What is the recommended dose adjustment for colistin (polymyxin E) in a pediatric patient under 15 with impaired renal function?

Colistin Pediatric Renal Dose Adjustment

Yes, there are specific pediatric renal dose adjustment guidelines for colistin: always give the full loading dose of 0.15 MU/kg (approximately 5 mg CBA/kg) regardless of renal function, then adjust only the maintenance doses based on creatinine clearance. 1, 2

Loading Dose (Never Adjust for Renal Impairment)

• Administer 0.15 MU/kg (approximately 5 mg CBA/kg) as the loading dose in ALL pediatric patients, including those with renal dysfunction 3, 1
• This loading dose is critical to rapidly achieve therapeutic plasma concentrations and should never be reduced 1, 4

Maintenance Dose Adjustments by Renal Function

Normal Renal Function (CrCl ≥80 mL/min)

• Standard maintenance: 0.075 MU/kg every 12 hours (equivalent to 2.5-5 mg CBA/kg/day) 3, 2
• Divide into 2 to 4 doses per day 2

Mild Renal Impairment (CrCl 50-79 mL/min)

• 2.5 to 3.8 mg CBA/kg divided into 2 doses per day 2

Moderate Renal Impairment (CrCl 30-49 mL/min)

• 2.5 mg CBA/kg once daily or divided into 2 doses per day 1, 2

Severe Renal Impairment (CrCl 10-29 mL/min)

• 1.5 mg CBA/kg every 36 hours 1, 2

Continuous Renal Replacement Therapy (CRRT)

• Administer the full loading dose, then at least 9 million IU/day for maintenance 3
• Complex dose adjustments required; colistin is partially removed by CRRT 1

Critical Monitoring Requirements

• Monitor renal function 2-3 times per week during therapy 1, 4
• Nephrotoxicity occurs in 5.8% of pediatric patients, though one study reported up to 48.6% in critically ill children 1, 5
• Monitor electrolytes, particularly magnesium, and replace as necessary 1
• Acute kidney injury is a major predictor of clinical failure and mortality 3, 4

Important Caveats for Pediatric Dosing

Standard Doses May Be Inadequate

• FDA/EMA-recommended doses may be suboptimal when pathogen MIC is ≥1 mg/L 3, 6
• Pediatric patients with augmented renal clearance (ARC) or good renal function for their age may require higher doses than standard recommendations 3, 6
• A pharmacokinetic study showed that even at 33% above FDA/EMA recommendations, only 2 of 5 patients achieved target plasma concentrations ≥2 mg/L 6

Factors Affecting Colistin Clearance

• Creatinine clearance is the primary determinant of colistin dosing requirements 6, 7
• Presence of systemic inflammatory response syndrome (SIRS) decreases colistin clearance to 47.8% of baseline 7
• Total cumulative dose is an independent predictor of nephrotoxicity 5

Critical Pitfalls to Avoid

• Never reduce the loading dose in renal impairment—only adjust maintenance doses 1
• Do not underdose in an attempt to reduce nephrotoxicity, as subtherapeutic levels lead to treatment failure while still carrying nephrotoxic risk 4
• Do not use colistin monotherapy for serious infections—always combine with at least one additional agent 3, 1
• Do not co-administer with aminoglycosides unless absolutely necessary, as this dramatically increases nephrotoxicity 1, 8
• Do not continue therapy without monitoring renal function at least every 2-3 days 1

Dosing in Obese Patients

• Base dosing on ideal body weight, not actual body weight 2