What is the recommended dose of Polymyxin B (Polymyxin B) for a patient with Acute Kidney Injury (AKI)?

Polymyxin B Dosing in Acute Kidney Injury

Polymyxin B does not require dose adjustment in patients with AKI or any degree of renal impairment, including those on renal replacement therapy. 1, 2

Standard Dosing Regimen for All Patients with AKI

Administer a loading dose of 2-2.5 mg/kg followed by maintenance dosing of 1.5-3 mg/kg/day divided into two doses, regardless of renal function. 1, 2

Loading Dose

• Give 2-2.5 mg/kg as a single loading dose to all patients, including those with severe renal impairment or AKI 1
• For a 70 kg patient, this translates to 140-175 mg 1
• The loading dose is critical to achieve therapeutic levels rapidly and should never be reduced based on renal function 1

Maintenance Dose

• Administer 1.5-3 mg/kg/day divided into 2 doses (every 12 hours) 1, 2
• For a 70 kg patient, this is 105-210 mg/day in divided doses 1
• The FDA label specifies 15,000-25,000 units/kg/day for adults with normal kidney function, with reduction recommended for kidney impairment 2, but current guideline evidence from the Intensive Care Society contradicts this, stating no dose adjustment is needed 1

Key Pharmacokinetic Rationale

Polymyxin B clearance is not influenced by renal function, unlike colistin, making it the preferred polymyxin in patients with renal impairment. 1

• Polymyxin B undergoes minimal renal elimination 1
• Plasma concentrations remain stable regardless of creatinine clearance 1
• This is a critical distinction from colistin, which requires dose adjustment based on renal function 3

Dosing in Renal Replacement Therapy

No dose adjustment is necessary for patients on continuous renal replacement therapy (CRRT)—use the standard maintenance dose of 1.5-3 mg/kg/day. 4, 1

• CRRT does not significantly remove polymyxin B 1
• Continue the same loading and maintenance doses as patients not on dialysis 4, 1

Critical Dosing Considerations to Minimize Nephrotoxicity

Frequency of Administration

Administer polymyxin B twice daily rather than once daily to reduce nephrotoxicity risk. 5

• Once-daily dosing is associated with significantly higher rates of AKI (47% vs 17%, adjusted OR 2.5) 5
• Twice-daily dosing reduces nephrotoxicity without compromising efficacy 5

Avoid Excessive Cumulative Doses

• Higher cumulative doses are independently associated with increased AKI risk 6
• Limit treatment duration when clinically appropriate, as median cumulative doses above 1578 mg correlate with higher AKI rates 6

Discontinue Concurrent Nephrotoxins

Immediately discontinue all potentially nephrotoxic medications, particularly vancomycin, NSAIDs, and loop diuretics. 4, 6, 7

• Concomitant vancomycin is an independent predictor of AKI during polymyxin B therapy 6
• Loop diuretics significantly increase nephrotoxicity risk (OR 5.93) 7
• The combination of NSAIDs, diuretics, and ACE inhibitors/ARBs dramatically increases AKI risk 4

Monitoring During Therapy

Monitor serum creatinine and urine output closely throughout treatment, assessing for AKI using RIFLE criteria. 4

• Diagnose AKI when creatinine increases ≥0.3 mg/dL within 48 hours or ≥50% from baseline 4
• Monitor for urine output <0.5 mL/kg/h for >6 hours 4
• Watch for early signs including albuminuria, cellular casts, and azotemia 4
• The median time to AKI onset is 6-7 days 5

Common Pitfalls to Avoid

• Do not reduce the loading dose in patients with AKI—this compromises therapeutic efficacy without reducing nephrotoxicity 1
• Do not use once-daily dosing—this significantly increases AKI risk compared to twice-daily administration 5
• Do not continue vancomycin unnecessarily—it is an independent risk factor for polymyxin B-associated nephrotoxicity 6
• Do not ignore BMI—higher body mass index independently predicts AKI during polymyxin B therapy 6