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

Colistin Dosing in Renal Impairment

For patients with impaired renal function, administer a loading dose of 9 million IU (MU) of colistin methanesulfonate (CMS) regardless of renal function, followed by maintenance doses adjusted according to creatinine clearance: 2.5-3.8 mg/kg divided into 2 doses for mild impairment (CrCl 50-79 mL/min), 2.5 mg/kg once daily or divided into 2 doses for moderate impairment (CrCl 30-49 mL/min), and 1.5 mg/kg every 36 hours for severe impairment (CrCl 10-29 mL/min). 1

Loading Dose (All Patients)

• Always administer a loading dose of 9 million IU (equivalent to 5 mg/kg) regardless of renal function to rapidly achieve therapeutic levels 2, 3, 4
• The loading dose is critical because colistin has a relatively long half-life compared to dosing intervals, and the inactive prodrug CMS converts slowly to active colistin 3, 5
• This loading dose applies equally to patients with normal renal function, impaired renal function, and those on renal replacement therapy 3

Maintenance Dosing Based on Renal Function

Normal Renal Function (CrCl ≥80 mL/min)

• Maintenance dose: 4.5 million IU every 12 hours (total 9 MU/day) 2, 4
• Alternative weight-based dosing: 2.5-5 mg/kg/day divided into 2-4 doses 1
• For critically ill patients with severe sepsis/septic shock: 4.5 million IU every 12 hours is the recommended regimen 3

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

• Maintenance dose: 2.5-3.8 mg/kg divided into 2 doses per day 1
• Dose should be individually adjusted according to creatinine clearance 3

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

• Maintenance dose: 2.5 mg/kg once daily or divided into 2 doses per day 1

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

• Maintenance dose: 1.5 mg/kg every 36 hours 1
• Alternative dosing from National Kidney Foundation: 3.0-5.0 mg/kg IV every 24-36 hours 3

Renal Replacement Therapy

Continuous Renal Replacement Therapy (CRRT)

• Administer at least 9 million IU/day 3
• Consider polymyxin B as an alternative, as it does not require dose adjustment during CRRT and may have lower nephrotoxicity 3, 6

Intermittent Hemodialysis

• Maintenance dose: 2 million IU every 12 hours after the normal loading dose 3
• Alternative dosing: 3.0-5.0 mg/kg IV every 24 hours 3
• Schedule dialysis toward the end of a colistin dosage interval 3

Continuous Ambulatory Peritoneal Dialysis (CAPD)

• Loading dose of 300 mg colistin base activity (CBA) on day 1, followed by maintenance dose of 150-200 mg CBA daily 7
• CAPD clearance is low for both CMS and colistin, so doses should not be increased during CAPD 7

Administration Methods

• Administer as a 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties 3, 4
• For direct intermittent IV administration: slowly inject one-half of total daily dose over 3-5 minutes every 12 hours 1
• For continuous infusion: inject first half over 3-5 minutes, then infuse remaining half over 22-23 hours 1

Critical Monitoring Requirements

• Monitor renal function closely at baseline and 2-3 times per week during treatment 3
• This is a strong recommendation due to the significant risk of acute kidney injury, which is a major factor related to clinical failure and mortality 2, 4
• Acute kidney injury during colistin treatment is dose-dependent but most nephrotoxicity is reversible within one week 6

Important Dosing Considerations

Dosing Units and Conversions

• Colistin is administered as colistimethate sodium (CMS), an inactive prodrug 3, 4
• 1 million IU of colistin = 80 mg of CMS 3, 6
• Dosage should be based on ideal body weight in obese individuals 1

Common Pitfalls to Avoid

• Do not skip the loading dose in patients with renal impairment - the loading dose is essential regardless of renal function 3
• Many clinicians inappropriately fail to adjust maintenance doses according to renal function, particularly in patients with renal impairment 8
• Do not increase doses during CAPD, as clearance by peritoneal dialysis is minimal 7
• The recommended doses may be inadequate for pathogens with MIC ≥1 mg/L, particularly Pseudomonas species; consider combination therapy in these cases 2, 9

Alternative: Polymyxin B

• Consider polymyxin B as an alternative in patients with renal impairment, particularly those on CRRT 6
• Polymyxin B has significantly lower nephrotoxicity (11.8% vs 39.3% with colistin) 6
• Polymyxin B requires no dose adjustment during CRRT and is administered as the active drug 6
• Loading dose: 2-2.5 mg/kg; maintenance: 1.5-3 mg/kg/day with no adjustment needed for CRRT 6