What is the recommended dose of colistin (polymyxin E) for patients with chronic kidney disease (CKD)?

Colistin Dosing in Chronic Kidney Disease Patients

All CKD patients should receive a loading dose of 6-9 million IU (MU) of colistin regardless of renal function, followed by maintenance doses adjusted according to creatinine clearance, with close monitoring of renal function throughout therapy. 1, 2

Loading Dose (Critical First Step)

• Administer 6-9 million IU as a loading dose to ALL patients, regardless of degree of renal impairment 1
• This loading dose is essential because colistin has a relatively long half-life and therapeutic levels must be achieved rapidly 1
• The loading dose should never be reduced or omitted in CKD patients 1

Maintenance Dosing Based on Creatinine Clearance

For patients with normal renal function (CrCl ≥80 mL/min):

• 2.5-5 mg/kg/day divided into 2-4 doses 2
• Alternatively: 4.5 million IU every 12 hours for critically ill patients 3, 1

For mild renal impairment (CrCl 50-79 mL/min):

• 2.5-3.8 mg/kg divided into 2 doses per day 2

For moderate renal impairment (CrCl 30-49 mL/min):

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

For severe renal impairment (CrCl 10-29 mL/min):

• 1.5 mg/kg every 36 hours 2

For CrCl <10 mL/min:

• 3.0-5.0 mg/kg IV every 24-36 hours 3

Special Populations: Renal Replacement Therapy

Continuous Renal Replacement Therapy (CRRT):

• Administer at least 9 million IU/day 1
• Consider polymyxin B as an alternative since it requires no dose adjustment during CRRT 1, 4

Intermittent Hemodialysis:

• 2 million IU every 12 hours after normal loading dose 1
• Alternatively: 3.0-5.0 mg/kg IV every 24 hours 3
• Schedule dialysis toward the end of the colistin dosing interval 1

Administration Method

• Administer as a 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties 1
• For direct intermittent IV administration: inject slowly over 3-5 minutes 2

Critical Monitoring Requirements

Renal function must be monitored closely during therapy: 3, 1

• Check creatinine clearance at baseline
• Monitor 2-3 times per week during treatment 3
• Acute kidney injury is a major factor related to clinical failure and mortality 3, 4

Important Caveats and Pitfalls

Dosing considerations:

• Base dosing on ideal body weight in obese patients 2
• One million IU of colistin equals 80 mg of colistimethate sodium (CMS) 1, 5
• Colistin is administered as the inactive prodrug CMS 1

Nephrotoxicity risk factors:

• Daily colistin dose is significantly associated with nephrotoxicity development specifically in patients with eGFR <60 mL/min/1.73 m² 6
• In CKD patients with eGFR <60, the optimal cutoff dose to minimize nephrotoxicity is 2.87 mg/kg/day, with doses above this threshold carrying significantly higher risk (OR 2.34) 6
• Nephrotoxicity is dose-dependent and most cases are reversible within one week 4
• Concomitant vasopressor use and advanced age increase nephrotoxicity risk 7

Common underdosing problem:

• Studies show CKD patients frequently receive approximately half the recommended doses, resulting in subtherapeutic plasma concentrations 8
• Target steady-state plasma concentration is ≥2 mg/L, but 83% of underdosed CKD patients achieve <2 mg/L 8
• Despite concerns about nephrotoxicity in CKD, appropriate dosing is essential for efficacy 8

Alternative Consideration

Polymyxin B may be preferred in severe CKD: 4

• Loading dose: 2-2.5 mg/kg regardless of renal function 4
• Maintenance: 1.5-3 mg/kg/day with no adjustment needed for CRRT 4
• Lower nephrotoxicity incidence (11.8% vs 39.3% with colistin) 4
• No dose adjustment required during CRRT 1, 4