Abstract number: S539
The first clinically useful aminoglycoside, streptomycin, was isolated from a strain of Streptomyces griseus by Waksman and colleagues in 1943. This drug had remarkable activity against many species of Gram-positive and Gram-negative bacteria as well as the tubercle bacillus. However, when used as a single agent for treating tuberculosis, there was rapid emergence of resistance. That was subsequently overcome by using the drug in combination with other antituberculous agents. Over the next quarter century, a number of other aminoglycosidic aminocyclitol antibiotics were discovered, including neomycin (1949), kanamycin (1957), gentamicin (1963), and tobramycin (1967). During this time, extensive studies of the mechanism of action of the aminoglycosides carried out, and based on detailed information concerning mechanisms of enzymatic resistance, it became possible to provide a number of chemical modifications of the basic aminoglycoside structure to overcome resistance. Thus drugs such as amikacin (1972), dibekacin, and others were developed specifically to overcome mechanisms of enzymatic inactivation. Work in this arena has continued to the present, with several aminoglycosides, including SPX-1212 and ACHN-490, in preclinical or early clinical development for the treatment of infections due to organisms resistant to standard aminoglycosides. The issue of nephro- and ototoxicity has plagued all of the aminoglycosides, and although the currently available agents vary in their toxicity, it has been impossible thus far to design a compound in this class of antimicrobial agents completely devoid of oto- and/or nephrotoxicity.
|Session name:||Abstracts of 21st ECCMID / 27th ICC|
|Location:||Milan, Italy, 7 - 10 May 2011|
|Back to top|