Aminoglycosides are still widely used alone or in combination with a b
eta-lactam antibiotic for the treatment of severe Gram negative infect
ion, Oto- and nephrotoxicity are the major side effects associated wit
h the use of these drugs. Although several risk factors associated wit
h aminoglycoside nephrotoxicity have been identified, only few therape
utic approaches were suggested to reduce the incidence of their toxici
ty in patients. The single daily injection is the only approach actual
ly used to reduce the renal toxicity of aminoglycosides in patients. H
owever, the relationship between the nephrotoxicity of aminoglycosides
and the time of the day these drugs should be given has never been ex
plored in patients. Data obtained in laboratory animals indicated that
temporal variations can be detected in the renal toxicity of aminogly
cosides: the nephrotoxicity was observed during the rest period of the
animals while no toxicity was found at other times of the day. Other
studies suggested also that food intake can modulate the temporal vari
ations in the nephrotoxicity of aminoglycosides. A better knowledge of
the risk factors associated with the renal toxicity of aminoglycoside
s, a reduction in the number of daily injections of aminoglycosides, a
dministration of aminoglycosides at the time of the lowest toxicity of
the drug in patients submitted to an appropriate diet are the most in
teresting approaches to reduce the incidence of the renal toxicity of
these agents.