The aminoglycosides are among the oldest antibiotics, dating back to the purification of streptomycin from the bacterium Streptomyces griseus in 1944. Neomycin became available in 1949, followed by gentamicin in 1963, tobramycin in 1967, and amikacin in 1972.
The aminoglycosides are positively charged molecules that are quite large, although still only one-third the size of vancomycin. Each aminoglycoside molecule consists of two or more sugars bound by a glycosidic linkage to a central six-membered ring that contains amino group substituents. The name aminoglycoside is derived from the amino
Rather, the positively charged nature of aminoglycosides allows them to bind to the negatively charged outer membrane and results in the formation of transient holes through which the antibiotic molecules move. Access to the bacterial ribosomes, which are the targets of aminoglycosides, still requires penetration of the bacterial cytoplasmic membrane. This is accomplished by an energy-dependent active bacterial transport mechanism that requires oxygen and an active proton motive force.
For these reasons, aminoglycosides work poorly in anaerobic and acidic environments such as abscesses and have no activity against anaerobic bacteria. Each aminoglycoside acts by binding to the 30S subunit of the bacterial ribosome, which causes mismatching between the mRNA codon and the charged aminoacyl-tRNA. This in turn promotes protein mistranslation.
Streptomycin is the oldest aminoglycoside and is rarely used today. It is still a second-line agent in the treatment of tuberculosis. Also, because of differences in resistance mechanisms, streptomycin remains effective against some strains of enterococci that are resistant to the synergistic effects of gentamicin and other aminoglycosides.
Gentamicin is the most commonly used of the aminoglycosides. It is active against both aerobic gram-negative and aerobic gram-positive bacteria.
For practical purposes, tobramycin has the same spectrum of activity as gentamicin and is used similarly. In general, most gentamicin-resistant strains also lack susceptibility to tobramycin. Unlike gentamicin, however, tobramycin lacks activity against enterococci and should not be used for infections caused by this bacterium.
Strains of aerobic gram-negative bacteria that are resistant to gentamicin and tobramycin may remain susceptible to amikacin. Thus, this agent has better overall activity against these bacteria. Like tobramycin, however, amikacin lacks clinically significant activity against enterococci.