tobramycin (9.79), and netilmycin (9.80). Amikacin (9.81), a semi-synthetic analog of
kanamycin, has also been used clinically. The great usefulness of aminoglycosides
arises from their ability to treat infections caused by Gram-negative bacilli. In this
regard, they complement the β-lactam antibacterials and may be used in combination in
the empirical treatment of life-threatening infections. Bacterial strains develop resistance
to aminoglycosides.
The aminoglycosides decrease the fidelity of translation by binding to the 30S sub-
unit of the ribosome. This permits the formation of the peptide initiation complex but
prohibits any subsequent addition of amino acids to the peptide. This effect is due to the
inhibition of polymerization as well as to the failure of tRNA and mRNA codon recog-
nition. Aminoglycosides are ototoxic (i.e., may produce partial deafness), damaging the
auditory nerve. Kanamycin is less toxic. Since aminoglycosides are concentrated in the
kidney, they may occasionally cause kidney damage.
Among the aminoglycoside antibiotics, streptomycin and kanamycin are very important.
Streptomycin contains a diguanidine derivative of 1,3-diaminoinositol (streptidine),
a specific hexofuranose (streptose) carrying a 3-aldehyde group, and N-methyl-2-
glucosamine. Kanamycin is somewhat simpler, being derived from a 1,3-diamino-
2-deoxyinositol, a 3-glucosamine, and a 6-glucosamine. Both antibiotics have a fairly
wide antibiotic spectrum, but practically they enjoy unique use as agents for the treatment
of tuberculosis. Tuberculosis was a widely fatal form of chronic pneumonia, sometimes
called the white plague, that exacted a devastating toll on humanity more than a century
ago. Despite misconceptions to the contrary, tuberculosis (“TB”) is still not uncommon
as a clinical problem.
9.4.3.3 Antibacterials Targeting the Ribosomal 50S Subunit: Chloramphenicol
Chloramphenicol (9.82) is a product of a Streptomyces species. Its structure is remarkably
simple, and it is obtained synthetically rather than by fermentation. It is a broad-spectrum
EXOGENOUS PATHOGENS AND TOXINS 575