Colistin

Source: Wikipedia, the free encyclopedia.
Colistin
Clinical data
Trade namesXylistin, Coly-Mycin M, Colobreathe, others
AHFS/Drugs.comMonograph
MedlinePlusa682860
License data
QJ51XB01 (WHO)
Legal status
Legal status
Pharmacokinetic data
Bioavailability0%
Elimination half-life5 hours
Identifiers
  • 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
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
  • Key:YKQOSKADJPQZHB-QNPLFGSASA-N checkY
 ☒NcheckY (what is this?)  (verify)

Colistin, also known as polymyxin E, is an

injected into a muscle, or inhaled, and colistin sulfate is mainly applied to the skin or taken by mouth.[10] Colistimethate sodium[11] 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.[12]

Common side effects of the injectable form include

cytoplasmic membrane, which generally results in bacterial cell death.[8]

Colistin was discovered in 1947 and colistimethate sodium was approved for medical use in the United States in 1970.

generic medication.[16] It is derived from bacteria of the genus Paenibacillus.[10]

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:[17][18]

  • 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 is used to attack P. aeruginosa biofilm infection in lungs of patients with cystic fibrosis.[19] 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.[20] This is because surviving tolerant cells migrate to the top of the biofilm via pili and form new aggregates via quorum sensing.[21]

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

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.[22][23] Colistimethate sodium has also been given intrathecally and intraventricularly in Acinetobacter baumannii and Pseudomonas aeruginosa meningitis and ventriculitis[24][25][26][27] 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. Colistin sulfate is also used in topical creams, powders, and otic solutions.
  • Colistin A (polymyxin E1) and colistin B (polymyxin E2) can be purified individually to research and study their effects and potencies as separate compounds.

Dosage

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

  • Colomycin 1,000,000 units is 80 mg colistimethate;[29]
  • Coly-mycin M 150 mg colistin base is 360 mg colistimethate or 4,500,000 units.[30]

Because colistin was introduced into clinical practice over 50 years ago, it was never subject to the regulations that modern drugs are subject to, and therefore there is no standardised dosing of colistin and no detailed trials on pharmacology or pharmacokinetics. The optimal dosing of colistin for most infections is therefore unknown. 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. Coly-Mycin has a recommended dose of 2.5 to 5 mg/kg colistin base a day, which is equivalent to 6 to 12 mg/kg colistimethate sodium per day. For a 60 kg man, therefore, the recommended dose for Colomycin is 240 to 480 mg of colistimethate sodium, yet the recommended dose for Coly-Mycin is 360 to 720 mg of colistimethate sodium. Likewise, 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. This complete absence of any regulation or standardisation of dose makes intravenous colistin dosing difficult for the physician. [citation needed]

Colistin has been used in combination with rifampicin; evidence of in vitro synergy exists,[31][32] and the combination has been used successfully in patients.[33] There is also in vitro evidence of synergy for colistimethate sodium used in combination with other antipseudomonal antibiotics.[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.[36]

Resistance

Resistance to colistin is rare, but has been described. As of 2017, no agreement exists about how to define colistin resistance. The Société Française de Microbiologie [fr] uses a MIC cut-off of 2 mg/L, whereas the British Society for Antimicrobial Chemotherapy sets a MIC cutoff of 4 mg/L or less as sensitive, and 8 mg/L or more as resistant. No standards for describing colistin sensitivity are given in the United States.

The first known colistin-resistance gene in a plasmid which can be transferred between bacterial strains is mcr-1. It was found in 2011 in China on a pig farm where colistin is routinely used and became publicly known in November 2015.[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.[40] It is found in certain strains of the bacteria Paenibacillus polymyxa.[citation needed]

India reported the first detailed colistin-resistance study, which mapped 13 colistin-resistant infections recorded over 18 months. It concluded that pan-drug-resistant infections, particularly those in the bloodstream, have a higher mortality. Multiple other cases were reported from other Indian hospitals.[41][42] 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 increasing.[43] Colistin-resistant E. coli was identified in the United States in May 2016.[44]

A recent review from 2016 to 2021 fount that E. coli is the dominant species harbouring mcr genes. Plasmid - mediated colistin resistance is also conferred upon other species that carry different genes resistant to antibiotics. The emergence of the mcr-9 gene is quite remarkable.[45]

Use of colistin to treat Acinetobacter baumannii infections has led to the development of resistant bacterial strains. They have also developed resistance to the antimicrobial compounds

antimicrobial peptides in vitro and more effective at killing infected caterpillars.[47]

Not all resistance to colistin and some other antibiotics is due to the presence of resistance genes.[48] Heteroresistance, the phenomenon wherein apparently genetically identical microbes exhibit a range of resistance to an antibiotic,[49] has been observed in some species of Enterobacter since at least 2016[48] and was observed in some strains of Klebsiella pneumoniae in 2017–2018.[50] In some cases this phenomenon has significant clinical consequences.[50]

Inherently resistant

Variable resistance

Adverse reactions

The main toxicities described with intravenous treatment are nephrotoxicity (damage to the kidneys) and neurotoxicity (damage to the nerves),[52][53][54][55] but this may reflect the very high doses given, which are much higher than the doses currently recommended by any manufacturer and for which no adjustment was made for pre-existing renal disease. Neuro- and nephrotoxic effects appear to be transient and subside on discontinuation of therapy or reduction in dose.[56]

At a dose of 160 mg colistimethate IV every eight hours, very little nephrotoxicity is seen.[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.[59] Colistin-induced nephrotoxicity is particularly likely in patients with hypoalbuminemia.[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.[63]

Mechanism of action

Colistin is a

cytoplasmic membrane just like a detergent, solubilizing the membrane in an aqueous environment.[citation needed] This effect is bactericidal even in an isosmolar environment.[citation needed
]

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.[65][66]

History

Colistin was first isolated in Japan in 1949 by Y. Koyama, from a flask of fermenting Bacillus polymyxa var. colistinus,[67] and became available for clinical use in 1959.[68]

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. 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.[69]

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.[70]

Biosynthesis

The biosynthesis of colistin requires the use of three amino acids:

epimerization domain (E), and a condensation domain (C). Cyclization is accomplished by a thioesterase.[71] 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.

The loading domain 6-methylheptanoic acid is shown in salmon; yellow is 2,4-diaminobutryic acid; light blue is threonine; magenta is leucine.

References

  1. ^ "Drug Product Database". Health Canada. 25 April 2012. Retrieved 13 January 2022.
  2. ^ "Colobreathe 1,662,500 IU inhalation powder, Hard Capsules – Summary of Product Characteristics (SmPC)". (emc). Retrieved 16 November 2020.
  3. ^ "Colomycin 1 million International Units (IU) Powder for solution for injection, infusion or inhalation – Summary of Product Characteristics (SmPC)". (emc). 27 May 2020. Retrieved 16 November 2020.
  4. ^ "Promixin 1 million International Units (IU) Powder for Nebuliser Solution – Summary of Product Characteristics (SmPC)". (emc). 23 September 2020. Retrieved 16 November 2020.
  5. ^ "Coly-Mycin M- colistimethate injection". DailyMed. 3 December 2018. Retrieved 16 November 2020.
  6. ^ "Colobreathe EPAR". European Medicines Agency. 17 September 2018. Retrieved 16 November 2020.
  7. PMID 28238870
    .
  8. ^ a b c d e f g "Colistimethate Sodium Monograph for Professionals". Drugs.com. Retrieved 6 November 2019.
  9. ^
    S2CID 13158593
    .
  10. ^
    ISBN 9781437720600
    .
  11. PMID 16723551
    .
  12. PMID 26676364
    .
  13. ^ "Colistimethate (Coly Mycin M) Use During Pregnancy". Drugs.com. Retrieved 11 November 2019.
  14. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  15. ISBN 9789241515528
    .
  16. ISBN 9780857113382
    .
  17. ^ "Polymyxin E (Colistin) – The Antimicrobial Index Knowledgebase – TOKU-E". Archived from the original on 28 May 2016. Retrieved 28 May 2016.
  18. ^ "Colistin sulfate, USP Susceptibility and Minimum Inhibitory Concentration (MIC) Data" (PDF). 3 March 2016. Archived (PDF) from the original on 2016-03-04. Retrieved 2014-02-10.
  19. PMID 20942647
    .
  20. S2CID 44556845
    .
  21. PMID 26892159
    .
  22. PMID 12971377
    .
  23. ^
    ISBN 978-0-306-43902-5. Archived from the original
    on 2012-02-07.
  24. PMID 15190037
    .
  25. PMID 17214907
    .
  26. PMID 16442632
    .
  27. S2CID 25679033
    .
  28. PMID 16931410
    .
  29. ^ a b "Colomycin Injection". Summary of Product Characteristics. electronic Medicines Compendium (eMC). 18 May 2016. Archived from the original on 16 July 2017. Retrieved 3 June 2017.
  30. ^ "COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS: COLISTIN: SUMMARY REPORT (2)" (PDF). European Medicines Agency. January 2002. Archived from the original (PDF) on 18 July 2006. NB. Colistin base has an assigned potency of 30 000 IU/mg
  31. S2CID 12205902
    .
  32. PMID 9598783
    .
  33. PMID 16008625
    .
  34. PMID 11856210
    .
  35. ^ "Promixin 1 million International Units (IU) Powder for Nebuliser Solution". Patient Information Leafle. electronic Medicines Compendium (eMC). 12 January 2016. Archived from the original on 16 July 2017.
  36. PMID 29042767
    .
  37. PMID 26603172
    .
  38. ^ Zhang S. "Resistance to the Antibiotic of Last Resort Is Silently Spreading". The Atlantic. Archived from the original on 2017-01-13. Retrieved 2017-01-12.
  39. ^ McKenna M (2015-12-03). "Apocalypse Pig Redux: Last-Resort Resistance in Europe". Phenomena. Archived from the original on 28 May 2016. Retrieved 28 May 2016.
  40. ^ "First discovery in United States of colistin resistance in a human E. coli infection". www.sciencedaily.com. Archived from the original on 2016-05-27. Retrieved 2016-05-27.
  41. ^ "Emergence of Pan drug resistance amongst gram negative bacteria! The First case series from India". December 2014.
  42. ^ "New worry: Resistance to 'last antibiotic' surfaces in India". The Times of India. 28 December 2014. Archived from the original on 31 December 2014.
  43. S2CID 33476061
    .
  44. ^ "Discovery of first mcr-1 gene in E. coli bacteria found in a human in United States". cdc.gov. U.S. Department of Health and Human Services. 31 May 2016. Archived from the original on 2016-07-11. Retrieved 6 July 2016.
  45. S2CID 246826086
    .
  46. PMID 23695834
    .
  47. PMID 37094804
    .
  48. ^ a b McKay B (6 March 2018). "Common 'Superbug' Found to Disguise Resistance to Potent Antibiotic". wsj.com. Wall Street Journal. Archived from the original on 2018-04-03. Retrieved 1 Nov 2018.
  49. PMID 25567227
    .
  50. ^
    PMID 29511071
    .
  51. PMID 12974973
    .
  52. PMID 14008070
    .
  53. PMID 5448745
    .
  54. PMID 9762785
    .
  55. PMID 15620821
    .
  56. S2CID 38084953
    .
  57. S2CID 42625124
    .
  58. PMID 10926333
    .
  59. PMID 12228836
    .
  60. PMID 30097635
    .
  61. PMID 8146414
    .
  62. PMID 16678502
    .
  63. PMID 17323867
    .
  64. PMID 16931410
    .
  65. PMID 15044428
    .
  66. PMID 12709357
    .
  67. ^ Koyama Y, Kurosasa A, Tsuchiya A, Takakuta K (1950). "A new antibiotic 'colistin' produced by spore-forming soil bacteria". J Antibiot (Tokyo). 3.
  68. ^ MacLaren G, Spelman D (22 November 2022). Hopper DC, Hall KK (eds.). "Colistin: An overview". UpToDate. Wolters Kluwer. Archived from the original on 2016-05-31. Retrieved 2016-06-06.
  69. S2CID 21679015
    .
  70. ^ Schoenmakers K (21 October 2020). "How China is getting its farmers to kick their antibiotics habit". Nature. Retrieved 2 August 2021.
  71. ^ Dewick PM (2009). Medicinal Natural Products (Third ed.). John Wiley & Sons.

Further reading

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Colistin&oldid=1213906899"