3-12. THE AMINOGLYCOSIDES
a. These agents are a result of a systematic search to find an antibiotic that was
effective against gram negative bacteria. During this research, a strain of
actinomycetes, Streptomyces griseus, was isolated. It produced a potent antimicrobial
leading to the discovery of streptomycin. These agents are bactericidal in nature; their
MOA is to inhibit protein synthesis.
b. The body normally cannot absorb these agents when administered orally.
They must be administered by either IM or IV routes. They are widely distributed in
body fluids, except the CSF and the eye. They are found mainly in extracellular fluid.
c. The aminoglycosides are excreted unchanged by glomerular filtration.
Elimination is dependent almost exclusively on renal function. The incidence of
nephrotoxicity and ototoxicity is directly related to the concentration to which
aminoglycosides accumulates in the serum.
d. The initial dose for these agents depends, of course, on the agent used. After
the initial dose has been administered, it is best to use serum peak and trough levels to
estimate subsequent doses. Consistent peak serum levels seem to make the patient
more prone to ototoxicity. Elevated trough levels lead to nephrotoxicity.
e. Streptomycin is occasionally used in combination with isoniazid in the
treatment of tuberculosis. Neomycin and kanamycin are seldom used parenterally.
When used in their oral form, they suppress the flora of the GI tract prior to surgery.
Occasionally, kanamycin is used parenterally by pediatricians for gram negative
bacteria; it is not effective against Pseudomonas. Gentamicin, tobramycin, and
amikacin, in combination with carbenicillin, are used primarily in serious gram-negative
infections, especially Pseudomonas aeruginosa. Amikacin is the most effective
aminoglycoside against gentamicin resistant strains and is generally reserved for these
f. Ototoxicity, which is some cases may be irreversible, occurs more frequently
with the use of streptomycin, neomycin, and kanamycin. This reaction causes cochlear
and vestibular damage leading to hearing loss, vertigo, ataxia, and loss of balance.
g. The incidence of nephrotoxicity, which is irreversible, occurs about 2-10
percent of the time and is more prevalent with the use of neomycin than any of the other
agents. The factors that contribute to the incidence are: dose of the agent used, pre-
existing renal damage, and contracted intravascular volume caused by the use of
h. Prolonged high doses of any of the aminoglycosides may exert a curare-like
effect on various body systems.