It is derived from bacteria of the genus Paenibacillus. Medical uses
Antibacterial spectrum
Colistin has been effective in treating infections caused by Pseudomonas, Escherichia, and Klebsiella species. The following represents minimum inhibitory concentration (MIC) susceptibility data for a few medically significant microorganisms:
Escherichia coli: 0.12–128 μg/mL
Klebsiella pneumoniae: 0.25–128 μg/mL
Pseudomonas aeruginosa: ≤0.06–16 μg/mLFor example, colistin in combination with other drugs is used to attack P. aeruginosa biofilm infection in lungs of patients with cystic fibrosis. Biofilms have a low-oxygen environment below the surface where bacteria are metabolically inactive, and colistin is highly effective in this environment. However, P. aeruginosa reside in the top layers of the biofilm, where they remain metabolically active. This is because surviving tolerant cells migrate to the top of the biofilm via pili and form new aggregates via quorum sensing. Administration and dosage
Forms
Two forms of colistin are available commercially: colistin sulfate and colistimethate sodium (colistin methanesulfonate sodium, colistin sulfomethate sodium). Colistin sulfate is cationic; colistimethate sodium is anionic. Colistin sulfate is stable, whereas colistimethate sodium is readily hydrolysed to a variety of methanesulfonated derivatives. Colistin sulfate and colistimethate sodium are eliminated from the body by different routes. With respect to Pseudomonas aeruginosa, colistimethate is the inactive prodrug of colistin. The two drugs are not interchangeable. Colistimethate sodium may be used to treat Pseudomonas aeruginosa infections in patients with cystic fibrosis, and it has come into recent use for treating multidrug-resistant Acinetobacter infection, although resistant forms have been reported.
As multi-drug resistant bacteria became more prevalent in the 1990s, colistin started to get a second look as an emergency solution, in spite of toxicity.Colistin has also been used in agriculture, particularly in China from the 1980s onwards. Chinese production for agriculture exceeded 2700 tons in 2015. China banned colistin use for livestock growth promotion in 2016. Biosynthesis
The biosynthesis of colistin requires the use of three amino acids: threonine, leucine, and 2,4-diaminobutryic acid. The linear form of colistin is synthesized before cycliziation. Non-ribosomal peptide biosynthesis begins with a loading module and then the addition of each subsequent amino acid. The subsequent amino acids are added with the help of an adenylation domain (A), a peptidyl carrier protein domain (PCP), an epimerization domain (E), and a condensation domain (C). Cyclization is accomplished by a thioesterase. The first step is to have a loading domain, 6-methylheptanoic acid, associate with the A and PCP domains. Now with a C, A, and PCP domain that is associated with 2,4-diaminobutryic acid. This continues with each amino acid until the linear peptide chain is completed. The last module will have a thioesterase to complete the cyclization and form the product colistin. References
Further reading
Reardon S (December 2015). "Spread of antibiotic-resistance gene does not spell bacterial apocalypse — yet". Nature. doi:10.1038/nature.2015.19037. External links
"Colistimethate sodium". Drug Information Portal. U.S. National Library of Medicine. "Colistin sulfate". Drug Information Portal. U.S. National Library of Medicine. "Colistin topics page (bibliography)". Science.gov.