What are the recommended loading and maintenance doses of colistin (polymyxin E) injection for a patient with impaired renal function?

Colistin Dosing: Loading and Maintenance Doses

Loading Dose (Stat Dose)

Administer a loading dose of 9 million international units (IU) of colistin methanesulfonate (CMS) intravenously to all patients regardless of renal function. 1, 2, 3

• This loading dose is equivalent to approximately 5 mg/kg or 300 mg colistin base activity (CBA) 2, 3
• The loading dose is critical because colistin displays a relatively long half-life in relation to dosing intervals, and without it, therapeutic plasma concentrations may not be achieved for 2-3 days 1, 2
• Administer the loading dose slowly over 3-5 minutes 4
• Do not reduce the loading dose for renal impairment - the same 9 million IU loading dose applies to all patients, including those on dialysis 1, 2, 5

Maintenance Doses

For Patients with Normal Renal Function (CrCl ≥80 mL/min)

Administer 4.5 million IU every 12 hours (total 9 million IU/day) for critically ill patients with severe infections. 1, 2, 3

• Alternative dosing: 2.5-5 mg/kg/day divided into 2-4 doses 4, 3
• The FDA-approved dosing range is 2.5-5 mg/kg per day in 2-4 divided doses, but critically ill patients typically require the higher end 4
• Extended 4-hour infusions may optimize pharmacokinetic/pharmacodynamic properties 2, 3

For Patients with Renal Impairment

Adjust maintenance doses according to creatinine clearance using the following algorithm: 1, 4

• Mild impairment (CrCl 50-79 mL/min): 2.5-3.8 mg/kg divided into 2 doses per day 4
• Moderate impairment (CrCl 30-49 mL/min): 2.5 mg/kg once daily or divided into 2 doses per day 4
• Severe impairment (CrCl 10-29 mL/min): 1.5 mg/kg every 36 hours 4

Alternative formula-based dosing for maintenance: 2.5 mg × (1.5 × CrCl + 30) IV every 12 hours 1

For Patients on Renal Replacement Therapy

Continuous Renal Replacement Therapy (CRRT):

• Administer at least 9 million IU/day (4.5 million IU every 12 hours) 1, 2
• Use the normal loading dose of 9 million IU 1, 2
• Do not reduce doses for CRRT as extracorporeal clearance can cause substantial removal of colistin 6

Intermittent Hemodialysis:

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

Critical Dosing Conversions

• 1 million IU of colistin = approximately 80 mg of colistimethate sodium (CMS) = approximately 30 mg colistin base activity 1, 2, 3
• Colistin is administered as the inactive prodrug CMS, which converts to active colistin in vivo 2, 3, 7

Important Clinical Pitfalls

Avoid these common errors:

• Never skip the loading dose - without it, suboptimal plasma concentrations persist for 2-3 days, potentially leading to treatment failure 1, 2
• Do not reduce the loading dose for renal impairment - only maintenance doses require adjustment 1, 2, 5
• Do not rely solely on serum creatinine - use calculated creatinine clearance (CKD-EPI formula) for dose adjustments, as serum creatinine can be misleading in critically ill patients 8
• Monitor renal function closely - check at baseline and 2-3 times per week during treatment, as acute kidney injury is a major factor related to clinical failure and mortality 2, 5
• Use ideal body weight for obese patients when calculating doses 4

Alternative: Polymyxin B

Consider polymyxin B as an alternative, particularly in patients with renal impairment or on CRRT. 1, 5

• Loading dose: 2-2.5 mg/kg regardless of renal function 1, 5
• Maintenance dose: 1.5-3 mg/kg/day (or 2.5-3.0 mg/kg/day divided in 2 daily doses) 1, 5
• No dose adjustment needed for CRRT 1, 5
• Lower incidence of nephrotoxicity compared to colistin (11.8% vs 39.3%) 5
• Plasma concentrations not influenced by renal function 1, 5