What is the recommended dosage administration for Colistin (polymyxin E) in patients with impaired renal function?

Colistin Dosage Administration 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 regardless of renal function, followed by maintenance doses based on the degree of renal impairment. 1, 2

Dosing Recommendations Based on Renal Function

Loading Dose

• A loading dose of 6-9 million IU (international units) should be administered to all patients regardless of renal function to rapidly achieve therapeutic levels 1
• The loading dose is critical as colistin displays a relatively long half-life in relation to dosing intervals 1

Maintenance Dosing by Renal Function Category

Normal Renal Function (CrCl ≥80 mL/min):

• 2.5-5 mg/kg/day divided into 2-4 doses, or 9 million IU/day in 2-3 divided doses 1, 2
• For critically ill patients with severe sepsis/septic shock: 4.5 million IU every 12 hours 1

Mild Renal Impairment (CrCl 50-79 mL/min):

• 2.5-3.8 mg/kg/day divided into 2 doses 2
• Maintenance dose should be individually adjusted according to creatinine clearance 1

Moderate Renal Impairment (CrCl 30-49 mL/min):

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

Severe Renal Impairment (CrCl 10-29 mL/min):

• 1.5 mg/kg every 36 hours 2

Special Populations

Patients on Renal Replacement Therapy

Continuous Renal Replacement Therapy (CRRT):

• A dose of at least 9 million IU/day is recommended 1
• Polymyxin B may be a suitable alternative as it doesn't require dose adjustment during CRRT 1

Intermittent Hemodialysis:

• 2 million IU every 12 hours with a normal loading dose 1
• Schedule dialysis toward the end of a colistin dosage interval 1

Obese Patients

• Dosing should be based on ideal body weight rather than actual body weight 2, 3
• Patients with BMI ≥31.5 kg/m² have higher risk of nephrotoxicity (OR 3.1) 3

Administration Methods

Intravenous Administration:

• Direct intermittent: Slowly inject half the total daily dose over 3-5 minutes every 12 hours 2
• Continuous infusion: Inject half the total daily dose over 3-5 minutes, then infuse remaining half over next 22-23 hours 2
• A 4-hour infusion is suggested to optimize pharmacokinetic/pharmacodynamic properties 1

Monitoring and Considerations

• Therapeutic drug monitoring may be valuable for optimizing colistin exposure in critically ill patients with fluctuating renal clearance 4
• Nephrotoxicity risk factors include: BMI ≥31.5 kg/m², diabetes, prolonged hospitalization before colistin administration, and advanced age 3
• Colistin is administered as colistimethate sodium (CMS), an inactive prodrug 1
• One million IU of colistin is equivalent to 80 mg of CMS 1

Important Caveats

• Colistin plasma concentrations for antibacterial effect overlap with those causing nephrotoxicity, requiring careful dosing 5
• Patients with high creatinine clearance (≥80 mL/min) may have difficulty achieving target concentrations even with maximum allowed doses 5
• Polymyxin B may be associated with lower incidence of renal failure compared to colistin 1
• For critically ill patients with multidrug-resistant infections, the recommended doses may be inadequate to maintain optimal Cmax/MIC ratio, particularly for Pseudomonas infections 6