Polymyxin Antimicrobial Coverage
Polymyxins (polymyxin B and colistin/polymyxin E) are effective against most Gram-negative bacteria, particularly Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacterales (except Proteus species), but are not effective against Gram-positive bacteria or fungi.
Spectrum of Activity
Covered Organisms
- Polymyxins have excellent activity against most Gram-negative bacilli, with the notable exception of the Proteus group 1
- Primary targets include:
- Pseudomonas aeruginosa (drug of choice for susceptible strains) 1
- Acinetobacter baumannii, particularly carbapenem-resistant strains 2, 3
- Escherichia coli (especially urinary tract infections) 1, 4
- Klebsiella pneumoniae, including carbapenem-resistant strains 2, 4
- Aerobacter aerogenes (now Enterobacter aerogenes), specifically in bacteremia 1
- Haemophilus influenzae, specifically in meningeal infections 1
Resistant Organisms
- All Gram-positive bacteria are intrinsically resistant to polymyxins 1, 5
- Fungi are resistant to polymyxins 1
- Gram-negative cocci are resistant to polymyxins 1
- Proteus species are intrinsically resistant 1
- Some Enterobacter species show reduced susceptibility (only 76% susceptible in some studies) 6
Mechanism of Action
- Polymyxins increase the permeability of bacterial cell membranes, leading to cell death 1
- They bind to lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria, disrupting membrane integrity 4, 5
- This mechanism explains why they are ineffective against Gram-positive bacteria, which lack an outer membrane with LPS 1, 5
Clinical Applications
- Polymyxins are considered last-resort antibiotics for multidrug-resistant (MDR) Gram-negative infections 2, 3
- They are particularly valuable for treating:
- For respiratory infections, aerosolized polymyxin may be used in addition to intravenous administration 2
Important Considerations
- Polymyxins have been revived in clinical practice due to the increasing prevalence of MDR Gram-negative bacteria 4
- Combination therapy with polymyxins and other antibiotics (particularly carbapenems) may improve outcomes in severe infections 2, 3
- Nephrotoxicity is a significant concern with polymyxin therapy, requiring careful monitoring of renal function 3, 4
- Resistance to polymyxins, while still relatively uncommon, is an emerging concern 9, 6
Pitfalls to Avoid
- Do not use polymyxins for Proteus infections, as these organisms are intrinsically resistant 1
- Avoid monotherapy for severe infections caused by highly resistant pathogens; combination therapy is often preferred 3
- Remember that polymyxins have no activity against Gram-positive pathogens, so they should not be used for mixed infections without appropriate Gram-positive coverage 1
- Polymyxin activity is reduced by approximately 50% in the presence of serum, which may affect dosing considerations 1