How should I prepare and administer an intravenous Polymyxin B infusion, including loading and maintenance doses, dilution, infusion rate, and monitoring?

Polymyxin B Intravenous Infusion Administration

Administer polymyxin B with a loading dose of 2-2.5 mg/kg intravenously, followed by maintenance dosing of 1.5-3 mg/kg/day divided into two doses every 12 hours, with no dose reduction required for renal impairment including patients on continuous renal replacement therapy. 1

Loading Dose Protocol

Always initiate therapy with a loading dose of 2-2.5 mg/kg (equivalent to 20,000-25,000 units/kg) to rapidly achieve therapeutic plasma concentrations on the first day. 2, 1

• Give the loading dose to all patients regardless of renal function status, including those with severe renal dysfunction or on CRRT 1
• The loading dose should be infused over 60-90 minutes 3
• Failure to administer a loading dose results in subtherapeutic levels for the first 24-48 hours 4

Maintenance Dosing Regimen

Administer 1.5-3 mg/kg/day (15,000-30,000 units/kg/day) divided into two equal doses given every 12 hours. 2, 1

• For a 70 kg patient, this equals 105-210 mg/day or 1.05-2.1 million units/day 1
• The FDA label states maximum daily dose should not exceed 25,000 units/kg/day for adults and children with normal kidney function 3
• For severe infections, target the higher end of the dosing range (2.5-3 mg/kg/day) 5, 4

Preparation and Dilution

Dissolve 500,000 units of polymyxin B in 300-500 mL of 5% Dextrose Injection or 0.9% Sodium Chloride for continuous intravenous infusion. 3

• Each vial contains 500,000 units (equivalent to 50 mg) 3
• Reconstitute the powder completely before adding to the infusion solution 3
• Solutions should be stored under refrigeration and any unused portions discarded after 72 hours 3

Infusion Rate and Administration

Infuse each dose over 60-90 minutes every 12 hours. 3

• Avoid rapid bolus injection to minimize adverse effects 3
• Continuous infusion may be suitable as an alternative to intermittent dosing 2
• Use a dedicated intravenous line when possible to avoid incompatibilities 3

Critical Renal Function Considerations

Do not reduce polymyxin B doses for renal impairment—this is the most important distinction from colistin. 1, 4

• Maintain standard dosing of 1.5-3 mg/kg/day even in severe renal dysfunction 1
• No dose adjustment is necessary for patients on CRRT 2, 1
• Polymyxin B clearance is weight-based and not renal-dependent 1
• This contradicts older FDA labeling but is supported by current pharmacokinetic evidence 1, 6

Combination Therapy Requirements

Use polymyxin B in combination therapy rather than monotherapy for carbapenem-resistant infections. 2, 4

• For carbapenem-resistant Enterobacterales bloodstream infections, combine with tigecycline or extended-infusion meropenem (1 g over 3 hours every 8 hours) 2
• For ventilator-associated pneumonia caused by carbapenem-resistant pathogens, combine intravenous polymyxin B with adjunctive inhaled colistin (not inhaled polymyxin B) 2
• For Acinetobacter infections sensitive only to polymyxins, combine with another active agent when possible 2

Therapeutic Drug Monitoring

Target a steady-state average plasma concentration of approximately 3.35 mg/L with an optimal AUC₀₋₂₄h of 50-100 mg·h/L. 1, 4

• Therapeutic drug monitoring is encouraged to optimize dosing and minimize toxicity 1, 5
• Monitor renal function routinely during treatment to detect early nephrotoxicity 1
• Drug level assessment and dose adjustments are required to attain optimal therapeutic outcomes 1

Nephrotoxicity Risk Management

Polymyxin B has significantly lower nephrotoxicity than colistin (11.8% vs 39.3%). 4

• Avoid concurrent nephrotoxic agents, particularly the combination of NSAIDs, diuretics, and ACE inhibitors/ARBs 5, 4
• Avoid combination with aminoglycosides when possible 4
• Monitor serum creatinine at baseline and every 2-3 days during therapy 1

Duration of Therapy

Treat for 7 days for hospital-acquired or ventilator-associated pneumonia. 2

• For carbapenem-resistant Enterobacterales bloodstream infections, treat for 7-14 days 2
• For complicated urinary tract infections, treat for 5-7 days 2
• Adjust duration based on infection site, source control, underlying comorbidities, and initial response to therapy 2

Critical Dosing Conversion

1 mg polymyxin B sulfate = 10,000 units; 1 million international units (MIU) = 100 mg polymyxin B sulfate. 1, 5

• This differs significantly from colistin, where 1 million IU ≈ 80 mg colistimethate sodium (CMS) = 33 mg colistin base activity 5
• Do not confuse polymyxin B with colistin dosing—they have different unit conversions and dosing requirements 4

Common Pitfalls to Avoid

• Never omit the loading dose—this is the most common error leading to treatment failure in the first 24-48 hours 1, 4
• Never reduce doses for renal impairment—this outdated practice leads to underdosing 1, 4
• Never use as monotherapy for carbapenem-resistant infections when combination therapy is feasible 4
• Never confuse polymyxin B units with colistin units—the conversion factors are completely different 5, 4