トブラマイシン

外観

白色～黄赤色～緑色粉末～結晶

解説

C18H37N5O9(467.51)．Streptomyces tenebrariusが産生するアミノ配糖体抗生物質．融点218～225 ℃．[α]²⁰_D＋129°(水)．3′-デオキシカナマイシンBに相当する．塩基性の水溶性物質で，メタノールに難溶．グラム陽性菌および緑膿菌を含むグラム陰性菌に殺菌的に作用する．トブラマイシンは，カナマイシン耐性の原因であるリン酸化されるヒドロキシ基がないために，カナマイシン耐性菌にも有効である．抗菌活性は強いが，腎および聴器毒性も強い．硫酸塩として pH を調整した水溶液が注射や点眼に用いられる．LD50 441 mg/kg(マウス，皮下)．[CAS 32986-56-4][CAS 79645-27-5:硫酸塩] 森北出版「化学辞典（第2版）

効能

抗生物質, タンパク質合成阻害薬

商品名

トブラシン (日東メディック); トブラシン (東和薬品); トービイ (ノバルティスファーマ)

説明

Tobramycin is one component (factor 6) of a mixture produced by fermentation of Streptomyces tenebrari us. Lacking the C-3′ hydroxyl group, it is not a substrate for APH(3′)-1 and APH(3′)-II and so has an intrinsically broader spectrum than kanamycin. It is a substrate, however, for adenylation at C-2′ by ANT (2′) and acetylation at C-3 by AAC(3)-I and AAC(3)-II and at C-2′ by AAC(2′).

化学的特性

White or almost white powder.

使用

Tobramycin is an aminoglycoside antibiotic.

定義

ChEBI: A amino cyclitol glycoside that is kanamycin B lacking the 3-hydroxy substituent from the 2,6-diaminoglucose ring.

適応症

Tobramycin is highly active with respect to Gram-negative microorganisms (blue-pus bacillus and gastric bacilli, rabbit fever, serratia, providencia, enterobacteria, proteus, salmonella, shigella), as well as Gram-positive microorganisms (staphylococci, including those resistant to penicillin and some cephalosporins), and a few strains of streptococci.
It is used for severe bacterial infections: peritonitis, sepsis, meningitis, osteomyelitis, endocarditis, pneumonia, pleural empyema, pulmonary abscess, purulent skin infections and soft tissue infections, and infections of the urinary tract caused by microorganisms that are sensitive to the drug. Synonyms of this drug are nebicine, obracine, and others.

抗菌性

In-vitro activity against Ps. aeruginosa is usually somewhat greater than that of gentamicin; against other organisms activity is similar or a little lower. Other Pseudomonas species are generally resistant, as are streptococci and most anaerobic bacteria. Other organisms usually susceptible in vitro include Acinetobacter, Legionella and Yersinia spp. Alkaligenes, Flavobacterium spp. and Mycobacterium spp. are resistant. It exhibits bactericidal activity at concentrations close to the MIC and bactericidal synergy typical of aminoglycosides in combination with penicillins or cephalosporins.

獲得抵抗性

It is inactivated by many aminoglycoside-modifying enzymes that inactivate gentamicin. However, AAC(3′)-I does not confer tobramycin resistance and AAC(3′)-II confers a lower degree of tobramycin resistance than of gentamicin resistance. Conversely, ANT(4′) confers tobramycin but not gentamicin resistance, as do some types of AAC(6′). Overproduction of APH(3′), conferring a low degree of resistance to tobramycin (MIC 8 mg/L), but not gentamicin (MIC 2 mg/L), was ascribed to ‘trapping’ rather than phosphorylation.
Resistance rates are generally similar to those of gentamicin, although they may vary locally because of the prevalence of particular enzyme types.

生物活性

Pharmacologically, tobramycin is quite similar to gentamicin. The drug is somewhat more active against Ps. aeruginosa than gentamicin. Tobramycin also acts synergistically with penicillin, but to a lesser degree than gentamicin.

臨床応用

Severe infections caused by susceptible micro-organisms Ps. aeruginosa infections, including chronic pulmonary infections in cystic fibrosis (administration by injection or nebulizer)
For practical purposes use is identical to that of gentamicin, except possibly for Pseudomonas infection, where it has somewhat greater activity against gentamicin-susceptible and some gentamicin-resistant strains. Its value as a substitute for gentamicin in the speculative treatment of severe undiagnosed infection is offset by its lower activity against other organisms that may be implicated.
It has been used extensively to treat Ps. aeruginosa infections in patients with cystic fibrosis.