Colistin Renal Dose Adjustment in Pediatric Patients
For pediatric patients with renal impairment, reduce the colistin maintenance dose (not the loading dose) based on creatinine clearance, using 2.5 mg CBA/kg once daily for moderate impairment (CrCl 30-49 mL/min) and 1.5 mg CBA/kg every 36 hours for severe impairment (CrCl 10-29 mL/min), while always administering the full loading dose of 0.15 MU/kg (approximately 5 mg CBA/kg) regardless of renal function. 1
Loading Dose: No Adjustment Required
- Always administer the full loading dose regardless of renal function to rapidly achieve therapeutic levels 2, 3
- Pediatric loading dose: 0.15 MU/kg (equivalent to approximately 5 mg CBA/kg) 4, 5
- This principle applies universally—even in severe renal impairment or dialysis, the loading dose must not be reduced 3
Maintenance Dose: Adjust Based on Creatinine Clearance
The FDA label provides the framework for dose adjustment in renal impairment, though it does not specify pediatric-specific cutoffs 1:
Normal Renal Function (CrCl ≥80 mL/min)
- 2.5 to 5 mg CBA/kg/day divided into 2-4 doses 1
- Standard dosing: 0.075 MU/kg every 12 hours (equivalent to 2.5-5 mg CBA/kg/day) 4, 5
Mild Renal Impairment (CrCl 50-79 mL/min)
- 2.5 to 3.8 mg CBA/kg divided into 2 doses per day 1
Moderate Renal Impairment (CrCl 30-49 mL/min)
- 2.5 mg CBA/kg once daily or divided into 2 doses per day 1
Severe Renal Impairment (CrCl 10-29 mL/min)
- 1.5 mg CBA/kg every 36 hours 1
Critical Considerations for Pediatric Dosing
Serum Creatinine as a Key Covariate
- Serum creatinine is a significant covariate in colistin clearance in children 6
- For children with SCr 0.1-0.3 mg/dL targeting Css,avg of 1 mg/L: use 7.5 mg CBA/kg/day 6
- For children with SCr >0.3 mg/dL targeting Css,avg of 1 mg/L: use 5 mg CBA/kg/day 6
Augmented Renal Clearance (ARC)
- Pediatric patients with ARC or good renal function for their age may require higher doses than FDA/EMA recommendations 4, 7
- Standard doses may be inadequate when pathogen MIC is ≥1 mg/L 4, 2
- Recent studies used doses of 6.6 to 11.6 mg CBA/kg/day in critically ill children with good outcomes 8
Systemic Inflammatory Response Syndrome (SIRS)
- Presence of SIRS decreases colistin clearance to 47.8% of baseline 8
- Patients with SIRS require lower doses to achieve target concentrations 8
Mandatory Monitoring Requirements
- Monitor renal function 2-3 times per week during colistin therapy 2, 3
- Nephrotoxicity risk in pediatric patients: 5.8% 2
- Acute kidney injury is a major factor related to clinical failure and mortality 4, 3
- Monitor electrolytes, particularly magnesium, and replace as necessary 2
Critical Pitfalls to Avoid
- Never reduce the loading dose in renal impairment—only adjust maintenance doses 3
- Do not underdose in an attempt to reduce nephrotoxicity, as subtherapeutic levels lead to treatment failure while still carrying nephrotoxic risk 3
- Do not use colistin monotherapy for serious infections—always combine with at least one additional agent 4, 2
- Do not co-administer with aminoglycosides unless absolutely necessary, as this dramatically increases nephrotoxicity 2