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

Recommended Colistin Dose for Adults with Normal Renal Function

For adults with normal renal function, administer a loading dose of 9 million international units (MIU) of colistin methanesulfonate (CMS) initially, followed by a maintenance dose of 4.5 MIU every 12 hours (total 9 MIU daily). 1, 2

Loading Dose Rationale

• The 9 MIU loading dose (equivalent to 5 mg/kg) is critical and should be given to all patients regardless of renal function to rapidly achieve therapeutic levels 1, 2
• This loading dose is necessary because colistin has a relatively long half-life in relation to dosing intervals, and the inactive prodrug (CMS) converts slowly to active colistin 3, 2
• The loading dose is supported by pharmacodynamic studies in critically ill patients and international consensus guidelines 1

Maintenance Dosing

• After the loading dose, give 4.5 MIU every 12 hours (total daily dose of 9 MIU) for patients with normal renal function 1, 2
• Alternative weight-based dosing: 2.5-5 mg/kg/day divided into 2-4 doses 3, 4
• The FDA label recommends 2.5 to 5 mg/kg per day in 2 to 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
• For direct intermittent administration: inject one-half of the total daily dose over 3-5 minutes every 12 hours 4
• Continuous infusion is an alternative: inject 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 during colistin therapy - this is a strong recommendation despite low-quality evidence 1, 2
• Acute kidney injury during and after colistin treatment is one of the most important factors related to clinical failure and mortality 1, 2
• Patients at higher risk for kidney injury include the elderly and those with chronic kidney disease 1

Important Dosing Considerations

Conversion and Units

• Colistin is administered as colistimethate sodium (CMS), an inactive prodrug 3, 2
• One million IU of colistin equals 80 mg of CMS 3, 2

Obese Patients

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

Combination Therapy

• The use of colistin-based combination therapy remains controversial with very low-quality evidence 1, 2
• Consider combination with one or more additional agents to which the pathogen displays in vitro susceptibility 1

Common Pitfalls to Avoid

• Do not skip the loading dose - failure to give an adequate loading dose results in subtherapeutic levels during the critical early treatment period 3, 2
• Do not use standard maintenance doses in renal impairment - the maintenance dose must be adjusted for creatinine clearance, though the loading dose remains the same 3, 4
• Be aware that the standard 9 MIU daily dose may be insufficient for patients with augmented renal clearance or infections with MIC ≥1.0 mg/L 3, 5

Nephrotoxicity Risk

• Nephrotoxicity is dose-dependent and occurs in approximately 11.8-39.3% of patients depending on the formulation used 6
• Most nephrotoxicity is reversible within one week of discontinuation 6
• High-dose colistin (9 MIU daily) is associated with increased nephrotoxicity compared to lower doses 7
• Consider polymyxin B as an alternative in patients at high risk for renal injury, as it has lower nephrotoxicity rates 6