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Mechanisms of Resistance to Aminoglycoside Antibiotics

1982; Springer Science+Business Media; Linguagem: Inglês

10.1007/978-3-642-68579-8_6

1865-0325

Hitoshi Umezawa, Shinichi Kondo,

Microbial Natural Products and Biosynthesis

During the early 1950s when strongly resistant organisms had not yet appeared, the chemotherapy of most bacterial infections was assumed to be possible. However, tubercle bacilli soon became resistant to streptomycin and new active agents were required for the treatment of tuberculosis. At that time, Umezawa discovered the aminoglycoside antibiotic, kanamycin, in the search for new water-soluble basic antibiotics (H. Umezawa et al. 1957). Kanamycin was evaluated as an effective agent for the treatment of infections with resistant staphylococci and streptomycin-resistant tuberculosis, and later for the treatment of infections with resistant gram-negative bacteria. However, after widespread use of the antibiotic, in 1965 kanamycin-resistant strains appeared in patients, although at a frequency of less than 5%. Therefore, Umezawa undertook studies on the biochemical mechanisms of resistance to aminoglycoside antibiotics (H. Umezawa et al. 1967 a, b). The results of these studies suggested structures which would be active against resistant strains and many derivatives of aminoglycoside antibiotics were synthesized. Among these, 3',4'-dideoxykanamycin B (dibekacin) (H. Umezawa et al. 1971) was useful in the treatment of infections with resistant gram-positive and -negative bacteria, including pseudomonas, and was marketed in 1975.