Colistin Dosing in Adults with Normal Renal Function
For adults with normal renal function, administer a loading dose of 9 million IU (MIU) of colistimethate sodium followed by a maintenance dose of 4.5 MIU every 12 hours (total 9 MIU daily). 1, 2
Loading Dose
- A loading dose of 9 MIU (equivalent to 5 mg/kg) is essential regardless of renal function to rapidly achieve therapeutic plasma concentrations 1, 2
- The loading dose is critical because colistin has a relatively long half-life compared to the dosing interval, and without it, therapeutic levels are delayed 1, 3
- Alternative loading dose range of 6-9 MIU is acceptable, though 9 MIU is preferred for critically ill patients 1, 3
Maintenance Dosing
- For patients with creatinine clearance ≥80 mL/min, give 4.5 MIU every 12 hours (total daily dose of 9 MIU) 1, 2
- This can also be expressed as 2.5-5 mg/kg/day divided into 2-4 doses 4, 2
- The FDA label recommends 2.5-5 mg/kg per day in 2-4 divided doses for patients with normal renal function 4
Administration Method
- Administer as a 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties 3, 2
- Alternatively, the FDA label describes direct intermittent administration over 3-5 minutes every 12 hours or continuous infusion 4
Critical Monitoring Requirements
- Monitor renal function closely during therapy as acute kidney injury is a major risk factor for clinical failure and mortality 1, 2
- Nephrotoxicity occurs in approximately 5% of patients by day 7, though higher rates have been reported with high-dose regimens 5, 6
Important Dosing Considerations
Conversion and Formulation
- Colistin is administered as colistimethate sodium (CMS), an inactive prodrug that converts to active colistin in vivo 3, 2
- 1 million IU equals 80 mg of CMS 3, 2
Weight-Based Dosing
- In obese patients, calculate dose based on ideal body weight, not actual body weight 4
Evidence Quality and Caveats
The recommended high-dose regimen (9 MIU loading, 9 MIU daily maintenance) is supported by international consensus guidelines and pharmacodynamic studies 1, 2. However, one large prospective cohort study found no mortality benefit with high-dose colistin (9 MIU daily) compared to lower doses (median 4 MIU daily), and high-dose regimens were associated with significantly more nephrotoxicity (OR 2.12) 6. Despite this, the guidelines prioritize achieving adequate plasma concentrations, as subtherapeutic levels are associated with clinical failure 5.
Common pitfall: Many clinicians underdose colistin, particularly in patients with normal or augmented renal clearance, leading to subtherapeutic drug levels 7, 5. The standard 9 MIU daily dose may still be insufficient for pathogens with MIC ≥1.0 mg/L 8.