アミノ配糖体薬剤の新しい使い方と聴器毒性

抄録

Aminoglycoside antibiotics (AGs) are used in the treatment of serious infections with gram-negative bacilli or with staphylococci. Their major limitations are their nephro-and ototoxic side effects.
The daily dose has generally been administered to patients in two or three divided doses or continuous infusions. Such regimens were originally devised to avoid excessively high peak serum concentrations that were feared to be toxic.
The relationship between pharmacodynamic characteristics of serum concentrations and the ototoxicity of AGs is complex and multifactorial, but in recent years, the risk of ototoxicity has been considered to be related not to peak but to trough serum concentrations. Therefore, the risk of ototoxicity would be minimized with lower trough serum concentrations. Less frequent administrations produce lower trough serum concentrations.
On the other hand, it has been clarified that the rate of bactericidal activity of AGs is concentration-dependent, i.e. higher concentrations result in a faster and greater reduction in the number of bacteria. Moreover, AGs induce prolonged postantibiotic effects against gram-positive and gram-negative bacilli.
On the basis of this information, it seems that less frequent doses of AGs may be feasible and even advantageous, and a once-daily dosage regimen has been evaluated experimentally and clinically.
We believe that once-daily dosing with high peak serum concentrations is less toxic than divided intermittent doses or continuous infusions. The toxicity and efficacy of a once-daily dosage regimen should be evaluated by further experimental studies and clinical trials.