In a hemodialysis patient, should colistimethate sodium (colistin) be administered once daily or twice daily?

Colistin Dosing in Hemodialysis: Twice Daily Administration is Recommended

For patients on hemodialysis, colistin (colistimethate sodium) should be administered twice daily rather than once daily. This recommendation is based on the substantial removal of colistin during dialysis sessions and the need to maintain therapeutic plasma concentrations.

Rationale for Twice Daily Dosing

Pharmacokinetic Evidence in Dialysis Patients

The FDA-approved dosing for colistin explicitly recommends divided dosing in patients with renal impairment 1. For patients with severe renal impairment (CrCl 10-29 mL/min, which includes HD patients), the label specifies 1.5 mg/kg every 36 hours, but this applies to non-dialysis scenarios.

During hemodialysis, colistin clearance increases dramatically:

• In sustained low-efficiency dialysis (SLED), extracorporeal clearance accounts for 67.4% of total colistin clearance on dialysis days 2
• The apparent colistin SLED clearance was 3.49 L/h compared to 1.69 L/h on non-dialysis days 2
• This represents a more than 2-fold increase in drug elimination during dialysis

Guideline-Based Dosing Framework

Current guidelines recommend for critically ill patients with normal renal function: 4.5 MU twice daily as maintenance dosing after a 9 MU loading dose 3. This twice-daily regimen is supported by international consensus and pharmacodynamic studies.

Specific Dosing Algorithm for HD Patients

On Dialysis Days:

1. Administer colistin twice daily (typically 150 mg colistin base activity every 12 hours)
2. Time one dose to occur during or immediately after dialysis to compensate for dialysis-related removal
3. Give the second dose 12 hours later

On Non-Dialysis Days:

• Continue twice-daily dosing to maintain steady-state concentrations
• The standard dose of 150 mg colistin base activity twice daily is appropriate for most HD patients 2

Loading Dose Consideration:

• Consider a loading dose of 9 MU (or 6 MU if body weight <60 kg) on day 1, regardless of renal function, to rapidly achieve therapeutic levels 4

Critical Clinical Considerations

Why Once Daily is Inadequate:

Once-daily dosing fails to account for:

• The dramatic increase in colistin clearance during HD sessions
• The need to maintain plasma concentrations above the minimum inhibitory concentration (MIC) throughout the dosing interval
• The concentration-dependent killing characteristics of colistin

Monitoring Requirements:

• Close renal function monitoring is mandatory, even in HD patients, as colistin can cause additional nephrotoxicity 3
• Monitor for neurotoxicity (paresthesias, seizures), which can occur even with appropriate dosing in dialysis patients 5
• Consider therapeutic drug monitoring when available, targeting average steady-state concentrations (Css,avg) of ≥2 mg/L 6

Common Pitfalls to Avoid:

1. Do not use once-daily dosing assuming HD patients have "no renal function" - residual renal function and dialysis removal patterns require divided dosing
2. Do not skip the post-dialysis supplemental dose - this is when colistin levels are lowest
3. Do not assume standard renal dosing charts apply - HD patients require individualized consideration of dialysis timing and frequency

Practical Implementation

Recommended regimen for intermittent HD (3x/week):

• Loading dose: 9 MU on day 1
• Maintenance: 150 mg (approximately 4.5 MU) colistin base activity twice daily
• On dialysis days: Give one dose immediately post-dialysis, second dose 12 hours later
• On non-dialysis days: Continue twice-daily dosing at 12-hour intervals

This approach balances the need for adequate antibacterial effect (targeting fAUC/MIC ≥12) while minimizing the risk of accumulation and toxicity 7.