Polymyxins
Summary
Polymyxins (polymyxin B and colistin/polymyxin E) are cationic polypeptide antibiotics that act as detergents on bacterial cell membranes, used as last-line agents against multidrug-resistant (MDR) gram-negative organisms. They are nephrotoxic and neurotoxic, limiting their use to severe infections like MDR Pseudomonas, Acinetobacter, and Klebsiella (including carbapenem-resistant strains).
Detail
Mechanism: Polymyxins bind to lipopolysaccharide (LPS) and phospholipids in the outer membrane of gram-negative bacteria, disrupting membrane integrity in a detergent-like fashion, causing leakage of cellular contents and bacterial death. This action is bactericidal and concentration-dependent.
Spectrum: Effective against gram-negative rods, including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, E. coli, and Enterobacter. Notably inactive against gram-positive bacteria and Proteus species (due to LPS structural differences).
Clinical Use: Reserved as a 'last resort' therapy for multidrug-resistant (MDR) and carbapenem-resistant gram-negative infections due to toxicity profile. Can be administered IV, inhaled (for cystic fibrosis-related Pseudomonas infections), or topically.
Toxicity: - Nephrotoxicity: Dose-limiting, due to renal tubular damage; requires careful renal function monitoring and dose adjustment. - Neurotoxicity: Paresthesias, dizziness, neuromuscular blockade (can worsen myasthenia gravis), and ataxia.
Resistance Mechanisms: Modification of LPS (e.g., addition of aminoarabinose via mcr-1 plasmid-mediated gene, altering the lipid A target) reduces the negative charge needed for polymyxin binding—this is a growing concern as mcr-1 confers transferable colistin resistance.
High-Yield Associations: Polymyxins are often tested in the context of antibiotics used for MDR gram-negative 'superbugs' and as an example of mechanism-based toxicity trade-offs (efficacy vs. nephrotoxicity/neurotoxicity). Remember: 'Polymyxins are polycationic, bind LPS, used for resistant gram-negative rods, but have renal/neuro toxicity.'
Sources
- First Aid for the USMLE Step 1
- Katzung's Basic & Clinical Pharmacology
- Sanford Guide to Antimicrobial Therapy
- UpToDate: Polymyxins (colistin and polymyxin B)
Reviewed by Medusa editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.