title: A meta-analysis of extended-interval dosing versus multiple daily dosing of aminoglycosides.
abstract: We conducted a meta-analysis of 22 randomized, controlled trials in which extended-interval dosing of aminoglycosides was compared with multiple daily dosing. When we classified intermediate outcomes as successes, we found that patients receiving extended-interval dosing were at significantly reduced risk of clinical treatment failure (risk difference, -3.4%; 95% confidence interval [CI], -6.7% to -0.2%; P = .039) and that there was a trend toward reduced risk of bacteriologic failure (risk difference, -1.7%; 95% CI, -5.4% to +2.1%; P = .38). Reclassification of intermediate outcomes as failures yielded similar results. There was significant heterogeneity among the trials, necessitating cautious interpretation of these outcomes. There were negligible differences in the risk of nephrotoxicity (risk difference, -0.6%; 95% CI, -2.4% to +1.1%; P = .46) and ototoxicity (risk difference, +0.3%; 95% CI, -1.2% to +1.8%; P = .71). We conclude that for many indications, extended-interval dosing of aminoglycosides appears to be as effective as conventional dosing, with similar rates of toxicity. The added convenience of extended-interval dosing makes it an attractive alternative to conventional dosing.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Bailey
authors.forename: J R
authors.initials: JR
authors.lastname: Little
authors.forename: B
authors.initials: B
authors.lastname: Littenberg
authors.forename: R M
authors.initials: RM
authors.lastname: Reichley
authors.forename: W C
authors.initials: WC
authors.lastname: Dunagan
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006311:Hearing Disorders / Q000139:chemically induced*; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents