What is the recommended administration protocol for Polymyxin B in a patient with a suspected or confirmed bacterial infection and potential impaired renal function?

How to Administer Polymyxin B

Administer polymyxin B with a loading dose of 2-2.5 mg/kg followed by maintenance dosing of 1.5-3 mg/kg/day divided into two daily intravenous doses, with NO dose reduction required for renal impairment. 1, 2

Loading Dose Protocol

• Always initiate therapy with a loading dose of 2-2.5 mg/kg to rapidly achieve therapeutic plasma concentrations on the first day, regardless of renal function status 1, 2
• The loading dose must be given to all patients, including those with severe renal dysfunction or on continuous renal replacement therapy (CRRT) 1
• For a 70 kg patient, this translates to 140-175 mg as the loading dose 1

Maintenance Dosing

• Administer 1.5-3 mg/kg/day divided into two doses (every 12 hours) as the standard maintenance regimen 1, 2
• For a 70 kg patient, the maintenance dose is 105-210 mg/day divided into two doses 1
• The total daily dose must not exceed 25,000 units/kg/day (approximately 2.5 mg/kg/day when converted from units) 3

Critical Renal Function Considerations

Polymyxin B does NOT require dose adjustment for renal impairment - this is the most important distinction from colistin and contradicts older FDA labeling 1, 4, 5

• Polymyxin B plasma concentration is not influenced by renal function, as its clearance is predominantly non-renal with only 4% urinary recovery 6
• Research demonstrates comparable exposures (AUC 63.5 ± 16.6 mg·h/L in normal renal function vs 56.0 ± 17.5 mg·h/L in renal insufficiency, P=0.42) 5
• Do not reduce doses in patients with renal impairment - maintain standard dosing of 1.5-3 mg/kg/day even in severe renal dysfunction 1, 2
• No dose adjustment is necessary for patients on CRRT 1, 4

Important Caveat on Renal Dosing

While the most recent guidelines 1, 4, 2 and high-quality pharmacokinetic studies 5, 6 strongly support no dose adjustment for renal impairment, one 2021 study 7 suggests dose reduction may improve PK/PD target attainment. However, prioritize the consensus guideline recommendations of no dose adjustment, as polymyxin B clearance shows no correlation with creatinine clearance (r²=0.008) 6.

Preparation and Administration

• Intravenous route: Dissolve 500,000 polymyxin B units in 300-500 mL of 5% Dextrose Injection for continuous drip 3
• Administer as intravenous infusion every 12 hours 1, 2, 3
• Avoid intramuscular administration due to severe pain at injection sites 3

Combination Therapy Requirements

• Use polymyxin B in combination therapy rather than monotherapy for carbapenem-resistant infections 2
• 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) 8
• Consider combination with tigecycline or meropenem (extended infusion) for carbapenem-resistant Enterobacterales bloodstream infections 8

Nephrotoxicity Risk Management

Polymyxin B has significantly lower nephrotoxicity than colistin (11.8% vs 39.3%) 4, 2

Risk Factors to Monitor

• Daily dose by actual body weight (HR=1.73 for nephrotoxicity onset) 9
• Concurrent use of vancomycin (HR=1.89) 9
• Concurrent use of contrast media (HR=1.79) 9

Nephrotoxicity Prevention

• Avoid concurrent nephrotoxic agents: aminoglycosides, NSAIDs, diuretics, ACE inhibitors/ARBs 1, 2
• Monitor renal function closely throughout therapy 4
• Median onset of nephrotoxicity is 9 days when it occurs 9

Therapeutic Drug Monitoring

• Target steady-state average concentration of approximately 3.35 mg/L 1, 2
• Optimal AUCss,24h target is 50-100 mg·h/L 2
• Therapeutic drug monitoring is encouraged to optimize dosing and minimize toxicity 1

Common Pitfalls to Avoid

• Do not omit the loading dose - failure to load results in subtherapeutic levels for the first 24-48 hours 2
• Do not confuse polymyxin B with colistin dosing - they have different unit conversions (1 million IU colistin = 80 mg CMS, not polymyxin B) 4, 2
• Do not reduce doses based on renal function - this contradicts current pharmacokinetic evidence despite older FDA labeling 1, 2, 5
• Do not use as monotherapy for carbapenem-resistant infections when combination therapy is feasible 2

Duration of Therapy

• For HAP/VAP: 7-day course of antimicrobial therapy 8
• For carbapenem-resistant Enterobacterales bloodstream infections: 7-14 days 8

Storage and Stability

• Solutions for parenteral use should be stored under refrigeration 3
• Discard any unused portions after 72 hours 3