What is the recommended colistin (colistimethate sodium) dosing regimen, including loading and maintenance doses, for an adult on chronic intermittent hemodialysis three times per week?

Colistin Dosing in Patients on Maintenance Hemodialysis (MHD)

For adult patients on chronic intermittent hemodialysis three times per week, administer a normal loading dose of 6-9 million IU colistimethate sodium (CMS), followed by a maintenance dose of 2 million IU every 12 hours, with dialysis scheduled toward the end of the dosing interval. 1

Loading Dose Strategy

• All patients require a loading dose of 6-9 million IU (equivalent to approximately 5 mg/kg colistin base activity) regardless of renal function, including those on hemodialysis 1, 2
• The loading dose is critical because colistin has a relatively long half-life (8.4 hours in dialysis patients) compared to the dosing interval, and plasma concentrations remain suboptimal for 2-3 days before reaching steady state without adequate loading 1, 3
• This loading dose should be given on day 1 to rapidly achieve therapeutic plasma levels 2

Maintenance Dosing for Intermittent Hemodialysis

• The maintenance regimen is 2 million IU CMS every 12 hours after the loading dose 1
• This is substantially lower than the 4.5 million IU every 12 hours used in patients with normal renal function, reflecting reduced clearance in dialysis patients 1, 2
• An alternative evidence-based approach suggests 3.0-5.0 mg/kg IV every 24 hours for intermittent hemodialysis patients 2

Timing of Dialysis Sessions

• Schedule hemodialysis sessions toward the end of a CMS dosage interval to minimize drug removal during dialysis 1
• This timing strategy optimizes drug exposure while accounting for the modest dialytic clearance of colistin 3

Key Pharmacokinetic Considerations

• Colistin clearance by intermittent hemodialysis is relatively low compared to continuous renal replacement therapy 3
• The terminal half-life of colistin in end-stage renal disease patients is approximately 13.2 hours, significantly longer than in patients with normal renal function 3
• CAPD clearance of colistin is only 0.101 liter/h, confirming that dialytic removal is modest and does not necessitate dose escalation 3

Critical Monitoring Requirements

• Monitor renal function closely at baseline and 2-3 times per week during treatment, as acute kidney injury during colistin therapy is associated with clinical failure and higher mortality 2
• Even in dialysis patients, nephrotoxicity monitoring remains important as residual renal function may be affected 2

Alternative: Polymyxin B

• Consider polymyxin B as an alternative agent (loading dose 2-2.5 mg/kg, maintenance 1.5-3 mg/kg/day) if available, as it requires no dose adjustment for renal replacement therapy and has lower nephrotoxicity rates (11.8% vs 39.3% with colistin) 4
• Polymyxin B plasma concentrations are not influenced by renal function, simplifying dosing in dialysis patients 1, 4

Common Pitfalls to Avoid

• Do not omit the loading dose in dialysis patients—this is a frequent error that leads to prolonged subtherapeutic levels 1, 2
• Do not use the same maintenance doses as in patients with normal renal function (4.5 million IU every 12 hours), as this will cause drug accumulation and increased toxicity risk 1
• Do not schedule dialysis immediately after colistin administration, as this reduces drug exposure unnecessarily 1
• For pathogens with MIC ≥1 mg/L, monotherapy may be inadequate; strongly consider combination therapy with another active agent based on susceptibility testing 2