Polymyxin Dosing in Adults with Renal Impairment
Direct Recommendation
Polymyxin B is the preferred polymyxin agent for patients with renal impairment because it does not require dose adjustment based on renal function, unlike colistin. 1, 2
Polymyxin B Dosing (Preferred Agent)
Standard Dosing Regimen
- Loading dose: 2-2.5 mg/kg administered to ALL patients regardless of renal function 1, 2
- Maintenance dose: 1.5-3 mg/kg/day divided into 2 doses (every 12 hours) 1, 2
- No dose adjustment required for any degree of renal impairment, including severe renal dysfunction 1, 2
Practical Example
- For a 70 kg patient: Loading dose = 140-175 mg, followed by maintenance dose = 105-210 mg/day divided into 2 doses 1
Renal Replacement Therapy
- No dose adjustment needed for continuous renal replacement therapy (CRRT) 1, 2
- Standard dosing of 1.5-3 mg/kg/day should be maintained 1
Key Pharmacokinetic Rationale
- Polymyxin B is administered as the active drug (not a prodrug) 2
- Plasma concentrations are not influenced by renal function 1, 2, 3
- Predominantly non-renal clearance with median urinary recovery of only 4% 3
- Total body clearance shows no correlation with creatinine clearance (r² = 0.008) 3
Colistin Dosing (Alternative if Polymyxin B Unavailable)
Standard Dosing Regimen
- Loading dose: 6-9 million IU for ALL patients regardless of renal function 4, 2
- Maintenance dose for normal renal function: 4.5 million IU every 12 hours 4
- Maintenance dose MUST be adjusted based on creatinine clearance for renal impairment 4, 2
Renal Impairment Adjustments
- Severe renal impairment: 3.0-5.0 mg/kg IV every 24-36 hours 4
- Intermittent hemodialysis: 3.0-5.0 mg/kg IV every 24 hours 4
- CRRT: At least 9 million IU/day 4
Administration Considerations
- Colistin is administered as colistimethate sodium (CMS), an inactive prodrug 4, 2
- 1 million IU of colistin = 80 mg of CMS 4, 2
- Consider 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties 4
Critical Safety Considerations
Nephrotoxicity Comparison
- Polymyxin B has significantly lower nephrotoxicity: 11.8% vs 39.3% with colistin 2
- Colistin-associated nephrotoxicity occurs earlier and more frequently 2
- Colistin nephrotoxicity shows adjusted hazard ratio of 2.27 (95% CI 1.35-3.82) compared to polymyxin B 2
Monitoring Requirements
- Renal function must be monitored at baseline and 2-3 times per week during treatment 4, 1
- Acute kidney injury during treatment is a major factor related to clinical failure and mortality 4, 2
- Consider therapeutic drug monitoring for polymyxin B with target steady-state concentration of approximately 3.35 mg/L 1
Drug Interactions to Avoid
- Avoid concurrent nephrotoxic agents: aminoglycosides, NSAIDs, diuretics, ACE inhibitors/ARBs 1
Common Pitfalls to Avoid
Critical Errors
- Do NOT reduce polymyxin B dose in renal impairment - this is a common error based on outdated FDA labeling 1, 5, 3
- Do NOT skip the loading dose - both agents require loading doses regardless of renal function to rapidly achieve therapeutic levels 4, 1
- Do NOT use colistin maintenance doses without renal adjustment - unlike polymyxin B, colistin requires individualized dosing based on creatinine clearance 4, 2
High MIC Pathogens
- For pathogens with MIC ≥2 mg/L, even maximal polymyxin doses may be inadequate 4, 6
- Consider combination therapy for organisms with MIC ≥1 mg/L, particularly Pseudomonas species 4
- Probability of target attainment drops substantially for MICs ≥2 mg/L even with maximum recommended doses 6
Evidence Quality Note
The most recent guidelines (2025-2026) from the Intensive Care Society consistently recommend no dose adjustment for polymyxin B in renal impairment 1, 2, which is supported by multiple pharmacokinetic studies demonstrating no correlation between polymyxin B clearance and renal function 5, 3. However, one 2021 population PK study 7 and a 2023 study 8 suggest decreased clearance in renal insufficiency, creating some controversy. Despite this conflicting research data, the guideline consensus strongly favors no dose adjustment, prioritizing the consistent pharmacokinetic evidence showing predominantly non-renal clearance. 1, 2, 3