What is the typical dosing regimen for polymyxin B and colistin (polymyxin E) in patients with normal renal function?

Polymyxin B and Colistin Dosing in Patients with Normal Renal Function

For patients with normal renal function, polymyxin B should be dosed at 1.5-3 mg/kg/day divided into 2 doses with a loading dose of 2-2.5 mg/kg, while colistin (polymyxin E) should be administered with a loading dose of 6-9 million IU followed by 4.5 million IU every 12 hours. 1, 2, 3

Polymyxin B Dosing

Standard Dosing

• Loading dose: 2-2.5 mg/kg 1
• Maintenance dose: 1.5-3 mg/kg/day divided into 2 doses 1
• FDA labeling recommends 15,000 to 25,000 units/kg/day for adults with normal renal function 3
  • Note: 1 mg of polymyxin B = 10,000 units

Administration

• Can be administered as continuous infusion 1
• Intravenous administration is preferred over intramuscular due to severe pain at injection sites 3
• Dosing should be based on actual body weight, though some guidelines suggest using ideal body weight for obese patients 2

Colistin (Polymyxin E) Dosing

Standard Dosing

• Loading dose: 6-9 million IU (equivalent to 5 mg/kg colistin base activity) 1, 2
  • Loading dose should be administered to all patients regardless of renal function
• Maintenance dose: 9 million IU/day divided into 2-3 doses 1
  • Typically administered as 4.5 million IU every 12 hours 2
• FDA labeling recommends 2.5-5 mg/kg/day of colistin base activity divided into 2-4 doses 4

Administration

• Administered as colistimethate sodium (CMS), which is the inactive prodrug of colistin
• Extended interval dosing (4.5 million IU every 12 hours) is recommended for critically ill patients 2
• Important conversion: 1 million IU of colistin is equivalent to approximately 80 mg of CMS or 30 mg of colistin base activity 1, 2

Clinical Considerations

Pharmacokinetic Considerations

• Polymyxin B clearance is not significantly affected by renal function, with recent studies showing comparable drug exposure in patients with normal and impaired renal function 5, 6
• Colistin requires a loading dose because plasma concentrations may be suboptimal for 2-3 days before reaching steady state 1
• Polymyxin B may be preferred over colistin in patients with renal impairment as it doesn't require dosage adjustments based on renal function 1, 6

Monitoring

• Close monitoring of renal function is essential during therapy with both agents, as 14-20% of patients may develop acute kidney injury 2
• Therapeutic drug monitoring may be beneficial but is not widely available

Common Pitfalls

1. Inconsistent dosing units: Colistin may be prescribed in different units (IU vs. mg), which can lead to dosing errors 2
2. Inadequate loading doses: Failure to administer loading doses can result in suboptimal plasma concentrations for several days 1
3. Inappropriate renal dose adjustments for polymyxin B: Unlike colistin, polymyxin B dosing should not be adjusted based on renal function 6

Indications and Duration

• Reserved for infections caused by multidrug-resistant gram-negative bacteria
• Treatment duration depends on infection site:
  • Complicated urinary tract infections: 5-10 days
  • Complicated intra-abdominal infections: 5-10 days
  • Ventilator-associated or hospital-acquired pneumonia: 10-14 days
  • Bacteremia: 10-14 days 2

Both polymyxin B and colistin are critical last-line antibiotics for multidrug-resistant gram-negative infections, and their use should be guided by antimicrobial susceptibility testing and, when possible, infectious disease consultation.