WordNet

any of several toxic antibiotics obtained from a particular soil bacterium

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/09/22 22:03:54」(JST)

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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 B 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] Polymixin B is a component of triple antibiotic ointment.

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.^[7]

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.^[8]

Gram-negative bacteria can develop resistance to polymyxins through various modifications of the LPS structure that inhibit the binding of polymyxins to LPS.^[9]

Antibiotic resistance to this drug has been increasing, especially in southern China. Recently the gene mcr-1, which confers the antibiotic resistance, has been isolated from Enterobacteriaceae bacteria plasmids which will increase the likelihood of its spread globally.^[10]^[11]

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.^[12]

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
^ Velkov, Tony; Roberts, Kade D; Nation, Roger L; Thompson, Philip E; Li, Jian (2013-06-01). "Pharmacology of polymyxins: new insights into an 'old' class of antibiotics". Future microbiology. 8 (6). doi:10.2217/fmb.13.39. ISSN 1746-0913. PMC 3852176. PMID 23701329.
^ Tsubery, H.; Ofek, I.; Cohen, S.; Fridkin, M. (2000-01-01). "Structure activity relationship study of polymyxin B nonapeptide". Advances in Experimental Medicine and Biology. 479: 219–222. doi:10.1007/0-306-46831-X_18. ISSN 0065-2598. PMID 10897422.
^ 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.
^ "Antibiotic resistance threatens the efficacy of prophylaxis - The Lancet Infectious Diseases". thelancet.com. Retrieved 2015-11-19.
^ Liu YY; et al. (18 November 2015). "Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study". The Lancet. doi:10.1016/S1473-3099(15)00424-7.
^ Yokoyama et al. 2000. FEMS Microbiol. Lett. 192:139-144.

UpToDate Contents

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1. アシネトバクター感染：治療および予防 acinetobacter infection treatment and prevention
2. コリスチン：概要 colistin an overview
3. カルバペネマーゼ産生グラム陰性桿菌の概要 overview of carbapenemase producing gram negative bacilli
4. ステノトロフォモナス・マルトフィリア stenotrophomonas maltophilia
5. 緑膿菌性肺炎 pseudomonas aeruginosa pneumonia

English Journal

Pseudomonas aeruginosa produces phosphatidyltris(hydroxymethyl)aminomethane and derivatives when grown in Tris-buffered medium.

Abbes I1, Rihouey C2, Hardouin J3, Dé E4, Jouenne T5, Alexandre S6.
Biochimica et biophysica acta.Biochim Biophys Acta.2016 Aug;1861(8 Pt A):703-14. doi: 10.1016/j.bbalip.2016.04.017. Epub 2016 Apr 26.
For optimal growth of a microorganism, the pH of the culture medium should be set at an optimum value. For that reason, growth media require buffering agents. We show in this study that, when grown in a medium supplemented with tris(hydroxymethyl)aminomethane (Tris), Pseudomonas aeruginosa is able t
PMID 27126915

Letter to the editor: Escherichia coli harbouring mcr-1 gene isolated from poultry not exposed to polymyxins in Brazil.

Lentz SA1, de Lima-Morales D, Cuppertino VM, Nunes Lde S, da Motta AS, Zavascki AP, Barth AL, Martins AF.
Euro surveillance : bulletin Européen sur les maladies transmissibles = European communicable disease bulletin.Euro Surveill.2016 Jun 30;21(26). doi: 10.2807/1560-7917.ES.2016.21.26.30267.
PMID 27390134

Japanese Journal

新規粘膜アジュバントとしてのポリペプチド系抗生物質の検討

遠藤正宏,菅野祐幸,堤玲子 [他],松川直美,佐藤成大,吉野直人
岩手医学雑誌 64(3), 195-208, 2012-08-01
NAID 110009460988

ポリミキシン(ポリミキシンB,コリスチン)

柳秀高
呼吸器内科 20(6), 521-526, 2011-12-00
NAID 40019188627

Related Pictures

and Polymyxins by MikeJenny For CF Patients, Polymyxins Come Back Into The efficacy of polymyxins compared with rate in patients treated with polymyxins membrane Polymyxins DNA replication (D Mind Map branch: polymyxins

★リンクテーブル★

リンク元

「抗菌薬」

　　[★]

英: antibacterial drug, antibacterial
関: 抗生剤、薬理学、抗菌薬一覧、抗細菌薬

first aid step 1 2006 p.165

定義

細菌/微生物に静菌作用、殺菌作用を示す物質。結果として、人において病原性を除去する目的で使用される。
このうち、微生物によって産生される物質を抗生物質と呼ぶ

作用機序による分類

細胞壁合成阻害：βラクタム系抗菌薬(ペニシリン系抗菌薬、セフェム系抗菌薬、モノバクタム系抗菌薬、カルバペネム系抗菌薬)
核酸合成阻害　：ニューキノロン系抗菌薬、メトロニダゾール
タンパク質合成阻害

30S：アミノグリコシド系抗菌薬、テトラサイクリン系抗菌薬
50S：マクロライド系抗菌薬、クリンダマイシン、クロラムフェニコール、ストレプトグラミン系抗菌薬、オキソゾリニドン系抗菌薬(リゾネリド)

代謝拮抗：サルファ剤(サルファメソキサゾール、トリメトプリム)

first aid step 1 2006 p.165

	Mechanism of action	Drugs
1	Block cell wall synthesis by inhibition of peptidoglycan cross-linking	penicillin, ampicillin, ticarcillin, piperacillin, imipenem, aztreonam, cephalosporins
2	Block peptidoglycan synthesis	bacitracin, vancomycin, cycloserine
3	Disrupt bacterial/fungal cell membranes	polymyxins
4	Disrupt fungal cell membranes	amphotericin B, nystatin, fluconazole/azoles
5	Block nucleotide synthesis	sulfonamides, trimethoprim
6	Block DNA topoisomerases	quinolones
7	Block mRNA synthesis	rifampin
8	Block protein synthesis at 50S ribosomal subunit	chloramphenicol, erythromycin/macrolides, lincomycin, clindamycin, streptogramins (quinupristin, dalfopristin), linezolid
9	Block protein synthesis at 30S ribosomal subunit	aminoglycosides, tetracyclines, spectinomycin 　ATuSi　→　あつし

薬物動態

濃度依存性：アミノグリコシド系抗菌薬、ニューロキノロン系抗菌薬
時間依存性：βラクタム系抗菌薬

治療期間

小児

尾内一信 ; 第 39 回日本小児感染症学会教育講演 2 小児感染症の抗菌薬療法 -耐性菌時代の適正使用-

感染臓器・臨床診断	原因菌	投与期間（抗菌薬）
髄膜炎	インフルエンザ菌	7-10日
	肺炎球菌	10-14日
	髄膜炎菌	7-10日
	GBS，腸内細菌，リステリア	21日
中耳炎	＜2 歳	10日
中耳炎	2 歳≦	5-7日
咽頭炎	A 群連鎖球菌	10日(ペニシリン系薬)
咽頭炎	A 群連鎖球菌	5日(セフェム系薬)
肺炎	肺炎球菌，インフルエンザ菌	解熱後3-4日
	黄色ブドウ球菌	3-4週間
	マイコプラズマ，クラミジア	10-21日
腎臓、膀胱炎、腎盂腎炎	大腸菌，プロテウス，腸球菌	3日
腎臓、膀胱炎、腎盂腎炎	大腸菌，プロテウス，腸球菌	14日
骨髄炎	黄色ブドウ球菌	21日
骨髄炎	連鎖球菌，インフルエンザ菌	14日

主要な感染症の抗菌薬投与期間

感染レジマニュ p.27

骨	骨髄炎		4-6週
耳鼻咽喉	中耳炎		5-7日
	副鼻腔炎		5-14日
	A群溶連菌咽頭炎		10日
肺	肺炎	肺炎球菌	7-10日 or 解熱後3日間
		インフルエンザ菌	10-14日
		マイコプラズマ	14日(7-10日)
		レジオネラ	21日
	肺化膿症		28-42日
心臓	感染性心内膜炎	α連鎖球菌	2-4週
		黄色ブドウ球菌	4-6週
消化管	腸炎	赤痢菌	3日
		チフス	14日(5-7日)
		パラチフス
	腹膜炎	特発性	5日
		二次性	10-14日
胆肝膵	肝膿瘍	細菌性	4-8週
		アメーバ性	10日
尿路	膀胱炎		3日
	急性腎盂腎炎		14日(7-10日)
	急性腎盂腎炎・再発		6週
	慢性前立腺炎		1-3ヶ月
髄腔	髄膜炎	インフルエンザ菌	7-10日
		髄膜炎菌
		肺炎球菌	10-14日
		リステリア	21日
敗血症	敗血症	コアグラーゼ陰性ブドウ球菌	5-7日
		黄色ブドウ球菌	28日(14日)
		グラム陰性桿菌	14日(7-14日)
		カンジダ	血液培養陰性化後, 14日

ソース不明

シャント感染：黄色ブドウ球菌：頭蓋内デバイスの感染の場合、髄液培養陰性+10日間

妊婦に避けるべき抗菌薬

Antibiotics to avoid in pregnancy
Sulfonamides––kernicterus.
Aminoglycosides––ototoxicity.
Fluoroquinolones––cartilage damage.
Erythromycin––acute cholestatic hepatitis in mom

(and clarithromycin––embryotoxic).

Metronidazole––mutagenesis.
Tetracyclines––discolored teeth, inhibition of bone growth.
Ribavirin (antiviral)––teratogenic.
Griseofulvin (antifungal)––teratogenic.
Chloramphenicol––“gray baby.”
SAFE Moms Take Really Good Care.

使っても良い

YN.H-24

βラクタム系
エリスロマイシン、アジスロマイシン

参考

抗菌薬インターネットブック

まとまっていてよい

http://www.antibiotic-books.jp

抗菌薬一覧

[pmid3027012-1] 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.

[2] Polymyxins at the US National Library of Medicine Medical Subject Headings (MeSH)

[3] 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

[pmid12569104-4] 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.

[pmid16507149-5] 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.

[6] Staff, Medicine.net. Last reviewed 16 April 2014 Neomycin/polymyxin/hydrocortisone suspension - otic, Cortisporin, Pediotic

[7] Velkov, Tony; Roberts, Kade D; Nation, Roger L; Thompson, Philip E; Li, Jian (2013-06-01). "Pharmacology of polymyxins: new insights into an 'old' class of antibiotics". Future microbiology. 8 (6). doi:10.2217/fmb.13.39. ISSN 1746-0913. PMC 3852176. PMID 23701329.

[8] Tsubery, H.; Ofek, I.; Cohen, S.; Fridkin, M. (2000-01-01). "Structure activity relationship study of polymyxin B nonapeptide". Advances in Experimental Medicine and Biology. 479: 219–222. doi:10.1007/0-306-46831-X_18. ISSN 0065-2598. PMID 10897422.

[pmid15951433-9] 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.

[10] "Antibiotic resistance threatens the efficacy of prophylaxis - The Lancet Infectious Diseases". thelancet.com. Retrieved 2015-11-19.

[11] Liu YY; et al. (18 November 2015). "Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study". The Lancet. doi:10.1016/S1473-3099(15)00424-7.

[12] Yokoyama et al. 2000. FEMS Microbiol. Lett. 192:139-144.

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案内

polymyxins