WordNet

an antibiotic produced by the actinomycete Streptomyces griseus and used to treat tuberculosis
antibiotic consisting of a hydrogenated form of streptomycin; used against tuberculosis and tularemia and Gram-negative organisms

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ストレプトマイシン(結核の特効薬)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/07/10 18:29:31」(JST)

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Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic.^[3] Streptomycin cannot be given orally, but must be administered by regular intramuscular injections. An adverse effect of this medicine is ototoxicity, nephrotoxicity, fetal auditory toxicity and neuromuscular paralysis.

Mechanism of action

Streptomycin is a protein synthesis inhibitor. It binds to the small 16S rRNA of the 30S subunit of the bacterial ribosome, interfering with the binding of formyl-methionyl-tRNA to the 30S subunit.^[4] This leads to codon misreading, eventual inhibition of protein synthesis and ultimately death of microbial cells through mechanisms that are still not understood. Speculation on this mechanism indicates that the binding of the molecule to the 30S subunit interferes with 50S subunit association with the mRNA strand. This results in an unstable ribosomal-mRNA complex, leading to a frameshift mutation and defective protein synthesis; leading to cell death.^[5] Humans have structurally different ribosomes from bacteria, thereby allowing the selectivity of this antibiotic for bacteria. However at low concentrations Streptomycin only inhibits growth of the bacteria by inducing prokaryotic ribosomes to misread mRNA.^[6] Streptomycin is an antibiotic that inhibits both Gram-positive and Gram-negative bacteria,^[7] and is therefore a useful broad-spectrum antibiotic.

History

Streptomycin was first isolated on October 19, 1943, by Albert Schatz, a graduate student, in the laboratory of Selman Abraham Waksman at Rutgers University.^[8] Dr. Waksman and his laboratory discovered several antibiotics, including actinomycin, clavacin, streptothricin, streptomycin, grisein, neomycin, fradicin, candicidin and candidin. Of these, streptomycin and neomycin found extensive application in the treatment of numerous infectious diseases. Streptomycin was the first antibiotic that could be used to cure the disease tuberculosis; early production of the drug was dominated by Merck & Co. under George W. Merck.

The first randomized trial of streptomycin against pulmonary tuberculosis was carried out in 1946-1947 by the MRC Tuberculosis Research Unit under the chairmanship of Sir Geoffrey Marshall (1887–1982). The trial was both double-blind and placebo-controlled. It is widely accepted to have been the first randomised curative trial.^[9] Results showed efficacy against TB, albeit with minor toxicity and acquired bacterial resistance to the drug.^[10]

Uses

Treatment of diseases

Infective endocarditis caused by enterococcus when the organism is not sensitive to Gentamicin
Tuberculosis in combination with other anti-TB drugs. It is not the first-line treatment, except in medically under-served populations where the cost of more expensive treatments is prohibitive.
Plague (Yersinia pestis) has historically been treated with it as the first-line treatment. It is approved for this purpose by the U.S. Food and Drug Administration.
In veterinary medicine, streptomycin is the first-line antibiotic for use against gram negative bacteria in large animals (horses, cattle, sheep etc.). It is commonly combined with procaine penicillin for intramuscular injection.

While streptomycin is traditionally given intramuscularly (indeed, in many countries it is only licensed to be used intramuscularly), the drug may also be administered intravenously.^[2]

Pesticide

Streptomycin is also used as a pesticide, to combat the growth of bacteria, fungi, and algae. Streptomycin controls bacterial and fungal diseases of certain fruit, vegetables, seed, and ornamental crops, and controls algae in ornamental ponds and aquaria. A major use is in the control of fireblight on apple and pear trees. As in medical applications, extensive use can be associated with the development of resistant strains.

Cell culture

Streptomycin, in combination with penicillin, is used in a standard antibiotic cocktail to prevent bacterial infection in cell culture.

References

^ "Taking Streptomycin during pregnancy and breastfeeding". Drug Safety Site. 2006. http://drugsafetysite.com/streptomycin. Retrieved 2010-05-25.
^ ^a ^b Zhu M, Burman WJ, Jaresko GS, Berning SE, Jelliffe RW, Peloquin CA. (October 2001). "Population pharmacokinetics of intravenous and intramuscular streptomycin in patients with tuberculosis". Pharmacotherapy 21 (9): 1037–1045. DOI:10.1592/phco.21.13.1037.34625. PMID 11560193. http://www.medscape.com/viewarticle/409778. Retrieved 2010-05-25.
^ Singh B, Mitchison DA (16 January 1954). "Bactericidal Activity of Streptomycin and Isoniazid Against Tubercle Bacilli". British Medical Journal 1 (4854): 130–132. DOI:10.1136/bmj.1.4854.130. PMC 2084433. PMID 13106497. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2084433.
^ Sharma D, Cukras AR, Rogers EJ, Southworth DR, Green R (7 December 2007). "Mutational analysis of S12 protein and implications for the accuracy of decoding by the ribosome". Journal of Molecular Biology.
^ Raymon, Lionel P. (2011). COMLEX Level 1 Pharmacology Lecture Notes. Miami, FL: Kaplan, Inc.. pp. 181. ISBN CM4024K.
^ Voet, Donald & Voet, Judith G. (2004). Biochemistry (3rd ed.). John Wiley & Sons. p. 1341. ISBN [[Special:BookSources/0-471-19250-X|0-471-19250-X]].
^ Jan-Thorsten Schantz; Kee-Woei Ng (2004). A manual for primary human cell culture. World Scientific. p. 89.
^ Comroe JH Jr (1978). "Pay dirt: the story of streptomycin. Part I: from Waksman to Waksman". American Review of Respiratory Disease 117 (4): 773–781. PMID 417651.
^ Metcalfe NH, Sir Geoffrey Marshall (1887-1982), Journal of Medical Biography 2011; 19: 10-14.
^ D'Arcy Hart, Philip (28 August 1999). "A change in scientific approach: from alternation to randomised allocation in clinical trials in the 1940s". British Medical Journal.

UpToDate Contents

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5. 薬剤耐性結核の疫学および分子メカニズム epidemiology and molecular mechanisms of drug resistant tuberculosis

English Journal

Epidemiology of isoniazid resistance mutations and their effect on tuberculosis treatment outcomes.

Huyen MN, Cobelens FG, Buu TN, Lan NT, Dung NH, Kremer K, Tiemersma EW, van Soolingen D.SourcePham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2013 Aug;57(8):3620-7. doi: 10.1128/AAC.00077-13. Epub 2013 May 20.
Isoniazid resistance is highly prevalent in Vietnam. We investigated the molecular and epidemiological characteristics and the association with first-line treatment outcomes of the main isoniazid resistance mutations in Mycobacterium tuberculosis in codon 315 of the katG and in the promoter region o
PMID 23689727

Isolation and characterization of Keratinibaculum paraultunense gen. nov., sp. nov., a novel thermophilic, anaerobic bacterium with keratinolytic activity.

Huang Y, Sun Y, Ma S, Chen L, Zhang H, Deng Y.SourceBiogas Institute of Ministry of Agriculture, Chengdu, China; Key Laboratory of Development and Application of Rural Renewable Energy, Ministry of Agriculture, Chengdu, China.
FEMS microbiology letters.FEMS Microbiol Lett.2013 Aug;345(1):56-63. doi: 10.1111/1574-6968.12184. Epub 2013 Jun 27.
A novel thermophilic, anaerobic, keratinolytic bacterium designated KD-1 was isolated from grassy marshland. Strain KD-1 was a spore-forming rod with a Gram-positive type cell wall, but stained Gram-negative. The temperature, pH, and NaCl concentration range necessary for growth was 30-65 °C (opti
PMID 23710623

Effect of ribosome-targeting antibiotics on streptomycin-resistant Mycobacterium mutants in the rpsL gene.

Pelchovich G, Zhuravlev A, Gophna U.SourceDepartment of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel.
International journal of antimicrobial agents.Int J Antimicrob Agents.2013 Aug;42(2):129-32. doi: 10.1016/j.ijantimicag.2013.04.001. Epub 2013 May 10.
Streptomycin (Sm) was the first antibiotic used against Mycobacterium tuberculosis, the aetiological agent of tuberculosis (TB). However, point mutations in the rpsL gene can generate resistance to Sm, which is why spontaneous resistance to this antibiotic emerges so rapidly during treatment. Here w
PMID 23664678

Japanese Journal

Axenic culture of Brachionus plicatilis using antibiotics

Suga Koushirou,Tanaka Yukari,Sakakura Yoshitaka,Hagiwara Atsushi
Hydrobiologia 662(1), 113-119, 2011-03
… In order to render rotifer culture axenic, we tested five antibiotics: ampicillin (Amp), chloramphenicol (Cp), kanamycin (Km), nalidixic acid (Na), and streptomycin (Sm) at 30-100 μg/ml. …
NAID 120002560114

Effect of Pamamycin-607 on Secondary Metabolite Production by Streptomyces spp.

HASHIMOTO Makoto,KATSURA Hirotaka,KATO Risako,KAWAIDE Hiroshi,NATSUME Masahiro
Bioscience, Biotechnology, and Biochemistry 75(9), 1722-1726, 2011
… Pamamycin-607 also stimulated the respective production of streptomycin by S. …
NAID 130000940068

Related Pictures

★リンクテーブル★

リンク元	「アミノグリコシド系抗菌薬」「ストレプトマイシン」「SM」
拡張検索	「dihydrostreptomycin」「dihydrostreptomycin sulfate」「familial streptomycin-induced hearing loss」「streptomycin sulfate」

「アミノグリコシド系抗菌薬」

Streptomycin
Systematic (IUPAC) name
	5-(2,4-diguanidino-; 3,5,6-trihydroxy-cyclohexoxy)- 4-[4,5-dihydroxy-6-(hydroxymethyl); -3-methylamino-tetrahydropyran-2-yl] oxy-3-hydroxy-2-methyl; -tetrahydrofuran-3-carbaldehyde
Clinical data
AHFS/Drugs.com	monograph
Pregnancy cat.	DM
Legal status	POM (UK) ℞-only (US)
Routes	Intramuscular, intravenous
Pharmacokinetic data
Bioavailability	84% to 88% (est.)
Half-life	5 to 6 hours
Excretion	Renal
Identifiers
CAS number	57-92-1
ATC code	A07AA04 J01GA01
PubChem	CID 19649
DrugBank	DB01082
ChemSpider	18508
UNII	Y45QSO73OB
KEGG	D08531
ChEBI	CHEBI:17076
ChEMBL	CHEMBL1201194
NIAID ChemDB	07346
Chemical data
Formula	C21H39N7O12
Mol. mass	581.574 g/mol
	SMILES C[C@H]1[C@@]([C@H]([C@@H](O1)O[C@@H]2[C@H]([C@@H]([C@H]([C@@H]([C@H]2O)O)N=C(N)N)O)N=C(N)N)O[C@H]3[C@H]([C@@H]([C@H]([C@@H](O3)CO)O)O)NC)(C=O)O;
	InChI InChI=1S/C21H39N7O12/c1-5-21(36,4-30)16(40-17-9(26-2)13(34)10(31)6(3-29)38-17)18(37-5)39-15-8(28-20(24)25)11(32)7(27-19(22)23)12(33)14(15)35/h4-18,26,29,31-36H,3H2,1-2H3,(H4,22,23,27)(H4,24,25,28)/t5-,6-,7+,8-,9-,10-,11+,12-,13-,14+,15+,16-,17-,18-,21+/m0/s1 ; Key:UCSJYZPVAKXKNQ-HZYVHMACSA-N ;
Physical data
Melt. point	12 °C (54 °F)
(what is this?) (verify);

　　[★]

英: aminoglycoside antibiotic
関: 抗菌薬、アミノグリコシド系薬、アミノグリコシド

GOO. chapter.45

タンパク質合成阻害による抗菌薬は静菌的なのもが多いが、アミノグリコシド系抗菌薬は「殺菌的」に作用

構造

amino sugars linked to an aminocyclitol ring by glycosidic bonds (GOO.1155)
名前の通りアミノ基-NH₂を多数有しているため正電荷を帯びる

→経口吸収不良

→脳脊髄液に移行しにくい。

→腎排泄されやすい

動態

内服不可能→外来患者に使いにくい
細胞膜(内膜)の通過は膜電位ポテンシャルに依存している。ここが律速段階となる。　→　細胞内移行性悪

阻害、拮抗要素：二価陽イオン、高浸透圧、pHの低下、嫌気的条件

膿瘍など嫌気的条件、酸性の高浸透圧尿など細菌の膜電位ポテンシャルが低下する場合に薬効低下

作用機序

30Sリボソームに作用してタンパク質合成を阻害

1. 翻訳開始を阻害
2. 翻訳を停止させる
3. 誤ったアミノ酸を取り込ませる

異常蛋白が細胞膜に挿入され、膜の透過性を変えてさらにアミノグリコシド系抗菌薬の取り込みを促す

薬理作用

薬効は迅速。濃度依存的。
post-antibiotic effectがある。

抗菌薬の血漿濃度がminnimum inhibitory concentration以下になっても殺菌活性が残存。殺菌活性の残存時間は濃度依存的

抗菌スペクトル

広い

副作用

腎障害：近位尿細管の壊死変性。用量依存的
耳毒性：CN VIII障害。内耳の有毛細胞を破壊。用量依存的
神経・筋遮断作用：(稀であるが)神経筋遮断作用(およびこれによる無呼吸)を呈する。遮断作用はネオマイシンが一番強く、カナマイシン、アミカシン、ゲンタマイシン、トブラマイシンがこれに続く。通常、胸腔内、腹腔に大量投与した時に生じるが、静脈内、筋肉内、あるいは経口投与でも起こりうる。大抵の発作(神経筋接合部が遮断される発作)は麻酔薬やその他の神経筋接合部遮断薬の投与で生じる(←どういう意味？)。重症筋無力症の患者はアミノグリコシド系抗菌薬による神経筋接合部遮断作用を受けやすい。(GOO.1164)