Aminoglycosidic Aminocyclitol Antibiotics-A Wonder, But Toxic Drugs:Developments and Clinical Implications

摘要

Aminoglycosides are aminoglycosidic aminocyclitols that contain amino sugars linked to an aminocyclitol ringnby glycosidic bonds. Although relatively toxic compared with other classes of antibiotics, they remain primarily usefulndrugs in the treatment of infections caused by gram-negative bacteria. Since the advent of streptomycin by Waksman andnco-workers, a series of milestone compounds like kanamycin, gentamicin, and tobramycin were introduced for the treatmentnof gram-negative bacillary infections. In 1970s, the semisynthetic aminoglycosides dibekacin, amikacin, andnnetilmicin demonstrated the possibility of obtaining compounds active against resistant strains that had developed resistancenmechanisms towards earlier aminoglycosides. However, since then, the pace of development of new aminoglycosidesnhas markedly slowed down. This review not only provides the comprehensive accounts of the developments in aminoglycosidenantibiotics, but also provides insight about the mechanism of action and resistance, current efforts to developnaminoglycoside mimetics that target RNA, and potential strategies to overcome inactivation of aminoglycosides by aminoglycoside-nmodifying enzymes. Some of the interesting clinical implications like natural aminoglycoside resistancesntypical of common pathogens, prediction of responsible aminoglycoside-modifying enzyme from antibiogram data, andnthe use of liposomal-encapsulated aminoglycosides to increase the therapeutic index have also been discussed.