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What is the evidence for once-daily aminoglycoside therapy?

Abstract：

:Aminoglycosides are important antibacterial agents for the treatment of serious infection. Evidence suggests that high peak plasma concentrations must be achieved early in the course of treatment if these agents are to be effective, but prolonged high concentrations may cause ototoxicity and nephrotoxicity. Peak plasma concentrations of 6 to 10 mg/L and trough concentrations of less than 2 mg/L for gentamicin and tobramycin have been traditional goals of therapy. Extensive recent evidence from in vitro, animal and human studies suggests that these target concentrations need revision. Aminoglycosides display concentration-dependent bacterial killing, have a long postantibiotic effect, and induce adaptive resistance in Gram-negative bacteria. All of these factors support the use of larger doses of aminoglycosides that are given less frequently than conventional therapy. Studies in vitro support this approach, showing greater activity when aminoglycosides are given less frequently. Animal studies comparing different dosage intervals have shown varying results, with only a slight bias favouring the longer dosage interval. However, the short elimination half-lives for the drugs in animals limit the applicability of these models to humans. Importantly, there is convincing evidence in animal studies that nephrotoxicity and ototoxicity are both reduced when the same total daily dose is administered in less frequent doses. There have been at least 29 clinical trials comparing once-daily administration of aminoglycosides with conventional administration 2 to 4 times daily. In general, efficacy has not been shown to be different between regimens, although one trial showed an advantage for once-daily administration compared with administration 3 times daily. A small number of trials have shown less nephrotoxicity and ototoxicity with once-daily administration, leading several authors to suggest that there is sufficient evidence to warrant a change to once-daily administration of aminoglycosides. However, once-daily administration has not been well studied in the paediatric population, or in patients with renal failure or endocarditis, and cannot be recommended in these patients as yet. The choice of a 24-hour dosage interval is somewhat arbitrary, and the optimal interval may not necessarily be 24 hours. No studies have included dosage adjustment based on pharmacokinetic modelling methods, and the effect of this on treatment outcome needs to be assessed. The best method of administering aminoglycosides once daily is yet to be determined.

journal_name

Clin Pharmacokinet

journal_title

Clinical pharmacokinetics

authors

Barclay ML,Begg EJ,Hickling KG

doi

10.2165/00003088-199427010-00004

subject

Has Abstract

pub_date

1994-07-01 00:00:00

pages

32-48

issue

eissn

0312-5963

issn

1179-1926

journal_volume

pub_type

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What is the evidence for once-daily aminoglycoside therapy?