What is the dosing regimen for colistin (polymyxin E) in patients with impaired renal function?

Colistin Dosing in Patients with Impaired Renal Function

In patients with impaired renal function, colistin dosing must be reduced based on creatinine clearance, with specific adjustments ranging from 2.5-3.8 mg/kg divided into 2 doses for mild impairment down to 1.5 mg/kg every 36 hours for severe impairment, while all patients regardless of renal function should receive the full 9 MU loading dose. 1

Loading Dose (All Patients)

• Always administer a loading dose of 9 million units (MU) regardless of renal function status 2, 3
• This loading dose is equivalent to 5 mg/kg and is critical due to colistin's relatively long half-life 3
• The loading dose should not be adjusted for renal impairment 1

Maintenance Dosing Based on Renal Function

Normal Renal Function (CrCl ≥80 mL/min)

• Maintenance dose: 4.5 MU every 12 hours (9 MU/day total) 2, 3
• Alternative calculation: 2.5 mg × [(1.5 × CrCl) + 30] twice daily 2
• Equivalent to 2.5-5 mg/kg/day divided into 2-4 doses 1

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

• Maintenance dose: 2.5-3.8 mg/kg divided into 2 doses per day 1

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

• Maintenance dose: 2.5 mg/kg once daily or divided into 2 doses per day 1

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

• Maintenance dose: 1.5 mg/kg every 36 hours 1

Special Renal Replacement Situations

Intermittent Hemodialysis

• Dosing regimen: 1.5 MU twice daily on non-hemodialysis days 4
• On hemodialysis days: Give 1.5 MU twice daily PLUS an additional 1.5 MU supplemental dose after the hemodialysis session (total 4.5 MU on HD days) 4
• Schedule hemodialysis at the end of a dosing interval when possible 4
• Colistin clearance is increased 3-fold in ICU patients on hemodialysis compared to those with preserved renal function 4

Continuous Ambulatory Peritoneal Dialysis (CAPD)

• Loading dose: 300 mg colistin base activity (CBA) on day 1 5
• Maintenance dose: 150-200 mg CBA daily 5
• CAPD clearance is very low for both colistin methanesulfonate and formed colistin (0.088-0.101 L/h), so doses should not be increased during CAPD 5
• Terminal half-life is prolonged to 13.2 hours for colistin in CAPD patients 5

Continuous Renal Replacement Therapy (CRRT)

• Dose: At least 9 million IU/day 3

Critical Monitoring Requirements

• Renal function must be closely monitored during colistin therapy (strong recommendation) 2, 3, 6
• Acute kidney injury during and after colistin treatment is one of the most important factors related to clinical failure and mortality 2
• There is no current consensus regarding frequency of dose adjustment and timing of withdrawal in the presence of acute kidney injury 2
• Clinicians should weigh benefits and harms in patients at higher risk for kidney injury, such as the elderly or those with chronic kidney disease 2

Important Caveats and Pitfalls

Augmented Renal Clearance (ARC)

• Patients with ARC (CrCl >130 mL/min) commonly receive standard doses of 9 MU daily, but may require higher cumulative doses or longer treatment duration 7
• Current guidelines do not recommend dose adjustment for ARC, though this remains an area of uncertainty 7
• One case report demonstrated a patient with fluctuating renal clearance required up to 3 × 6 MU daily (18 MU/day) to achieve therapeutic levels, exceeding approved maximum doses 8

Dosing Units and Conversions

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

Administration Method

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

Nephrotoxicity Risk

• Acute tubular necrosis is the most common kidney lesion associated with colistin use 9
• Nephrotoxicity was observed in only 8% of patients in one retrospective study, with serum creatinine actually decreasing by an average of 0.2 mg/dL during treatment 10
• Consider alternative antibiotics (newer β-lactam/β-lactamase inhibitors) when available due to lower nephrotoxicity risk 9