Extended dosage intervals for aminoglycosides

Abstract

The rationale for and effectiveness of extended dosage intervals for aminoglycosides are discussed. Aminoglycosides can be given once daily despite an elimination half-life of two to three hours because of the postantibiotic effect (PAE) of these agents. Aminoglycosides have a prolonged PAE against a variety of common gram-negative and gram-positive organisms. Higher serum aminoglycoside concentrations are associated with longer PAEs and increased bactericidal activity. Once-daily administration may reduce the potential for adaptive postexposure resistance by allowing less contact time between organism and drug. A major concern with aminoglycosides is the risk of nephrotoxicity and ototoxicity. The uptake of specific aminoglycosides by renal cortical cells is saturable; a longer dosage interval may decrease the risk of nephrotoxicity because higher transient serum aminoglycoside levels appear to be less nephrotoxic than lower but more persistent serum concentrations. Once-daily administration may reduce the risk of ototoxicity through a similar mechanism. An increasing number of clinical trials suggest tht once-daily administration of aminoglycosides and regimens involving shorter dosage intervals are equally effective in patients with normal renal function and gram-negative infections and that once-daily administration may reduce the frequency of toxicity or delay it. Patients with renal dysfunction or neutropenia may also benefit from once-daily administration. Most trials have been small, and in some of them other antimicrobials were given concurrently. Although more study is needed, the evidence to date suggests that once-daily administration of aminoglycosides is as effective as traditional regimens entailing shorter dosage intervals and may reduce the potential for toxicity.