What is the recommended use and dosage of Polymyxin B (Polymyxin B) for a patient with severe multidrug-resistant gram-negative bacterial infection and impaired renal function?

Polymyxin B for Severe Multidrug-Resistant Gram-Negative Infections with Renal Impairment

For patients with severe MDR gram-negative infections and impaired renal function, polymyxin B is preferred over colistin and should be used in combination therapy at a loading dose of 2-2.5 mg/kg followed by 1.5-3 mg/kg/day divided into two daily doses, with no dose adjustment required for renal dysfunction. 1, 2

Why Polymyxin B Over Colistin in Renal Impairment

Polymyxin B is the superior polymyxin choice when renal function is compromised because:

• Plasma concentrations are not influenced by renal function, eliminating the need for dose adjustments in renal failure 1
• Nephrotoxicity incidence appears lower compared to colistin (adjusted HR 2.27 for colistin vs polymyxin B) 1, 3
• No dose modification is necessary for patients on continuous renal replacement therapy 1
• Polymyxin B is administered as the active drug, not as an inactive prodrug like colistimethate sodium (CMS), avoiding the 2-3 day delay to reach therapeutic levels seen with colistin 1

Dosing Protocol

Loading Dose (Critical for Rapid Therapeutic Levels)

• Administer 2-2.5 mg/kg as a loading dose to achieve optimal plasma levels on day one 1
• This loading dose is essential regardless of renal function 1

Maintenance Dosing

According to FDA labeling and international guidelines:

• 15,000-25,000 units/kg/day (1.5-2.5 mg/kg/day) divided every 12 hours for adults with normal kidney function 2
• Maximum daily dose: 25,000 units/kg/day 2
• For renal impairment: Reduce from 15,000 units/kg downward based on severity 2
• Conversion: 1 mg polymyxin B = 10,000 units 1, 2

Renal Replacement Therapy

• No dose adjustment necessary for continuous renal replacement therapy 1
• This represents a major practical advantage over colistin 1

Combination Therapy is Mandatory

Polymyxin B should never be used as monotherapy for severe infections. 1, 4

Evidence for Combination Therapy

• Combination therapy reduces treatment failure by 119 per 1000 patients (RR 0.82,95% CI 0.72-0.93) 1
• Pathogen eradication failure reduced by 74 per 1000 patients (RR 0.81,95% CI 0.67-0.98) 1
• Mortality reduction demonstrated in CRE infections (35.7% vs 55.5% for monotherapy; OR 0.46,95% CI 0.30-0.69) 4

Recommended Combination Partners by Pathogen

For Carbapenem-Resistant Acinetobacter baumannii (CRAB):

• Polymyxin B + meropenem when carbapenem MIC ≤32 mg/L, using extended 3-hour infusion 1, 4
• Alternative: Polymyxin B + rifampicin or ampicillin-sulbactam 1

For Carbapenem-Resistant Enterobacterales (CRE):

• Polymyxin B + meropenem when carbapenem MIC ≤8 mg/L 1, 4
• Alternative: Polymyxin B + aminoglycoside or fosfomycin 4

For Carbapenem-Resistant Pseudomonas aeruginosa (CRPA):

• Polymyxin B + aminoglycoside, fosfomycin, or carbapenem (if MIC ≤8 mg/L) 4
• Two in vitro active drugs required for severe infections 4

Respiratory Tract Infections: Add Aerosolized Polymyxin B

For pneumonia or VAP caused by carbapenem-resistant organisms, add aerosolized polymyxin B to intravenous therapy. 4

• This combination reduces mortality (RR 0.86,95% CI 0.72-1.03) 4
• Clinical treatment failure reduced (RR 0.82,95% CI 0.70-0.96) 4
• Pathogen eradication failure reduced (RR 0.84,95% CI 0.69-1.03) 4

Monitoring and Toxicity Management

Nephrotoxicity Profile

• Occurs in approximately 14% of patients with normal baseline renal function, up to 45.8% in broader populations 3
• Typically reversible upon drug discontinuation 3
• Lower nephrotoxicity compared to colistin in critically ill patients 1, 3

Essential Monitoring

• Monitor renal function closely throughout treatment, particularly in elderly patients and those with elevated baseline creatinine 3
• Perform therapeutic drug monitoring (TDM) when available due to high interpatient variability 1, 3
• Avoid concurrent nephrotoxic drugs (vancomycin, contrast media, aminoglycosides) whenever possible 1, 3

Critical Pitfalls to Avoid

1. Never omit the loading dose - Without it, therapeutic levels are delayed by days 1
2. Never use monotherapy for severe infections - Combination therapy is essential for treatment success 1, 4
3. Do not reduce dose for renal impairment as aggressively as with colistin - Polymyxin B pharmacokinetics are not significantly affected by renal function 1
4. Watch for dosing unit confusion - 1 mg polymyxin B = 10,000 units (different from colistin conversion) 1, 2
5. Do not use for empiric therapy in VAP/HAP unless high local prevalence of MDR organisms - Reserve for documented resistant infections or outbreak settings 1

When Polymyxin B is NOT the Answer

Newer agents should be prioritized when available and active in vitro:

• Ceftolozane-tazobactam for CRPA (dramatically lower nephrotoxicity: adjusted OR 0.08,95% CI 0.03-0.22) 4
• Ceftazidime-avibactam for CRE 4
• Ampicillin-sulbactam for sulbactam-susceptible CRAB 4