Role of Polymyxin B in Treatment of Gram-Negative Bacterial Infections
Polymyxin B should be used as a last-resort antibiotic for multidrug-resistant gram-negative bacterial infections when less toxic alternatives are ineffective or contraindicated, particularly for carbapenem-resistant organisms. 1, 2
Indications and Spectrum of Activity
- Polymyxin B is active against most gram-negative bacilli except Proteus species, with bactericidal activity through disruption of bacterial cell membrane permeability 1
- FDA-approved indications include infections caused by susceptible strains of:
- Pseudomonas aeruginosa (urinary tract, meningeal, and bloodstream infections)
- Haemophilus influenzae (specifically meningeal infections)
- Escherichia coli (specifically urinary tract infections)
- Aerobacter aerogenes (specifically bacteremia)
- Klebsiella pneumoniae (specifically bacteremia) 1
- Particularly valuable for carbapenem-resistant gram-negative bacteria (CRGNB) including:
Treatment Recommendations
For Carbapenem-Resistant Pseudomonas aeruginosa (CRPA)
- For severe CRPA infections: Combination therapy with polymyxin B plus another in vitro active agent is suggested (weak recommendation, very low-quality evidence) 3, 2
- For non-severe CRPA infections: Monotherapy with polymyxin B may be appropriate 2
- When available, newer agents like ceftolozane-tazobactam are preferred over polymyxin B due to lower nephrotoxicity 2
For Carbapenem-Resistant Acinetobacter baumannii (CRAB)
- Polymyxin-carbapenem combinations rank first in improving clinical cure (SUCRA 91.7%) and second in microbiological cure (SUCRA 68.7%) among treatment regimens for CRAB pneumonia 3
- For CRAB pneumonia and bloodstream infections, polymyxin-meropenem combination is recommended, especially when carbapenem MIC is ≤32 mg/L 3
For Respiratory Tract Infections
- Aerosolized polymyxin B in addition to intravenous administration is suggested for CRGNB respiratory tract infections (weak recommendation, low-quality evidence) 3
- This combination may reduce mortality (RR=0.86,95% CI 0.72-1.03), clinical treatment failure (RR=0.82,95% CI 0.70-0.96), and pathogen eradication failure (RR=0.84,95% CI 0.69-1.03) 3
Dosing Considerations
- For critically ill patients with colistin (related polymyxin), a loading dose of 9 MU (5 mg/kg) followed by maintenance dose of 4.5 MU twice daily is suggested (strong recommendation, low-quality evidence) 3
- Renal function monitoring is essential as polymyxins are primarily eliminated by the kidneys 1, 4
- Polymyxin B appears to have less nephrotoxicity compared to colistin 2, 5
Combination Therapy Rationale
- Combination therapy may:
Toxicity and Monitoring
- Nephrotoxicity is the major concern, occurring in approximately 14% of patients with normal baseline renal function 4
- Risk factors for nephrotoxicity include older age (76 vs. 59 years, p=0.02) 4
- Regular monitoring of renal function is strongly recommended during treatment 2, 5
Limitations and Challenges
- Polymyxin B has poor tissue diffusion and does not cross the blood-brain barrier (except when administered intrathecally) 1
- Serum levels are low due to 50% activity loss in the presence of serum 1
- Resistance to polymyxins is emerging, highlighting the need for appropriate stewardship 5
- Novel polymyxin derivatives with fewer positive charges are being developed to reduce nephrotoxicity while maintaining antibacterial activity 6
Implementation Considerations
- Polymyxin B should be reserved for infections caused by multidrug-resistant gram-negative bacteria when less toxic alternatives are ineffective or contraindicated 1, 7
- For aerosolized administration, close monitoring for bronchospasm is recommended 3
- Combination with other antibiotics should be considered based on susceptibility testing and site of infection 2, 8