Therapeutic initiatives for the avoidance of aminoglycoside toxicity.

Aminoglycosides continue to be indispensable in the management of serious and life-threatening aerobic gram-negative infections. On an annual basis in the United States, they are used in the management of four million patients. Despite their clinical utility, they continue to manifest a high profile of toxic side effects such as nephrotoxicity and ototoxicity with the rare occurrence of neuromuscular toxicity. Animal experimental models have been invaluable in elucidating the pathophysiologic mechanisms by which aminoglycosides damage the kidney and the inner ear. However, it is from clinical therapeutic experience and prospective clinical trials that we have been able to solidly define the risk factors that accentuate the development of aminoglycoside-related toxicity. The clinical toxicity of these agents can be kept to a minimum by ensuring the use of an appropriate dose, for periods of time not exceeding nine to ten days, in a well-hydrated, normokalemic patient. Special subpopulation groups such as the elderly, the obese, those with preexisting renal disease, or patients who need the concurrent use of other nephrotoxins, require special care in the monitoring of their aminoglycoside therapy to ensure a safe and effective clinical outcome.