What is the appropriate colistin loading and maintenance dosing for an adult patient with severe renal impairment (eGFR approximately 6 mL/min/1.73 m²)?

Colistin Dosing in Severe Renal Impairment (eGFR 6 mL/min/1.73 m²)

For an adult patient with eGFR 6 mL/min/1.73 m², administer a full loading dose of 9 million units (MU) intravenously, followed by a maintenance dose of 2 million units every 12 hours if not on dialysis, or 2 million units every 12 hours if on intermittent hemodialysis (scheduled toward the end of the dosing interval). 1

Loading Dose (Critical First Step)

• Always give the full loading dose of 9 million units (≈5 mg colistin base activity/kg) intravenously regardless of renal function 1
• The loading dose is non-negotiable because colistin has a long half-life; omitting it results in subtherapeutic levels for 48-72 hours, increasing treatment failure risk 1
• Never reduce the loading dose in renal impairment—only maintenance doses require adjustment 1

Maintenance Dosing for eGFR 6 mL/min/1.73 m²

If NOT on Dialysis:

• Administer 2 million units every 12 hours 1
• This severe renal impairment (eGFR <10 mL/min) requires substantial dose reduction from the standard 4.5 million units every 12 hours used in normal renal function 1

If on Intermittent Hemodialysis:

• Give 2 million units every 12 hours with the standard loading dose of 9 million units 1
• Schedule dialysis sessions toward the end of the colistin dosing interval to minimize drug removal 1
• Dialysis clearance of colistin is low (0.088-0.101 L/h), so aggressive dose increases are not needed 2

If on Continuous Renal Replacement Therapy (CRRT):

• Administer 3 million units every 8 hours (total 9 million units daily) 1
• Do not reduce the dose for CRRT; patients require at least 9 million units per day to maintain therapeutic levels 1
• CRRT significantly removes colistin, necessitating higher maintenance doses than intermittent hemodialysis 1

Critical Monitoring Requirements

• Monitor renal function at baseline and 2-3 times per week during therapy 1
• Acute kidney injury during colistin treatment is a major determinant of clinical failure and mortality 3, 1
• The risk of nephrotoxicity is dose-dependent but paradoxically, underdosing leads to treatment failure while still carrying nephrotoxic risk 1
• Monitor electrolytes, particularly magnesium, and replace as necessary 4

Combination Therapy Mandate

• Never use colistin as monotherapy for serious infections 1
• Combine colistin with at least one additional agent (preferably a carbapenem or another active drug based on susceptibility testing) to improve clinical outcomes and reduce resistance selection 3, 1
• If no susceptible second agent is available, combine with a nonsusceptible agent with the lowest minimum inhibitory concentration 3

Critical Pitfalls to Avoid

• Do not skip the loading dose—this is the most common error and results in delayed therapeutic concentrations for 2-3 days 1
• Do not use standard maintenance doses (4.5 million units every 12 hours) in severe renal impairment—this dramatically increases nephrotoxicity risk without improving efficacy 1
• Do not co-administer with aminoglycosides unless absolutely necessary—this combination dramatically increases nephrotoxicity 1
• Do not reduce CRRT doses to match non-dialysis renal impairment doses—CRRT removes substantial colistin and requires full dosing 1

Alternative Consideration: Polymyxin B

• Consider polymyxin B as an alternative in severe renal impairment 5
• Polymyxin B requires no dose adjustment during CRRT and has lower nephrotoxicity rates (11.8% vs 39.3% with colistin) 5
• Polymyxin B dosing: loading dose 2-2.5 mg/kg, maintenance 1.5-3 mg/kg/day with no adjustment needed for renal impairment or CRRT 5

Dosing Conversion Reference

• 1 million units colistin = 80 mg colistimethate sodium (CMS) = 33 mg colistin base activity (CBA) 1
• Accurate conversion is essential to avoid 2-3 fold dosing errors 1