What is the recommended dosage of Polymyxin B, in million units, for a critically ill patient with a severe infection and potentially impaired renal function?

Polymyxin B Dosage in Million Units

For critically ill patients with severe infections, administer Polymyxin B at 2-2.5 mg/kg loading dose (equivalent to 20,000-25,000 units/kg), followed by 1.5-3 mg/kg/day (15,000-30,000 units/kg/day) divided into two doses every 12 hours, with NO dose reduction required for renal impairment. 1, 2

Conversion Between Units and Milligrams

• 1 mg of Polymyxin B = 10,000 units 1
• For a 70 kg patient, the loading dose would be 140-175 mg (1.4-1.75 million units) 2
• Maintenance dosing for a 70 kg patient would be 105-210 mg/day (1.05-2.1 million units/day) divided into two doses 2

Loading Dose Protocol (Critical First Step)

• Always initiate therapy with a loading dose of 2-2.5 mg/kg (20,000-25,000 units/kg) to rapidly achieve therapeutic plasma concentrations on day one 1, 2
• The loading dose must be administered to ALL patients, regardless of renal function status, including those with severe renal dysfunction or on continuous renal replacement therapy (CRRT) 2
• This loading dose is essential because polymyxin B requires time to reach steady-state concentrations without it 1

Maintenance Dosing Regimen

• Standard maintenance: 1.5-3 mg/kg/day (15,000-30,000 units/kg/day) divided into two doses every 12 hours 1, 2
• The FDA label states 15,000-25,000 units/kg/day for adults and children with normal kidney function 3
• Higher doses up to 25,000 units/kg/day may be used but should not be exceeded 3
• Continuous infusion may be suitable as an alternative to divided dosing 1

Critical Renal Function Considerations (Major Distinction from Colistin)

This is the most important clinical distinction: Polymyxin B does NOT require dose adjustment for renal impairment, which directly contradicts older FDA labeling. 2, 4

• Maintain standard dosing of 1.5-3 mg/kg/day even in severe renal dysfunction 2, 4
• Polymyxin B plasma concentrations are not influenced by renal function 1, 5
• No dose adjustment is necessary for patients on CRRT 1, 2, 4
• Research confirms comparable polymyxin B exposures (AUC 63.5 ± 16.6 mg·h/L vs 56.0 ± 17.5 mg·h/L) in patients with normal versus impaired renal function 6
• Polymyxin B is predominantly non-renally cleared with median urinary recovery of only 4.04% 5

Common Pitfall to Avoid

• Do NOT reduce doses based on creatinine clearance - this is outdated practice from older FDA labeling that has been contradicted by modern pharmacokinetic studies 2, 6, 5
• The FDA label recommendation to reduce doses in renal impairment should be disregarded based on current evidence 2, 6

Nephrotoxicity Profile (Advantage Over Colistin)

• Polymyxin B has significantly lower nephrotoxicity than colistin (11.8% vs 39.3%) 2, 4
• The incidence of renal failure is lower with polymyxin B compared to colistin 1, 4
• Despite lower nephrotoxicity, renal function should still be monitored during therapy 4

Therapeutic Drug Monitoring

• Target steady-state average concentration: approximately 3.35 mg/L 2
• Optimal AUCss,24h target: 50-100 mg·h/L 2, 7
• Therapeutic drug monitoring is encouraged to optimize dosing and minimize toxicity 2

Combination Therapy Requirements

• Use polymyxin B in combination therapy rather than monotherapy for carbapenem-resistant infections 2
• For VAP/HAP caused by carbapenem-resistant pathogens sensitive only to polymyxins, combine intravenous polymyxin B with adjunctive inhaled colistin (not inhaled polymyxin B) 2
• Consider combination with tigecycline or meropenem (extended infusion) for carbapenem-resistant Enterobacterales bloodstream infections 2

Duration of Therapy

• 7-day course for HAP/VAP 2
• 7-14 day course for carbapenem-resistant Enterobacterales bloodstream infections 2