Single or multiple daily doses of aminoglycosides: a meta- analysis

Abstract

Objective: To assess relative efficacy and toxicity of aminoglycosides given by single daily dose compared with multiple daily doses. Design: Meta-analysis of 21 randomised trials identified through MEDLARS (1966 to January 1995). Data were overviewed with fixed effects and random effects models and with meta-regression analysis. Subjects: Total of 3091 patients with bacterial infection, most without pre-existing renal disease. Interventions: Patients were randomised to receive aminoglycosides once daily or multiple times daily with similar total daily dose. Main outcome measures: Clinical failure of treatment, nephrotoxicity, ototoxicity, and mortality. Results: Single daily dose regimen produced a non-significant decrease in risk of antibiotic failures (random effects risk ratio 0.83 (95% confidence interval 0.57 to 1.21)). Benefit of once daily dosing was greater when the percentage of pseudomonas isolates in a trial was larger. Once daily administration reduced risk of nephrotoxicity (fixed effects risk ratio 0.74 (0.54 to 1.00)). Similar trends were noted for patients with febrile neutropenia and for children. There was no significant difference in ototoxicity between the two dosing regimens, but the power of the pooled trials to detect a meaningful difference was low. There was no significant difference in mortality. Conclusions: Once daily administration of aminoglycosides in patients without pre-existing renal impairment is as effective as multiple daily dosing, has a lower risk of nephrotoxicity, and no greater risk of ototoxicity. Given the additional convenience and reduced cost, once daily dosing should be the preferred mode of administration. Key messages This meta-analysis shows that single daily doses of aminoglycosides were about 25% less nephrotoxic than and at least as effective clinically as multiple daily doses The dosing schedule did not significantly affect the incidence of ototoxicity, but the power to detect a difference was small Once daily dosing was non-significantly more effective in patients with febrile neutropenia and in children, and the apparent benefit of once daily dosing increased with increasing proportion of pseudomonas isolates in a trial Besides the convenience of once daily dosing, reduced costs of drug administration and omission of measurements of peak antibiotic concentrations should result in substantial cost savings