What is the recommended dose of Polymyxin B (antibiotic) for a patient with Impaired renal function?

Polymyxin B Dosing in Patients with Impaired Renal Function

Polymyxin B does NOT require dose reduction in patients with renal impairment, and the standard dosing regimen should be maintained regardless of creatinine clearance. 1, 2

Standard Dosing Regimen for All Renal Function Levels

Loading Dose:

• Administer 2-2.5 mg/kg as a loading dose to all patients, including those with severe renal dysfunction 1, 2, 3
• This loading dose is critical to rapidly achieve therapeutic plasma concentrations on day one 2

Maintenance Dose:

• 1.5-3 mg/kg/day divided into 2 doses (every 12 hours) 1, 2, 3
• The FDA label specifies 15,000-25,000 units/kg/day for adults with normal kidney function, which should be reduced "downward" for kidney impairment, but this recommendation contradicts current pharmacokinetic evidence 3

Why No Dose Adjustment is Needed

Pharmacokinetic Rationale:

• Polymyxin B plasma concentrations are NOT influenced by renal function, unlike colistin (polymyxin E) 1, 2
• Polymyxin B clearance is calculated based on body weight, not creatinine clearance 2
• Clinical studies demonstrate comparable drug exposures (AUC) between patients with normal renal function (63.5 ± 16.6 mg·h/L) versus renal insufficiency (56.0 ± 17.5 mg·h/L), with no statistically significant difference (P = 0.42) 4
• A 2021 population pharmacokinetic study found that while creatinine clearance was a significant covariate on clearance, the between-subject variability was only 13%, suggesting minimal clinical impact 5

Special Considerations for Continuous Renal Replacement Therapy (CRRT)

CRRT Dosing:

• Use the same standard dose of 1.5-3 mg/kg/day without adjustment 1, 2
• No dose modification is necessary during CRRT because polymyxin B is not significantly removed by dialysis 2, 6
• A case report successfully used a loading dose of 2.5 mg/kg followed by maintenance doses during continuous venovenous hemodialysis 7

Critical Safety Monitoring

Nephrotoxicity Considerations:

• Monitor renal function closely during treatment, as nephrotoxicity occurs in approximately 55% of patients 8
• Avoid concurrent nephrotoxic agents (aminoglycosides, NSAIDs, diuretics, ACE inhibitors/ARBs) 1, 6
• Polymyxin B has a lower incidence of nephrotoxicity compared to colistin, making it preferable in patients with existing renal dysfunction 2, 9

Therapeutic Drug Monitoring:

• TDM is encouraged where available to optimize dosing and minimize toxicity 1, 6
• Target steady-state average concentration (Css,avg) of approximately 3.35 ± 1.06 mg/L 8

Common Pitfall to Avoid

The FDA label's recommendation to reduce polymyxin B dose in renal impairment is outdated and contradicts current pharmacokinetic evidence. 3, 4 Multiple recent studies and international guidelines demonstrate that dose reduction in renal insufficiency leads to subtherapeutic levels and treatment failure. 5, 4, 10 The 2015 Intensive Care Medicine guidelines explicitly state that polymyxin B dosing should be based on body weight with the same dose used in patients on CRRT. 1

Practical Dosing Example

For a 70 kg patient with severe renal impairment (CrCL <30 mL/min):

• Loading dose: 140-175 mg (2-2.5 mg/kg) infused over 1-2 hours 2
• Maintenance dose: 105-210 mg/day (1.5-3 mg/kg/day) divided into 2 doses of 52.5-105 mg every 12 hours 2
• No reduction needed despite severe renal impairment 2, 4