatment of Carbapenem-Resistant Acinetobacter baumannii in Elderly Patients with Renal Impairment
For an elderly patient with impaired renal function and suspected carbapenem-resistant Acinetobacter baumannii (CRAB) infection, initiate combination therapy with colistin (using a loading dose of 5 mg CBA/kg IV followed by renally-adjusted maintenance dosing) plus high-dose ampicillin-sulbactam (3g sulbactam every 8 hours as a 4-hour infusion), provided the sulbactam MIC is ≤4 mg/L. 1
Initial Empiric Treatment Approach
Start with combination therapy immediately when CRAB is clinically suspected, as early appropriate antimicrobial therapy consistently improves survival. 2 The backbone of therapy must be colistin with appropriate loading and maintenance dosing, combined with a second active agent. 1, 3
Colistin Dosing in Renal Impairment
Always administer a loading dose of 6-9 million IU (or 5 mg CBA/kg) regardless of renal function, as colistin has a long half-life and suboptimal plasma concentrations occur for 2-3 days without loading. 4, 1
For maintenance dosing with renal impairment, use the formula: 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours. 1, 5
For creatinine clearance 50-79 mL/min: 2.5-3.8 mg/kg divided into 2 doses per day 5
For creatinine clearance 30-49 mL/min: 2.5 mg/kg once daily or divided into 2 doses 5
For creatinine clearance 10-29 mL/min: 1.5 mg/kg every 36 hours 5
Selection of Second Agent Based on Susceptibility
If Sulbactam-Susceptible (MIC ≤4 mg/L)
Ampicillin-sulbactam is strongly preferred over polymyxin monotherapy due to superior safety profile with comparable efficacy. 4, 1, 6
- Dose: 3g sulbactam every 8 hours (9-12g/day total) as a 4-hour infusion 4, 7
- Nephrotoxicity is significantly lower with sulbactam (15.3%) compared to colistin (33%), though clinical cure rates are comparable 4
- The 4-hour infusion optimizes pharmacokinetic/pharmacodynamic properties and allows treatment of isolates with MIC up to 8 mg/L 4, 7
If Carbapenem MIC ≤32 mg/L
Add high-dose carbapenem (meropenem 2g every 8 hours) to colistin despite resistance, as this combination shows benefit at these MIC levels. 1 However, avoid this combination if carbapenem MIC >32 mg/L due to lack of benefit and potential toxicity. 7
Alternative Second Agent Options
- High-dose tigecycline: 200mg loading dose, then 100mg every 12 hours (always in combination, never as monotherapy for bacteremia due to suboptimal serum concentrations) 4, 7
- Rifampicin: 600mg daily or every 12 hours (always in combination) 4
- Fosfomycin: 12-24g/day in 3-4 doses (always in combination) 4, 7
Critical Monitoring Requirements
Monitor renal function closely as nephrotoxicity occurs in up to 33% of colistin-treated patients and up to 57% with polymyxin-based regimens. 4, 8 In elderly patients with baseline renal impairment, this risk is substantially elevated. 8
- Check serum creatinine every 2-3 days during therapy 1
- Adjust colistin dosing immediately if creatinine clearance changes 5
- Consider switching to sulbactam-based therapy if nephrotoxicity develops and isolate is sulbactam-susceptible 4, 6
Combinations to Avoid
Never combine colistin with rifampin alone, as this lacks proven clinical benefit despite microbiological eradication. 4, 7
Never combine colistin with vancomycin or other glycopeptides, as this increases nephrotoxicity without added benefit—particularly dangerous in elderly patients with renal impairment. 4, 1, 7
Treatment Duration
Maintain therapy for 2 weeks for severe infections including pneumonia, bacteremia, or septic shock. 7 For less severe infections without bacteremia, 7-10 days may be sufficient. 6
Site-Specific Considerations
For Pneumonia
- IV colistin with loading dose plus high-dose carbapenem (if MIC ≤32 mg/L) or sulbactam 1
- Consider nebulized colistin as adjunctive therapy (though evidence is limited) 7
For Bloodstream Infections
- Same regimen as pneumonia 1
- Never use tigecycline as monotherapy due to suboptimal serum concentrations and higher failure rates 7
For Urinary Tract Infections
- Ampicillin-sulbactam 3g sulbactam every 8 hours as first-line if sulbactam-susceptible 1
- Colistin achieves excellent urinary concentrations and is preferred if sulbactam-resistant 1
Common Pitfalls in Elderly Patients with Renal Impairment
- Failing to give a loading dose of colistin leads to 2-3 days of subtherapeutic levels and increased mortality 4, 1
- Using standard colistin maintenance doses without renal adjustment causes severe nephrotoxicity 5
- Delaying therapy while awaiting cultures in critically ill patients with known CRAB colonization increases mortality 7
- Using tigecycline monotherapy for bacteremia results in treatment failure 7
- Overlooking sulbactam susceptibility testing, missing the opportunity to use a safer, equally effective agent 4, 6