Aminoglycoside Antibiotics

TLDR

Aminoglycoside antibiotics, discovered 50 years ago, remain the most widely used antibiotics worldwide due to their high efficacy and low cost, despite a decline in use during the 1970s and 1980s caused by renal and auditory toxicity. This review summarizes the drugs’ chemistry, antibacterial actions, acute side effects, ototoxicity pathophysiology, pharmacokinetics, cellular mechanisms, and recent therapeutic advances to prevent hearing loss.

Abstract

In the 50 years since their discovery, the aminoglycoside antibiotics have seen unprecedented use. Discarded in the 1940s, they were the long-sought remedy for tuberculosis and other serious bacterial infections. The side effects of renal and auditory toxicity, however, led to a decline of their use in most countries in the 1970s and 1980s. Nevertheless, today the aminoglycosides are still the most commonly used antibiotics worldwide thanks to the combination of their high efficacy with low cost. This review first summarizes the history, chemistry, antibacterial actions and acute side effects of the drugs. It then details the pathophysiology of aminoglycoside ototoxicity including experimental and clinical observations, risk factors and incidence. Pharmacokinetics, cellular actions and our current understanding of the underlying molecular mechanisms of ototoxicity are discussed at length. The review concludes with recent advances towards therapeutic intervention to prevent aminoglycoside ototoxicity.