How should Polymyxin B be administered intravenously, including loading dose, maintenance dose, infusion method, reconstitution, and monitoring in an adult patient?

Polymyxin B Intravenous Administration Protocol

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. 1

Loading Dose Protocol

• Always initiate therapy with a loading dose of 2-2.5 mg/kg (approximately 20,000-25,000 units/kg) to rapidly achieve therapeutic plasma concentrations on day 1. 1
• The loading dose must be administered regardless of renal function status, including patients with severe renal dysfunction or on continuous renal replacement therapy (CRRT). 1
• For a 70 kg patient, this translates to 140-175 mg (1.4-1.75 million international units). 1
• Failure to administer a loading dose results in subtherapeutic levels for the first 24-48 hours. 2

Reconstitution and Infusion Method

• Dissolve 500,000 polymyxin B units in 300-500 mL of 5% Dextrose Injection for intravenous administration. 3
• Administer as an intravenous infusion over 60 minutes for each dose. 4
• Alternatively, continuous intravenous infusion can be used instead of intermittent dosing. 1
• Store reconstituted solutions under refrigeration and discard any unused portions after 72 hours. 3

Maintenance Dosing

• Standard maintenance regimen is 1.5-3 mg/kg/day (15,000-30,000 units/kg/day), divided into two equal doses administered every 12 hours. 1
• For a 70 kg patient, this equals 105-210 mg/day (1.05-2.1 million international units/day) divided into two doses. 1
• The FDA label states a maximum of 25,000 units/kg/day for adults and children with normal kidney function. 3
• Do not reduce doses in patients with any degree of renal impairment, including severe renal dysfunction, as polymyxin B clearance is weight-based and not renal-dependent. 1, 5

Critical Renal Function Considerations

• No dose adjustment is necessary for patients on CRRT, as polymyxin B clearance is not significantly affected by renal replacement therapy. 1
• This represents the most important distinction from colistin and contradicts older FDA labeling. 1
• Polymyxin B is predominantly cleared by nonrenal pathways, with only 0.04-8.1% recovered unchanged in urine. 5, 4
• Creatinine clearance does not correlate with polymyxin B total body clearance (r² = 0.008). 5

Combination Therapy Requirements

• Polymyxin B must be used in combination therapy rather than monotherapy for carbapenem-resistant infections. 1, 2
• For carbapenem-resistant Enterobacterales bloodstream infections, combine with tigecycline or extended-infusion meropenem (1 g over 3 hours every 8 hours) based on susceptibility. 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). 6, 1
• For Acinetobacter infections susceptible only to polymyxins, pair with another active antimicrobial whenever feasible. 1

Therapeutic Drug Monitoring

• Target a steady-state average plasma concentration of approximately 3.35 mg/L. 1, 2
• Optimal AUC₀₋₂₄h target is 50-100 mg·h/L to balance efficacy and toxicity. 1
• Therapeutic drug monitoring is strongly encouraged to individualize dosing and minimize toxicity, given substantial interpatient pharmacokinetic variability. 1, 7
• Monitor renal function routinely during treatment to detect early nephrotoxicity. 1

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
• Duration should be individualized based on infection site, source control, patient comorbidities, and clinical response. 1

Nephrotoxicity Risk Management

• Polymyxin B has significantly lower nephrotoxicity than colistin (11.8% vs 39.3%). 1, 2
• Avoid concurrent nephrotoxic agents including aminoglycosides, NSAIDs, diuretics, and ACE inhibitors/ARBs. 2
• Monitor renal function closely throughout therapy. 8

Critical Pitfalls to Avoid

• Do not confuse polymyxin B with colistin dosing: 1 mg polymyxin B sulfate = 10,000 units; 1 million international units = 100 mg polymyxin B sulfate. 1
• Do not reduce doses based on renal function, as this contradicts current pharmacokinetic evidence despite older FDA labeling recommendations. 1, 2
• Do not omit the loading dose, as this results in inadequate drug exposure during the critical first 24-48 hours. 2
• Do not use as monotherapy for carbapenem-resistant infections when combination therapy is feasible. 2