The antibacterial actions of
the aminoglycosides in-volve two possibly synergistic effects. First, the
posi-tively charged aminoglycoside binds to negatively charged sites on the
outer bacterial membrane, thereby disrupting membrane integrity. It is likely
that the aminoglycoside-induced bacterial outer membrane degradation accounts
for the rapid concentration-dependent bactericidal effect of these compounds.
Second, aminoglycosides bind to various sites on bacte-rial 30S ribosomal
subunits, disrupting the initiation of protein synthesis and inducing errors in
the translation of messenger RNA to peptides. They also bind to sites on
bacterial 50S ribosomal subunits, although the sig-nificance of this binding is
uncertain. In addition, they have a postantibiotic effect; that is, they
continue to sup-press bacterial regrowth even after removal of the an-tibiotic
from the bacterial microenvironment. It is likely that ribosome disruption
accounts for this postantibi-otic activity.
The postantibiotic effect is
characterized by pro-longed suppression of bacterial regrowth after the
ini-tially high aminoglycoside concentration has fallen to a subinhibitory
level. Perhaps resumption of bacterial ri-bosomal function requires the
time-consuming synthe-sis of new ribosomes after their disruption by aminogly-cosides.
The postantibiotic effect explains why aminoglycosides can be given in single
daily doses de-spite their short half-life.
aminoglycosides through the outer bacterial membrane occurs both by outer
membrane disruption and by diffusion through outer membrane porins. Penetration
through the inner bacterial mem-brane occurs in two phases. The first requires
that the cytosol have a negative electron potential and therefore be inhibited
by the presence of a low pH. The second phase depends on aerobic bacterial
metabolism and therefore will be inhibited by low oxygen tension. The latter
two observations are of considerable clinical rele-vance, since both a low pH
and a low oxygen tension frequently occur in bacterial abscesses. Administration
of β-lactam antibiotics will reverse the negative effects of both low pH and
low oxygen tension on the ability of aminoglycosides to penetrate into
bacteria; this ability accounts in part for the synergism that occurs between
aminoglycoside and β-lactam antibiotic drugs.