What is the recommended dose of polymyxin B (Polymyxin B) for adults?

Polymyxin B Dosing for Adults

The recommended dose of polymyxin B for adults is 2.5-3.0 mg/kg/day divided into two daily intravenous doses, with a loading dose of 2-2.5 mg/kg to rapidly achieve therapeutic levels. 1

Standard Dosing Regimen

Loading Dose

• Administer 2-2.5 mg/kg as a loading dose to achieve optimal plasma levels on the first day 1
• This loading dose is critical for rapid attainment of therapeutic concentrations 1

Maintenance Dose

• 1.5-3.0 mg/kg/day divided into 2 doses (typically every 12 hours) 1
• FDA-approved dosing: 15,000-25,000 units/kg/day (equivalent to 1.5-2.5 mg/kg/day, as 1 mg = 10,000 units) 2
• Maximum daily dose should not exceed 25,000 units/kg/day 2

Infusion Method

• Dissolve 500,000 polymyxin B units in 300-500 mL of 5% Dextrose Injection for continuous drip 2
• Infusions may be given every 12 hours 2

Renal Function Considerations

A critical distinction: Unlike colistin, polymyxin B does NOT require dose adjustment based on renal function. 1, 3

• Polymyxin B plasma concentrations are not influenced by renal function 1
• Studies demonstrate no significant difference in polymyxin B exposure between patients with normal renal function (AUC 63.5 ± 16.6 mg·h/L) versus renal insufficiency (AUC 56.0 ± 17.5 mg·h/L, P = 0.42) 3
• No dosage adjustment necessary for patients on continuous renal replacement therapy (CRRT) 1, 4
• This represents a major advantage over colistin, which requires complex dose adjustments 1

Important Caveat

The FDA label recommends dose reduction for renal impairment 2, but recent high-quality evidence contradicts this recommendation 1, 3. The 2015 Intensive Care Medicine guidelines and 2017 pharmacokinetic studies support maintaining standard dosing regardless of renal function 1, 3.

Clinical Context and Indications

When to Use Polymyxin B

• Reserved for multidrug-resistant gram-negative infections where resistance exists to all beta-lactams, fluoroquinolones, and other first-line agents 4
• Should only be used in settings with high prevalence of multidrug resistance and local expertise 1
• Considered a last-resort agent for carbapenem-resistant gram-negative bacterial infections 4

Specific Infection Types

For hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP):

• Use as part of combination therapy with gram-positive coverage and another antipseudomonal agent 1
• Polymyxin B 2.5-3.0 mg/kg/day divided in 2 daily IV doses 1

Monitoring and Safety

Nephrotoxicity Considerations

• Polymyxin B has lower incidence of renal failure compared to colistin 1, 5
• Regular monitoring of renal function is still recommended during therapy 4
• Consider therapeutic drug monitoring where available 4

Target Exposure

• Target AUC₂₄ₕ: 50-100 mg·h/L for optimal efficacy while minimizing nephrotoxicity 6
• For severe infections with MIC ≥2 mg/L, higher doses may be needed but increase nephrotoxicity risk 7, 8

Practical Dosing Algorithm

1. Calculate loading dose: 2-2.5 mg/kg actual body weight 1
2. Administer loading dose as 3-hour infusion 8
3. Calculate maintenance dose: 1.25-1.5 mg/kg every 12 hours 1, 8
4. Do NOT adjust for renal function (contrary to older recommendations) 1, 3
5. Continue same dose if patient requires CRRT 1, 4
6. Monitor renal function but maintain dosing unless severe toxicity develops 4