Recommended Colistin Dosing for Adults with Normal Renal Function
For adult patients with normal renal function, colistin should be administered with a loading dose of 9 million international units (MIU) followed by a maintenance dose of 4.5 MIU every 12 hours (9 MIU/day). 1
Dosing Regimen
- A loading dose of 9 MIU is critical to rapidly achieve therapeutic levels due to colistin's relatively long half-life in relation to dosing intervals 1, 2
- For maintenance therapy in patients with normal renal function (creatinine clearance ≥80 mL/min), the recommended dose is 4.5 MIU every 12 hours 1, 2
- Alternative weight-based dosing is 2.5-5 mg/kg/day divided into 2-4 doses 1, 3
- In obese individuals, dosing should be based on ideal body weight rather than actual body weight 3
Administration Methods
- Colistin should be administered as a slow intravenous infusion over 3-5 minutes for direct intermittent administration 3
- A 4-hour infusion is suggested to optimize pharmacokinetic/pharmacodynamic properties 1
- For continuous infusion, administer half the daily dose over 3-5 minutes, then the remaining half over the next 22-23 hours 3
Important Considerations
Dosing Units and Conversions
- Colistin is administered as colistimethate sodium (CMS), an inactive prodrug 1
- One million IU of colistin is equivalent to 80 mg of CMS 1
- The FDA label indicates that a 150 mg vial should be reconstituted with 2 mL Sterile Water for Injection to provide a concentration equivalent to 75 mg/mL colistin base activity 3
Monitoring and Safety
- Renal function should be closely monitored during colistin therapy as acute kidney injury is a significant risk factor for clinical failure and mortality 1
- Nephrotoxicity typically develops within 3.8 ± 0.8 days of starting colistin therapy 4
- Higher daily doses (≥300 mg) are associated with increased risk of nephrotoxicity 4, 5
- Colistin is significantly more nephrotoxic than Polymyxin B (39.3% vs 11.8% nephrotoxicity rate) when administered in currently recommended doses 4
Special Considerations
- For critically ill patients with severe sepsis/septic shock, high extended-interval maintenance doses (4.5 MIU every 12 hours) are recommended 2
- Patients with augmented renal clearance (ARC) may receive standard doses but might require longer duration of therapy 6
- For patients with impaired renal function, the maintenance dose should be individually adjusted according to creatinine clearance 7
- For patients on continuous renal replacement therapy, a dose of at least 9 MIU/day is recommended 7, 2
Limitations of Current Dosing Recommendations
- For patients with creatinine clearance ≥80 mL/min, even maximum allowed daily doses may not achieve target plasma concentrations in all patients 8
- Pharmacokinetic studies show wide inter-individual variation in colistin parameters, which may affect optimal dosing 9
- The recommended dose may be inadequate to maintain optimal C(max)/MIC ratios for certain pathogens, particularly Pseudomonas species 9