Polymyxin B Dosing for Systemic Infections Caused by Multidrug-Resistant Gram-Negative Bacteria
For treating systemic infections caused by multidrug-resistant gram-negative bacteria, the recommended dose of Polymyxin B is 15,000 to 25,000 units/kg/day divided into two doses for adults with normal renal function. 1
Standard Dosing Recommendations
- For adults with normal renal function: 15,000-25,000 units/kg/day divided into two doses administered intravenously 1
- Dose should be reduced from 15,000 units/kg downward for individuals with kidney impairment 1
- Infusions may be given every 12 hours, with total daily dose not exceeding 25,000 units/kg/day 1
- For administration, dissolve 500,000 polymyxin B units in 300-500 mL of 5% Dextrose Injection for continuous drip 1
Special Populations
- Infants with normal kidney function may receive up to 40,000 units/kg/day without adverse effects 1
- Higher doses (up to 45,000 units/kg/day) have been used in limited clinical studies for treating premature and newborn infants with sepsis caused by Pseudomonas aeruginosa 1
- Elderly patients may require dose adjustment as renal failure development has been significantly associated with older age (76 versus 59 years, p = 0.02) 2
Clinical Efficacy and Safety Considerations
- Polymyxin B has demonstrated rapid in vitro bactericidal activity against major MDR Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae 3
- Acquired resistance to polymyxin B remains relatively rare among these pathogens 3
- Nephrotoxicity rates with modern use are lower than historically reported, with recent studies showing renal failure in approximately 14% of patients 2
- Development of renal failure appears independent of daily and cumulative doses but is associated with older age 2
Combination Therapy Considerations
- For severe infections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA), combination therapy with two in vitro active drugs is suggested 4
- For carbapenem-resistant Acinetobacter baumannii (CRAB) infections, polymyxin-based combination therapy is recommended 4
- When treating intra-abdominal infections caused by carbapenem-resistant Enterobacterales (CRE), polymyxin-based combination therapy is recommended, with selection of the combination agent based on susceptibility testing results 4
Monitoring and Precautions
- Regular monitoring of renal function is essential during treatment 2
- Solutions for parenteral use should be stored under refrigeration, and any unused portions should be discarded after 72 hours 1
- Avoid total systemic and ophthalmic instillation over 25,000 units/kg/day 1
Alternative Routes of Administration
- Intramuscular administration is not recommended routinely because of severe pain at injection sites 1
- For Pseudomonas aeruginosa meningitis, intrathecal administration may be considered at 50,000 units once daily for adults and children over 2 years of age 1
Polymyxin B remains a valuable last-resort treatment option for multidrug-resistant gram-negative infections when other antibiotics are ineffective, with better safety profile than historically reported when used at appropriate doses with careful monitoring.