What is the recommended dosing regimen for polymyxin B (polymyxin B sulfate) in a critically ill adult patient with normal renal function?

Polymyxin B Sulfate Dosing in Critically Ill Adults with Normal Renal Function

For critically ill adults with normal renal function, administer polymyxin B as a loading dose of 2-2.5 mg/kg followed by a maintenance dose of 1.5-3 mg/kg/day divided into 2 doses every 12 hours, always in combination therapy rather than monotherapy. 1, 2

Loading Dose Strategy

• Administer 2-2.5 mg/kg as a loading dose to rapidly achieve therapeutic plasma concentrations on the first day 1, 2
• For a 70 kg patient, this translates to 140-175 mg as the initial dose 1
• Never omit the loading dose—failure to load results in subtherapeutic levels for the first 24-48 hours 2

Maintenance Dosing

• Give 1.5-3 mg/kg/day divided into 2 doses every 12 hours 1, 2
• For a 70 kg patient, this equals 105-210 mg/day split into two administrations 1
• The total daily dose must not exceed 25,000 units/kg/day (equivalent to 2.5 mg/kg/day, since 1 mg = 10,000 units) 3

Critical Dosing Principle: No Renal Adjustment Needed

Despite older FDA labeling recommending dose reduction in renal impairment, current evidence demonstrates that polymyxin B clearance is minimally affected by renal function and dose adjustment is NOT necessary. 1, 2, 4

• Polymyxin B is eliminated mainly by nonrenal pathways, with only 0.04-0.86% recovered unchanged in urine 5
• Steady-state exposures are comparable between patients with normal renal function (AUC 63.5 ± 16.6 mg·h/L) and those with renal insufficiency (AUC 56.0 ± 17.5 mg·h/L, p=0.42) 4
• This contradicts the FDA label but is supported by robust pharmacokinetic evidence 2, 4

Combination Therapy Requirement

Polymyxin B must be used in combination therapy, not as monotherapy, for carbapenem-resistant Gram-negative infections. 6, 2

• Combination therapy reduces treatment failures by 119 per 1000 patients (RR 0.82,95% CI 0.72-0.93) compared to monotherapy 6
• Pathogen eradication failure is reduced by 74 per 1000 patients with combination therapy (RR 0.81,95% CI 0.67-0.98) 6
• Preferred combinations include polymyxin B plus an antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, or meropenem) for ventilator-associated pneumonia 2
• Consider polymyxin-carbapenem combination if meropenem MIC is ≤8 mg/L for CRE or ≤32 mg/L for CRAB, using extended infusion of meropenem over 3 hours 6

Therapeutic Drug Monitoring

• Target steady-state average concentration of approximately 3.35 mg/L 1, 2
• Optimal AUCss,24h is 50-100 mg·h/L 2
• TDM is encouraged where possible to optimize dosing and minimize toxicity 6, 1

Nephrotoxicity Risk Management

Avoid concurrent nephrotoxic agents to minimize kidney injury risk. 1, 2

• Do not combine with aminoglycosides, NSAIDs, diuretics, or ACE inhibitors/ARBs 1, 2
• Polymyxin B has significantly lower nephrotoxicity than colistin (11.8% vs 39.3%) 2, 7
• Monitor renal function during treatment 6, 7

Critical Pitfalls to Avoid

• Do not confuse polymyxin B with colistin dosing—they have different unit conversions (polymyxin B: 1 mg = 10,000 units; colistin: 1 million U = 80 mg CMS = 33 mg CBA) 6, 2
• Do not reduce doses based on renal function alone in patients with normal baseline function—this practice is outdated 2, 4
• Do not use as monotherapy when combination therapy is feasible 2
• Do not skip the loading dose even in patients you perceive as high-risk 1, 2

Administration Details

• Dissolve 500,000 units (50 mg) in 300-500 mL of 5% dextrose for continuous IV infusion 3
• Infusions are given every 12 hours 3
• Store solutions under refrigeration and discard unused portions after 72 hours 3