The key role of aminoglycosides in antibacterial therapy and prophylaxis

The discovery that aminosugars found in nature kill common bacteria initiated use of a new class of antibiotics that have played a key role in the management of several major medical problems over the past 40 years. The rapid bactericidal effect of the aminoglycosides on aerobic Gram-negative bacilli has expanded their use to approximately 6% of all our general hospital patients. These agents have many desirable properties, but also have the potential for producing ototoxicity and nephrotoxicity that imposes pharmacological limitations on their optimum use. The experience of earlier investigations demonstrated the need for quantitative measurements and individual patient dosing which has reduced the risk of toxicity many fold. Using sensitive measurements, toxic manifestations can be classified as detectable by laboratory means only, some that have clinical expression and rarely a lasting handicap. Semisynthetic modification of kanamycin (amikacin) and sissomicin (netilmicin) protects these compounds against inactivation by most bacterial enzymes and preserves their effectiveness. Netilmicin seems to have less potential for causing toxicity, especially ototoxicity that is irreversible, and offers the possibility of further gains through pharmacological flexibility without crippling toxicity.