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Colistin (polymyxin E) is a polymyxin antibiotic produced by certain strains of Paenibacillus polymyxa var. colistinus. Colistin is a mixture of cyclic polypeptides colistin A and B. Colistin is effective against most Gram-negative bacilli and is used as a polypeptide antibiotic. It is commercially available as 'Xylistin' (India, marketed by CIpla Pharmaceuticals ltd) and 'Koolistin' (India, registered and marketed by Biocon ltd)

Colistin is a decades-old drug that fell out of favor due to its nephrotoxicity. It remains one of the last-resort antibiotics for multidrug-resistant Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter.^[1] NDM-1 metallo-β-lactamase multidrug-resistant Enterobacteriaceae have also shown susceptibility to Colistin.^[2]

1 History
2 Administration and dosage
- 2.1 Forms
- 2.2 Dosage
3 Mode of action
4 Spectrum of bacterial susceptibility
5 Resistance
- 5.1 Exceptional (inherently colistin resistant) Gram-negative bacteria
- 5.2 Gram-negative organisms with variable resistance to colistin
6 Pharmacokinetics
7 Adverse reactions
8 References

History

Colistin was derived from a flask of fermenting bacteria by a Japanese researcher in 1949.^[3]

Administration and dosage

Forms

There are two forms of colistin 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, but 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 cystic fibrosis patients, and it has come into recent use for treating multidrug-resistant Acinetobacter infection, although resistant forms have been reported.^[4]^[5] Colistimethate sodium has also been given intrathecally and intraventricularly in Acinetobacter baumanii and Pseudomonas aeruginosa meningitis/ventriculitis ^[6]^[7]^[8]^[9] Some studies have indicated that colistin may be useful for treating infections caused by carbapenem-resistant isolates of Acinetobacter baumannii.^[5]

Colistin sulfate may be used to treat intestinal infections, or to suppress colonic flora. Colistin sulfate is also used as 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 very different labeling of the parenteral products of colistin methanesulfonate in different parts of the world was first revealed by Li et al.^[10] Colistimethate sodium manufactured by Xellia (Colomycin injection) is prescribed in international units, but 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;^[11]
Coly-mycin M 150 mg "colistin base" is 360 mg colistimethate or 4,500,000 units.^[12]

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 will depend on the manufacturer. This complete absence of any regulation or standardisation of dose makes intravenous colistin dosing difficult for any physician.^{[citation needed]}

Colistin has been used in combination with rifampicin, and there is in-vitro evidence of synergy,^[13]^[14] and the combination has been used successfully in patients.^[15] There is also in-vitro evidence of synergy for colistimethate sodium used in combination with other antipseudomonal antibiotics.^[16]

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.^[17]^[18]

Mode of action

Colistin is polycationic and has both hydrophilic and lipophilic moieties. These poly-cationic regions interact with the bacterial outer membrane, by displacing 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. This effect is bactericidal even in an isosmolaric environment.

Spectrum of bacterial susceptibility

Colistin has been effective in treating infections caused by Pseudomonas, Escherichia, and Klebsiella genera. The following represents 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/ml

^[19]^[20]

Colestin in combination with other drugs are used to attack P. aeruginosa biofilm infection in lungs of CF patients.^[21] Biofilms have a low oxygen environment below the surface where bacteria are metabolically inactive. Colestin is highly effective in this environment. However, P. aeruginosa in the outer layers where they are metabolically active can develop resistance to colestin.^[22] Consequently, a drug combination attacking both the inactive and active forms of P. aeruginosa is highly effective.

Resistance

Resistance to colistin is currently rare, but is described. At present there is no agreement about how to look for colistin resistance. The Société Française de Microbiologie uses a cut off of 2 mg/l, whereas the British Society for Antimicrobial Chemotherapy sets a cutoff of 4 mg/l or less as sensitive, and 8 mg/ml or more as resistant. There are not currently any US standards for measuring colistin sensitivity.

India reported the first clear and 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.^[23]^[24]

Use of colistin to treat Acinetobacter baumannii infections has, as with other antibiotics, led to the development of resistant bacterial strains. These resistant strains have also been shown to develop resistance to antimicrobial compounds, including LL-37 and lysozyme, produced as part of the human host's immune system.^[25]

Exceptional (inherently colistin resistant) Gram-negative bacteria

Brucella
Burkholderia cepacia
Chryseobacterium indologenes
Edwardsiella
Elizabethkingia meningoseptica
Francisella tularensis spp.
Gram-negative cocci
Helicobacter pylori
Moraxella catarrhalis
Morganella spp.
Neisseria gonorrheae and Neisseria meningitidis
Proteus
Providencia
Serratia

Some strains of Stenotrophomonas maltophilia^[26]

Gram-negative organisms with variable resistance to colistin

Aeromonas
Vibrio
Prevotella
Fusobacterium

Pharmacokinetics

There is no clinically useful absorption of colistin from 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 yet not characterised.^[27]^[28]

Adverse reactions

The main toxicities described with intravenous treatment are nephrotoxicity (damage to the kidneys) and neurotoxicity (damage to the nerves),^[29]^[30]^[31]^[32] 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 renal disease. Neuro- and nephrotoxic effects appear to be transient and subside on discontinuation of therapy or reduction in dose.^[33]

At a dose of 160 mg colistimethate IV every eight hours, very little nephrotoxicity is seen.^[34]^[35] Indeed, colistin appears to have less toxicity than the aminoglycosides that subsequently replaced it, and colistin has been used for extended periods of up to six months with no ill effects.^[36]

The main toxicity described with aerosolised treatment is bronchospasm,^[37] which can be treated or prevented with the use of beta2-agonists such as salbutamol ^[38] or following a desensitisation protocol.^[39]

References

^ Falagas ME, Grammatikos AP, Michalopoulos A (October 2008). "Potential of old-generation antibiotics to address current need for new antibiotics". Expert review of anti-infective therapy 6 (5): 593–600. doi:10.1586/14787210.6.5.593. PMID 18847400.
^ Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R et al. (2010). "Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study". The Lancet Infectious Diseases 10 (9): 597–602. doi:10.1016/S1473-3099(10)70143-2. PMC 2933358. PMID 20705517.
^ Vastag, Brian (2012), "NIH Superbug Outbreak Shows Lack of Antibiotics", The Washington Post, Saturday, 25 August 2012; pg A2.
^ Reis AO, Luz DA, Tognim MC, Sader HS, Gales AC (2003). "Polymyxin-Resistant Acinetobacter spp. Isolates: What Is Next?". Emerg Infect Dis 9: 1025–7. doi:10.3201/eid0908.030052. PMID 12971377.
^ ^a ^b Towner K J (2008). "Molecular Basis of Antibiotic Resistance in Acinetobacter spp.". Acinetobacter Molecular Biology. Caister Academic Press. ISBN 0-306-43902-6. [http://www.horizonpress.com/acineto.
^ Benifla M, Zucker G, Cohen A, Alkan M (2004). "Successful treatment of Acinetobacter meningitis with intrathecal polymyxin". J Antimicrobial Chemotherapy 54 (1): 290–293. doi:10.1093/jac/dkh289. PMID 15190037.
^ Yagmur R, Esen F (2006). "Intrathecal colistin for treatment of Pseudomonas aeruginosa ventriculitis: report of a case with successful outcome". Critical Care 10 (6): 428. doi:10.1186/cc5088. PMC 1794456. PMID 17214907.
^ Motaouakkil S, Charra B, Hachimi A, Nejmi H, Benslama A, Elmdaghri N et al. (2006). "Colistin and rifampicin in the treatment of nosocomial infections from multiresistant Acinetobacter baumannii". Journal of Infection 53 (4): 274–278. doi:10.1016/j.jinf.2005.11.019. PMID 16442632.
^ Karakitsos D, Paramythiotou E, Samonis G, Karabinis A (2006). "Is intraventricular colistin an effective and safe treatment for post-surgical ventriculitis in the intensive care unit?". Acta Anaesthesiol Scand. 50 (10): 1309–1310. doi:10.1111/j.1399-6576.2006.01126.x. PMID 17067336.
^ Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K, Rayner CR et al. (2006). "Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections". Lancet Infect Dis 6 (9): 589–601. doi:10.1016/s1473-3099(06)70580-1. PMID 16931410.
^ Colomycin injection [Summary of product characteristics]. http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=1590
^ http://www.emea.europa.eu/pdfs/vet/mrls/081502en.pdf; NB. Colistin base has an assigned potency of 30 000 IU/mg
^ Ahmed N, Wahlgren NG (2003). "In vitro interaction of colistin and rifampin on multidrug-resistant Pseudomonas aeruginosa". J Chemother 15 (4): 235–38. doi:10.1159/000069498. PMID 12686786.
^ Hogg GM, Barr JG, Webb CH (1998). "In-vitro activity of the combination of colistin and rifampicin against multidrug-resistant strains of Acinetobacter baumannii". J Antimicrob Chemother 41 (4): 494–95. doi:10.1093/jac/41.4.494.
^ Petrosillo N, Chinello P, Proietti MF, Cecchini L, Masala M, Franchi C et al. (2005). "Combined colistin and rifampicin therapy for carbapenem-resistant Acinetobacter baumannii infections: clinical outcome and adverse events". Clin Microbiol Infect 11 (8): 682–83. doi:10.1111/j.1469-0691.2005.01198.x. PMID 16008625.
^ MacGowan AP, Rynn C, Wootton M, Bowker KE, Holt HA, Reeves DS (1999). "In vitro assessment of colistin's antipseudomonal antimicrobial interactions with other antibiotics". Clin Microbiol Infect. 5: 32–36. doi:10.1111/j.1469-0691.1999.tb00095.x.
^ Promixin [Summary of Product Characteristics] http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=13532
^ Colomycin Injection [Summary of Product Characteristics] http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=1590
^ http://antibiotics.toku-e.com/antimicrobial_958_2.html
^ http://www.toku-e.com/Assets/MIC/Colistin%20sulfate%20USP.pdf
^ http://jid.oxfordjournals.org/content/202/10/1585.full
^ http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2958.2008.06152.x/abstract;jsessionid=DF7FE9FDA4AE6A3C4AE6C2BE11DD0E5A.f03t01
^ "New worry: Resistance to 'last antibiotic' surfaces in India". Dec 28, 2014.
^ "Emergence of Pan drug resistance amongst gram negative bacteria! The First case series from India". Dec 2014.
^ Napier BA, Burd EM, Satola SW, Cagle SM, Ray SM, McGann P et al. (21 May 2013). "Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in Acinetobacter baumannii". MBio 4 (3): e00021–13–e00021–13. doi:10.1128/mBio.00021-13. PMID 23695834.
^ Markou N, Apostolakos H, Koumoudiou C, Athanasiou M, Koutsoukou A, Alamanos I et al. (2003). "Intravenous colistin in the treatment of sepsis from multiresistant Gram-negative bacilli in critically ill patients". Crit Care 7 (5): R78–83. doi:10.1186/cc2358. PMC 270720. PMID 12974973.
^ Li J, Milne RW, Nation RL, Turnidge JD, Smeaton TC, Coulthard K (2004). "Pharmacokinetics of colistin methanesulphonate and colistin in rats following an intravenous dose of colistin methanesulphonate". J Antimicrob Chemother. 53 (5): 837–40. doi:10.1093/jac/dkh167. PMID 15044428.
^ Li J, Milne RW, Nation RL, Turnidge JD, Smeaton TC, Coulthard K (2003). "Use of High-Performance Liquid Chromatography To Study the Pharmacokinetics of Colistin Sulfate in Rats following Intravenous Administration". Antimicrob Agents Chemother 47 (5): 1766–70. doi:10.1128/AAC.47.5.1766-1770.2003. PMC 153303. PMID 12709357.
^ Wolinsky E, Hines JD (1962). "Neurotoxic and nephrotoxic effects of colistin in patients with renal disease". N Engl J Med 266 (15): 759–68. doi:10.1056/NEJM196204122661505. PMID 14008070.
^ Koch-Weser J, Sidel VW, Federman EB, Kanarek P, Finer DC, Eaton AE (1970). "Adverse effects of sodium colistimethate. Manifestations and specific reaction rates during 317 courses of therapy". Annals of Internal Medicine 72 (6): 857–68. doi:10.7326/0003-4819-72-6-857. PMID 5448745.
^ Ledson MJ, Gallagher MJ, Cowperthwaite C, Convery RP, Walshaw MJ (1998). "Four years' experience of intravenous colomycin in an adult cystic fibrosis unit". Eur Respir J 12 (3): 592–94. doi:10.1183/09031936.98.12030592. PMID 9762785.
^ Li J, Nation RL, Milne RW, Turnidge JD, Coulthard K (2005). "Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria". Int J Antimicrob Agents 25 (1): 11–25. doi:10.1016/j.ijantimicag.2004.10.001. PMID 15620821.
^ Beringer P (2001). "The clinical use of colistin in patients with cystic fibrosis". Current Opinion in Pulmonary Medicine 7 (6): 434–440. doi:10.1097/00063198-200111000-00013.
^ Conway SP, Etherington C, Munday J, Goldman MH, Strong JJ, Wootton M (2000). "Safety and tolerability of bolus intravenous colistin in acute respiratory exacerbation in adults with cystic fibrosis". Annals of Pharmacotherapy 34 (11): 1238–42. doi:10.1345/aph.19370. PMID 11098334.
^ Littlewood JM, Koch C, Lambert PA, Høiby N, Elborn JS, Conway SP et al. (2000). "A ten year review of Colomycin". Respir Med 94 (7): 632–40. doi:10.1053/rmed.2000.0834. PMID 10926333.
^ Stein A, Raoult D (2002). "Colistin: an antimicrobial for the 21st century?". Clin Infect Dis 35 (7): 901–2. doi:10.1086/342570. PMID 12228836.
^ Maddison J, Dodd M, Webb AK (1994). "Nebulized colistin causes chest tightness in adults with cystic fibrosis". Respir Med. 88 (2): 145–147. doi:10.1016/0954-6111(94)90028-0.
^ Kamin W, Schwabe A, Krämer I (2006). "Inhalation solutions: which one are allowed to be mixed? Physico-chemical compatibility of drug solutions in nebulizers". J Cyst Fibros. 5 (4): 205–213. doi:10.1016/j.jcf.2006.03.007. PMID 16678502.
^ Domínguez-Ortega J, Manteiga E, Abad-Schilling C, Juretzcke MA, Sánchez-Rubio J, Kindelan C (2007). "Induced tolerance to nebulized colistin after severe reaction to the drug". J Investig Allergol Clin Immunol 17 (1): 59–61. PMID 17323867.

UpToDate Contents

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1. コリスチン：概要 colistin an overview
2. アシネトバクター感染：治療および予防 acinetobacter infection treatment and prevention
3. 嚢胞性線維症：肺疾患に対する抗菌薬療法 cystic fibrosis antibiotic therapy for lung disease
4. グラム陰性桿菌性髄膜炎：治療 gram negative bacillary meningitis treatment
5. 緑膿菌感染症に対する抗菌薬治療の原則 principles of antimicrobial therapy of pseudomonas aeruginosa infections

English Journal

Efficacy and toxicity of aerosolised colistin in ventilator-associated pneumonia: a prospective, randomised trial.

Abdellatif S1, Trifi A2, Daly F1, Mahjoub K1, Nasri R1, Ben Lakhal S1.
Annals of intensive care.Ann Intensive Care.2016 Dec;6(1):26. doi: 10.1186/s13613-016-0127-7. Epub 2016 Mar 31.
BACKGROUND: Cases of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) gram-negative bacilli (GNB) mainly Acinetobacter baumannii, Pseudomonas aeruginosa and enterobacteria are common in hospitalised patients of Tunisian intensive care units (ICUs). Parenteral colistin has been
PMID 27033711

Chromosomal Locations of mcr-1 and blaCTX-M-15 in Fluoroquinolone-Resistant Escherichia coli ST410.

Falgenhauer L, Waezsada SE, Gwozdzinski K, Ghosh H, Doijad S, Bunk B, Spröer C, Imirzalioglu C, Seifert H, Irrgang A, Fischer J, Guerra B, Käsbohrer A, Overmann J, Goesmann A, Chakraborty T.
Emerging infectious diseases.Emerg Infect Dis.2016 Sep 15;22(9). doi: 10.3201/eid2209.160692. [Epub ahead of print]
PMID 27322919

Possible Transmission of mcr-1-Harboring Escherichia coli between Companion Animals and Human.

Zhang XF, Doi Y, Huang X, Li HY, Zhong LL, Zeng KJ, Zhang YF, Patil S, Tian GB.
Emerging infectious diseases.Emerg Infect Dis.2016 Sep 15;22(9). doi: 10.3201/eid2209.160464. [Epub ahead of print]
PMID 27191649

Japanese Journal

Efficacy and Safety Profile Comparison of Colistin and Tigecycline on the Extensively Drug Resistant Acinetobacter baumannii

Kwon Sung Hee,Ahn Hye Lim,Han Ok Yeon [他]
Biological & pharmaceutical bulletin 37(3), 340-346, 2014-03
NAID 40019992530

カラムスイッチング-オンカラム蛍光誘導体化LC法による鶏肉中コリスチンの分析

坂本泰洋,方波見志織,岩崎雄介,伊藤里恵,斉藤貢一
日本食品化学学会誌 20(3), 209-214, 2013-12-24
… A simple, rapid, and precise method was developed for the determination of colistin [CL: mixture of colistin-A (CLA) and colistin-B (CLB)] in chicken tissues by LC/FL using an on-column fluorescence derivatization and column-switching technique. …
NAID 110009686105

カラムスイッチング-オンカラム蛍光誘導体化LC法による鶏肉中コリスチンの分析

坂本泰洋,方波見志織,岩崎雄介 [他]
日本食品化学学会誌 20(3), 209-214, 2013
NAID 40019935131

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★リンクテーブル★

リンク元	「コリスチン」「CL」
拡張検索	「colistin sodium methanesulfonate」「colistin sulfate」

「コリスチン」

Colistin
Systematic (IUPAC) name
	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
Trade names	Coly-mycinm; Coly-monas(India)
Pregnancy; category	C;
Legal status	PoM (UK), not available in US;
Routes of; administration	topical, oral, intravenous, inhaled
Pharmacokinetic data
Bioavailability	0%
Half-life	5 hours
Identifiers
CAS Registry Number	1264-72-8
ATC code	A07AA10 J01XB01 QJ51XB01
PubChem	CID: 5311054
DrugBank	DB00803
ChemSpider	4470591
UNII	WP15DXU577
KEGG	D02138
ChEMBL	CHEMBL501505
Chemical data
Formula	C52H98N16O13
Molecular mass	1155.4495 g/mol
	SMILES 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 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 ; Key:YKQOSKADJPQZHB-QNPLFGSASA-N ;
(what is this?) (verify)

　　[★]

英: colistin CL
ラ: colistinum
化: 硫酸コリスチン colistin sulfate、コリスチンメタンスルホン酸ナトリウム colistin sodium methane sulfonate
商: コリマイシン、メタコリマイシン。(点眼液、眼軟膏)エコリシン、エリコリ(コリスチン、エリスロマイシン)。(点眼液、眼軟膏)コリナコール、コリマイ、オフサロン(クロラムフェニコール、コリスチン)。コリマイフォーム(フラジオマイシン、コリスチン)。polymyxin E
関: 主としてグラム陰性菌に作用するもの

「CL」

　　[★]

「colistin sodium methanesulfonate」

　　[★]

コリスチンメタンスルホン酸ナトリウム

関: colistimethate

「colistin sulfate」

　　[★]

硫酸コリスチン

関: colistin

[1] Falagas ME, Grammatikos AP, Michalopoulos A (October 2008). "Potential of old-generation antibiotics to address current need for new antibiotics". Expert review of anti-infective therapy 6 (5): 593–600. doi:10.1586/14787210.6.5.593. PMID 18847400.

[Kumarasamy-2] Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R et al. (2010). "Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study". The Lancet Infectious Diseases 10 (9): 597–602. doi:10.1016/S1473-3099(10)70143-2. PMC 2933358. PMID 20705517.

[3] Vastag, Brian (2012), "NIH Superbug Outbreak Shows Lack of Antibiotics", The Washington Post, Saturday, 25 August 2012; pg A2.

[4] Reis AO, Luz DA, Tognim MC, Sader HS, Gales AC (2003). "Polymyxin-Resistant Acinetobacter spp. Isolates: What Is Next?". Emerg Infect Dis 9: 1025–7. doi:10.3201/eid0908.030052. PMID 12971377.

[Towner-5] Towner K J (2008). "Molecular Basis of Antibiotic Resistance in Acinetobacter spp.". Acinetobacter Molecular Biology. Caister Academic Press. ISBN 0-306-43902-6. [http://www.horizonpress.com/acineto.

[6] Benifla M, Zucker G, Cohen A, Alkan M (2004). "Successful treatment of Acinetobacter meningitis with intrathecal polymyxin". J Antimicrobial Chemotherapy 54 (1): 290–293. doi:10.1093/jac/dkh289. PMID 15190037.

[7] Yagmur R, Esen F (2006). "Intrathecal colistin for treatment of Pseudomonas aeruginosa ventriculitis: report of a case with successful outcome". Critical Care 10 (6): 428. doi:10.1186/cc5088. PMC 1794456. PMID 17214907.

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[12] ttp://www.emea.europa.eu/pdfs/vet/mrls/081502en.pdf; NB. Colistin base has an assigned potency of 30 000 IU/mg

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[19] ttp://antibiotics.toku-e.com/antimicrobial_958_2.html

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