Polymyxin B Dosage
For adults with normal renal function, administer a loading dose of 2–2.5 mg/kg followed by a maintenance dose of 1.5–3 mg/kg/day divided into 2 doses every 12 hours. 1
Adult Dosing
Standard Dosing (Normal Renal Function)
- Loading dose: 2–2.5 mg/kg administered to all patients, including those with renal dysfunction 1
- Maintenance dose: 1.5–3 mg/kg/day divided into 2 doses (every 12 hours) 1
- Alternative: Continuous infusion may be suitable 1
The loading dose is critical to achieve optimal plasma levels on the first day, as polymyxin B does not require time to reach steady state like colistin 1.
Renal Impairment Adjustments
A key advantage of polymyxin B over colistin is that plasma concentrations are not influenced by renal function 1. However, recent evidence suggests dose adjustment may still be warranted:
- Moderate renal impairment (CrCL 42 mL/min): Consider a fixed maintenance dose of 60 mg every 12 hours after the standard loading dose 2
- Severe renal impairment/dialysis: Reduce from the standard 15,000 units/kg downward 3
- Continuous renal replacement therapy (CRRT): No dose adjustment necessary; use the same dose as patients with normal renal function 1
Recent pharmacokinetic studies demonstrate that polymyxin B clearance is significantly lower in patients with renal insufficiency (2.1 L/h vs 3.9 L/h in normal function) 4, 5. This puts patients at increased risk of toxicity, particularly nephrotoxicity which occurs in approximately 15% of patients 1.
Pediatric Dosing
Intravenous Administration
- Standard dose: 15,000–25,000 units/kg/day in children with normal kidney function 3
- Infants with normal renal function: May receive up to 40,000 units/kg/day without adverse effects 3
- Premature/newborn infants: Doses as high as 45,000 units/kg/day have been used for Pseudomonas aeruginosa sepsis in limited studies 3
Intramuscular Administration (Not Routinely Recommended)
- Adults and children: 25,000–30,000 units/kg/day, reduced in renal impairment 3
- Infants: Up to 40,000 units/kg/day with normal kidney function 3
Note: IM administration causes severe pain at injection sites, particularly in infants and children 3.
Critical Dosing Considerations
Conversion Units
Pay careful attention to unit conversions to avoid dosing errors:
- Polymyxin B sulfate: 1 mg = 10,000 units 6
- This differs from colistin: 1 million IU = 80 mg CMS = 33 mg CBA 6
Monitoring Requirements
Renal function monitoring is mandatory during polymyxin B treatment 6. The incidence of renal failure appears lower with polymyxin B than colistin (15.3% vs 33%) 1, but nephrotoxicity remains a significant concern.
- Therapeutic drug monitoring (TDM): Strongly encouraged where available 6
- Early monitoring in burn patients: Check renal function within 3 days of initiation 7
- Target AUC₀₋₂₄: 50–100 mg·h/L for optimal efficacy while minimizing toxicity 2, 4
Drug Interactions
Avoid concurrent use of other nephrotoxic or ototoxic drugs (including aminoglycosides) with polymyxin B 6.
Special Populations
Dialysis-Dependent Patients
For patients on continuous veno-venous hemodialysis (CVVHD):
- Loading dose: 200 mg (standard) 4
- Maintenance dose: Fixed dose of 100 mg every 12 hours 4
- No dose increase required despite dialysis, as recovery rate from dialysate is only 22% 4
Convective RRT modalities (CVVH, CVVHDF) increase clearance and may require higher doses, while diffusive modalities (CVVHD) show variable effects 8.
Lung Transplant Recipients
Creatinine clearance significantly affects polymyxin B clearance in this population 9. Dose adjustment based on renal function is necessary, as standard regimens may generate subtherapeutic exposure for organisms with MIC ≥2 mg/L 9.
Clinical Pitfalls
Suboptimal dosing: The FDA-approved label recommends 15,000–25,000 units/kg/day, but recent evidence suggests this may be inadequate for severe infections, particularly with MIC ≥2 mg/L 9, 5
Over-dosing in renal impairment: While polymyxin B clearance is less affected by renal function than colistin, recent studies show significantly decreased clearance in renal insufficiency 4, 5. Consider dose reduction to avoid toxicity.
Delayed loading dose: Always administer the loading dose regardless of renal function to achieve therapeutic levels rapidly 1
Monotherapy: Polymyxin B combination therapy is strongly preferred over monotherapy for carbapenem-resistant Gram-negative infections, with combination therapy reducing treatment failures by approximately 119 per 1000 patients 6