Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, or Acinetobacter. It comes in two forms: colistimethate sodium can be injected into a vein, injected into a muscle, or inhaled, and colistin sulfate is mainly applied to the skin or taken by mouth. Colistimethate sodium is a prodrug; it is produced by the reaction of colistin with formaldehyde and sodium bisulfite, which leads to the addition of a sulfomethyl group to the primary amines of colistin. Colistimethate sodium is less toxic than colistin when administered parenterally. In aqueous solutions it undergoes hydrolysis to form a complex mixture of partially sulfomethylated derivatives, as well as  colistin. Resistance to colistin began to appear as of 2015.Common side effects of the injectable form include kidney problems and neurological problems. Other serious side effects may include anaphylaxis, muscle weakness, and Clostridium difficile-associated diarrhea. The inhaled form may result in constriction of the bronchioles. It is unclear if use during pregnancy is safe for the fetus. Colistin is in the polymyxin class of medications. It works by breaking down the cytoplasmic membrane, which generally results in bacterial cell death.Colistin was discovered in 1947 and colistimethate sodium was approved for medical use in the United States in 1970. It is on the World Health Organizations List of Essential Medicines. The World Health Organization classifies colistin as critically important for human medicine. It is available as a generic medication.
Colistin-induced nephrotoxicity is particularly likely in patients with hypoalbuminemia.The main toxicity described with aerosolised treatment is bronchospasm,  which can be treated or prevented with the use of β2-adrenergic receptor agonists such as salbutamol or following a desensitisation protocol. Mechanism of action
Colistin is a polycationic peptide and has both hydrophilic and lipophilic moieties. These cationic regions interact with the bacterial outer membrane by displacing magnesium and calcium bacterial counter ions in the lipopolysaccharide. The hydrophobic and hydrophilic regions interact with the cytoplasmic membrane just like a detergent, solubilizing the membrane in an aqueous environment. This effect is bactericidal even in an isosmolar environment.Colistin binds to lipopolysaccharides and phospholipids in the outer cell membrane of Gram-negative bacteria. It competitively displaces divalent cations (Ca2+ and Mg2+) from the phosphate groups of membrane lipids, which leads to disruption of the outer cell membrane, leakage of intracellular contents and bacterial death. Pharmacokinetics
No clinically useful absorption of colistin occurs in the gastrointestinal tract. For systemic infection, colistin must therefore be given by injection. Colistimethate is eliminated by the kidneys, but colistin is eliminated by non-renal mechanism(s) that are as of yet not characterised. History
Colistin was first isolated in Japan in 1949 by Y. Koyama, from a flask of fermenting Bacillus polymyxa var. colistinus, and became available for clinical use in 1959.Colistimethate sodium, a less toxic prodrug, became available for injection in 1959. In the 1980s, polymyxin use was widely discontinued because of nephro- and neurotoxicity.