What is the recommended dose of Colistin (polymyxin E) for a patient with normal renal function?

Colistin Dosage for Patients with Normal Renal Function

For patients with normal renal function, the recommended colistin dose is a loading dose of 9 million international units (MU) followed by a maintenance dose of 4.5 MU every 12 hours. 1

Dosing Regimen

Loading Dose

• A loading dose of 9 MU (equivalent to 5 mg/kg) of colistin should be administered to rapidly achieve therapeutic levels regardless of renal function 1, 2
• The loading dose is critical due to colistin's relatively long half-life in relation to dosing intervals 2

Maintenance Dose for Normal Renal Function

• For patients with normal renal function: 4.5 MU every 12 hours (9 MU/day) 1
• Alternative dosing based on weight: 2.5-5 mg/kg/day divided into 2-4 doses 2, 3
• FDA labeling recommends 2.5 to 5 mg/kg per day of colistin base activity in 2 to 4 divided doses for patients with normal renal function 3

Administration Methods

• Intravenous administration can be given as:
  • Direct intermittent administration: Inject half the total daily dose over 3-5 minutes every 12 hours 3
  • Continuous infusion: Administer half the dose over 3-5 minutes, then the remaining half over the next 22-23 hours 3
• A 4-hour infusion is suggested to optimize pharmacokinetic/pharmacodynamic properties 2

Important Considerations

Dosing Units and Conversions

• Colistin is administered as colistimethate sodium (CMS), an inactive prodrug 2
• One million IU of colistin is equivalent to 80 mg of CMS 2
• In obese individuals, dosage should be based on ideal body weight 3

Monitoring and Safety

• Renal function should be closely monitored during colistin therapy (Strong recommendation) 1
• Acute kidney injury during and after colistin treatment is a significant factor related to clinical failure and mortality 1
• Higher colistin doses have been associated with improved microbiological success but also increased risk of nephrotoxicity 4, 5

Efficacy Considerations

• Studies have shown that higher colistin doses correlate with improved microbiological success (adjusted odds ratio per 1 mg/kg/day = 1.74) 4
• The target average steady-state plasma colistin concentration (Css,avg) should be ≥2 mg/L for optimal efficacy 6
• For patients with creatinine clearance ≥80 mL/min, achieving target concentrations may be challenging even with maximum doses 6

Special Considerations

• Polymyxin B may be a suitable alternative with potentially lower nephrotoxicity compared to colistin (39.3% vs 11.8% nephrotoxicity rate) 5
• For urinary tract infections, lower doses may be effective due to higher urinary concentrations of colistin 7
• Combination therapy with colistin remains controversial (Weak recommendation) 1

Dose Adjustments

• For patients with impaired renal function, dose adjustments are necessary 1, 3
• For critically ill patients on continuous renal replacement therapy, a dose of at least 9 million IU/day is recommended 2