Colistin (Polymyxin E)

Coly-Mycin M / Colomycin / Promixin

Colistin, also called polymyxin E, is a cyclic lipopeptide antibiotic in the same family as polymyxin B, produced by Paenibacillus polymyxa. It kills Gram-negative bacteria by binding lipid A within the lipopolysaccharide of the outer membrane and inserting its fatty-acid tail, disrupting the membrane in a detergent-like way that makes the envelope leaky and unstable. Like polymyxin B, its target is on the Gram-negative outer membrane, so it has no activity against Gram-positive organisms. A defining feature of colistin is how it is administered. For systemic and inhaled use it is given as colistimethate sodium (CMS), an inactive prodrug that must be converted to active colistin in the body. This conversion adds pharmacological complexity — active drug levels build gradually and vary — which historically led to underdosing and is why modern practice emphasizes loading doses and careful exposure targets. Colistin is used intravenously as a last-resort agent for serious multidrug-resistant Gram-negative infections (carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii), and inhaled colistimethate is used to manage chronic Pseudomonas lung infection in conditions such as cystic fibrosis. Colistin's principal dose-limiting toxicities are nephrotoxicity and neurotoxicity, mirroring polymyxin B, so systemic use is reserved and closely monitored. Transferable colistin resistance carried by the mcr genes is a globally significant public-health threat because colistin is often a drug of last resort. Colistin is an approved prescription medicine used within specialist infectious-disease care — not a research or consumer peptide — and dosing (especially the prodrug conversion) is a matter for clinicians.