Colistin Dosing for Hemodialysis Patients
For patients on intermittent hemodialysis 3 times weekly, give a loading dose of 9 MU colistin methanesulfonate (CMS), followed by 1.5 mg/kg colistin base activity every 36 hours on non-dialysis days, with supplemental dosing after each dialysis session.
Dosing Algorithm for HD Patients
Initial Loading Dose
- Always start with 9 MU CMS loading dose regardless of renal function 1
- This ensures rapid achievement of therapeutic concentrations and is critical given colistin's pharmacokinetics
Maintenance Dosing on Non-Dialysis Days
According to FDA labeling, patients with severe renal impairment (CrCl 10-29 mL/min, which includes HD patients) should receive 1.5 mg/kg every 36 hours 2. This represents the baseline dosing between dialysis sessions.
Supplemental Dosing After Dialysis
- Hemodialysis significantly removes colistin, with extracorporeal clearance accounting for substantial drug elimination 3
- Research demonstrates that HD patients require supplemental dosing after each dialysis session to maintain therapeutic concentrations 4
- The supplemental dose should be approximately 50-75% of the maintenance dose administered immediately post-dialysis 4
Practical Dosing Schedule Example
For a typical HD patient (3x/week schedule: Monday/Wednesday/Friday):
Day 1 (Monday - Dialysis day):
- Loading dose: 9 MU CMS
- Post-HD supplemental dose: 1.5 mg/kg
Day 2 (Tuesday - Non-dialysis):
- No dose (within 36-hour interval)
Day 3 (Wednesday - Dialysis day):
- Maintenance dose: 1.5 mg/kg (given pre-HD if possible)
- Post-HD supplemental dose: 1.5 mg/kg
Day 4 (Thursday - Non-dialysis):
- No dose
Day 5 (Friday - Dialysis day):
- Maintenance dose: 1.5 mg/kg
- Post-HD supplemental dose: 1.5 mg/kg
Critical Monitoring Considerations
Target Concentration Challenges
- HD patients face significant risk of subtherapeutic concentrations 5, 3
- Standard dosing often fails to achieve the target average steady-state concentration (Css,avg) of ≥2 mg/L 4, 5
- For organisms with MIC ≥1 mg/L, even optimized regimens may provide inadequate exposure 6
Nephrotoxicity Monitoring
- Closely monitor renal function even in HD patients, as residual renal function may be lost 1
- Acute kidney injury during colistin treatment is associated with increased mortality 1
- The risk-benefit calculation differs in HD patients who have already lost renal function
Important Clinical Caveats
When Colistin May Be Inadequate
- Patients with preserved residual renal function may clear colistin faster and require higher doses 6, 7
- For pathogens with MIC ≥2 mg/L, monotherapy is unlikely to achieve pharmacodynamic targets regardless of dosing 6
- Consider combination therapy with a carbapenem or other agent, even if the organism appears non-susceptible in vitro 1
Dialysis Modality Matters
- The above recommendations apply specifically to intermittent hemodialysis
- Patients on continuous renal replacement therapy (CRRT) require different dosing: higher maintenance doses (closer to normal renal function dosing) due to continuous drug removal 7
- SLEDD (sustained low-efficiency daily dialysis) may remove up to 67% of total drug clearance and requires individualized approaches 3
Alternative Considerations
- Strongly consider newer β-lactam/β-lactamase inhibitors (ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam) if the organism is susceptible 1
- These agents have better safety profiles and more predictable pharmacokinetics in HD patients