What is the recommended intravenous dosing regimen of polymyxin B for an adult patient with a multidrug‑resistant Gram‑negative infection, including loading dose, maintenance dose, renal‑function adjustments, monitoring, and contraindications?

Polymyxin B Intravenous Dosing for Multidrug-Resistant Gram-Negative Infections

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 (every 12 hours), with no dose reduction required for renal impairment. 1, 2, 3

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, 3
• The loading dose must be given to all patients, including those with severe renal dysfunction or on continuous renal replacement therapy (CRRT). 1, 3
• For a 70 kg patient, this translates to 140-175 mg as the loading dose. 3

Maintenance Dosing Regimen

• Administer 1.5-3 mg/kg/day divided into two doses (every 12 hours) as the standard maintenance regimen. 1, 2, 3
• For a 70 kg patient, the maintenance dose is 105-210 mg/day divided into two doses. 1, 3
• The typical dosing is 2.5-3.0 mg/kg/day divided in 2 daily IV doses for most patients. 4

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, 2, 3

• Maintain standard dosing of 1.5-3 mg/kg/day even in severe renal dysfunction. 1, 2, 3
• No dose adjustment is necessary for patients on CRRT. 1, 3
• Polymyxin B clearance is based on body weight, and renal function does not significantly affect its pharmacokinetics. 3
• The plasma concentration is not influenced by renal function, unlike colistin which requires complex renal-based dosing adjustments. 2, 3

Common Pitfall to Avoid

Do not reduce doses in patients with renal impairment—this is a critical error that leads to subtherapeutic levels and treatment failure. 1, 2

Combination Therapy Requirements

Use polymyxin B in combination therapy rather than monotherapy for carbapenem-resistant infections. 1, 2

• Combination therapy reduces treatment failure by 119 per 1000 patients (RR 0.82,95% CI 0.72-0.93) and pathogen eradication failure by 74 per 1000 patients (RR 0.81,95% CI 0.67-0.98). 2
• For carbapenem-resistant Enterobacterales (CRE), combine with tigecycline or meropenem (extended infusion) based on susceptibility testing. 2, 4
• 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). 1
• Combination therapy with polymyxin B and antimicrobials lacking in vitro activity showed lower 30-day mortality (42.4% vs 67.6%, P=0.03) compared to monotherapy in critically ill patients. 5

Nephrotoxicity Risk Management and Monitoring

• Polymyxin B has significantly lower nephrotoxicity than colistin (11.8% vs 39.3%). 1
• Monitor renal function closely throughout treatment, particularly in elderly patients and those with elevated baseline creatinine. 2
• Avoid concurrent nephrotoxic agents such as aminoglycosides, NSAIDs, diuretics, and ACE inhibitors/ARBs to minimize nephrotoxicity risk. 3
• In patients with baseline renal insufficiency, nephrotoxicity occurred in 55% of cases, with mean onset at 7.5 ± 2.3 days (range 4-10 days) after initiation. 6

Therapeutic Drug Monitoring

• Target a steady-state average concentration of approximately 3.35 mg/L. 1, 3
• Optimal AUCss,24h target is 50-100 mg·h/L. 1
• Therapeutic drug monitoring is encouraged to optimize dosing and minimize toxicity due to high interpatient variability. 1, 2
• The mean volume of distribution is 47.2 L and elimination half-life is 13.6 hours. 7

Duration of Therapy

• For hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP), administer a 7-day course of antimicrobial therapy. 1
• For carbapenem-resistant Enterobacterales bloodstream infections, a 7-14 day course is recommended. 1
• Mean duration in clinical practice has been 19 days (range 2-57 days) for respiratory tract infections. 8

Contraindications and Precautions

• Polymyxin B should be reserved for settings where there is a high prevalence of multidrug resistance and local expertise in using this medication. 4
• Drug levels and adjustment of doses and/or intervals are required for optimal outcomes. 4
• Avoid monotherapy for severe infections, as combination therapy is essential for treatment success. 2