Polymyxin B Loading Dose for Serious Gram-Negative Infections
Administer a loading dose of 2–2.5 mg/kg intravenously on day 1, regardless of renal function, to rapidly achieve therapeutic plasma concentrations. 1
Loading Dose Protocol
- Give 2–2.5 mg/kg IV as a single loading dose (approximately 20,000–25,000 units/kg, or 1.4–1.75 million international units for a 70-kg adult) on the first day of therapy 1
- The loading dose is mandatory for all patients, including those with severe renal dysfunction or on continuous renal replacement therapy (CRRT), because renal impairment does not affect initial drug exposure 1
- This loading dose rapidly achieves the target steady-state average plasma concentration of approximately 3.35 mg/L on day 1, which would otherwise take 2–3 days to reach with maintenance dosing alone 1, 2
Maintenance Dosing Following the Load
- After the loading dose, initiate maintenance therapy at 1.5–3 mg/kg/day divided into two equal doses every 12 hours (for a 70-kg patient, this equals 105–210 mg/day or 1.05–2.1 million international units/day) 1
- The standard maintenance regimen most commonly used is 2.5–3.0 mg/kg/day divided into two daily IV doses 3, 4
- No dose reduction is required for renal impairment, including patients on CRRT—this is the most critical distinction from colistin and contradicts older FDA labeling 1, 5, 6
Critical Renal Function Considerations
- Polymyxin B clearance is weight-based and not renally dependent, so maintain standard dosing even in severe renal dysfunction 1
- Studies demonstrate comparable polymyxin B exposures (AUC 63.5 ± 16.6 mg·h/L vs 56.0 ± 17.5 mg·h/L, P = 0.42) in patients with normal renal function versus renal insufficiency receiving the same doses 6
- Polymyxin B has significantly lower nephrotoxicity than colistin (11.8% vs 39.3%), making it the preferred polymyxin in patients with or at risk for renal impairment 5, 4
Combination Therapy Requirements
- Always use polymyxin B in combination therapy rather than monotherapy for carbapenem-resistant infections 3, 1, 4
- For carbapenem-resistant Enterobacterales bloodstream infections, combine with tigecycline or extended-infusion meropenem (1 g over 3 hours every 8 hours) when the meropenem MIC is ≤8 mg/L for CRE or ≤32 mg/L for CRAB 3, 1
- For ventilator-associated pneumonia caused by carbapenem-resistant pathogens, add adjunctive inhaled colistin (not inhaled polymyxin B) to intravenous polymyxin B 1
Therapeutic Drug Monitoring
- Target a steady-state average concentration of approximately 3.35 mg/L and an AUC₀₋₂₄h of 50–100 mg·h/L to balance efficacy and minimize toxicity 1, 2
- Therapeutic drug monitoring is strongly encouraged to individualize dosing and optimize outcomes 3, 1
- Monitor renal function closely during therapy, as nephrotoxicity remains dose-dependent despite lower rates than colistin 3, 5
Common Pitfalls to Avoid
- Do not omit the loading dose—failure to administer it results in subtherapeutic levels for the first 24–48 hours, compromising early bacterial killing 1, 4
- Do not reduce doses in renal impairment—this outdated practice leads to treatment failure, as polymyxin B pharmacokinetics are not significantly affected by creatinine clearance 1, 5, 6
- Do not confuse polymyxin B with colistin dosing—polymyxin B: 1 mg = 10,000 units; colistin: 1 million IU = 80 mg CMS = 33 mg colistin base activity 3, 1
- Avoid concurrent nephrotoxic agents (aminoglycosides, NSAIDs, diuretics, ACE inhibitors/ARBs) to minimize additive nephrotoxicity risk 3, 4
Duration of Therapy
- Hospital-acquired or ventilator-associated pneumonia: 7 days 1
- Carbapenem-resistant Enterobacterales bloodstream infections: 7–14 days 1
- Complicated urinary tract infections: 5–7 days 1