WordNet

antibiotic (trade name Lincocin) obtained from a streptomyces bacterium and used in the treatment of certain penicillin-resistant infections (同)Lincocin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/03/12 15:54:51」(JST)

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Lincomycin is a lincosamide antibiotic that comes from the actinomyces Streptomyces lincolnensis. It has been structurally modified by thionyl chloride to its more commonly known 7-chloro-7-deoxy derivative, clindamycin. It is available with the brand name of Lincobect and Lincocin in Pakistan market.

Uses

Although similar in structure, antibacterial spectrum, and in mechanism of action to macrolides, they are also effective against other species as well, i.e., actinomycetes, mycoplasma, and some species of Plasmodium.

However, because of its adverse effects and toxicity, it is rarely used today and reserved for patients allergic to penicillin or where bacteria has developed resistance.

Clinical pharmacology

Intramuscular administration of a single dose of 600 mg of Lincomycin produces average peak serum levels of 11.6 micrograms/ml at 60 minutes, and maintains therapeutic levels for 17 to 20 hours, for most susceptible gram-positive organisms. Urinary excretion after this dose ranges from 1.8 to 24.8 percent (mean: 17.3 percent).

A two-hour intravenous infusion of 600 mg of Lincomycin achieves average peak serum levels of 15.9 micrograms/ml and yields therapeutic levels for 14 hours for most susceptible gram-positive organisms. Urinary excretion ranges from 4.9 to 30.3 percent (mean: 13.8 percent).

The biological half-life after IM or IV administration is 5.4 ± 1.0 hours. The serum half-life of lincomycin may be prolonged in patients with severe impairment of renal function, compared to patients with normal renal function. In patients with abnormal hepatic function, serum half-life may be twofold longer than in patients with normal hepatic function. Hemodialysis and peritoneal dialysis are not effective in removing lincomycin from the serum.

Tissue level studies indicate that bile is an important route of excretion. Significant levels have been demonstrated in the majority of body tissues. Although lincomycin appears to diffuse in the cerebrospinal fluid (CSF), levels of lincomycin in the CSF appear inadequate for the treatment of meningitis.

Biosynthesis

Lincomycin is an antibiotic classified as a constituent of the lincosamide group, which typically feature a 6,8-dideoxy-6-aminooctose lincosamine.^[1] In Lincomycin A, this sugar moiety (referred to as methylthiolincosamide) is linked via an amide bond to an amino acid derivative (referred to as propylhygric acid). Lincomycin biosynthesis occurs via a biphasic pathway producing propylproline and methylthiolincosamide followed by condensation of these subunits to N-demethyllincomycin and methyllation by S-adenosylmethionine to produce the antibiotic lincomycin.

In the biosynthesis of the amino acid moiety of lincomycin, tyrosine comprises seven of the nine carbons in the prophylhygric acid, while the remaining two carbons are added in reactions with S-adenosylmethionine.^[2]^[3]^[4]^[5] Glucose is converted via glycolysis and the hexose monophosphate pathway to phosphoenolpyruvate and erythrose-4-phosphate, respectively, which are converted via the shikimate pathway to tyrosine and dihydroxyphenylalanine. Although the multistep conversion of dihydroxyphenylalanine to propylproline remains unknown, experiments involving accumulation of 1,2,3,6-tetradehydro-propylproline in mutants lacking a reductase requiring lincomycin cosynthetic factor suggests a biosynthetic scheme that Kuo and coworkers have modified from Brahme et al.^[4]^[5] to accommodate the remaining steps leading to propylproline.^[6]^[7]

The biosynthesis of the methythiolincosamide sugar moiety is still not entirely known, although two different pathways have been predicted.^[5]^[8] One possible pathway proposes the C8 carbon framework of methythiolincosamide originates from the condensation of a pentose (C5) unit, stemming from either the hexose monophosphate or condensation through a transketolase reaction with glyceraldehyde-3-phosphate and sedoheptulose-7-phosphate, and a C3 unit, added through a transaldolase reaction with sedoheptulose-7-phosphate. Once condensed, an octose (C8) unit is formed that can undergo isomerization to octose, dephosphorylation and reduction of the C8 carbon, transamination of 6-ketooctose, and thiomethylation of C1 to finally convert the octose unit to the methylthiolincosamide. A substantially different pathway for the formation of the methythiolincosamide proposes that its biosynthesis involves nucleotide activation followed by a series of modifications of dNTP-activated sugar intermediates. Eight genes, lmb-LMNZPOSQ, have been found to form a "sugar subcluster" which might be involved in this sugar metabolism.^[9]

Condensation of both the carboxyl group on the propylproline and the amine group of the methylthiolincosamide via an amide bond is catalyzed by N-Demethyllincomycin-synthetase and leads to the production of N-demethyllincomycin. N-Demethyllincomycin is then methylated by S-adenosylmethionine through N-Demethyllincomycin methyl transferase to form the final lincomycin product.^[10]

References

^ Spízek J, Rezanka T (February 2004). "Lincomycin, cultivation of producing strains and biosynthesis". Appl. Microbiol. Biotechnol. 63 (5): 510–9. doi:10.1007/s00253-003-1431-3. PMID 14593504.
^ Argoudelis AD, Eble TE, Fox JA, Mason DJ (August 1969). "Studies on the biosynthesis of lincomycin. IV. The origin of methyl groups". Biochemistry 8 (8): 3408–11. doi:10.1021/bi00836a040. PMID 5809230.
^ Witz DF, Hessler EJ, Miller TL (March 1971). "Bioconversion of tyrosine into the propylhygric acid moity of lincomycin". Biochemistry 10 (7): 1128–33. doi:10.1021/bi00783a005. PMID 5553319.
^ ^a ^b Brahme NM, Gonzalez JE, Mizsak S, Rolls JR, Hessler EJ, Hurley LH (1984a) Biosynthesis of the lincomycins. 2. Studies using stable isotopes on the biosynthesis of methylthiolincosaminide moiety of lincomycin A. J Am Chem Soc 106:7878–7883.
^ ^a ^b ^c Brahme NM, Gonzalez JE, Rolls JR, Hessler EJ, Mizsak S, Hurley LH (1984b) Biosynthesis of the lincomycins. 1. Studies using stable isotopes on the biosynthesis of the propyl- and ethyl-Lhygric aci moieties of lincomycin A and B. J Am Chem Soc 106:7873–7878.
^ Kuo MS, Yurek DA, Coats JH, Li GP (March 1989). "Isolation and identification of 7,8-didemethyl-8-hydroxy-5-deazariboflavin, an unusual cosynthetic factor in streptomycetes, from Streptomyces lincolnensis". J. Antibiot. 42 (3): 475–8. PMID 2708143.
^ Kuo MS, Yurek DA, Coats JH, Chung ST, Li GP (November 1992). "Isolation and identification of 3-propylidene-delta 1-pyrroline-5-carboxylic acid, a biosynthetic precursor of lincomycin". J. Antibiot. 45 (11): 1773–7. PMID 1468986.
^ Peschke U, Schmidt H, Zhang HZ, Piepersberg W (June 1995). "Molecular characterization of the lincomycin-production gene cluster of Streptomyces lincolnensis 78-11". Mol. Microbiol. 16 (6): 1137–56. doi:10.1111/j.1365-2958.1995.tb02338.x. PMID 8577249.
^ Pissowotzki K, Mansouri K, Piepersberg W (December 1991). "Genetics of streptomycin production in Streptomyces griseus: molecular structure and putative function of genes strELMB2N". Mol. Gen. Genet. 231 (1): 113–23. doi:10.1007/BF00293829. PMID 1661369.
^ Patt TE, Horvath BA (1985) Isolation and characterization of Ndemethyllincomycin methyltransferase. In: Abstracts, 13th International Congress of Biochemistry, Amsterdam, The Netherlands, August 25–30 1985

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. クリンダマイシン：概要 clindamycin an overview
2. Q熱の治療および予防 treatment and prevention of q fever
3. 門脈炎 pylephlebitis
4. 一般的ではないカンピロバクター種および関連細菌の感染 infection with less common campylobacter species and related bacteria
5. 嫌気菌：ヒトの正常細菌叢における歴史および役割 anaerobic bacteria history and role in normal human flora

English Journal

Characterization of Treponema spp. isolates from pigs with ear necrosis and shoulder ulcers.

Svartström O, Karlsson F, Fellström C, Pringle M.SourceDepartment of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, SE-75007 Uppsala, Sweden. Electronic address: olov.svartstrom@slu.se.
Veterinary microbiology.Vet Microbiol.2013 Oct 25;166(3-4):617-23. doi: 10.1016/j.vetmic.2013.07.005. Epub 2013 Jul 17.
Ear necrosis and shoulder ulcers in pigs are animal welfare problems and ethical issues that can cause economic losses for producers. Spirochetes have been observed microscopically in scrapings from pig ulcers since the early 1900s, but have until recently not been cultured and therefore not charact
PMID 23948134

In Vitro Susceptibility of Mycoplasma hyopneumoniae Field Isolates and Occurrence of Fluoroquinolone, Macrolides and Lincomycin Resistance.

Thongkamkoon P, Narongsak W, Kobayashi H, Pathanasophon P, Kishima M, Yamamoto K.SourceNational Institute of Animal Health, Bangkok 10900, Thailand.
The Journal of veterinary medical science / the Japanese Society of Veterinary Science.J Vet Med Sci.2013 Sep 3;75(8):1067-70. Epub 2013 Mar 15.
A total of 159 Thai isolates of Mycoplasma hyopneumoniae isolated from pneumonic lungs of pigs during 2006-2011 were investigated for their in vitro susceptibility to 12 antimicrobial agents. Low activity of chlortetracycline was indicated by the MIC range from 3.12-100 μg/ml and MIC90 of 50 μg/ml
PMID 23503167

Isolation and analysis of tetracycline-resistant Mycoplasma agalactiae strains from an infected goat herd in Cyprus - short communication.

Filioussis G, Ioannou I, Petridou E, Avraam M, Giadinis ND, Kritas SK.SourceAristotle University of Thessaloniki Department of Microbiology and Infectious Diseases, Faculty of Veterinary Medicine Thessaloniki 54124 Greece.
Acta veterinaria Hungarica.Acta Vet Hung.2013 Sep;61(3):291-6. doi: 10.1556/AVet.2013.018.
A major concern with the use of tetracycline against mycoplasmas is the development of resistance. Infections in small ruminants due to tetracyclineresistant Mycoplasma agalactiae strains are becoming a frequent problem worldwide. In the present paper the detection and analysis of three tetracycline
PMID 23921341

Japanese Journal

2008～2011年にタイで分離されたMycoplasma hyosynoviaeの抗菌剤感受性

THONGKAMKOON Pacharee,NARONGSAK Watcharachai,小林秀樹 [他]
家畜衛生学雑誌 = The Japanese journal of animal hygiene 40(1), 1-6, 2014-04
NAID 40020063649

Synthesis of novel lincomycin derivatives and their in vitro antibacterial activities

UMEMURA Eijiro,WAKIYAMA Yoshinari,KUMURA Ko,UEDA Kazutaka,MASAKI Satomi,WATANABE Takashi,YAMAMOTO Mikio,HIRAI Yoko,FUSHIMI Hideki,YOSHIDA Takuji,AJITO Keiichi
Journal of antibiotics 66(3), 195-198, 2013-03-25
NAID 10031163121

Effects of flow field on the metabolic characteristics of Streptomyces lincolnensis in the industrial fermentation of lincomycin

LI Xiao,ZHANG Jiang,TAN Ya-Li,LI Zhi-Hong,YU Xue-Feng,XIA Jian-Ye,CHU Ju,GE You-Qun
Journal of bioscience and bioengineering 115(1), 27-31, 2013-01-25
NAID 10031172773

Related Pictures

★リンクテーブル★

リンク元	「抗菌薬」「リンコマイシン」「LCM」
拡張検索	「lincomycin hydrochloride」

「抗菌薬」

Lincomycin
Systematic (IUPAC) name
	(2S,4R)-N-[(1R,2R)-2-hydroxy-1-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(methylsulfanyl)oxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a609005
Pregnancy cat.	C (US)
Legal status	℞-only (US)
Routes	IM/IV
Pharmacokinetic data
Bioavailability	100% (IM or IV)
Half-life	5.4 ± 1.0 hours after IM or IV administration
Excretion	renal and biliary
Identifiers
CAS number	154-21-2
ATC code	J01FF02
PubChem	CID 3000540
DrugBank	DB01627
ChemSpider	2272112
UNII	BOD072YW0F
KEGG	D00223
ChEMBL	CHEMBL1447
Chemical data
Formula	C18H34N2O6S
Mol. mass	406.538 g/mol
SMILES	eMolecules & PubChem
	InChI InChI=1S/C18H34N2O6S/c1-5-6-10-7-11(20(3)8-10)17(25)19-12(9(2)21)16-14(23)13(22)15(24)18(26-16)27-4/h9-16,18,21-24H,5-8H2,1-4H3,(H,19,25)/t9-,10-,11+,12-,13+,14-,15-,16-,18-/m1/s1 ; Key:OJMMVQQUTAEWLP-KIDUDLJLSA-N ;
(what is this?) (verify);

　　[★]

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

「リンコマイシン」

　　[★]

英: lincomycin, LCM
ラ: lincomycinum
化: 塩酸リンコマイシン lincomycin hydrochloride
商: リンコメイス、リズピオン、ペランコシン、リンコシン、ルニアマイシン
関: リンコマイシン系抗菌薬、抗菌薬

概念

マクロライド系抗菌薬と類似の抗菌スペクトルを有する。

グラム陽性菌、グラム陰性球菌、嫌気性菌

機序：蛋白質の合成阻害。50Sリボソームサブユニットの機能を阻害。50SリボソームサブユニットのA部位、P部位に結合してペプチド結合の形成を阻害する(クロラムフェニコールに類似)。静菌的に作用。

「LCM」

　　[★]

「lincomycin hydrochloride」

　　[★] 塩酸リンコマイシン、リンコマイシン lincomycin

[pmid14593504-0] Spízek J, Rezanka T (February 2004). "Lincomycin, cultivation of producing strains and biosynthesis". Appl. Microbiol. Biotechnol. 63 (5): 510–9. doi:10.1007/s00253-003-1431-3. PMID 14593504.

[pmid5809230-1] Argoudelis AD, Eble TE, Fox JA, Mason DJ (August 1969). "Studies on the biosynthesis of lincomycin. IV. The origin of methyl groups". Biochemistry 8 (8): 3408–11. doi:10.1021/bi00836a040. PMID 5809230.

[pmid5553319-2] Witz DF, Hessler EJ, Miller TL (March 1971). "Bioconversion of tyrosine into the propylhygric acid moity of lincomycin". Biochemistry 10 (7): 1128–33. doi:10.1021/bi00783a005. PMID 5553319.

[Brahme-3] Brahme NM, Gonzalez JE, Mizsak S, Rolls JR, Hessler EJ, Hurley LH (1984a) Biosynthesis of the lincomycins. 2. Studies using stable isotopes on the biosynthesis of methylthiolincosaminide moiety of lincomycin A. J Am Chem Soc 106:7878–7883.

[Brahme_a-4] Brahme NM, Gonzalez JE, Rolls JR, Hessler EJ, Mizsak S, Hurley LH (1984b) Biosynthesis of the lincomycins. 1. Studies using stable isotopes on the biosynthesis of the propyl- and ethyl-Lhygric aci moieties of lincomycin A and B. J Am Chem Soc 106:7873–7878.

[pmid2708143-5] Kuo MS, Yurek DA, Coats JH, Li GP (March 1989). "Isolation and identification of 7,8-didemethyl-8-hydroxy-5-deazariboflavin, an unusual cosynthetic factor in streptomycetes, from Streptomyces lincolnensis". J. Antibiot. 42 (3): 475–8. PMID 2708143.

[pmid1468986-6] Kuo MS, Yurek DA, Coats JH, Chung ST, Li GP (November 1992). "Isolation and identification of 3-propylidene-delta 1-pyrroline-5-carboxylic acid, a biosynthetic precursor of lincomycin". J. Antibiot. 45 (11): 1773–7. PMID 1468986.

[pmid8577249-7] Peschke U, Schmidt H, Zhang HZ, Piepersberg W (June 1995). "Molecular characterization of the lincomycin-production gene cluster of Streptomyces lincolnensis 78-11". Mol. Microbiol. 16 (6): 1137–56. doi:10.1111/j.1365-2958.1995.tb02338.x. PMID 8577249.

[pmid1661369-8] Pissowotzki K, Mansouri K, Piepersberg W (December 1991). "Genetics of streptomycin production in Streptomyces griseus: molecular structure and putative function of genes strELMB2N". Mol. Gen. Genet. 231 (1): 113–23. doi:10.1007/BF00293829. PMID 1661369.

[9] Patt TE, Horvath BA (1985) Isolation and characterization of Ndemethyllincomycin methyltransferase. In: Abstracts, 13th International Congress of Biochemistry, Amsterdam, The Netherlands, August 25–30 1985

匿名

検索

案内

案内

lincomycin