What is the recommended dose of Colistin (polymyxin E) for patients with normal or impaired renal function?

Colistin Dosing Recommendations

All patients should receive a loading dose of 9 million IU (equivalent to 5 mg/kg) of colistin regardless of renal function, followed by maintenance dosing adjusted based on creatinine clearance. 1, 2

Loading Dose (All Patients)

• Administer 9 million IU (MU) as a loading dose to rapidly achieve therapeutic levels, regardless of renal function status 1, 2
• This loading dose is critical because colistin has a relatively long half-life in relation to dosing intervals, and therapeutic levels must be achieved quickly 1, 2
• The loading dose is equivalent to 5 mg/kg of colistin base activity 2

Maintenance Dosing Based on Renal Function

Normal Renal Function (CrCl ≥80 mL/min)

• Standard maintenance dose: 4.5 million IU every 12 hours (total 9 million IU/day) 1, 2
• Alternative weight-based dosing: 2.5-5 mg/kg/day divided into 2-4 doses 1, 3
• 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 divided into 2 doses per day 3
• Maintenance dose should be individually adjusted according to creatinine clearance 1

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

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

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

• 1.5 mg/kg every 36 hours 3

Renal Replacement Therapy

Continuous Renal Replacement Therapy (CRRT)

• Administer at least 9 million IU/day 1, 2
• Give the normal loading dose of 9 million IU initially 1
• Consider polymyxin B as an alternative since it doesn't require dose adjustment during CRRT 1, 4

Intermittent Hemodialysis

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

Continuous Ambulatory Peritoneal Dialysis (CAPD)

• Loading dose: 300 mg CBA on day 1 5
• Maintenance: 150-200 mg CBA daily 5
• CAPD clearance is low for both CMS and colistin, so doses should not be increased 5

Administration Method

• Administer as a 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties 1, 2
• For IV administration, can use direct intermittent injection (over 3-5 minutes) or continuous infusion 3

Critical Dosing Considerations

Important Conversions

• Colistin is administered as colistimethate sodium (CMS), an inactive prodrug 1, 2, 4
• 1 million IU of colistin = 80 mg of CMS 1, 2, 4

Dosing in Obesity

• Base dosing on ideal body weight, not actual body weight 3

Monitoring Requirements

• Close monitoring of renal function is mandatory during colistin therapy 2
• Acute kidney injury during and after colistin treatment significantly impacts clinical failure and mortality 2
• Colistin-associated nephrotoxicity occurs earlier and more frequently than with polymyxin B 4

Common Pitfalls to Avoid

• Do not skip the loading dose in patients with renal impairment - the loading dose is given regardless of renal function 1, 2
• Do not use actual body weight in obese patients - this leads to overdosing 3
• Do not increase doses during CAPD - clearance by CAPD is minimal 5
• Many patients with renal impairment receive doses not in accordance with recommendations, leading to either subtherapeutic or toxic levels 6
• The standard 9 MU daily dose may be inadequate for pathogens with MIC ≥1 μg/mL, particularly Pseudomonas species 7, 8