Aminoglycoside ototoxicity: prevention in sight?
Despite the development of new antibiotics, the aminoglycosides are still indispensable in the treatment of life-threatening diseases. Worldwide they are the most commonly used antibiotics, and their use is expected to increase in the wake of the rising incidence of tuberculosis. The most prominent side effects of aminoglycoside treatment--cochlear, vestibular, and renal impairment--are a limiting factor in the utility of these drugs. A novel mechanism of gentamicin ototoxicity is based on observations of iron chelation and free radical formation. Predictions from this mechanism have led to successful therapeutic prevention of ototoxicity by use of iron chelators and radical scavengers in guinea pigs. The drugs used for this interventive treatment affect neither serum levels of gentamicin nor its antibacterial efficacy. Because these drugs are in clinical use, the suggested protective treatment should lend itself to clinical trials.
Schacht
J
J
Kresge Hearing Research Institute, University of Michigan, Ann Arbor 48109-0506, USA.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D000995:Antitubercular Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003051:Cochlea / Q000187:drug effects*; D004195:Disease Models, Animal; D004363:Drug Utilization; D016166:Free Radical Scavengers / Q000627:therapeutic use; D005609:Free Radicals / Q000378:metabolism; D005839:Gentamicins / Q000009:adverse effects / Q000097:blood; D014943:Global Health; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects; D006801:Humans; D015994:Incidence; D007502:Iron Chelating Agents / Q000378:metabolism / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects; D014376:Tuberculosis / Q000188:drug therapy; D014722:Vestibule, Labyrinth / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D016166:Free Radical Scavengers; D005609:Free Radicals; D005839:Gentamicins; D007502:Iron Chelating Agents