Is polymyxin B (Poly B) or colistin better for treating patients with impaired renal function?

Polymyxin B is Better for Patients with Impaired Renal Function

For patients with impaired renal function, polymyxin B is the preferred polymyxin antibiotic due to significantly lower nephrotoxicity rates, no requirement for dose adjustment during renal replacement therapy, and more predictable pharmacokinetics independent of renal function. 1, 2, 3

Key Pharmacokinetic Differences

Polymyxin B has critical advantages in renal impairment:

• Polymyxin B is administered as the active drug (not a prodrug), and its plasma concentration is not influenced by renal function 1
• Colistin is given as colistimethate sodium (CMS), an inactive prodrug that requires conversion and is heavily dependent on renal clearance 2, 4
• Polymyxin B requires no dose adjustment during continuous renal replacement therapy (CRRT), while colistin requires complex adjustments 1, 2

Nephrotoxicity Evidence

The nephrotoxicity profile strongly favors polymyxin B:

• In a prospective study comparing currently recommended doses, colistin caused nephrotoxicity in 39.3% of patients versus only 11.8% with polymyxin B 3
• The incidence of renal failure is lower with polymyxin B than colistin 1
• Colistin-associated nephrotoxicity occurs earlier and is more frequent than with polymyxin B 2
• Meta-analysis data shows colistin has a 37% increased risk of developing nephrotoxicity compared to polymyxin B (RR = 1.37,95% CI: 1.13-1.67) 5

Dosing Recommendations

For polymyxin B in renal impairment:

• Loading dose: 2-2.5 mg/kg regardless of renal function 1
• Maintenance dose: 1.5-3 mg/kg/day with no adjustment needed for CRRT 1, 2
• Dose adjustments are not necessary during renal replacement therapy 1

For colistin (if polymyxin B unavailable):

• Loading dose: 6-9 million IU regardless of renal function 1, 4
• Maintenance dose must be individually adjusted according to creatinine clearance 1, 4
• For intermittent hemodialysis: 2 million IU every 12 hours with dialysis scheduled toward the end of dosing interval 1, 4
• For CRRT: at least 9 million IU/day, though data are inconsistent 1, 4

Clinical Pitfalls to Avoid

Common dosing errors with colistin in renal impairment:

• In 43% of cases, colistin dose adjustment did not follow manufacturer recommendations, mainly in patients with renal impairment 6
• Failure to give a loading dose regardless of renal function leads to subtherapeutic levels 4
• Acute kidney injury during colistin treatment is a major factor related to clinical failure and mortality 1, 7

Monitoring Requirements

Both agents require close renal function monitoring, but polymyxin B offers practical advantages:

• Renal function must be closely monitored during therapy with either agent 1, 2
• Colistin nephrotoxicity is dose-dependent, with daily doses ≥300 mg associated with higher toxicity 3
• Most nephrotoxicity (75% with colistin, 83.3% with polymyxin B) is reversible within one week 3
• Mean onset of nephrotoxicity: 3.8 days with colistin versus 4.2 days with polymyxin B 3