Recommended Colistin Dosing for Normal and Impaired Renal Function
The recommended dosing regimen for colistin is a loading dose of 9 million IU (equivalent to 5 mg/kg) for all patients regardless of renal function, followed by a maintenance dose of 2.5 to 5 mg/kg per day divided into 2 to 4 doses for patients with normal renal function, with specific dose adjustments required for renal impairment. 1, 2
Dosing for Normal Renal Function
For patients with normal renal function (creatinine clearance ≥80 mL/min):
- Loading dose: 9 million IU (5 mg/kg) of colistin base activity 1
- Maintenance dose: 2.5 to 5 mg/kg per day divided into 2 to 4 doses 2
Administration Methods
- Intravenous administration:
- Direct intermittent: Inject half the total daily dose over 3-5 minutes every 12 hours
- Continuous infusion: Inject half the total daily dose over 3-5 minutes, then administer the remaining half over the next 22-23 hours 2
Dosing for Impaired Renal Function
Dose adjustments based on creatinine clearance (CrCl) 1, 2:
| Renal Function | CrCl (mL/min) | Recommended Dosage |
|---|---|---|
| Normal | ≥80 | 2.5 to 5 mg/kg/day divided into 2-4 doses |
| Mild impairment | 50-79 | 2.5 to 3.8 mg/kg/day divided into 2 doses |
| Moderate impairment | 30-49 | 2.5 mg/kg/day once daily or divided into 2 doses |
| Severe impairment | 10-29 | 1.5 mg/kg every 36 hours |
Important Considerations for Renal Impairment
- Maintain the loading dose of 9 million IU regardless of renal function 1
- For patients on hemodialysis:
- Schedule dialysis toward the end of a dosing interval
- Administer a supplemental dose of 1.5 million IU after each hemodialysis session 1
- For patients on continuous renal replacement therapy (CRRT):
- Higher doses may be required due to significant extracorporeal clearance
- A modified regimen with a loading dose of 9 MU followed by 3 MU every 8 hours may be appropriate 3
Monitoring and Safety
- Renal function monitoring is essential during colistin therapy, as 14-20% of patients may develop acute kidney injury 1
- Higher incidence of AKI (60%) has been observed with high-dose regimens compared to conventional dosing (15%) 4
- Nephrotoxicity typically develops after 3-4 days of therapy 4, 5
- Colistin appears to be more nephrotoxic than Polymyxin B (39.3% vs 11.8%) when used in currently recommended doses 5
Dosing Pitfalls and Caveats
- Inconsistent dosing units can lead to medication errors - colistin may be prescribed in different units (IU vs. mg) 1
- In obese patients, dosing should be based on ideal body weight, not actual body weight 2
- Inadequate loading doses can result in suboptimal plasma concentrations for 2-3 days 1
- Doses based on body weight alone without considering renal function may lead to increased mortality 6
- For patients with augmented renal clearance (ARC), standard dosing may be inadequate, and higher cumulative doses may be needed 7
Special Populations
- Critically ill patients may require higher doses due to altered pharmacokinetics 1
- For patients with multidrug-resistant Pseudomonas infections, standard dosing may result in suboptimal Cmax/MIC ratios 6
- Consider alternative therapies such as ceftolozane-tazobactam or imipenem-relebactam for carbapenem-resistant Pseudomonas aeruginosa if susceptible 1
Remember that colistin should be reserved for infections proven or strongly suspected to be caused by susceptible bacteria due to its potential toxicity, and infectious disease consultation is strongly recommended for management of resistant infections 1.