What is the recommended dosing regimen for injectable Polymyxin B in adults (including weight‑based dose, maximum daily dose, and renal adjustment) and in pediatric patients?

Polymyxin B Dosing

Administer polymyxin B with a loading dose of 2-2.5 mg/kg followed by maintenance dosing of 1.5-3 mg/kg/day divided into two daily intravenous doses (every 12 hours), with no dose reduction required for renal impairment. 1, 2

Loading Dose Protocol

• Always initiate therapy with a loading dose of 2-2.5 mg/kg to rapidly achieve therapeutic plasma concentrations on the first day, regardless of renal function status. 1, 2
• The loading dose must be given to all patients, including those with severe renal dysfunction or on continuous renal replacement therapy (CRRT). 1, 2
• For a 70 kg patient, this translates to 140-175 mg as the loading dose. 2

Maintenance Dosing

• Administer 1.5-3 mg/kg/day divided into two doses (every 12 hours) as the standard maintenance regimen. 1, 2
• For a 70 kg patient, the maintenance dose is 105-210 mg/day divided into two doses. 1, 2
• The FDA label states 15,000-25,000 units/kg/day for adults and children with normal kidney function (equivalent to 1.5-2.5 mg/kg/day, as 10,000 units = 1 mg). 3

Critical Renal Function Considerations

This is the most important distinction from colistin and contradicts older FDA labeling:

• Do not reduce doses in patients with renal impairment—maintain standard dosing of 1.5-3 mg/kg/day even in severe renal dysfunction. 1, 2, 4
• Polymyxin B clearance is not influenced by renal function, unlike colistin, because it undergoes predominantly non-renal clearance. 1, 5
• No dose adjustment is necessary for patients on CRRT. 1, 2, 4
• The FDA label recommends dose reduction for renal impairment, but this is outdated and contradicted by current pharmacokinetic evidence showing no correlation between polymyxin B clearance and creatinine clearance. 3, 5

Common Pitfall to Avoid

• Do not follow the FDA label's recommendation to reduce polymyxin B dosing in renal impairment—this is based on outdated data and will lead to subtherapeutic levels. 1, 2, 5

Pediatric Dosing

• Children receive the same weight-based dosing as adults: 1.5-3 mg/kg/day divided into two doses, with a loading dose of 2-2.5 mg/kg. 6
• The FDA label states infants with normal kidney function may receive up to 40,000 units/kg/day (4 mg/kg/day) without adverse effects. 3
• Current dosing for pediatric patients is acceptable when MICs are <0.5 mg/L; higher doses may be needed for higher MICs. 6

Maximum Daily Dose

• The FDA label states the total daily dose must not exceed 25,000 units/kg/day (2.5 mg/kg/day). 3
• However, current guidelines recommend up to 3 mg/kg/day based on pharmacokinetic/pharmacodynamic data. 1, 2

Therapeutic Drug Monitoring

• Target a steady-state average concentration (Css,avg) of approximately 3.35 mg/L. 1, 7
• Optimal AUCss,24h target is 50-100 mg·h/L. 1, 6
• Therapeutic drug monitoring is encouraged to optimize dosing and minimize toxicity. 1

Nephrotoxicity Risk

• Polymyxin B has significantly lower nephrotoxicity than colistin (11.8% vs 39.3%). 1, 4
• Avoid concurrent nephrotoxic agents such as aminoglycosides, NSAIDs, diuretics, and ACE inhibitors/ARBs. 2

Combination Therapy

• Use polymyxin B in combination therapy rather than monotherapy for carbapenem-resistant infections. 1
• For ventilator-associated pneumonia (VAP) or hospital-acquired pneumonia (HAP) caused by carbapenem-resistant pathogens sensitive only to polymyxins, combine intravenous polymyxin B with adjunctive inhaled colistin (not inhaled polymyxin B). 1, 4
• Consider combination with tigecycline or meropenem (extended infusion) for carbapenem-resistant Enterobacterales bloodstream infections. 1

Duration of Therapy

• For hospital-acquired pneumonia/ventilator-associated pneumonia: 7 days. 1
• For carbapenem-resistant Enterobacterales bloodstream infections: 7-14 days. 1

Special Routes of Administration

Intrathecal (for meningitis)

• Adults and children over 2 years: 50,000 units (5 mg) once daily for 3-4 days, then every other day for at least 2 weeks after CSF cultures are negative. 8, 3
• Children under 2 years: 20,000 units (2 mg) once daily for 3-4 days, then 25,000 units every other day. 3

Intramuscular

• Not recommended routinely due to severe pain at injection sites. 3
• If used: 25,000-30,000 units/kg/day (2.5-3 mg/kg/day) divided every 4-6 hours, reduced in renal impairment per FDA label. 3