What is the recommended dosage and usage of Polymyxin B for treating multidrug-resistant Gram-negative bacterial infections?

Polymyxin B Dosage and Usage for Multidrug-Resistant Gram-Negative Bacterial Infections

The recommended dosage of Polymyxin B for treating multidrug-resistant gram-negative bacterial infections is 15,000-25,000 units/kg/day intravenously in adults with normal renal function, divided every 12 hours, with dose reduction required in renal impairment. 1

Dosing Guidelines

Intravenous Administration

• Standard adult dose: 15,000-25,000 units/kg/day divided every 12 hours 1
• Loading dose: 2-2.5 mg/kg 2
• Maintenance dose: 1.5-3 mg/kg/day in 2 divided doses 2
• Administration method: Dissolve 500,000 polymyxin B units in 300-500 mL of 5% Dextrose Injection for continuous drip 1

Special Populations

• Renal impairment: Reduce dose from 15,000 units/kg downward based on severity of kidney dysfunction 1
• Infants with normal renal function: May receive up to 40,000 units/kg/day 1
• Elderly patients: Use with caution as older age (76 vs. 59 years) is significantly associated with higher risk of renal failure 3

Route-Specific Dosing

• Intrathecal (for Pseudomonas aeruginosa meningitis):

  • Adults and children >2 years: 50,000 units once daily for 3-4 days, then 50,000 units every other day for at least 2 weeks after CSF cultures are negative 1
  • Children <2 years: 20,000 units once daily for 3-4 days, then 25,000 units every other day 1

• Ophthalmic (for Pseudomonas aeruginosa eye infections):

  • 10,000-25,000 units/mL solution, 1-3 drops every hour, increasing intervals as response indicates 1
  • Subconjunctival injection up to 100,000 units/day may be used 1

Clinical Applications

Indicated Infections

• Carbapenem-resistant Enterobacterales (CRE) 2
• Carbapenem-resistant Acinetobacter baumannii (CRAB) 2
• Carbapenem-resistant Pseudomonas aeruginosa (CRPA) 4
• Multidrug-resistant gram-negative respiratory tract infections 5

Treatment Duration

• Bloodstream infections: 7-14 days 2
• Complicated urinary tract infections: 5-7 days 2
• Complicated intra-abdominal infections: 5-7 days 2
• Pneumonia (VAP/HAP): 7-14 days 4

Combination Therapy

Polymyxin combination therapy is recommended over monotherapy for treating CRGNB infections 2. Preferred combinations include:

• Polymyxin B + meropenem (extended infusion for 3 hours if meropenem MIC ≤8 mg/L for CRE or ≤32 mg/L for CRAB) 2
• Polymyxin B + tigecycline (loading dose 100 mg, then 50 mg every 12 hours) 2
• Polymyxin B + rifampicin (600 mg/day or 600 mg/12h) 2
• Polymyxin B + fosfomycin (12-24 g/day in 3-4 doses) 2

Monitoring and Safety

Nephrotoxicity Management

• Monitor renal function regularly throughout treatment 2
• Avoid concurrent use of other nephrotoxic or ototoxic drugs 2
• Nephrotoxicity occurs in approximately 14% of patients with normal baseline renal function 3
• Higher risk in elderly patients (mean age 76 years) 3

Pharmacokinetic Considerations

• Mean volume of distribution: 47.2 L 6
• Elimination half-life: 13.6 hours 6
• Unlike colistin, polymyxin B dosing is not significantly affected by renal function, and dosage adjustments are not necessary in patients on renal replacement therapy 2

Important Conversions and Equivalents

• Polymyxin B: 1 mg = 10,000 units 2
• For comparison with colistin: 1 million IU of colistin ≈ 33 mg colistin base activity (CBA) ≈ 80 mg colistimethate sodium (CMS) 2

Clinical Pearls

• Polymyxin B may have lower incidence of renal failure compared to colistin 2
• Microbiological clearance rates of approximately 88% have been reported 3
• Consider newer agents like ceftazidime-avibactam or imipenem-cilastatin-relebactam if the organism is susceptible, as these have better safety profiles 4
• Intramuscular administration is not recommended due to severe pain at injection sites 1
• Solutions for parenteral use should be stored under refrigeration, and unused portions discarded after 72 hours 1