What are the recommended polymyxin B loading and maintenance doses expressed in million international units (MIU) for a 70‑kg adult with normal renal function, and how should the doses be adjusted for renal or hepatic impairment and for intrathecal administration?

Polymyxin B Dosing in Million International Units (MIU)

Standard Intravenous Dosing for 70-kg Adult with Normal Renal Function

For a 70-kg adult with normal renal function, administer a loading dose of 1.4–1.75 MIU (140,000–175,000 units) followed by maintenance dosing of 1.05–2.1 MIU/day (105,000–210,000 units/day) divided into two doses every 12 hours. 1, 2, 3

Loading Dose Protocol

• Always initiate with a loading dose of 2–2.5 mg/kg (equivalent to 20,000–25,000 units/kg), which translates to 1.4–1.75 MIU for a 70-kg patient 1, 2
• The loading dose must be given to all patients regardless of renal function status to achieve therapeutic plasma concentrations on day one 3, 4
• Conversion: 1 mg polymyxin B sulfate = 10,000 units 1

Maintenance Dosing

• Standard maintenance: 1.5–3 mg/kg/day (15,000–30,000 units/kg/day) divided into two doses 1, 3
• For a 70-kg patient: 1.05–2.1 MIU/day (105,000–210,000 units/day) given as 0.525–1.05 MIU every 12 hours 2, 3
• The FDA label states 15,000–25,000 units/kg/day for adults with normal kidney function 5

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Critical Dosing Principle: No Renal Adjustment Required

Polymyxin B does NOT require dose reduction for renal impairment—this is the most important distinction from colistin and contradicts older FDA labeling. 1, 2, 3

Renal Insufficiency Dosing

• Maintain the same loading dose (2–2.5 mg/kg or 1.4–1.75 MIU for 70-kg patient) even in severe renal dysfunction 1, 2
• Maintain standard maintenance dosing (1.5–3 mg/kg/day or 1.05–2.1 MIU/day) without reduction 1, 2, 3
• Polymyxin B clearance is calculated based on body weight, and plasma concentration is not significantly influenced by renal function 1, 2
• Recent pharmacokinetic studies confirm comparable exposures between patients with normal and impaired renal function at standard doses 6

Continuous Renal Replacement Therapy (CRRT)

• No dose adjustment necessary for patients on CRRT—use standard dosing of 1.5–3 mg/kg/day 1, 2
• Dialysate recovery is approximately 22%, which does not significantly impact systemic exposure 7

Common Pitfall to Avoid

The FDA label recommends dose reduction for renal impairment (from 15,000 units/kg downward) 5, but this recommendation is outdated and contradicted by current pharmacokinetic evidence and international guidelines 1, 2, 3, 6. Modern practice maintains standard dosing regardless of renal function.

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Hepatic Impairment

No specific dose adjustment is recommended for hepatic impairment, as polymyxin B is not hepatically metabolized and renal excretion is the primary elimination route 1. However, therapeutic drug monitoring is encouraged in complex patients 1, 3.

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Intrathecal Administration

For intrathecal use in patients >2 years with CNS infections (e.g., Pseudomonas aeruginosa meningitis), administer 50,000 units (0.05 MIU or approximately 5 mg) once daily for 3–4 days, then every other day for at least 2 weeks after CSF cultures become negative. 3, 5

Intrathecal Dosing Details

• Adults and children >2 years: 50,000 units (0.05 MIU) once daily intrathecally for 3–4 days, then 50,000 units every other day 5
• Children <2 years: 20,000 units (0.02 MIU) once daily for 3–4 days, then 25,000 units (0.025 MIU) every other day 5
• Continue for at least 2 weeks after CSF cultures are negative and glucose normalizes 3, 5

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Essential Safety Considerations

Nephrotoxicity Management

• Polymyxin B has significantly lower nephrotoxicity than colistin (11.8% vs 39.3%) 3, 4
• Avoid concurrent nephrotoxic agents including aminoglycosides, NSAIDs, diuretics, and ACE inhibitors/ARBs 2, 3
• Monitor renal function during treatment 1

Therapeutic Drug Monitoring

• Target steady-state average concentration: approximately 3.35 mg/L 2, 3, 8
• Optimal AUCss,24h: 50–100 mg·h/L 3
• TDM is encouraged to optimize dosing and minimize toxicity 1, 2, 3

Combination Therapy Requirement

• Polymyxin B should be used in combination therapy rather than monotherapy for carbapenem-resistant infections 1, 3, 4
• Consider combinations with tigecycline, extended-infusion meropenem (if MIC ≤8 mg/L for CRE or ≤32 mg/L for CRAB), or other active agents based on susceptibility 1, 3

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Dosing Conversion Reference

Critical conversion for polymyxin B sulfate: 1

• 1 mg polymyxin B sulfate = 10,000 units
• 1 MIU = 100 mg polymyxin B sulfate
• For a 70-kg patient:
  • Loading dose: 140–175 mg = 1.4–1.75 MIU
  • Maintenance dose: 105–210 mg/day = 1.05–2.1 MIU/day

Do not confuse with colistin dosing, which uses different conversions and requires renal adjustment 1, 4.