A Meta-Analysis of the Relative Efficacy and Toxicity of Single Daily Dosing Versus Multiple Daily Dosing of Aminoglycosides

Abstract

We performed a meta-analysis of the efficacy and toxicity of single daily dosing (SDD) vs. multiple daily dosing of aminoglycosides and summarized the results of the four previously published meta-analyses on this subject. Our analysis showed that the overall clinical response rate favored SDD therapy (mean difference, +3.06%; 95% confidence limit [CL], +0.17% to +5.95%; P = .04). However, we found no significant difference in the overall microbiological response rates (mean difference, +1.25%; 95% CL, -0.40% to +2.89%) or in the clinical response rates (mean difference, +0.62%; 95% CL, -2.48% to +3.71%) when patients who received adjunctive antimicrobial therapy were excluded from the analysis. No significant differences were found in the incidences of nephrotoxicity, ototoxicity, or vestibular toxicity; the summary differences in the rates of these toxicities were -0.18% (95% CL, -2.17% to +1.81%), +1.38% (95% CL, -0.99% to +3.75%), and -3.05% (95% CL, -10.69% to +4.59%), respectively. These results are similar to those of the previously published meta-analyses.

Extended-Interval Aminoglycoside Administration for Children: A Meta-analysis

“…[9][10][11][12][13][14][15][16]48 Those meta-analyses showed no difference in clinical efficacy between ODD and MDD 9,13,14,16 or even better efficacy with ODD. [10][11][12]15 With the exception of severely ill children, clinical failures were uncommon in the trials we analyzed, regardless of the regimen used. Moreover, clinical failures tended to be less frequent with ODD administration.…”

“…These features include concentration-dependent bactericidal activity, postantibiotic effect (which allows continued efficacy even when serum concentrations fall below expected minimal inhibitory concentrations), decreased risk of adaptive resistance, and diminished accumulation in renal tubules and the inner ear. [3][4][5][6][7][8] Conventional MDD for adult patients has been abandoned gradually in favor of ODD, and results from meta-analyses of randomized, clinical trials show diminished 9 or comparable [10][11][12][13][14][15][16] nephrotoxicity, better [10][11][12]15 or comparable 9,13,14,16 efficacy, and comparable ototoxicity [9][10][11]15,16 with ODD versus MDD among adults.…”

Toxicity of single daily dose gentamicin in stem cell transplantation

“…4 A meta-analysis failed to detect a correlation between increasing age and the relative incidence of nephrotoxicity or auditory toxicity among patients receiving SDD regimens rather than MDD regimens. 26 Patients experiencing ototoxicity in our study tended to be older (53 years) than patients who did not experience this complication (41 years). Age may have played a role in the increased incidence of ototoxicity in our patients.…”

“…At least eight meta-analyses of clinical trials comparing SDD and MDD of aminoglycosides have been published. [21][22][23][24][25][26][27] Unfortunately, the majority of published studies used in these meta-analyses have methodological flaws and do not permit a definitive assessment of toxicity of SDD vs MDD aminoglycosides. These flaws include small sample size, different aminoglycosides studied, variations in definitions of nephrotoxicity and ototoxicity and failure to account for concurrent use of nephro-and ototoxins.…”

Management of sepsis: from evidence to clinical practice

“…The choice of empirical therapy depends on: the patient's medical history, its origin (community or nosocomial infection), recent antibiotics assumption (previous 3 months), data on local antibiotic resistance and the presence of particular pathogens that have previously colonized or have been a source of infection for the patient. 7 Every patient should receive the dose in relation to renal and hepatic function and the serum concentration 10,[40][41] of some antimicrobials should be monitored.…”