Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia.
In aqueous solutions, it undergoes hydrolysis to form a complex mixture of partially sulfomethylated derivatives, as well as colistin.
The following represents minimum inhibitory concentration (MIC) susceptibility data for a few medically significant microorganisms:[17][18] For example, colistin in combination with other drugs is used to attack P. aeruginosa biofilm infection in lungs of patients with cystic fibrosis.
[20] This is because surviving tolerant cells migrate to the top of the biofilm via pili and form new aggregates via quorum sensing.
Colistin sulfate is stable, whereas colistimethate sodium is readily hydrolysed to a variety of methanesulfonated derivatives.
Colomycin has a recommended intravenous dose of 1 to 2 million units three times daily for patients weighing 60 kg or more with normal renal function.
[34] Colistimethate sodium aerosol (Promixin; Colomycin Injection) is used to treat pulmonary infections, especially in cystic fibrosis.
In the UK, the recommended adult dose is 1–2 million units (80–160 mg) nebulised colistimethate twice daily.
[35][29] Nebulized colistin has also been used to decrease severe exacerbations in patients with chronic obstructive pulmonary disease and infection with Pseudomonas aeruginosa.
[37][38] The presence of this plasmid-borne gene was confirmed starting December 2015 in South-East Asia, several European countries,[39] and the United States.
[45] Use of colistin to treat Acinetobacter baumannii infections has led to the development of resistant bacterial strains.
This cross-resistance is caused by gain-of-function mutations to the pmrB gene, which controls the expression of lipid A phosphoethanolamine transferases (similar to mcr-1) located on the bacterial chromosome.
[46] Similar results have been obtained with mcr-1 positive E. coli, which became better at surviving a mixture of animal antimicrobial peptides in vitro and more effective at killing infected caterpillars.
Neuro- and nephrotoxic effects appear to be transient and subside on discontinuation of therapy or reduction in dose.
[57][58] Indeed, colistin appears to have less toxicity than the aminoglycosides that subsequently replaced it, and it has been used for extended periods up to six months with no ill effects.
[60] The main toxicity described with aerosolised treatment is bronchospasm,[61] which can be treated or prevented with the use of β2-adrenergic receptor agonists such as salbutamol[62] or following a desensitisation protocol.
[citation needed] Colistin binds to lipopolysaccharides and phospholipids in the outer cell membrane of Gram-negative bacteria.
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.
Non-ribosomal peptide biosynthesis begins with a loading module and then the addition of each subsequent amino acid.