polymyxine

Polymyxine, or polymyxins, refer to a class of antibiotics produced by Bacillus polymyxa. The main clinically relevant members are polymyxin B and polymyxin E (colistin). They are cationic, amphipathic lipopeptides with a cyclic peptide structure and a fatty acid tail.

Mechanism of action: Polymyxins target the outer membranes of Gram-negative bacteria by binding to lipopolysaccharide and phospholipids, disrupting membrane integrity and causing leakage of intracellular contents. They are bactericidal against many Gram-negative pathogens but have little activity against most Gram-positive bacteria and anaerobes. Their activity is enhanced by the presence of divalent cations and by certain membrane conditions.

Spectrum and use: Polymyxins are mainly active against MDR Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, and various Enterobacterales. Activity varies among strains, and their effectiveness is influenced by resistance mechanisms. They are not reliable for routine Gram-positive infections.

Administration and pharmacokinetics: Polymyxins have limited oral bioavailability; systemic infections are treated with parenteral polymyxins, while inhaled or nebulized formulations may be used for pneumonia. Colistin is administered as colistimethate sodium, a prodrug that is converted to active colistin in vivo. Dosing requires careful adjustment for renal function and close monitoring.

Adverse effects and resistance: The principal risks are nephrotoxicity and neurotoxicity, which can limit use and require monitoring. Resistance can arise via modification of lipopolysaccharide or other outer membrane changes, including plasmid-mediated mcr genes. Due to toxicity and emerging resistance, polymyxins are generally reserved for treat­ment of severe, multidrug-resistant Gram-negative infections when other options are unavailable.