What is the recommended colistimethate sodium (colistin) dosing regimen for a patient on chronic intermittent hemodialysis?

Colistin Dosing in Patients on Maintenance Hemodialysis

For patients on chronic intermittent hemodialysis, administer a loading dose of 9 million IU (or 6 million IU if body weight <60 kg) 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 on hemodialysis require a loading dose of 9 million IU (equivalent to 5 mg/kg CBA) regardless of renal function to rapidly achieve therapeutic plasma concentrations 1, 2
• The loading dose is critical because colistin displays a relatively long half-life in relation to dosing intervals, and without it, therapeutic levels are not achieved promptly 1, 2
• For patients weighing <60 kg, reduce the loading dose to 6 million IU 3

Maintenance Dosing for Intermittent Hemodialysis

• The recommended maintenance dose is 2 million IU every 12 hours after the loading dose 1
• This dosing achieves target steady-state colistin concentrations (Css,avg ≥2 mg/L) in >80% of patients on intermittent hemodialysis 4
• Alternative dosing recommendations suggest 3.0-5.0 mg/kg IV every 24 hours for patients on intermittent hemodialysis 1

Timing of Dialysis Sessions

• Schedule hemodialysis sessions toward the end of a colistin dosing interval to minimize drug removal during dialysis 1
• This timing strategy helps maintain therapeutic drug levels throughout the dosing period 1

Critical Monitoring Requirements

• Monitor renal function closely at baseline and 2-3 times per week during treatment 1
• Acute kidney injury during and after colistin treatment is one of the most important factors related to clinical failure and mortality 5, 1
• Most colistin-associated nephrotoxicity is reversible within one week, but close monitoring remains essential 6

Important Dosing Conversions

• 1 million IU of colistin equals 80 mg of colistimethate sodium (CMS) 1, 2
• 1 million IU of colistin methanesulfonate equals 33 mg of colistin base activity (CBA) 1
• Colistin is administered as CMS, an inactive prodrug that converts to active colistin in vivo 1, 2

Common Pitfalls to Avoid

• Do not omit the loading dose - failure to administer a loading dose results in subtherapeutic colistin levels for the first 2-3 days of therapy, which may lead to treatment failure 1, 2
• Do not use normal renal function dosing - patients on hemodialysis require significantly reduced maintenance doses compared to those with normal renal function (2 million IU q12h vs 4.5 million IU q12h) 1, 2
• Do not schedule dialysis immediately after colistin administration - this removes the drug before it can achieve therapeutic effect 1

Alternative Considerations

• Polymyxin B may be a suitable alternative as it doesn't require dose adjustment during renal replacement therapy and has lower nephrotoxicity rates (11.8% vs 39.3% with colistin) 6
• For patients on continuous renal replacement therapy (CRRT) rather than intermittent hemodialysis, higher doses of at least 9 million IU/day are recommended 1, 3

Combination Therapy Considerations

• The use of colistin-based combination therapy remains controversial with weak evidence supporting either monotherapy or combination approaches 5
• If combination therapy is chosen, select agents with in vitro susceptibility when available, or consider combining with agents showing the lowest MIC even if technically non-susceptible 5