Once-daily aminoglycoside dosing in immunocompetent adults: A meta-analysis

Objective: To compare the efficacy, nephrotoxicity, and ototoxicity of once-daily aminoglycoside dosing with those of standard aminoglycoside regimens in immunocompetent adults. Data Sources: A structured MEDLINE search from 1966 to April 1995 using the keywords aminoglycosides, drug administration schedule, and adult; bibliographic searching of review articles, position papers, and references of the selected articles; contact with primary authors of selected articles to obtain information not in the published reports and lists of potentially relevant articles. Study Selection: Randomized, controlled trials that 1) compared an intravenous once-daily aminoglycoside regimen with a standard aminoglycoside regimen in infected immunocompetent adults and 2) examined efficacy, mortality, or toxicity. Data Extraction: For each selected study, two indepen dent reviewers assessed methodologic quality and abstracted data. The heterogeneity of individual study risk ratios was assessed and data were pooled using a random-effects model. Results: Forty-two studies were reviewed for possible inclusion. Thirteen independent studies met the selection criteria, and their results were pooled. The trials had a mean methodologic quality score of 0.69 (range, 0.50 to 0.91). Heterogeneity exists among the individual risk ratios for clinical cure (P = 0.07); significant heterogeneity does not exist for the other outcomes. For the pooled efficacy outcomes, the risk ratio for bacteriologic cure is 1.02 (95% CI, 0.99 to 1.05), and the risk ratio for mortality is 0.91 (CI, 0.63 to 1.31). For the pooled toxicity outcomes, the risk ratio for nephrotoxicity is 0.87 (CI, 0.60 to 1.26), and the risk ratio for ototoxicity is 0.67 (CI, 0.35 to 1.28). Conclusions: Standard and once-daily aminoglycoside dosing regimens are equivalent with regard to bacteriologic cure, and once-daily dosing shows a trend toward reduced mortality and toxicity. However, additional studies are needed for more precise estimates of mortality and toxicity risk ratios. The equivalency of the dosing regimens, the ease of administration, reduced nursing time, and reduced variability in the timing of drug administration that are associated with once-daily dosing may mean that the once-daily regimen is clinically advantageous.