What is the appropriate polymyxin B dosing in million IU for a 70‑kg adult, including loading and maintenance doses, and are any adjustments needed for renal impairment or continuous renal replacement therapy?

Polymyxin B Dosing in Million IU for a 70-kg Adult

For a 70-kg adult, administer a loading dose of 2–2.5 mg/kg (140–175 mg, equivalent to approximately 1.4–1.75 million IU) followed by maintenance dosing of 1.5–3 mg/kg/day (105–210 mg/day, equivalent to approximately 1.05–2.1 million IU/day) divided into two doses every 12 hours, with no dose adjustment required for renal impairment or continuous renal replacement therapy. 1, 2

Conversion Between mg and Million IU

• Polymyxin B: 1 mg = approximately 10,000 IU (0.01 million IU) 3
• This conversion is critical for accurate dosing when prescribing in million IU rather than mg

Loading Dose Protocol

• Always initiate therapy with a loading dose of 2–2.5 mg/kg (140–175 mg for 70 kg, or 1.4–1.75 million IU) to rapidly achieve therapeutic plasma concentrations on the first day 1, 2
• The loading dose must be administered to all patients, including those with severe renal dysfunction or on CRRT, as polymyxin B pharmacokinetics are not significantly influenced by renal function 1, 2
• Failure to give a loading dose results in subtherapeutic concentrations for the first 24–48 hours 4

Maintenance Dosing

• Standard maintenance: 1.5–3 mg/kg/day (105–210 mg/day for 70 kg, or 1.05–2.1 million IU/day) divided into two doses every 12 hours 4, 1, 2
• For a 70-kg patient, this translates to 52.5–105 mg (0.525–1.05 million IU) every 12 hours 1
• Recent evidence suggests maintenance doses ≥2.5 mg/kg/day (≥175 mg/day or ≥1.75 million IU/day) achieve ≥90% probability of target attainment for pathogens with MIC ≤2 mg/L 5
• Fixed dosing (≥150 mg/day or ≥1.5 million IU/day) may be more appropriate than strict weight-based dosing for patients weighing 45–90 kg 5

Renal Impairment and CRRT: No Dose Adjustment Required

• Polymyxin B does not require dose reduction for renal impairment—this is the most critical distinction from colistin and contradicts older FDA labeling 1, 2
• Polymyxin B is primarily eliminated via non-renal pathways, and plasma concentrations are not significantly influenced by renal function 4, 6
• Maintain standard dosing of 1.5–3 mg/kg/day (1.05–2.1 million IU/day for 70 kg) even in severe renal dysfunction 1, 2
• No dose adjustment is necessary for patients on CRRT—use the same maintenance dose of 1.5–3 mg/kg/day 4, 1, 2
• Some recent data suggest a weak relationship between polymyxin B clearance and creatinine clearance, but this does not translate into clinically significant dose-normalized exposure variations across a wide range of renal function 5, 6

Critical Distinction from Colistin

• Do not confuse polymyxin B dosing with colistin dosing—colistin requires dose adjustment for renal impairment, while polymyxin B does not 1, 2
• Colistin is administered as an inactive prodrug (colistimethate sodium) and has different pharmacokinetics 4, 7
• Polymyxin B has significantly lower nephrotoxicity than colistin (11.8% vs 39.3%), making it preferable in patients with existing renal dysfunction 1, 2

FDA Labeling Caveat

• The FDA label recommends dose reduction for renal impairment (from 15,000 units/kg downward), but this contradicts current guideline consensus 3
• Modern pharmacokinetic data demonstrate that polymyxin B clearance is not significantly affected by renal function, and current guidelines uniformly recommend no dose adjustment for renal impairment 4, 1, 2, 6
• The FDA label dosing (15,000–25,000 units/kg/day, or 1.5–2.5 mg/kg/day) aligns with current maintenance dose recommendations, but the renal adjustment recommendation is outdated 3

Therapeutic Drug Monitoring

• Target steady-state average concentration: approximately 3.35 mg/L 1
• Optimal AUCss,24h target: 50–100 mg·h/L 1
• Therapeutic drug monitoring is encouraged to optimize dosing and minimize toxicity, given substantial inter-patient variability in polymyxin B clearance and volume of distribution 1, 5

Combination Therapy

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

Practical Dosing Example for 70-kg Adult

• Loading dose: 140–175 mg (1.4–1.75 million IU) as a single dose 1, 2
• Maintenance dose: 105–210 mg/day (1.05–2.1 million IU/day) divided into 52.5–105 mg (0.525–1.05 million IU) every 12 hours 1, 2
• For optimal efficacy, target the higher end: 175 mg loading dose (1.75 million IU), then 87.5–105 mg (0.875–1.05 million IU) every 12 hours 5
• No adjustment needed for renal impairment or CRRT 1, 2

Common Pitfalls to Avoid

• Do not reduce the dose in renal impairment—this is the most common error based on outdated FDA labeling 1, 2, 3
• Do not omit the loading dose—this results in delayed therapeutic concentrations and increased risk of treatment failure 1, 2
• Do not confuse polymyxin B with colistin dosing—they have entirely different pharmacokinetics and dosing requirements 4, 1, 7
• Avoid concurrent nephrotoxic agents (aminoglycosides, NSAIDs, diuretics, ACE inhibitors/ARBs) to minimize nephrotoxicity risk 2