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

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 randomized 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.