Preclinical and clinical evaluation of once-daily aminoglycoside chemotherapy.

The rationale for and effectiveness of extended dosage intervals for aminoglycosides are reviewed. Aminoglycoside antibiotics have a prolonged postantibiotic effect against a variety of common Gram-negative and Gram-positive organisms: higher serum aminoglycoside levels are associated with a longer postantibiotic effect and increased bactericidal activity. Moreover once daily aminoglycoside administration may reduce the potential for adaptive postexposure resistance by allowing less contact time between bacteria and antibiotic. A longer dosage interval may decrease the risk of nephro- and ototoxicity. At least 33 published clinical trials suggest that once-daily administration of aminoglycosides and conventional regimens involving shorter dosage intervals are equally effective in patients with normal renal function and Gram-negative infections: besides, once-daily administration may reduce the frequency of aminoglycoside toxicity or delay it.