Extended dosage intervals for aminoglycosides.
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.
Department of Clinical Pharmacy Practice, School of Pharmacy, Auburn University, AL.
D P
DP
Rodman
A J
AJ
Maxwell
J T
JT
McKnight
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents