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 6-9 million IU (MU) regardless of renal status, followed by maintenance doses adjusted according to creatinine clearance using the formula: 2.5 mg × (1.5 × CrCl + 30) twice daily for critically ill patients. 1, 2

Loading Dose (All Patients)

• Always give a loading dose of 6-9 MU regardless of renal function to rapidly achieve therapeutic levels 1, 2
• The loading dose is critical because colistin has a relatively long half-life compared to dosing intervals 3, 2
• This translates to approximately 5 mg/kg 1, 3

Maintenance Dosing Based on Renal Function

Normal Renal Function (CrCl ≥80 mL/min)

• 4.5 MU every 12 hours (9 MU/day total) 1, 3
• Alternative: 2.5-5 mg/kg/day divided into 2-4 doses 3, 4

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

• 2.5-3.8 mg/kg divided into 2 doses per day 4
• Maintenance dose should be individually adjusted according to creatinine clearance 2

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

• 2.5 mg/kg once daily or divided into 2 doses per day 4

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

• 1.5 mg/kg every 36 hours 4

Special Populations

Continuous Renal Replacement Therapy (CRRT)

• At least 9 MU/day is recommended 3, 2
• Consider polymyxin B as an alternative since it requires no dose adjustment during CRRT 2, 5

Intermittent Hemodialysis

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

Administration Method

• Administer as a 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties 3, 2

Critical Monitoring Requirements

• Monitor renal function closely during therapy (strong recommendation) 1, 3
• Acute kidney injury during colistin treatment is one of the most important factors related to clinical failure and mortality 1, 5
• Baseline renal impairment and older age strongly predict AKI occurrence 6
• Colistin-associated nephrotoxicity is dose-dependent but most cases are reversible within one week 5

Important Dosing Considerations

Conversion and Units

• Colistin is administered as colistimethate sodium (CMS), an inactive prodrug 3, 2
• 1 million IU = 80 mg of CMS 3, 2

Common Pitfalls to Avoid

• Do not reduce doses in patients with augmented renal clearance - these patients may actually need higher doses for adequate exposure 7, 8
• The standard 9 MU daily dose may be insufficient for patients with normal renal function infected by pathogens with MIC ≥1.0 mg/L 9, 8
• In clinical practice, dose adjustment often does not follow recommendations, particularly in patients with renal impairment 7
• Higher colistin doses independently predict microbiological success but also increase AKI risk 10

Alternative Agent Consideration

• Polymyxin B may be preferred in renal impairment as it causes nephrotoxicity in only 11.8% versus 39.3% with colistin 5
• Polymyxin B requires no dose adjustment during CRRT and has plasma concentrations not influenced by renal function 5

Dosing in Obese Patients

• Base dosing on ideal body weight, not actual body weight 4