Recommended Dosing of Polymyxin B and Colistin for Patients with Impaired Renal Function
For patients with impaired renal function, polymyxin B does not require dosage adjustment based on renal function, while colistin requires significant dose reduction according to creatinine clearance. 1, 2
Polymyxin B Dosing
Loading Dose
- A loading dose of 2-2.5 mg/kg is recommended for all patients regardless of renal function to rapidly achieve therapeutic levels 1
Maintenance Dose
- For patients with normal renal function: 15,000-25,000 units/kg/day (equivalent to 1.5-2.5 mg/kg/day) divided into 2 doses 2
- For patients with impaired renal function: No dosage adjustment is necessary as polymyxin B clearance is not significantly affected by renal function 1, 3
- For patients on continuous renal replacement therapy: No dose adjustment is necessary 1
Administration
- Dissolve 500,000 polymyxin B units in 300-500 mL of 5% Dextrose Injection for continuous drip 2
- Weight-based dosing should be calculated using ideal body weight in obese patients 2
Colistin (Colistimethate Sodium) Dosing
Loading Dose
- A loading dose of 6-9 million IU (equivalent to 480-720 mg CMS) should be administered to all patients regardless of renal function 1, 4
Maintenance Dose Based on Renal Function
- Normal renal function: 4.5 million IU every 12 hours (9 million IU/day) 4, 5
- Mild renal impairment (CrCl 50-79 mL/min): 2.5-3.8 mg/kg/day divided into 2 doses 6
- Moderate renal impairment (CrCl 30-49 mL/min): 2.5 mg/kg/day once daily or divided into 2 doses 6
- Severe renal impairment (CrCl 10-29 mL/min): 1.5 mg/kg every 36 hours 6
Special Populations
- Continuous Renal Replacement Therapy: At least 9 million IU/day 1, 4
- Intermittent Hemodialysis: 2 million IU every 12 hours with a normal loading dose; schedule dialysis toward the end of a dosage interval 1, 4
Clinical Considerations
Nephrotoxicity Comparison
- Polymyxin B is associated with significantly lower nephrotoxicity (11.8%) compared to colistin (39.3%) when administered at currently recommended doses 7
- Nephrotoxicity with colistin is dose-dependent, with daily doses ≥300 mg associated with higher risk 7
- Mean onset of nephrotoxicity is 3.8 ± 0.8 days with colistin and 4.2 ± 0.7 days with polymyxin B 7
Pharmacokinetic Considerations
- Colistin is administered as colistimethate sodium (CMS), an inactive prodrug that requires conversion to active colistin 4
- One million IU of colistin is equivalent to 80 mg of CMS 4, 5
- Polymyxin B is not administered as a prodrug and displays more predictable pharmacokinetics 1
- Polymyxin B clearance shows remarkably low interindividual variability (32.4% coefficient of variation) and is not correlated with creatinine clearance (r² = 0.008) 3
Monitoring
- Renal function should be closely monitored during therapy with both agents 5
- Most cases of nephrotoxicity are reversible, with 75% of colistin cases and 83.3% of polymyxin B cases recovering renal function within one week 7
Practical Recommendations
- For patients with impaired renal function requiring polymyxin therapy, polymyxin B may be preferred over colistin due to its lower nephrotoxicity and lack of need for dosage adjustment 1, 7
- For critically ill patients with severe infections caused by highly resistant organisms (MIC ≥2 mg/L), higher doses may be necessary but carry increased risk of nephrotoxicity 8, 9
I hope this helps with your dosing decisions for these important last-line antibiotics.