What is the recommended dosage and administration of polymyxin B (Polymyxin B) for treating infections in critical care patients with normal renal function?

Polymyxin B Dosing and Administration in Critical Care

Standard Dosing Regimen

For critical care patients with normal renal function, administer polymyxin B at 2.5-3.0 mg/kg/day divided into 2 daily intravenous doses (equivalent to 25,000-30,000 units/kg/day), preceded by a loading dose of 2-2.5 mg/kg to rapidly achieve therapeutic plasma concentrations. 1, 2, 3

Loading Dose Protocol

• Administer 2-2.5 mg/kg as a loading dose to all patients on day 1, regardless of renal function status 2, 3
• This loading dose is critical for achieving optimal plasma levels immediately and should never be omitted 2
• For a 70 kg patient, this translates to 140-175 mg as the initial loading dose 2

Maintenance Dosing

• Standard maintenance: 1.5-3 mg/kg/day divided into 2 doses (every 12 hours) 2, 3, 4
• The FDA-approved range is 15,000-25,000 units/kg/day, with a maximum not exceeding 25,000 units/kg/day 4
• For a 70 kg patient, maintenance dosing is 105-210 mg/day divided into two doses 2

Reconstitution and Administration

Intravenous Preparation

• Dissolve 500,000 polymyxin B units in 300-500 mL of 5% Dextrose Injection for continuous drip administration 4
• Infusions should be given every 12 hours 4
• Store solutions under refrigeration and discard any unused portions after 72 hours 4

Unit Conversion (Critical)

• 1 mg polymyxin B = 10,000 units 3
• This differs significantly from colistin dosing conversions 3

Renal Impairment Considerations

Polymyxin B does NOT require dose adjustment for renal dysfunction, including severe renal impairment or continuous renal replacement therapy (CRRT). 2, 5, 3

Key Pharmacokinetic Rationale

• Polymyxin B plasma concentrations are not influenced by renal function 2, 5
• The drug is predominantly cleared by nonrenal pathways, with only 0.04%-0.86% recovered unchanged in urine 6
• Total body clearance shows no correlation with creatinine clearance (r² = 0.008) 7
• Research demonstrates comparable drug 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) 8

CRRT Patients

• Maintain standard dosing (1.5-3 mg/kg/day) without adjustment during continuous renal replacement therapy 2, 3
• No dose reduction is necessary despite dialysis 2

Combination Therapy Approach

Polymyxin B should be used in combination therapy rather than monotherapy for carbapenem-resistant infections. 3

Empiric Coverage for VAP

When treating ventilator-associated pneumonia with suspected multidrug-resistant gram-negative pathogens:

• Combine polymyxin B with an antipseudomonal β-lactam agent (piperacillin-tazobactam 4.5g IV q6h, cefepime 2g IV q8h, or meropenem 1g IV q8h) 1
• Reserve polymyxins for settings with high prevalence of multidrug resistance and local expertise 1

Therapeutic Drug Monitoring

Target steady-state average concentration (Css,avg) of approximately 3.35 mg/L, with an optimal AUCss,24h of 50-100 mg·h/L. 2, 9

Monitoring Benefits

• Achieving the therapeutic target AUCss,24h is independently associated with favorable clinical outcomes (OR = 13.15, p=0.015) 9
• 54.3% of monitored patients reached the therapeutic target in one study 9
• TDM is particularly valuable given the high plasma protein binding (78.5%-92.4% in critically ill patients) 6

Nephrotoxicity Risk Management

Polymyxin B has significantly lower nephrotoxicity compared to colistin (11.8% vs 39.3%). 5

Risk Factors for Nephrotoxicity

• Lower baseline creatinine clearance (OR = 0.96, p=0.008) 9
• Concomitant loop diuretics (OR = 5.93, p=0.046) 9
• Older age (76 vs 59 years, p=0.02) 10
• Overall AKI incidence is approximately 14-45% 9, 10

Critical Avoidance Strategies

• Avoid concurrent nephrotoxic agents: aminoglycosides, NSAIDs, diuretics, ACE inhibitors/ARBs 2, 3
• Monitor renal function closely throughout therapy 5
• Most nephrotoxicity is reversible within one week of discontinuation 5

Common Pitfalls

• Do NOT reduce doses in renal impairment - this contradicts older FDA labeling but is supported by current pharmacokinetic evidence 2, 8, 7
• 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 and dosing requirements 3
• Do NOT use as monotherapy for carbapenem-resistant infections when combination therapy is feasible 3

Special Populations

Infants

• May receive up to 40,000 units/kg/day without adverse effects in those with normal kidney function 4
• Doses as high as 45,000 units/kg/day have been used in premature and newborn infants for Pseudomonas aeruginosa sepsis 4