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Trade namesXylistin, Coly Mycin M, others
  • N-(4-amino-1-(1-(4-amino-1-oxo-1-(3,12,23-tris(2-aminoethyl)- 20-(1-hydroxyethyl)-6,9-diisobutyl-2,5,8,11,14,19,22-heptaoxo- 1,4,7,10,13,18-hexaazacyclotricosan-15-ylamino)butan-2-ylamino)- 3-hydroxybutan-2-ylamino)-1-oxobutan-2-yl)-N,5-dimethylheptanamide
Clinical data
Drug classAntibiotic
Main usesMultidrug-resistant Gram negative infections[1][2]
Side effectsKidney and neurological problems[2]
  • C
Routes of
Topical, by mouth, intravenous, inhaled
Defined daily dose9 MU (by mouth) [3]
9 MU (parenteral)[4]
3 MU (inhalation)[4]
External links
Legal status
  • UK: POM (Prescription only)
  • US: not available
Elimination half-life5 hours
Chemical and physical data
Molar mass1155.455 g·mol−1
3D model (JSmol)
  • O=C(N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H]1C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC1)[C@H](O)C)CCN)CCN)CC(C)C)CC(C)C)CCN)CCN)[C@H](O)C)CCN)CCCC(C)CC
  • InChI=1S/C52H98N16O13/c1-9-29(6)11-10-12-40(71)59-32(13-19-53)47(76)68-42(31(8)70)52(81)64-35(16-22-56)44(73)63-37-18-24-58-51(80)41(30(7)69)67-48(77)36(17-23-57)61-43(72)33(14-20-54)62-49(78)38(25-27(2)3)66-50(79)39(26-28(4)5)65-45(74)34(15-21-55)60-46(37)75/h27-39,41-42,69-70H,9-26,53-57H2,1-8H3,(H,58,80)(H,59,71)(H,60,75)(H,61,72)(H,62,78)(H,63,73)(H,64,81)(H,65,74)(H,66,79)(H,67,77)(H,68,76)/t29?,30-,31-,32+,33+,34+,35+,36+,37+,38+,39-,41+,42+/m1/s1 checkY

Colistin, also known as polymyxin E, is an antibiotic used as a last-resort for multidrug-resistant Gram negative infections including pneumonia.[1][2] These may involve bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, or Acinetobacter.[5] It comes in a form which can be injected into a vein or muscle or inhaled, known as colistimethate sodium and one which is applied to the skin or taken by mouth, known as colistin sulfate.[6] Resistance to colistin is beginning to appear as of 2017.[7]

Common side effects of the injectable form include kidney and neurological problems.[2] Other serious side effects may include anaphylaxis, muscle weakness, and Clostridium difficile-associated diarrhea.[2] The inhaled form may result in constriction of the bronchioles.[2] It is unclear if use during pregnancy is safe for the baby.[8] Colistin is in the polymyxin class of medications.[2] It works by breaking down the cytoplasmic membrane which generally results in bacterial cell death.[2]

Colistin was discovered in 1947 and colistimethate sodium was approved for medical use in the United States in 1970.[5][2] It is on the World Health Organization's List of Essential Medicines.[9] It is available as a generic medication.[10] Dosing is complicated and inconsistent.[11] In the United Kingdom it costs the NHS £18 for 10 vials of the injectable form (1 million units in each vial) as of 2021.[10] In the United States the dose is expressed as 'Colistin base' 150mg and costs about US$24 as of 2019.[12] It is derived from bacteria of the Paenibacillus type.[6]

Medical uses

It is in the 'reserve' group of the WHO AWaRe Classification.[13]

Antibacterial spectrum

Colistin has been effective in treating infections caused by Pseudomonas, Escherichia, and Klebsiella species. The following represents MIC susceptibility data for a few medically significant microorganisms:[14][15]

  • Escherichia coli: 0.12–128 μg/ml
  • Klebsiella pneumoniae: 0.25–128 μg/ml
  • Pseudomonas aeruginosa: ≤0.06–16 μg/ml

For example, colistin in combination with other drugs are used to attack P. aeruginosa biofilm infection [16] Biofilms have a low oxygen environment below the surface where bacteria are metabolically inactive and colistin is highly effective in this environment.[17] 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 motility and form new aggregates via quorum sensing.[18]

Administration and dosage


Two forms of colistin are available commercially: colistin sulfate and colistimethate sodium .[19] Colistin sulfate is cationic. Colistin sulfate and colistimethate sodium are eliminated from the body by different routes.[20] With respect to Pseudomonas aeruginosa, colistimethate is the inactive prodrug of colistin.[21]

  • Colistimethate sodium may be used to treat Pseudomonas aeruginosa infections in cystic fibrosis patients, and it has come into recent use for treating multidrug-resistant Acinetobacter infection, although resistant forms have been reported.[22][23] Colistimethate sodium has also been given intrathecally and intraventricularly in Acinetobacter baumannii and Acinetobacter baumannii [22][24] Some studies have indicated that colistin may be useful for treating infections caused by carbapenem-resistant isolates of Acinetobacter baumannii.[23]
  • Colistin sulfate may be used to treat intestinal infections, or to suppress colonic flora.[25] Colistin sulfate is also used as topical creams, powders, and otic solutions.[26]


The defined daily dose is 9 MU (by mouth)[3] 9 MU (parenteral)[4] and 3 MU (inhalation).[4]

Colistin sulfate and colistimethate sodium may both be given intravenously, but the dosing is complicated and inconsistent.[11] The very different labeling of the parenteral products of colistin methanesulfonate in different parts of the world was first revealed by Li et al.[27] Colistimethate sodium manufactured by Xellia (Colomycin injection) is prescribed in international units[28], but colistimethate sodium manufactured by Parkdale Pharmaceuticals (Coly-Mycin M Parenteral) is prescribed in milligrams[29]:

  • Colomycin 1,000,000 units is 80 mg colistimethate;[30]
  • Coly-mycin M 150 mg "colistin base" is 360 mg colistimethate or 4,500,000 units.[31]

Colomycin has a recommended intravenous dose of 1 to 3 million units three times daily for individuals weighing 40 kg or more with normal renal function.[32] Coly-Mycin has a recommended dose of 2.5 to 5 mg/kg a day[33] The recommended "maximum" dose for each preparation is different (480 mg for Colomycin and 720 mg for Coly-Mycin), each country has different generic preparations of colistin, and the recommended dose depends on the manufacturer. [34][35]

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.[36][30] Nebulized colistin has also been used to decrease severe exacerbations in patients with chronic obstructive pulmonary disease and infection with Pseudomonas aeruginosa.[37]


The first colistin-resistance gene in a plasmid which can be transferred between bacterial strains was found in 2011 in China and became publicly known in November 2015. [38]The presence of this plasmid-borne mcr-1 gene was confirmed starting December 2015 in South-East Asia, several European countries and the United States[39]

The Société Française de Microbiologie [fr] uses a cut-off of 2> mg/l[40], whereas the British Society for Antimicrobial Chemotherapy (for psuedomas) sets a cutoff of 4 mg/l or less as sensitive, and 4 mg/ml or more as resistant[41]. No standards for measuring colistin sensitivity are given in the US.[42]

The plasmid-borne mcr-1 gene has been found to confer resistance to colistin.[43] The first colistin-resistance gene in a plasmid which can be transferred between bacterial strains was found in 2011 and became publicly known in November 2015.[38][44] This plasmid-borne mcr-1 gene has since been isolated in China,[45] Europe[46] and the United States.[47]

India reported the first detailed colistin-resistance study which mapped 13 colistin-resistant cases recorded over 18 months. It concluded that pan-drug resistant infections, particularly those in the blood stream, have a higher mortality. Multiple other cases were reported from other Indian hospitals.[48][49] Although resistance to polymyxins is generally less than 10% it is more frequent in the Mediterranean and South-East Asia (Korea and Singapore), where colistin resistance rates are continually increasing.[50] Colistin-resistant E. coli was identified in the United States in May 2016.[51]

Use of colistin to treat Acinetobacter baumannii infections has led to the development of resistant bacterial strains. which have also developed resistance to antimicrobial compounds LL-37 and lysozyme, produced by the human immune system.[52]

It's worth noting that not all resistance to colisin and some other antibiotics is due to the presence of resistance genes.[53] Heteroresistance, the phenomenon wherein apparently genetically identical microbes exhibit a range of resistance to an antibiotic,[54] has been observed in some species of Enterobacter since at least 2016[53]

Resistant natural or acquired

Are the following:[55]

  • Pseudomonas aeruginosa
  • Acinetobacter baumannii
  • Escherichia coli
  • Salmonella spp
  • Klebsiella spp.
  • Serratia spp.
  • Proteus spp.
  • Burkholderia spp.
  • Enterobacteriaceae
  • Proteus spp.
  • Serratia marcescens
  • Morganella morganii
  • Providencia spp.
  • Pseudomonas mallei
  • Burkholderia cepacia
  • Chromobacterium spp.
  • Edwardsiella spp.
  • Brucella
  • Legionella
  • Vibrio cholera

Side effects

The main toxicities described with intravenous treatment are nephrotoxicity (damage to the kidneys) and neurotoxicity (damage to the nerves),[56][57]. Neuro- and nephrotoxic effects appear to be transient and subside on discontinuation, in a significant amount of those individuals given therapy or reduction in dose.[56]

At a dose of 160 mg colistimethate IV every eight hours, very little nephrotoxicity is seen.[58][59] 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 colistin-induced nephrotoxicity is particularly favoured in patients with hypoalbuminemia.[61]

The main toxicity described with aerosolised treatment is bronchospasm,[62] which can be treated or prevented with the use of beta2-agonists such as salbutamol[63]

Mechanism of action

Colistin is a polycationic peptide. These cationic regions interact with the bacterial outer membrane, by displacing magnesium and calcium bacterial counter ions in the lipopolysaccharide. Hydrophobic/hydrophilic regions interact with the cytoplasmic membrane just like a detergent, solubilizing the membrane in an aqueous environment.[50][64]


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 supposed to be eliminated by non-renal mechanism(s) that are as of yet not characterised.[65][66]


Colistin was first isolated in Japan in 1947 from a flask of fermenting Bacillus polymyxa var. colistinus by the Japanese scientist Koyama[67] and became available for clinical use in 1959.[11] In the 1980s, polymyxin use was widely discontinued because of nephro- and neurotoxicity. 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 toxic effects.[68]


The biosynthesis of colistin requires the use of three amino acids threonine, leucine, and 2,4-diaminobutryic acid. It is important to synthesis the linear form of colistin before cycliziation. Elongation of non ribosomal peptide biosynthesis begins by 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 utilizing a thioesterase.[69]

The salmon color refers to the loading domain 6-methyl-heptanoic acid, yellow is 2,4-diaminobutryic acid, light blue is threonine, and purple is leucine

See also


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