Recommended Dosing of Colistin for Patients with Normal and Impaired Renal Function
For all patients with normal or impaired renal function, a loading dose of 9 million international units (MU) of colistin should be administered regardless of renal function to rapidly achieve therapeutic levels. 1, 2
Dosing for Patients with Normal Renal Function
- A maintenance dose of 4.5 MU every 12 hours (equivalent to 9 MU/day) is recommended for patients with normal renal function 2
- Alternative weight-based dosing is 2.5-5 mg/kg/day divided into 2-4 doses 2, 3
- For critically ill patients with severe sepsis/septic shock and normal renal function, 4.5 million IU every 12 hours is recommended 1
- In obese individuals, dosage should be based on ideal body weight 3
Dosing for Patients with Impaired Renal Function
- Maintenance dose should be individually adjusted according to creatinine clearance 1
- For mild renal impairment (CrCl 50-79 mL/min): 2.5 to 3.8 mg/kg/day divided into 2 doses 3
- For moderate renal impairment (CrCl 30-49 mL/min): 2.5 mg/kg/day, once daily or divided into 2 doses 3
- For severe renal impairment (CrCl 10-29 mL/min): 1.5 mg/kg every 36 hours 3
Special Populations
Patients on Renal Replacement Therapy
- For patients on Continuous Renal Replacement Therapy (CRRT): A dose of at least 9 million IU/day is recommended 1, 2
- For patients on Intermittent Hemodialysis: 2 million IU every 12 hours with a normal loading dose 1
- Schedule dialysis toward the end of a colistin dosage interval for patients on Intermittent Hemodialysis 1
- Polymyxin B may be a suitable alternative as it doesn't require dose adjustment during CRRT 1, 4
Administration Methods
- A 4-hour infusion is suggested to optimize pharmacokinetic/pharmacodynamic properties 1, 2
- Direct intermittent administration: Slowly inject one-half of the total daily dose over a period of 3 to 5 minutes every 12 hours 3
- Continuous infusion: Slowly inject one-half of the total daily dose over 3 to 5 minutes, then add the remaining half to compatible IV solutions for infusion over the next 22-23 hours 3
Important Considerations
- Colistin is administered as colistimethate sodium (CMS), an inactive prodrug 1, 2
- One million IU of colistin is equivalent to 80 mg of CMS 1, 2, 4
- Renal function should be closely monitored during colistin therapy 2, 5
- Higher colistin doses are associated with better microbiological clearance but also with increased risk of nephrotoxicity 5
- Studies have shown that higher doses (9 MU/day) are associated with better microbiological clearance (66.2%) in critically ill patients 6
Common Pitfalls and Caveats
- Underdosing is a common problem, particularly in critically ill patients with serious infections 7, 5
- The recommended dose may be inadequate to maintain optimal pharmacokinetic/pharmacodynamic parameters for some pathogens, particularly Pseudomonas species 7
- Acute kidney injury is a significant concern, with studies reporting nephrotoxicity rates of 8-39.3% 6, 8
- Dose recommendations should be based primarily on creatinine clearance rather than body weight 7
- Polymyxin B may be associated with lower incidence of renal failure compared to colistin 1, 4