Polymyxin B Dosing in Units
Polymyxin B is dosed at 15,000 to 25,000 units/kg/day for adults and children with normal renal function, with 1 mg of polymyxin B equal to 10,000 units. 1
Standard Dosing Regimens
Intravenous Administration
- Adults and children: 15,000 to 25,000 units/kg body weight/day, divided every 12 hours, with a maximum daily dose not exceeding 25,000 units/kg/day 1
- Infants with normal kidney function: May receive up to 40,000 units/kg/day 1
- Premature and newborn infants: Doses as high as 45,000 units/kg/day have been used in limited studies for Pseudomonas aeruginosa sepsis 1
Intramuscular Administration (Not Routinely Recommended)
- Adults and children: 25,000 to 30,000 units/kg/day, divided at 4 or 6 hour intervals 1
- Note: IM route causes severe pain at injection sites, particularly in infants and children 1
Intrathecal Administration
- Adults and children over 2 years: 50,000 units once daily for 3-4 days, then 50,000 units every other day for at least 2 weeks after CSF cultures are negative 1
- Children under 2 years: 20,000 units once daily for 3-4 days, then 25,000 units every other day 1
Critical Dosing Conversion
The unit conversion for polymyxin B is: 1 mg = 10,000 units 2, 1
This differs significantly from colistin, where 1 million IU = approximately 80 mg of colistimethate sodium (CMS) = 33 mg colistin base activity 2, 3, 4
Dosing in Renal Impairment
Polymyxin B does NOT require dose adjustment based on renal function, unlike colistin. 5, 6
- Population pharmacokinetic studies demonstrate that polymyxin B clearance shows no correlation with creatinine clearance (r² = 0.008) 6
- Polymyxin B is predominantly non-renally cleared, with median urinary recovery of only 4.04% 6
- Total body clearance scaled by weight (0.0276 L/hour/kg) shows remarkably low interindividual variability (32.4% coefficient of variation) regardless of renal function 6
- However, recent evidence suggests dose adjustment may improve outcomes in renal insufficiency, with a loading dose of 2-2.5 mg/kg and maintenance of 1.5-3 mg/kg/day recommended 7, 8
Dosing for Specific Infections
Carbapenem-Resistant Gram-Negative Infections
- Bloodstream infections and pneumonia: Polymyxin B 2.5-3.0 mg/kg/day divided in 2 daily IV doses (equivalent to 25,000-30,000 units/kg/day) 2
- Combination therapy is strongly preferred over monotherapy for carbapenem-resistant infections 2
Hospital-Acquired/Ventilator-Associated Pneumonia
Critical Implementation Considerations
Loading Dose Strategy
- Unlike colistin, the FDA label does not specify a loading dose for polymyxin B 1
- However, clinical practice guidelines suggest a loading dose of 2-2.5 mg/kg to rapidly achieve therapeutic levels 7
Inadequate Dosing Pitfall
Doses below 15,000 units/kg/day (<1.5 mg/kg/day) are independently associated with treatment failure and increased mortality in critically ill patients 9
- Low polymyxin B doses were the strongest predictor of treatment failure (p = 0.002) and in-hospital mortality (p = 0.007) 9
- Mortality rate in one ICU cohort was 48.8%, with 82.9% attributed to treatment failure 9
Renal Replacement Therapy
- Continuous renal replacement therapy (CRRT): No dose adjustment necessary for polymyxin B 7, 3
- Intermittent hemodialysis: Standard dosing can be maintained 7
- This represents a significant advantage over colistin, which requires complex dose adjustments 3, 4
Nephrotoxicity Monitoring
- Monitor renal function closely during therapy, though polymyxin B is associated with lower incidence and later onset of nephrotoxicity compared to colistin 7, 4
- Avoid concurrent nephrotoxic agents, particularly the combination of NSAIDs, diuretics, and ACE inhibitors/ARBs 7
- Consider therapeutic drug monitoring where available 2