Colistin Loading Dose for Multidrug-Resistant Gram-Negative Infections
The recommended loading dose of colistin is 5 mg colistin base activity (CBA) per kg IV, which is equivalent to 6-9 million international units (MIU), administered regardless of renal function. 1
Dosing Specifications
Loading Dose Administration
- Administer 5 mg CBA/kg IV as a single loading dose 1
- This equates to approximately 6-9 million IU for most adult patients 1
- Give the loading dose to ALL patients, including those with renal dysfunction 1
- One million IU of colistin methanesulfonate (CMS) equals 33 mg colistin base activity 1 or 80 mg CMS 1, 2
Rationale for Loading Dose
The loading dose is critical because colistin has a long half-life (14.4 hours) relative to the dosing interval, resulting in suboptimal plasma concentrations for 2-3 days before reaching steady state without a loading dose 1, 3. Research demonstrates that plasma colistin concentrations remain insufficient for the first 48-72 hours when loading doses are omitted, which is associated with higher mortality 1, 3.
Maintenance Dosing Following Loading Dose
After the loading dose, maintenance dosing should be:
- 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours for patients with varying renal function 1
- For normal renal function: approximately 4.5 million IU every 12 hours (9 million IU/day total) 1
- Begin maintenance dosing 12-24 hours after the loading dose 1, 4
Administration Considerations
Infusion Method
- Administer as a slow IV infusion over 30 minutes to 1 hour 5, 4
- Some guidelines suggest 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties, particularly for strains with MIC of 8 mg/L 1, 2
- Avoid rapid bolus administration 5
Critical Pitfalls to Avoid
Do not reduce or omit the loading dose in patients with renal impairment - this is the most common dosing error. The loading dose should be given at full dose regardless of creatinine clearance because it is needed to rapidly achieve therapeutic concentrations 1, 2. Only the maintenance dose requires renal adjustment 1.
Do not underdose based on body weight alone - dosing should be calculated on ideal body weight in obese patients, not actual body weight 5. However, the loading dose of 5 mg CBA/kg should still be administered 1.
Avoid delaying the loading dose - subtherapeutic concentrations in the first 48-72 hours are associated with microbiological failure and increased mortality 1, 3, 6.
Monitoring Requirements
- Monitor renal function closely during therapy, as acute kidney injury occurs in approximately 20% of patients and is dose-related 6, 4
- Higher colistin doses (>2.9 mg/kg/day maintenance) correlate with better microbiological outcomes but increased nephrotoxicity risk 6
- Balance antibacterial efficacy against nephrotoxicity risk by ensuring adequate loading dose while monitoring for renal toxicity during maintenance therapy 2, 6
Special Populations
For patients on continuous renal replacement therapy (CRRT), the same loading dose of 5 mg CBA/kg should be administered, as CRRT clearance of colistin is minimal 1, 7. Maintenance doses may require adjustment based on residual renal function 7.