The aminoglycosides (Following Table ) are a group of powerful antibiotics used to treat serious infections caused by gramnegative aerobic bacilli. Because most of these drugs have potentially serious adverse effects, newer, less toxic drugs have replaced aminoglycosides in the treatment of less serious infections. Aminoglycosides include amikacin (Amikin), gentamicin (Garamycin), kanamycin (Kantrex), neomycin (Mycifradin), streptomycin (generic), and tobramycin (TOBI, Tobrex).
Therapeutic Actions and Indications
The aminoglycosides are bactericidal. They inhibit protein synthesis in susceptible strains of gram-negative bacteria. They irreversibly bind to a unit of the bacteria ribosomes, leading to misreading of the genetic code and cell death (Figure 9.1). These drugs are used to treat serious infections caused by susceptible strains of gram-negative bacteria, including Pseudomonas aeruginosa, E. coli, Proteus species, the Klebsiella–Enterobacter–Serratia group, Citrobacter species, and Staphylococcus species such as S. aureus. Aminoglycosides are indicated for the treatment of serious infections that are susceptible to penicillin when penicillin is contraindicated, and they can be used in severe infections before culture and sensitivity tests have been completed. See Table 9.1 for usual indications for each of these drugs.
The many serious adverse effects associated with aminoglycosides limit their usefulness. The drugs come with a black box warning alerting health care professionals to the serious risk of ototoxicity and nephrotoxicity. Central nervous system (CNS) effects include ototoxicity, possibly leading to irreversible deafness; vestibular paralysis resulting from drug effects on the auditory nerve; confusion; depression; disorientation; and numbness, tingling, and weakness related to drug effects on other nerves. Renal toxicity, which may progress to renal failure, is caused by direct drug toxicity in the glomerulus, meaning that the drug molecules cause damage (e.g., obstruction) directly to the kidney. Bone marrow depression may result from direct drug effects on the rapidly dividing cells in the bone marrow, leading, for example, to immune suppression and resultant superinfections.
GI effects include nausea, vomiting, diarrhea, weight loss, stomatitis, and hepatic toxicity. These effects are a result of direct GI irritation, loss of bacteria of the normal flora with resultant superinfections, and toxic effects in the mucous membranes and liver as the drug is metabolized. Cardiac effects can include palpitations, hypotension, and hypertension. Hypersensitivity reactions include purpura, rash, urticaria, and exfoliative dermatitis.