Colistin Dosage Recommendations
For patients with multidrug-resistant infections, a loading dose of 9 million international units (MU) of colistin should be administered regardless of renal function, followed by a maintenance dose of 4.5 MU every 12 hours in patients with normal renal function. 1, 2
Standard Dosing for Adults
- Loading dose: 9 MU (equivalent to 5 mg/kg) of colistin should be administered to rapidly achieve therapeutic levels, regardless of renal function 1, 3, 2
- Maintenance dose for normal renal function: 4.5 MU every 12 hours (9 MU/day) 1, 2
- Alternative weight-based dosing: 2.5-5 mg/kg/day divided into 2-4 doses 2, 4
Dosing in Renal Impairment
Maintenance dose should be adjusted according to creatinine clearance:
- Normal renal function (CrCl ≥80 mL/min): 2.5-5 mg/kg/day divided into 2-4 doses 3, 4
- Mild impairment (CrCl 50-79 mL/min): 2.5-3.8 mg/kg/day divided into 2 doses 4
- Moderate impairment (CrCl 30-49 mL/min): 2.5 mg/kg once daily or divided into 2 doses 4
- Severe impairment (CrCl 10-29 mL/min): 1.5 mg/kg every 36 hours 4
Special Populations
Patients on Renal Replacement Therapy
- Continuous Renal Replacement Therapy (CRRT): At least 9 MU/day is recommended 3
- Intermittent Hemodialysis: 2 MU every 12 hours with normal loading dose; schedule dialysis toward the end of a colistin dosage interval 3
Administration Methods
- Intravenous administration: A 4-hour infusion is suggested to optimize pharmacokinetic/pharmacodynamic properties 3, 2
- Direct intermittent administration: Slowly inject one-half of the total daily dose over 3-5 minutes every 12 hours 4
- Continuous infusion: Inject half of the total daily dose over 3-5 minutes, then administer the remaining half over the next 22-23 hours 4
Important Considerations
- Colistin is administered as colistimethate sodium (CMS), an inactive prodrug 3, 2
- One million IU of colistin is equivalent to 80 mg of CMS 3, 2, 5
- Renal function should be closely monitored during colistin therapy as acute kidney injury is a significant factor related to clinical failure and mortality 1, 2
- Higher colistin doses are associated with better microbiological clearance but also with increased risk of nephrotoxicity 6
- In studies, nephrotoxicity rates range from 29.4% to 53.7% of patients receiving colistin 7, 8
Combination Therapy
- The use of colistin-based combination therapy remains controversial (weak recommendation) 1, 2
- For respiratory infections, combining intravenous and inhaled colistin may improve clinical outcomes 7
Therapeutic Drug Monitoring
- Therapeutic drug monitoring may be valuable for optimizing colistin dosing, particularly in patients with fluctuating renal clearance 9
- Higher colistin doses independently predict microbiological success, which may partially explain the association with improved 7-day mortality 6
Common Pitfalls
- Relying solely on serum creatinine for dosing decisions can be misleading, especially in critically ill patients with augmented renal clearance 9
- Underdosing colistin may lead to treatment failure and potentially promote resistance 6
- Overdosing increases the risk of nephrotoxicity, which occurs in a significant proportion of patients 10, 8
- For urinary tract infections, lower doses may be effective due to higher urinary concentrations of colistin, potentially reducing nephrotoxicity 8