What is the best treatment option for an elderly patient with impaired renal function and non-valvular atrial fibrillation who has a suspected carbapenem-resistant Acinetobacter baumannii infection, considering the potential use of polymyxin (colistin)?

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 infection, initiate combination therapy with colistin (using a loading dose of 5 mg CBA/kg regardless of renal function) plus high-dose ampicillin-sulbactam (3g sulbactam every 8 hours as a 4-hour infusion), provided the sulbactam MIC is ≤4 mg/L. 1

Empirical Treatment Approach

• Start colistin immediately as part of empirical treatment in patients with high suspicion of carbapenem-resistant A. baumannii, particularly during outbreaks or in colonized patients 2
• Polymyxin is the cornerstone of empirical therapy for suspected carbapenem-resistant A. baumannii in critically ill patients 2
• Do not use tigecycline or sulbactam as monotherapy for empirical treatment 2

Critical Colistin Dosing in Renal Impairment

Loading Dose (Essential - Do Not Skip)

• Administer a loading dose of 5 mg CBA/kg (or 6-9 million IU) regardless of renal function to achieve optimal plasma concentrations immediately 1, 2
• Failure to give a loading dose results in 2-3 days of subtherapeutic levels and increased mortality 1, 2
• This is the single most common and dangerous pitfall in colistin therapy 1

Maintenance Dosing

• Use the formula: 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours for patients with renal impairment 1, 3
• For patients with creatinine clearance 50-79 mL/min: 2.5-3.8 mg/kg divided into 2 doses per day 4
• For patients with creatinine clearance 30-49 mL/min: 2.5 mg/kg once daily or divided into 2 doses 4
• For patients with creatinine clearance 10-29 mL/min: 1.5 mg/kg every 36 hours 4

Selection of Second Agent Based on Susceptibility

• Ampicillin-sulbactam is the preferred second agent for sulbactam-susceptible isolates (MIC ≤4 mg/L) due to superior safety profile and comparable efficacy to polymyxin monotherapy 1, 2
• Dose ampicillin-sulbactam at 3g sulbactam every 8 hours as a 4-hour infusion (9-12g/day total), which optimizes pharmacokinetic/pharmacodynamic properties and allows treatment of isolates with MIC up to 8 mg/L 1, 2
• Sulbactam demonstrates better outcomes than colistin in multiple studies: clinical cure rates are similar, but microbiologic cure rates at day 7 are significantly higher with sulbactam, and nephrotoxicity is lower (15.3% vs 33%) 2, 5

Nephrotoxicity Monitoring and Management

• Monitor renal function closely as nephrotoxicity occurs in up to 33% of patients receiving colistin 1, 2
• Nephrotoxicity is significantly higher with colistin (33%) compared to ampicillin-sulbactam (15.3%) 2, 5
• Adjust colistin dosing immediately if creatinine clearance changes 1
• Signs of impaired renal function include: diminishing urine output, rising BUN and serum creatinine, and decreased creatinine clearance 4
• If renal impairment develops, discontinue therapy immediately; if reinstatement is necessary, adjust dosing after drug plasma levels have fallen 4

Combinations to Avoid

• Do not combine colistin with rifampin alone - lacks proven clinical benefit despite microbiological eradication 1, 3
• Avoid combining colistin with vancomycin or other glycopeptides - increases nephrotoxicity without added benefit 1, 3
• Do not use aminoglycosides or other polymyxins concomitantly except with greatest caution due to neuromuscular junction interference 4
• Avoid sodium cephalothin with colistin as it enhances nephrotoxicity 4

Treatment Duration

• Maintain therapy for 14 days for severe infections including pneumonia, bacteremia, or septic shock 1
• For less severe infections without bacteremia: 7-10 days 1

Special Considerations for Elderly Patients

• Base dosing on ideal body weight in obese individuals, not actual body weight 4
• The decline in renal function with advanced age must be considered when dosing 4
• Elderly patients are at higher risk for nephrotoxicity and neuromuscular blockade 4

Alternative: Polymyxin B

• Polymyxin B may be a suitable alternative to colistin with potentially less nephrotoxicity 2
• Recommended dose: loading dose of 2-2.5 mg/kg, then 1.5-3 mg/kg/day in 2 doses 2
• Dose adjustment is not necessary for renal replacement therapy with polymyxin B 2
• Polymyxin B is available as an active drug (not a prodrug) and plasma concentration is not influenced by renal function 2

Common Pitfalls to Avoid

• Failing to administer a loading dose - leads to 2-3 days of subtherapeutic levels and increased mortality 1, 2
• Overlooking sulbactam susceptibility testing - misses opportunity to use a safer, equally effective agent 1
• Using tigecycline as monotherapy for bacteremia - results in treatment failure due to suboptimal serum concentrations 1
• Administering excessive colistin doses beyond renal excretory capacity - leads to toxic accumulation, further renal impairment, and potential neuromuscular blockade 4

Neuromuscular Complications

• Be vigilant for muscle weakness and apnea, which indicate interference with nerve transmission at neuromuscular junctions 4
• Avoid curariform muscle relaxants (tubocurarine), ether, succinylcholine, gallamine, and decamethonium as they potentiate neuromuscular blockade 4

Clinical Outcomes Data

• In carbapenem-resistant A. baumannii VAP, colistin was associated with higher microbiologic failure rates at day 7 (48% vs 18%), more significant elevation in creatinine, and increased 30-day mortality compared to ampicillin-sulbactam 5
• Overall good outcomes with colistin occur in 58% of patients, but only 25% for pneumonia cases 6
• Loading dose colistin increases 30-day survival by 1.70 times compared to non-loading dose (adjusted HR 1.70,95% CI 1.17-2.50) 7