A critical reevaluation of the "therapeutic range" of aminoglycosides

Abstract

Routine pharmacokinetic drug monitoring has become an inherent component of aminoglycoside therapy over the last 10-15 years. The intent of this monitoring is to improve the outcome of treatment and to decrease the incidence of toxicity through the attainment and maintenance of serum aminoglycoside concentrations within a normal therapeutic range. The primary objective of this review was to critically analyze the scientific support for the following premises: (1) there is a causal relation between peak serum aminoglycoside concentrations in serum and the outcome of treatment; (2) there is a causal relation between trough serum aminoglycoside concentrations in serum and the outcome of treatment; (3) outcome is improved by monitoring and maintenance of serum aminoglycoside concentrations in the normal therapeutic range; (4) there is a causal relation between serum aminoglycoside concentrations and toxicity; and (5) monitoring and maintenance of serum aminoglycoside concentrations within a normal therapeutic range decrease the risk of toxicity. After a critical review of the literature, it was concluded that the evidence was insufficient to support the presently accepted normal therapeutic range. Recommendations for the monitoring of aminoglycoside therapy were drawn up.