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

Colistin Dosing Recommendations

All patients should receive a loading dose of 6-9 million IU (equivalent to 5 mg/kg) regardless of renal function, followed by maintenance dosing adjusted according to creatinine clearance. 1, 2

Loading Dose (All Patients)

• Administer 9 million IU as a loading dose to all patients, regardless of renal function status 1, 2
• This loading dose is critical because colistin has a relatively long half-life compared to dosing intervals, and rapid achievement of therapeutic levels is essential 1, 2
• The loading dose is equivalent to approximately 5 mg/kg 2

Maintenance Dosing Based on Renal Function

Normal Renal Function (CrCL ≥80 mL/min)

• Administer 4.5 million IU every 12 hours (total 9 million IU/day) 1, 2, 3
• 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, use 4.5 million IU every 12 hours 1

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

• Administer 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)

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

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

• Administer 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
• Consider polymyxin B as an alternative, as it does not require dose adjustment during CRRT and has lower nephrotoxicity (11.8% vs 39.3% with colistin) 1, 4, 5

Intermittent Hemodialysis

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

Administration Method

• Infuse over 4 hours to optimize pharmacokinetic/pharmacodynamic properties 1, 2
• For direct intermittent administration: inject one-half of total daily dose over 3-5 minutes every 12 hours 3
• For continuous infusion: inject first half over 3-5 minutes, then infuse remaining half over 22-23 hours 3

Critical Monitoring and Safety Considerations

• Monitor renal function closely during therapy, as acute kidney injury is a major factor related to clinical failure and mortality 1, 2
• Colistin nephrotoxicity is dose-dependent, with doses ≥300 mg/day (approximately 3.75 million IU/day) associated with increased risk 5
• Most nephrotoxicity is reversible within one week, with 75% of patients recovering renal function 5
• Colistin-associated nephrotoxicity occurs earlier and more frequently than with polymyxin B 4

Important Dosing Conversions

• One million IU of colistin equals 80 mg of colistimethate sodium (CMS) 1, 4, 2
• Colistin is administered as the inactive prodrug colistimethate sodium 1, 2
• Dosing should be based on ideal body weight in obese individuals 3

Common Pitfalls to Avoid

• Do not skip the loading dose in patients with renal impairment—the loading dose remains the same regardless of renal function 1, 2
• Do not use actual body weight for dosing in obese patients; use ideal body weight 3
• The recommended label doses may be inadequate for pathogens with MIC ≥1 μg/mL, particularly in patients with normal or augmented renal clearance 6, 7
• In patients with augmented renal clearance, standard dosing may result in subtherapeutic levels 8, 7