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Once-daily aminoglycosides?

Severe bacterial infections where gram negative bacteria are present are usually treated with aminoglycosides. Broader spectrum antibiotic therapy is generally started before specific bacteriologic culture reports are available, so aminoglycosides typically would be given as well as other antibacterials. Peak concentrations in serum inhibit bacterial growth, but minimal trough concentrations may be required to avoid risks of damage to ears and kidneys. Randomised trials of once-daily against standard dosing have yielded conflicting results, and many had insufficient numbers of patients to answer the question. Meta-analysis may give the answer.

Meta-analysis

A group from Hamilton, Ontario, sought studies that were randomised and compared an intravenous once-daily aminoglycoside regimen against a standard regimen in immunocompetent adults [1]. They looked for evidence of bacteriologic or clinical cure, mortality, nephrotoxicity (an increase in serum creatinine of at least 35 to 45 µ mol/L) and ototoxicity (a 15 dB reduction in hearing at any frequency).

Results

They analysed 13 studies. Once-daily dosing made no difference to bacteriologic cure. They did not pool data for clinical cure, although 11 of 12 studies appear from their figures to have a risk ratio that included 1 (i.e., not significantly different).
Mortality, nephrotoxicity and ototoxicity were all lower with the once daily regimen, though without the difference from standard dosing being statistically significant. Point estimate numbers needed to treat to prevent one event with once-daily compared with more frequent dosing were 111 for mortality, 77 for nephrotoxicity and 61 for ototoxicity.

Comment

The meta-analysis showed that once-daily aminoglycoside dosing is equivalent to standard dosing in terms of bacteriological cure, and may be associated with reduced nephrotoxicity, ototoxicity and mortality. The authors have a useful discussion of the limits of their analysis because of the availability of trials, and point out some of the areas for research in this complicated area.

Reference:

  1. R Hatala, T Dinh, DJ Cook. Once-daily aminoglycoside dosing in immunocompetent adults: a meta-analysis. Annals of Internal Medicine 1996 124:717-25.



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