Polymyxin B Dosing for Adults
For adults with normal renal function, administer polymyxin B at 2.5-3.0 mg/kg/day (equivalent to 25,000-30,000 units/kg/day) divided into two daily intravenous doses, with a loading dose of 2-2.5 mg/kg to rapidly achieve therapeutic levels. 1, 2
Standard Dosing Regimen
- Loading dose: 2-2.5 mg/kg IV as a single dose, regardless of renal function 1
- Maintenance dose: 2.5-3.0 mg/kg/day divided into two doses (every 12 hours) 1, 2
- Maximum daily dose: Do not exceed 25,000 units/kg/day (2.5 mg/kg/day) per FDA labeling 2
- Unit conversion: 1 mg polymyxin B = 10,000 units 1, 2
Dosing in Renal Impairment
Unlike colistin, polymyxin B does NOT require dose adjustment based on creatinine clearance, though recent evidence suggests some adjustment may be beneficial. 1, 3
- The FDA label recommends dose reduction in renal impairment (from 15,000 units/kg downward), but this is based on outdated data 2
- Modern evidence shows polymyxin B clearance correlates poorly with creatinine clearance 4, 5
- For patients on continuous renal replacement therapy (CRRT), no dose adjustment is required 1, 3
- Recent population pharmacokinetic data suggests dose reduction in severe renal insufficiency may improve safety while maintaining efficacy 4
Critical Pitfall to Avoid
The FDA-approved labeling is outdated and contradicts current evidence. Do not routinely reduce polymyxin B doses in renal impairment unless using therapeutic drug monitoring or following newer pharmacokinetic models. 5, 6
Clinical Context and Combination Therapy
- Always use polymyxin B in combination therapy for carbapenem-resistant infections, never as monotherapy 7
- Common combinations include polymyxin B plus tigecycline, meropenem (extended infusion), or ceftazidime-avibactam 7
- For severe infections with MIC ≥2 mg/L, higher doses may be needed but increase nephrotoxicity risk 4
Nephrotoxicity Considerations
Polymyxin B causes significantly less nephrotoxicity than colistin (11.8% vs 39.3%) 8
- Nephrotoxicity typically occurs at 3-4 days of therapy 8
- Most nephrotoxicity is reversible within one week after discontinuation 8
- Avoid concurrent nephrotoxic agents (NSAIDs, diuretics, ACE inhibitors/ARBs) 1
- Monitor renal function closely throughout therapy 1, 3
Administration Details
- Dissolve 500,000 units in 300-500 mL of 5% dextrose for IV infusion 2
- Administer as continuous drip or divided doses every 12 hours 2
- Consider 4-hour infusion for optimal pharmacokinetic/pharmacodynamic properties 9
- Therapeutic drug monitoring should be considered where available 1