What is the recommended dose of colistin for adults with normal renal function?

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 recommendations range from 6-9 MIU, though the higher end (9 MIU) is preferred for critically ill patients 1, 3

Maintenance Dosing

• The standard maintenance dose is 4.5 MIU every 12 hours for patients with creatinine clearance above 50 mL/min 1, 2
• This translates to a total daily dose of 9 MIU/day 2
• The FDA-approved dosing is 2.5-5 mg/kg/day divided into 2-4 doses, which aligns with the 9 MIU daily recommendation 4
• For weight-based dosing, use 2.5-5 mg colistin base activity per kg per day divided into 2-4 doses 3, 4

Administration Method

• Administer as a 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties 3, 2
• For direct intermittent administration, inject slowly over 3-5 minutes 4
• Continuous infusion is an alternative: give half the daily dose over 3-5 minutes, then infuse the remaining half over 22-23 hours 4

Critical Monitoring Requirements

• Monitor renal function closely throughout therapy as acute kidney injury is a major risk factor for clinical failure and mortality 1, 2, 5
• Nephrotoxicity occurs in approximately 5% of patients by day 7, though higher doses (9 MIU daily) are associated with increased nephrotoxicity risk (OR 2.12) 6, 7
• Despite increased nephrotoxicity risk, high-dose regimens have not shown mortality benefit compared to lower doses in observational studies 7

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 of colistin equals 80 mg of CMS 3, 2

Obese Patients

• Base dosing on ideal body weight, not actual body weight 4

Pharmacokinetic Targets

• The recommended dosing aims to achieve a C_max/MIC ratio >8 for optimal bacterial killing 8
• Standard dosing may be inadequate for pathogens with MIC ≥1 mg/L, particularly Pseudomonas species 8, 9

Common Pitfalls to Avoid

• Do not skip the loading dose - this is the most common error and results in subtherapeutic levels for the first 24-48 hours 3, 2
• Do not reduce the maintenance dose in patients with normal renal function - dose adjustment is only needed when creatinine clearance falls below 50 mL/min 1
• Many clinicians inappropriately adjust doses in patients with normal renal function, leading to treatment failure 10
• In patients with augmented renal clearance (CrCL >130 mL/min), standard dosing may be insufficient and higher doses may be needed 10, 9

Alternative Agent

• Polymyxin B (1.5-3 mg/kg/day with a loading dose of 2-2.5 mg/kg) may be preferred as it has lower nephrotoxicity rates and does not require renal dose adjustment 1, 3