What is the recommended dose of colistin (polymyxin E) for a patient with impaired renal function?

Colistin Dosing in Patients with Impaired Renal Function

For patients with impaired renal function, colistin (polymyxin E) dosing should be adjusted according to creatinine clearance, with a loading dose of 6-9 million IU followed by maintenance doses adjusted based on the degree of renal impairment.

Dosing Algorithm Based on Renal Function

Loading Dose

• A loading dose of 6-9 million IU should be administered to all patients regardless of renal function 1, 2
• This is critical to rapidly achieve therapeutic levels and should not be skipped even in patients with renal impairment 1, 2

Maintenance Dosing Based on Creatinine Clearance

1. Normal renal function (CrCl ≥80 mL/min):

   • 4.5 million IU every 12 hours (9 million IU/day) 1

2. Mild renal impairment (CrCl 50-79 mL/min):

   • 2.5-3.8 mg/kg/day divided into 2 doses 3

3. Moderate renal impairment (CrCl 30-49 mL/min):

   • 2.5 mg/kg/day, either once daily or divided into 2 doses 3

4. Severe renal impairment (CrCl 10-29 mL/min):

   • 1.5 mg/kg every 36 hours 3

Special Situations

Continuous Renal Replacement Therapy (CRRT)

• A loading dose of 6-9 million IU followed by at least 9 million IU/day is recommended 1
• No dose adjustment is necessary when using polymyxin B as an alternative 1

Intermittent Hemodialysis

• Loading dose of 6-9 million IU followed by 2 million IU every 12 hours 1
• Dialysis should be performed toward the end of a colistin dosage interval 1

Administration Considerations

• Intravenous administration can be done as direct intermittent administration or continuous infusion 3
• For direct intermittent administration: administer half the total daily dose over 3-5 minutes every 12 hours 3
• For continuous infusion: administer half the total daily dose over 3-5 minutes, then infuse the remaining half over 22-23 hours 3

Monitoring and Safety

• Renal function must be closely monitored during colistin therapy 2
• 14-20% of patients may develop acute kidney injury during treatment 2
• Risk factors for nephrotoxicity include advanced age, pre-existing chronic kidney disease, and concomitant nephrotoxic medications 2

Common Pitfalls to Avoid

1. Inadequate loading dose: Failing to administer a loading dose results in suboptimal plasma concentrations for 2-3 days 1, 2
2. Incorrect dose calculation: Doses should be based on ideal body weight in obese patients 3
3. Failure to monitor renal function: Regular monitoring is essential as renal function may deteriorate during treatment 2
4. Inconsistent dosing units: Colistin may be prescribed in different units (IU vs. mg), which can lead to dosing errors 1

Alternative Considerations

• Polymyxin B may be a suitable alternative to colistin with potentially fewer side effects, particularly in patients with renal impairment 1
• For polymyxin B, the recommended dose is 1.5-3 mg/kg/day with a loading dose of 2-2.5 mg/kg 1
• Unlike colistin, polymyxin B dosing is not influenced by renal function, making it potentially safer in patients with fluctuating renal function 1

Colistin remains a critical antibiotic for treating multidrug-resistant gram-negative infections, but its use requires careful attention to dosing based on renal function to maximize efficacy while minimizing nephrotoxicity.