Polymyxin
A class of cyclic lipopeptide antibiotics that disrupt gram-negative bacterial cell membranes. Colistin (polymyxin E) and polymyxin B are approved drugs used as last-resort treatments for multidrug-resistant gram-negative infections. Their nephrotoxicity limits wider use.
Technical Context
Polymyxins are cyclic lipopeptides with a cationic peptide ring (positively charged diaminobutyric acid residues) linked to a fatty acid tail. Mechanism: electrostatic binding to lipopolysaccharide (LPS) in the gram-negative outer membrane → displacement of divalent cations (Mg2+, Ca2+) that stabilise LPS → outer membrane destabilisation → increased permeability → cell death. Colistin (polymyxin E, discovered 1949, reintroduced clinically after 2000 due to resistance crisis) is available as colistimethate sodium (inactive prodrug for IV/inhaled use) and colistin sulphate (for topical/oral use). Polymyxin B is used directly. Both have significant nephrotoxicity (incidence 20-60%) and neurotoxicity (paraesthesias, dizziness). Therapeutic drug monitoring of colistin is recommended due to the narrow therapeutic window. Polymyxin resistance (mcr genes encoding phosphoethanolamine transferases that modify LPS) is an emerging global concern.