ONCE-DAILY AMINOGLYCOSIDES: A META-ANALYSIS OF NONNEUTROPENIC AND NEUTROPENIC ADULTS
Pramodini B Kale-Pradhan, Suzette R Habowski,
Heather C Chase, and Frank C Castronova

OBJECTIVE: To compare the efficacy, nephrotoxicity, and ototoxicity of once-daily dosing of aminoglycosides versus conventional dosing.

DESIGN: Meta-analysis of 14 randomized trials identified through a MEDLINE search (January 1965–May 1996).

PATIENTS: Neutropenic and nonneutropenic adults.

INTERVENTIONS: Patients were randomly selected to receive an aminoglycoside once daily or in multiple daily doses.

MEASUREMENTS AND MAIN OUTCOMES: The outcomes considered were clinical cure, bacteriologic cure, nephrotoxicity, auditory toxicity, and vestibular toxicity. The data were analyzed in the following subgroups: (1) all trials, (2) nonneutropenic patients, (3) neutropenic patients, and (4) patients with undefined neutrophil status. For all trials the pooled risk ratio was 1.268 (95% CI 0.828 to 1.939) for clinical cure, and was 1.390 (95% CI 1.350 to 1.392) for bacteriologic cure. Nephrotoxicity had a pooled risk ratio of 0.765 (95% CI 0.468 to 1.252), that for auditory toxicity was 1.117 (95% CI 0.151 to 5.636), and that for vestibular toxicity was 1.155 (95% CI 0.221 to 6.039). Analysis of the subgroups, including a separate analysis of neutropenic patients, demonstrated similar results.

CONCLUSIONS: When all trials were considered, once-daily administration of aminoglycosides had similar efficacy and no increase in nephrotoxicity or ototoxicity compared with conventional aminoglycoside dosing.