・リミキシン　

WordNet

any of several toxic antibiotics obtained from a particular soil bacterium

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/04 14:40:02」(JST)

wiki en

Colistin

Polymyxin B (R=H is polymyxin B1, R=CH₃ is polymyxin B2)

Polymyxins are antibiotics,^[1] with a general structure consisting of a cyclic peptide with a long hydrophobic tail. They disrupt the structure of the bacterial cell membrane by interacting with its phospholipids. They are produced by nonribosomal peptide synthetase systems in Gram-positive bacteria such as Paenibacillus polymyxa^[2] and are selectively toxic for Gram-negative bacteria due to their specificity for the lipopolysaccharide molecule that exists within many Gram-negative outer membranes.

Polymyxins B and E (also known as colistin) are used in the treatment of Gram-negative bacterial infections. The global problem of advancing antimicrobial resistance has led to a renewed interest in their use recently.^[3]

Polymyxin M is also known as "mattacin".^[4]

Clinical use

Polymyxin antibiotics are relatively neurotoxic and nephrotoxic,^[5] so are usually used only as a last resort if modern antibiotics are ineffective or are contraindicated. Typical uses are for infections caused by strains of multiple drug-resistant Pseudomonas aeruginosa or carbapenemase-producing Enterobacteriaceae.

Polymyxins are not absorbed from the gastrointestinal tract, so another route of administration must be chosen, e.g., parenteral (often intravenously) or by inhalation (unless perhaps the targets are bacteria in the gastrointestinal tract). They are also used externally as a cream or drops to treat otitis externa (swimmers ear).^[6]

Polymyxins have less effect on Gram-positive organisms, and are sometimes combined with other agents (as with trimethoprim/polymyxin) to broaden the effective spectrum.

Mechanism of action

After binding to lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria, polymyxins disrupt both the outer and inner membranes. The hydrophobic tail is important in causing membrane damage, suggesting a detergent-like mode of action.

Removal of the hydrophobic tail of polymyxin B yields polymyxin nonapeptide, which still binds to LPS, but no longer kills the bacterial cell. However, it still detectably increases the permeability of the bacterial cell wall to other antibiotics, indicating it still causes some degree of membrane disorganization.

Gram-negative bacteria can develop resistance to polymyxins through various modifications of the LPS structure that inhibit the binding of polymyxins to LPS.^[7]

Use in biomedical research

Polymyxins are used to neutralize or absorb LPS, which contaminates samples intended for use in, e.g., immunological experiments. Minimization of LPS contamination can be important because LPS can evoke strong reactions from immune cells and, therefore, distort experimental results.

By increasing permeability of the bacterial membrane system, polymyxin is also used in clinical work to increase release of secreted toxins, such as Shiga toxin from Escherichia coli.^[8]

References

^ Dixon RA, Chopra I (November 1986). "Polymyxin B and polymyxin B nonapeptide alter cytoplasmic membrane permeability in Escherichia coli". J. Antimicrob. Chemother. 18 (5): 557–563. doi:10.1093/jac/18.5.557. PMID 3027012.
^ Polymyxins at the US National Library of Medicine Medical Subject Headings (MeSH)
^ Falagas ME, Grammatikos AP, Michalopoulos A. Potential of old-generation antibiotics to address current need for new antibiotics. Expert Rev Anti Infect Ther. 2008; 6(5):593-600 PMID 18847400
^ Martin NI, Hu H, Moake MM, et al. (April 2003). "Isolation, structural characterization, and properties of mattacin (polymyxin M), a cyclic peptide antibiotic produced by Paenibacillus kobensis M". J. Biol. Chem. 278 (15): 13124–13132. doi:10.1074/jbc.M212364200. PMID 12569104.
^ Falagas ME, Kasiakou SK (February 2006). "Toxicity of polymyxins: a systematic review of the evidence from old and recent studies". Crit Care 10 (1): R27. doi:10.1186/cc3995. PMC 1550802. PMID 16507149.
^ Staff, Medicine.net. Last reviewed 16 April 2014 Neomycin/polymyxin/hydrocortisone suspension - otic, Cortisporin, Pediotic
^ Tran AX, Lester ME, Stead CM, et al. (August 2005). "Resistance to the antimicrobial peptide polymyxin requires myristoylation of Escherichia coli and Salmonella typhimurium lipid A". J. Biol. Chem. 280 (31): 28186–28194. doi:10.1074/jbc.M505020200. PMID 15951433.
^ Yokoyama et al. 2000. FEMS Microbiol. Lett. 192:139-144.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 外耳炎：治療 external otitis treatment
2. 結膜炎 conjunctivitis
3. アシネトバクター感染：治療および予防 acinetobacter infection treatment and prevention
4. グラム陰性桿菌性髄膜炎：治療 gram negative bacillary meningitis treatment
5. コリスチン：概要 colistin an overview

English Journal

Reduction of endotoxin attenuates liver fibrosis through suppression of hepatic stellate cell activation and remission of intestinal permeability in a rat non-alcoholic steatohepatitis model.

Douhara A1, Moriya K1, Yoshiji H1, Noguchi R1, Namisaki T1, Kitade M1, Kaji K1, Aihara Y1, Nishimura N1, Takeda K1, Okura Y1, Kawaratani H1, Fukui H1.
Molecular medicine reports.Mol Med Rep.2015 Mar;11(3):1693-700. doi: 10.3892/mmr.2014.2995. Epub 2014 Nov 24.
Previous clinical studies have demonstrated that endotoxin/toll‑like receptor 4 (TLR4) signaling is critical in the inflammatory pathways associated with non‑alcoholic steatohepatitis (NASH). In human and animal studies, NASH was associated with portal lipopolysaccharide (LPS) and the plasma LP
PMID 25421042

Clinical, economic and societal impact of antibiotic resistance.

Barriere SL1.
Expert opinion on pharmacotherapy.Expert Opin Pharmacother.2015 Feb;16(2):151-3. doi: 10.1517/14656566.2015.983077. Epub 2014 Dec 6.
The concern over antibiotic resistance has been voiced since the discovery of modern antibiotics > 75 years ago. The concerns have only increased with time, with efforts to control resistance caused by widespread overuse of antibiotics in human medicine and far more than appreciated use in the fe
PMID 25483564

Development and validation of a high-performance liquid chromatography-fluorescence detection method for the accurate quantification of colistin in human plasma.

Chepyala D1, Tsai IL1, Sun HY2, Lin SW3, Kuo CH4.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.J Chromatogr B Analyt Technol Biomed Life Sci.2015 Feb 1;980:48-54. doi: 10.1016/j.jchromb.2014.12.015. Epub 2014 Dec 19.
Recently, colistin has become one of the most important drugs for treating infections caused by multidrug-resistant Gram-negative bacteria. Therapeutic drug monitoring is recommended to ensure the safety and efficacy of colistin and to improve clinical outcomes. This study developed an accurate and
PMID 25589254

Japanese Journal

研究・症例肺炎を契機に劇症型抗リン脂質抗体症候群を呈した抗リン脂質抗体症候群の1例

澁佐隆,大沼菊夫
日本胸部臨床 73(1), 97-102, 2014-01
NAID 40019935514

Toll-Like Receptors Required for Dermatophagoides farinae to Activate NF-κB

Kitajima Takaaki,Muroi Masashi,Yamashita Naomi,Tanamoto Ken-ichi
Biological and Pharmaceutical Bulletin 37(1), 74-80, 2014
… Polymyxin B inhibited CD14/TLR4/MD-2- and CD14/TLR2-mediated activation of NF-κB but not the activation in I-13.35 cells. …
NAID 130003382102