What is the recommended dosing regimen for colistin (colistimethate sodium) in patients with impaired renal function?

Renal Dose of Colistin

For patients with renal impairment, administer a loading dose of 6-9 million IU regardless of renal function, then adjust maintenance doses based on creatinine clearance using the FDA-approved dosing table, with close monitoring of renal function throughout therapy. 1, 2

Loading Dose (All Patients)

• Administer 6-9 million IU loading dose to ALL patients regardless of renal function to rapidly achieve therapeutic levels 1
• The loading dose is critical because colistin has a relatively long half-life compared to dosing intervals 1
• Do not reduce the loading dose in renal impairment 1, 2

Maintenance Dosing Based on Renal Function

Normal Renal Function (CrCl ≥80 mL/min)

• 2.5 to 5 mg/kg/day divided into 2-4 doses 2
• Alternatively, 4.5 million IU every 12 hours for critically ill patients with severe sepsis/septic shock 3, 1
• The higher end of dosing (9 million IU/day) is recommended based on pharmacodynamic studies in critically ill patients 3

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

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

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

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

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

• 1.5 mg/kg every 36 hours 2

Renal Replacement Therapy

Continuous Renal Replacement Therapy (CRRT)

• At least 9 million IU/day is recommended 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 of 300 mg CBA on day 1, followed by maintenance dose of 150-200 mg CBA daily 5
• CAPD clearance is low for both colistimethate sodium and formed colistin, so doses should not be increased during CAPD 5

Administration Considerations

• Administer as a 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties 1
• Colistin is given as colistimethate sodium (CMS), an inactive prodrug 1, 2
• 1 million IU of colistin = 80 mg of CMS 1, 6
• Base dosing on ideal body weight in obese individuals 2

Critical Monitoring Requirements

• Monitor renal function closely during colistin therapy as acute kidney injury is one of the most important factors related to clinical failure and mortality 3, 4
• Nephrotoxicity occurs in approximately 36% of patients receiving colistin 7
• Colistin-associated nephrotoxicity is dose-dependent and most cases are reversible within one week 4
• The number needed to harm for nephrotoxicity is 5 compared to β-lactam-based regimens 7

Important Caveats

• Despite higher colistin exposure in patients with acute renal insufficiency, some evidence suggests dose reduction may not be necessary based on a 2022 study showing no increased nephrotoxicity with standard dosing 8
• However, the FDA label and international guidelines recommend dose adjustment, which should take precedence in clinical practice 2, 3
• Creatinine clearance is the primary covariate affecting colistin clearance 8
• Many patients in real-world practice receive doses not in accordance with manufacturer recommendations, particularly those with renal impairment 9
• Consider polymyxin B as an alternative in patients with renal impairment, as it has lower nephrotoxicity (11.8% vs 39.3% with colistin) and doesn't require dose adjustment during CRRT 4