Colistin (also called polymyxin E) belongs to the polymyxin group of antibiotics . It was first isolated in Japan in 1949 from Bacillus polymyxa var. colistinus and became available for clinical use in 1959 [2,3]. Colistin was given as an intramuscular injection for the treatment of Gram-negative infections, but fell out of favor after aminoglycosides became available because of its significant side effects. It was later used as topical therapy as part of selective digestive tract decontamination and is still used in aerosolized form for patients with cystic fibrosis. (See "Cystic fibrosis: Antibiotic therapy for lung disease".)
More recently, a number of centers around the world have used colistin intravenously for otherwise panresistant nosocomial infections, especially those due to Pseudomonas and Acinetobacter spp [4-8].
The spectrum of activity, mechanisms of action and resistance, pharmacokinetics, interactions with other drugs, and adverse effects of colistin will be reviewed here. The clinical settings in which colistin may be used are discussed separately in the appropriate topic reviews.
MECHANISM OF ACTION
Colistin is a bactericidal drug that binds to lipopolysaccharides and phospholipids in the outer cell membrane of Gram-negative bacteria. It competitively displaces divalent cations from the phosphate groups of membrane lipids, which leads to disruption of the outer cell membrane, leakage of intracellular contents, and bacterial death [3,9,10].
In addition to its bactericidal effect, colistin can bind and neutralize lipopolysaccharide (LPS) and prevent the pathophysiologic effects of endotoxin in the circulation [11,12].