Guidelines for Using Polymyxin B in Treating Multidrug-Resistant Gram-Negative Bacterial Infections
Polymyxin B should be used as a last-resort treatment option for infections caused by multidrug-resistant gram-negative bacteria when newer, less toxic agents are unavailable or ineffective, with combination therapy recommended for severe infections. 1, 2
Indications and Spectrum of Activity
- Polymyxin B is indicated for treating infections caused by susceptible strains of Pseudomonas aeruginosa, particularly in the urinary tract, meninges, and bloodstream 2
- It is also effective against other multidrug-resistant gram-negative bacteria (MDR-GNB), including carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Enterobacterales (CRE) when less toxic drugs are ineffective or contraindicated 1, 2
- Polymyxin B may be used for infections caused by susceptible strains of Haemophilus influenzae (meningeal infections), Escherichia coli (urinary tract infections), Aerobacter aerogenes (bacteremia), and Klebsiella pneumoniae (bacteremia) 2
Treatment Recommendations by Pathogen
For Carbapenem-Resistant Pseudomonas aeruginosa (CRPA):
- For severe CRPA infections, combination therapy with polymyxin B plus another in vitro active agent is suggested (conditional recommendation, very low certainty of evidence) 3, 1
- For non-severe or low-risk CRPA infections, monotherapy with polymyxin B may be appropriate, selected based on the source of infection and antibiotic stewardship considerations 3, 1
For Carbapenem-Resistant Acinetobacter baumannii (CRAB):
- For CRAB infections, polymyxin B is a treatment option when the organism is resistant to sulbactam 3
- Strong recommendation against polymyxin-meropenem or polymyxin-rifampin combination therapy for CRAB infections 3
- For severe and high-risk CRAB infections, combination therapy including two in vitro active antibiotics among available options (polymyxin, aminoglycoside, tigecycline, sulbactam combinations) is suggested (conditional recommendation, very low-quality evidence) 3
Dosing Considerations
- A loading dose followed by maintenance dosing is recommended for critically ill patients 1
- Dosing should be adjusted based on patient weight and renal function 4
- For critically ill patients weighing 50 kg, an empirical polymyxin B dose of 2 mg/kg every 12 hours may be appropriate, while lower doses (1.25 mg/kg q12h for 75 kg patients and 1 mg/kg q12h for 100 kg patients) may be sufficient 4
- For general ward patients weighing 75 kg, 2 mg/kg every 12 hours is recommended 4
Administration Routes
- Intravenous administration is standard for systemic infections 2
- For respiratory tract infections, aerosolized polymyxin B in addition to intravenous administration may improve clinical outcomes 1, 5
- For meningeal infections, polymyxin B should be administered only by the intrathecal route 2
Combination Therapy Rationale
- Combination therapy with polymyxin B may reduce mortality, treatment failure, and pathogen eradication failure compared to polymyxin monotherapy 1
- Combination therapy may demonstrate synergistic effects against MDR-GNB in vitro and prevent emergence of resistant sub-populations 1, 6
- For pan-resistant carbapenem-resistant gram-negative bacteria (also resistant to polymyxins), treatment with the least resistant antibiotic(s) based on MICs relative to the breakpoints is considered good clinical practice 3
Monitoring and Toxicity
- Nephrotoxicity is a significant concern with polymyxin B, though it appears to be less common than previously reported and less frequent than with colistin 1, 7
- Renal function should be monitored regularly during treatment 1
- Nephrotoxicity risk increases with older age (76 versus 59 years, P = 0.02) but may be independent of daily and cumulative doses 7
- Development of renal failure during polymyxin B treatment is associated with increased mortality (57% versus overall 20%) 7
Special Considerations
- For carbapenem-resistant Acinetobacter baumannii with meropenem MIC ≤8 mg/L, carbapenem combination therapy using high-dose extended-infusion carbapenem dosing may be considered 3
- Optimal source control should always be prioritized to improve outcomes 8
- Therapeutic drug monitoring should be utilized when available 8