What is the appropriate colistimethate sodium (colistin) dosing regimen for adult patients based on creatinine clearance, including adjustments for intermittent hemodialysis and continuous renal replacement therapy?

Colistin Dosing Based on Creatinine Clearance

Loading Dose (All Patients)

Administer 9 million IU (≈5 mg/kg colistin base activity) intravenously as a loading dose to every patient, regardless of renal function or dialysis status. 1, 2

• This loading dose is non-negotiable because colistin's long half-life would otherwise result in sub-therapeutic plasma concentrations for 48-72 hours, substantially increasing treatment failure risk 1
• The loading dose should be reduced to 6 million IU only if body weight is <60 kg 3

Maintenance Dosing by Creatinine Clearance

Formula-Based Approach (Preferred Method)

Use the following formula to calculate maintenance doses every 12 hours: 1

Maintenance dose (mg CBA) = 2.5 × (1.5 × CrCl [mL/min] + 30)

This formula automatically adjusts for renal function and is the most precise method for dose individualization 1

Alternative Fixed-Dose Regimens

For patients with CrCl >50 mL/min (normal renal function):

• Standard dose: 4.5 million IU every 12 hours (9 million IU/day total) 1, 2
• For severe sepsis/septic shock: 4.5 million IU every 12 hours to overcome augmented renal clearance 1

For patients with CrCl 20-50 mL/min (mild-moderate impairment):

• Reduce maintenance dose according to the formula above, or use 3.0-5.0 mg/kg IV every 24-36 hours 1

For patients with CrCl 10-20 mL/min (severe impairment):

• 2 million IU every 12 hours 4

For patients with CrCl <10 mL/min (end-stage renal disease):

• 3.0-5.0 mg/kg IV every 24-36 hours 1

Renal Replacement Therapy Dosing

Continuous Renal Replacement Therapy (CRRT)

Give 9 million IU loading dose, then 3 million IU every 8 hours (9 million IU/day total). 1, 3

• Do NOT reduce the maintenance dose for CRRT—patients require at least 9 million IU/day because CRRT removes substantial amounts of colistin (accounting for 28% of total clearance) 1, 3
• CRRT clearance is significant enough that standard renal impairment dose reductions are inappropriate and lead to treatment failure 3, 5
• The 8-hour dosing interval (rather than 12-hour) is necessary to maintain therapeutic concentrations given enhanced extracorporeal elimination 3, 6

Intermittent Hemodialysis (IHD)

Give 9 million IU loading dose, then 2 million IU every 12 hours. 1

• Schedule dialysis sessions toward the end of the colistin dosing interval to minimize drug removal 1
• On non-dialysis days, continue the same 2 million IU every 12 hours regimen 7
• For patients with residual renal function (CrCl 10-20 mL/min), this same dose applies 4

Critical Dosing Conversions

1 million IU colistimethate sodium = 80 mg CMS = 33 mg colistin base activity (CBA) 1, 2

• Failure to use correct conversion factors results in 2-3 fold dosing errors 1
• Colistin is administered as the inactive prodrug colistimethate sodium (CMS), which converts to active colistin in vivo 1, 2

Administration Method

Infuse colistin over 4 hours to optimize pharmacokinetic/pharmacodynamic properties. 1, 2

Monitoring Requirements

Check renal function at baseline and 2-3 times per week during treatment. 1

• Acute kidney injury during colistin therapy is a major determinant of clinical failure and mortality 1, 2
• Colistin-associated nephrotoxicity is dose-dependent but typically reversible within one week after discontinuation 8
• Target steady-state trough concentrations of ≥2.5 mg/L for efficacy 3

Critical Pitfalls to Avoid

• Never omit the loading dose—this is the most common error and results in 48-72 hours of sub-therapeutic exposure 1
• Never reduce CRRT doses to match severe renal impairment dosing—CRRT patients need full doses (9 million IU/day) because of enhanced drug removal 1, 3, 5
• Never use colistin monotherapy for serious infections—combination with a carbapenem or other active agent improves outcomes and reduces resistance 1
• Do not base dosing on body weight alone—creatinine clearance is the primary determinant of maintenance dose requirements 4

Special Considerations

For patients with CrCl ≥80 mL/min, even maximum recommended doses may be inadequate to achieve therapeutic concentrations, particularly for pathogens with MIC ≥1 mg/L (especially Pseudomonas species) 1, 7

• In these cases, strongly consider combination therapy or alternative agents 1
• Target C_max/MIC ratio of >8 is often not achieved with standard dosing for Pseudomonas infections 4

Consider polymyxin B as an alternative in patients with renal impairment or on CRRT, as it requires no dose adjustment for renal function and has lower nephrotoxicity rates (11.8% vs 39.3% with colistin) 8