ストレプトマイシン 化学特性,用途語,生産方法
解説
Streptomyces griseusが産生するアミノ配糖体抗生物質．ペニシリンについで臨床応用された第2番目の抗生物質．硫酸塩は白色から淡黄白色の粉末．硫酸塩は分解点約230 ℃．[α]20D－79.5°(水)．28 ℃ で水に20 mg mL－1 以上，メタノールに0.85 mg mL－1 溶ける．
生物学のな役割
ペニシリンが効かないグラム陰性菌と結核菌に強い阻止活性をもつため，よく使用された．現在の結核治療は多剤を使用するが，ストレプトマイシンは第一選択薬の一つとして筋肉注射で使われる．細菌のリボソームの30Sおよび50Sの両サブユニットに結合して，タンパク質合成を阻害する．
効能
抗生物質, 抗結核薬, タンパク質合成阻害薬
毒性
LD50 600～1250 mg/kg(マウス，皮下注)
説明
The antibiotic streptomycin is an important and effective
chemical for the management of bacterial diseases of
fruit trees (especially apple), woody ornamentals, and
vegetables. Streptomycin was initially discovered in 1944
and was one of the first antibiotics to be utilized in
clinical medicine to control human diseases, and is still
important as a feed amendment for growth promotion
in agricultural animals. The widespread and diverse
usage of streptomycin has contributed to the currently
observed global streptomycin resistance (SmR) problem.
This problem is especially critical in plant disease
management, as there are few alternatives to streptomycin
available and, as a consequence of increased usage, SmR
has been increasingly observed among bacterial plant
pathogens.
化学的特性
Crystalline Powder
来歴
Streptomycin is discovered in 1944 of streptomycin drew immediate interest because it was the least toxic of the broad-spectrum antibiotics known at that time. Indeed, streptomycin was used to treat many gram-negative microbial infections, but because of the ease with which organisms developed resistance to it during treatment, many of these applications were abandoned when the tetracyclines, discussed later, became available. Streptomycin was the first parenterally administered antibiotic active against many microorganisms, but during the last several years, its use has been limited essentially to three situations: (1) the initial treatment of serious tuberculous infections, when the principal drugs of choice (isoniazid, rifampin) cannot be used because of their adverse effects on a particular patient; (2) treatment of enterococcal and other infections, in which synergism between a penicillin and an aminoglycoside is desired; and (3) treatment of certain uncommon infections (plague and tularemia).
使用
Control of bacterial shot-hole, bacterial rots, bacterial
canker, bacterial wilts, fire blight, and other diseases
caused by gram-positive species of bacteria in pome
fruit, stone fruit, citrus fruit, olives, vegetables, potatoes,
tobacco, cotton, and ornamentals. Chlorosis may occur on
grapes, pears, peaches, and some ornamentals. Formulation
types WP; Liquid. Incompatible with pyrethrins
and alkaline materials. A mixture of streptomycin and
oxytetracycline is highly effective for the control of bacterial
canker of peach, citrus canker, soft rot of vegetables,
and various other bacterial diseases. Selected tradenames
“Agrimycin 17” (sesquisulfate); “AS-50” (sesquisulfate).
定義
ChEBI: A amino cyclitol glycoside that consists of streptidine having a disaccharyl moiety attached at the 4-position. The parent of the streptomycin class
適応症
Streptomycin, an aminoglycoside antibiotic was the first drug shown to reduce tuberculosis
mortality. Streptomycin is bactericidal against M. tuberculosis
in vitro but is inactive against intracellular
organisms. Most M. tuberculosis strains and nontuberculosis
species, such as M. kansasii and M. aviumintracellulare,
are sensitive. Spontaneous resistance to
streptomycin, seen in approximately 1 in 106 tubercle
bacilli, is related to a point mutation that involves the
gene (rpsl or rrs) that encodes for ribosomal proteins
and binding sites.About 80% of strains that are resistant
to isoniazid and rifampin are also resistant to streptomycin.
世界保健機関（WHO）
Oral preparations of streptomycin, an aminoglycoside antibiotic
isolated from streptomyces griseus in 1944, were formerly widely used to treat
intestinal infections. There is no evidence that streptomycin is effective in this
indication and its widespread use promotes the emergence of resistant strains of
bacteria. The World Health Organization recommends that streptomycin should not
be used for the treatment of diarrhoea.
(Reference: (WHORUD) The Rational Use of Drugs, , , 1990)
抗菌性
It is less active than gentamicin group compounds
against most micro-organisms within the spectrum,but it is particularly active against mycobacteria, including
M. kansasii and most strains of M. ulcerans. Brucella (MIC
0.5 mg/L), Francisella, Pasteurella spp. and Yersinia pestis are
susceptible.
It is actively bactericidal, the speed of killing increasing
progressively with concentration. The antibacterial activity
is greatest in a slightly alkaline medium (pH 7.8) and is
considerably reduced below pH 6.0. It is so sensitive to the
effect of pH that the natural acidity of a solution of streptomycin
sulfate may be sufficient to depress its antibacterial
activity.
危険性
Damage to nerves and kidneys may result
from ingestion. Use restricted by FDA.
作用機序
The mechanism of action of STM and the aminoglycosides in general has not been fully elucidated. It is known that the STM inhibits protein synthesis, but additional effects on misreading of an mRNA template and membrane damage may contribute to the bactericidal action of ST M. Streptomycin is able to diffuse across the outer membrane of Mycobacterium tuberculosis and, ultimately, to penetrate the cytoplasmic membrane through an electrondependent process. Through studies regarding the mechanism of drug resistance, it has been proposed that STM induces a misreading of the genetic code and, thus, inhibits translational initiation. In ST M-resistant organisms, two changes have been discovered: First, S12 protein undergoes a change in which the lysine present at amino acids 43 and 88 in ribosomal protein S12 is replaced with arginine or threonine, and second, the pseudoknot conformation of 16S rRNA, which results from intramolecular base pairing between GCC bases in regions 524 to 526 of the rRNA to CGG bases in regions 505 to 507, is perturbed. It is thought that S12 protein stabilizes the pseudoknot, which is essential for 16S rRNA function. By some yet-to-be-defined mechanism, STM interferes with one or both of the normal actions of the 16S protein and 16S rRNA.
薬理学
Ototoxicity and nephrotoxicity are the major concerns
during administration of streptomycin and other
aminoglycosides. The toxic effects are dose related and
increase with age and underlying renal insufficiency.All
aminoglycosides require dose adjustment in renal failure
patients. Ototoxicity is severe when aminoglycosides
are combined with other potentially ototoxic
agents.
臨床応用
Tuberculosis (in combination with other antituberculosis drugs)
Infections caused by M. kansasii (in combination with other
antimycobacterial agents)
Plague and tularemia, including tularemia pneumonia
Bacterial endocarditis (in combination with a penicillin)
Brucellosis
Whipple’s disease (in combination with other antibiotics)
The most important use of streptomycin is in the treatment of
tuberculosis . Depression of vestibular function by
streptomycin has been used in the treatment of patients suffering
from Ménière’s disease.
安全性プロファイル
Poison by intravenous and subcutaneous routes. Moderately toxic by ingestion and intraperitoneal routes. An experimental teratogen. Human systemic effects by ingestion and intraperitoneal routes: change in vestibular functions, blood pressure decrease, eosinophilia, respiratory depression, and pulmonary changes. Human reproductive and teratogenic effects by unspecified routes: developmental abnormalities of the eye and ear and effects on newborn including postnatal measures or effects. Toxic to hdneys and central nervous system. Has been implicated in aplastic anemia. Experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits toxic fumes of NOX.
代謝
Streptomycin inhibits protein synthesis in bacterial cells
by binding to the 30S ribosomal subunit and causes misreading
of the genetic codes in protein synthesis (29).
Streptomycin-resistant strains are distributed in a wide
range of plant pathogenic bacteria, such as Xanthomonas
oryzae, X. citri, Pseudomonas tabaci, and P. lachrymans.
In agricultural use, the alternative or combined applications
of streptomycin and other chemicals with different
action mechanisms is recommended in order to reduce the
development of streptomycin-resistant strains in the field.
Mutants of E. coli highly resistant to streptomycin are
known to involve modification of the P10 protein of the
bacterial ribosome 30S subunit.
ストレプトマイシン 上流と下流の製品情報
原材料
準備製品