Polymyxin B Dosing in AKI and CKD: IDSA Recommendations
Polymyxin B does not require dose adjustment for renal impairment, including AKI and CKD, because its plasma concentration is not influenced by renal function—this represents a critical advantage over colistin. 1, 2, 3
Standard Dosing Regimen (Regardless of Renal Function)
Loading Dose
- Administer 2-2.5 mg/kg as a loading dose to achieve optimal plasma levels on the first day 1, 2, 3, 4
- This loading dose should be given to all patients, including those with severe renal dysfunction 3
Maintenance Dose
- 1.5-3 mg/kg/day divided into 2 doses (every 12 hours) 1, 2, 3, 4
- The FDA label states 15,000-25,000 units/kg/day for adults with normal kidney function, which should be reduced for renal impairment 5
- However, contemporary evidence from the Intensive Care Medicine task force contradicts the FDA label, demonstrating that polymyxin B clearance is based on body weight and renal function does not significantly affect its pharmacokinetics 1, 3
Practical Example
- For a 70 kg patient: Loading dose = 140-175 mg, Maintenance dose = 105-210 mg/day in 2 divided doses 3
- No reduction needed despite severe renal impairment 3
Renal Replacement Therapy Considerations
Continuous Renal Replacement Therapy (CRRT)
- No dose adjustment necessary during CRRT 1, 2, 3, 4
- Standard maintenance dose of 1.5-3 mg/kg/day should be continued 3
Intermittent Hemodialysis
- The guideline does not provide specific polymyxin B dosing for intermittent hemodialysis 1
- By extrapolation from CRRT data, standard dosing without adjustment is reasonable 2, 3
Critical Differences from Colistin
Polymyxin B has fundamental pharmacokinetic advantages over colistin in renal impairment:
- Polymyxin B is administered as the active drug, not as an inactive prodrug like colistimethate sodium (CMS) 1, 2
- Plasma concentration is not influenced by renal function, unlike colistin which requires complex renal-based dose adjustments 1, 2, 3
- Lower nephrotoxicity: Polymyxin B causes renal failure in 11.8% versus 39.3% with colistin 2
- No loading dose delay: Colistin requires 2-3 days to reach steady state without a loading dose, while polymyxin B achieves therapeutic levels immediately with appropriate loading 1
Nephrotoxicity Considerations and Monitoring
Risk Factors for AKI
- Higher cumulative dose is associated with increased AKI risk 6
- Concomitant vancomycin is an independent predictor of AKI 6
- Higher BMI correlates with increased nephrotoxicity 6
- Once-daily dosing paradoxically increases AKI risk compared to twice-daily dosing (47% vs 17%, adjusted OR 2.5) 7
Monitoring Requirements
- Close monitoring of renal function is mandatory during therapy 2
- An AUCss,24h >100 mg·h/L is a strong predictor of nephrotoxicity 8
- Most nephrotoxicity is reversible within one week of discontinuation 2
Nephrotoxicity Mitigation
- Avoid concurrent nephrotoxic agents, particularly the combination of NSAIDs, diuretics, and ACE inhibitors/ARBs 4
- Use twice-daily dosing rather than once-daily to reduce nephrotoxicity risk 7
- Consider therapeutic drug monitoring where available 4
Important Caveats
Conflicting Evidence on Renal Adjustment
- The FDA label recommends dose reduction for renal impairment 5
- Contemporary pharmacokinetic studies and international guidelines contradict this, showing no correlation between polymyxin B clearance and creatinine clearance 1, 9, 8, 10
- Recent research demonstrates that renal dosing adjustment may actually increase adverse events (nephrotoxicity 21.7% vs 6.5% with non-adjusted dosing) 10
- Prioritize the guideline evidence over the outdated FDA label for clinical decision-making 1, 2, 3
When Polymyxin B is Unavailable
If colistin must be used instead: