Polymyxin Treatment and Dosage for Multidrug-Resistant Gram-Negative Bacterial Infections
For infections caused by multidrug-resistant gram-negative bacteria, polymyxin B should be administered at 15,000 to 25,000 units/kg body weight/day intravenously in patients with normal renal function, with a loading dose followed by maintenance dosing for critically ill patients. 1, 2
Dosing Recommendations
Intravenous Administration
- For adults and children with normal renal function: 15,000 to 25,000 units/kg/day divided into doses given every 12 hours 1
- Loading dose followed by maintenance dosing is recommended for critically ill patients to achieve therapeutic concentrations rapidly 2
- Dose should be reduced from 15,000 units/kg downward for individuals with kidney impairment 1
- For infants with normal kidney function: up to 40,000 units/kg/day has been used safely 1
Special Populations
- Doses as high as 45,000 units/kg/day have been used in limited clinical studies for treating premature and newborn infants with Pseudomonas aeruginosa sepsis 1
- Therapeutic drug monitoring should be utilized when available to optimize dosing and minimize toxicity 2
Treatment Recommendations by Infection Type
Bloodstream Infections
- For carbapenem-resistant Enterobacterales (CRE): Polymyxin-based combination therapy with colistin 5 mg CBA/kg IV loading dose, then 2.5 mg CBA (1.5 CrCl + 30) IV q12h plus either:
- Tigecycline 100 mg IV loading dose, then 50 mg IV q12h, or
- Meropenem 1 g IV q8h by extended infusion (3 hours) 3
- Treatment duration: 7-14 days, individualized based on clinical response 3
Complicated Intra-abdominal Infections
- Polymyxin-based combinations: Colistin 5 mg CBA/kg IV loading dose, then 2.5 mg CBA (1.5 CrCl + 30) IV q12h plus either:
- Tigecycline 100 mg IV loading dose, then 50 mg IV q12h, or
- Meropenem 1 g IV q8h by extended infusion 3
- Treatment duration: 5-7 days, individualized based on source control and clinical response 3
Complicated Urinary Tract Infections
- Alternative options should be considered first if available (ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, or aminoglycosides) 3
- If polymyxin is necessary, use standard dosing with 5-7 days duration 3
Combination Therapy Considerations
- For severe infections caused by carbapenem-resistant Pseudomonas aeruginosa, combination therapy with polymyxin B plus another in vitro active agent is suggested 2, 4
- Combination therapy with polymyxin B may reduce mortality, treatment failure, and pathogen eradication failure compared to polymyxin monotherapy 2, 5
- Strong recommendation against polymyxin-meropenem or polymyxin-rifampin combination therapy for carbapenem-resistant Acinetobacter baumannii infections 2
Important Clinical Considerations
- Optimal source control should always be prioritized to improve outcomes 2
- Newer agents like ceftolozane-tazobactam should be used over polymyxin B when available and active in vitro due to lower nephrotoxicity 2
- Nephrotoxicity is a significant concern, occurring in approximately 10-55% of patients, typically developing after 4-10 days of therapy 5, 6
- For pan-resistant carbapenem-resistant gram-negative bacteria, treatment with the least resistant antibiotic(s) based on MICs relative to the breakpoints is recommended 2
- Microbiological clearance rates with polymyxin B have been reported at approximately 60-88% in clinical studies 7, 6