Aminoglycosides: single or multiple daily dosing?

Abstract

A number of randomised studies indicate that a single high dose of aminoglycoside every 24 h may be more efficient and less toxic than the same dose divided into multiple daily doses. In the meta-analysis of 16 studies described here, which included more than 1200 patients, the relative chance (i.e. the relative risk, RR) of cure of the single-dose regime compared with the multiple-dose regime was 1.027, indicating that the single daily dose regime had a 2.7% higher cure rate (NS). The RR of avoiding nephrotoxicity was 1.001 (NS) and the RR of avoiding ototoxicity was 1.001 (NS). It is concluded that there is no difference concerning efficacy and safety between single-dose and multiple-dose regimes for administration of aminoglycosides.

Extended-Interval Aminoglycoside Administration for Children: A Meta-analysis

“…[9][10][11][12][13][14][15][16]48 Those meta-analyses showed no difference in clinical efficacy between ODD and MDD 9,13,14,16 or even better efficacy with ODD. [10][11][12]15 With the exception of severely ill children, clinical failures were uncommon in the trials we analyzed, regardless of the regimen used.…”

“…Also, we observed a trend toward fewer bacteriologic failures, which again was consistent with the results of adult meta-analyses that evaluated this outcome. 10,11,14,15,48 One meta-analysis 9 of adult data suggested that ODD might reduce nephrotoxicity, whereas other meta-analyses [10][11][12][13][14][15]48 showed nonsignificant trends or no difference in nephrotoxicity outcomes. In our meta-analysis, we were not able to show any reduction in the risk of primary nephrotoxicity outcomes with ODD.…”

“…These results were consistent with the findings of meta-analyses of adult data, which showed no difference in ototoxicity rates between ODD and MDD. [10][11][12][13]15,16 Some limitations must be acknowledged. Selective reporting of outcome data was evident in this metaanalysis.…”

“…These features include concentration-dependent bactericidal activity, postantibiotic effect (which allows continued efficacy even when serum concentrations fall below expected minimal inhibitory concentrations), decreased risk of adaptive resistance, and diminished accumulation in renal tubules and the inner ear. [3][4][5][6][7][8] Conventional MDD for adult patients has been abandoned gradually in favor of ODD, and results from meta-analyses of randomized, clinical trials show diminished 9 or comparable [10][11][12][13][14][15][16] nephrotoxicity, better [10][11][12]15 or comparable 9,13,14,16 efficacy, and comparable ototoxicity [9][10][11]15,16 with ODD versus MDD among adults.…”

Pharmacokinetics and renal toxicity of three once-a-day doses of amikacin in cows

“…It is thought that pulse dosing minimises toxicity while reducing treatment failure, morbidity and mortality. Pulse dosing or high-peak-extendedinterval dosing of aminoglycosides was first used by Labowitz et al (1974) in man and it has been accepted that there is no significant difference in safety between pulse dosing and multiple-dose regimes (Galloe et al, 1995;Barza et al, 1996;Ferriols-Lisart and Alós-Almiñana, 1996). Furthermore, efficacy is thought to be superior when using pulse dosing of aminoglycosides (Tran Ba Huy and Deffrennes, 1988;Pettarossi et al, 1990;Campbell et al, 1996).…”