0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

Once-Daily Aminoglycoside Dosing in Immunocompetent Adults: A Meta-Analysis

Rosemarie Hatala, MD, MSc; Tuan Dinh, MSc, RPh; and Deborah J. Cook, MD, MSc
[+] Article and Author Information

From McMaster University, Hamilton, Ontario, Canada. Acknowledgments: The authors thank L. Griffith for statistical analysis and J.M. Aguado, D. Gilbert, P. Gonzalez, A. Herchuelz, E. Hippe, W. Kern, R. Maller, J. Prins, E. ter Braak, R.W. Vreede, and P.J. de Vries for their generous responses to our inquiries. Requests for Reprints: Rosemarie Hatala, MD, Department of Medicine, Henderson General Hospital, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada. Current Author Addresses: Dr. Hatala: Department of Medicine, Henderson General Hospital, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada.


Ann Intern Med. 1996;124(8):717-725. doi:10.7326/0003-4819-124-8-199604150-00003
Text Size: A A A

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 independent 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.

Figures

Grahic Jump Location
Figure 1.
Bacteriologic cure: once-daily compared with standard aminoglycoside dosing.P

Individual study and pooled risk ratios for bacteriologic cure, with 95% CIs. Risk ratios to the left of 1.0 favor standard aminoglycoside dosing; those to the right favor once-daily aminoglycoside dosing. N equals the total individual study sample for the outcome of bacteriologic cure. Test for heterogeneity, > 0.2.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Clinical cure: once-daily compared with standard aminoglycoside dosing.P

The individual study risk ratios for clinical cure, with 95% CIs. Risk ratios to the left of 1.0 favor standard aminoglycoside dosing; those to the right favor once-daily aminoglycoside dosing. N equals the total individual study sample for the outcome of clinical cure. Test for heterogeneity, = 0.07.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Nephrotoxicity: once-daily compared with standard aminoglycoside dosing.P

The individual study and pooled risk ratios for nephrotoxicity, with 95% CIs. Risk ratios to the left of 1.0 favor once-daily aminoglycoside dosing; those to the right favor standard aminoglycoside dosing. N equals the total individual study sample for the outcome of nephrotoxicity. Test for heterogeneity, > 0.2.

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)