Journal Article

Effect of Aminoglycoside and β-Lactam Combination Therapy versus β-Lactam Monotherapy on the Emergence of Antimicrobial Resistance: A Meta-analysis of Randomized, Controlled Trials

Ioannis A. Bliziotis, George Samonis, Konstantinos Z. Vardakas, Stavroula Chrysanthopoulou and Matthew E. Falagas

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 41, issue 2, pages 149-158
Published in print July 2005 | ISSN: 1058-4838
Published online July 2005 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/430912
Effect of Aminoglycoside and β-Lactam Combination Therapy versus β-Lactam Monotherapy on the Emergence of Antimicrobial Resistance: A Meta-analysis of Randomized, Controlled Trials

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Background. The addition of an aminoglycoside to a β-lactam therapy regimen has been suggested to have a beneficial effect in delaying or preventing the development of antimicrobial resistance. We studied the effect of aminoglycoside/β-lactam combination therapy versus β-lactam monotherapy on the emergence of resistance.

Methods. We performed a meta-analysis of randomized, controlled trials (RCTs) that compared aminoglycoside/β-lactam combination therapy with β-lactam monotherapy and that reported data regarding the emergence of resistance (primary outcome) and/or development of superinfection, treatment failure, treatment failure attributable to emergence of resistance, treatment failure attributable to superinfection, all-cause mortality during treatment, and mortality due to infection. Data for this meta-analysis were identified from the PubMed database, Current Contents database, Cochrane central register of controlled trials, and references in relevant articles.

Results. A total of 8 RCTs were included in the analysis. β-Lactam monotherapy was not associated with a greater emergence of resistance than was the aminoglycoside/β-lactam combination (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.56–1.47). Actually, β-lactam monotherapy was associated with fewer superinfections (OR, 0.62; 95% CI, 0.42–0.93) and fewer treatment failures (OR, 0.62; 95% CI, 0.38–1.01). Rates of treatment failure attributable to emergence of resistance (OR, 3.09; 95% CI, 0.75–12.82), treatment failure attributable to superinfection (OR, 0.60; 95% CI, 0.33–1.10), all-cause mortality during treatment (OR, 0.70; 95% CI, 0.40–1.25), and mortality due to infection (OR, 0.74; 95% CI, 0.46–1.21) did not differ significantly between the 2 regimens.

Conclusions. Compared with β-lactam monotherapy, the aminoglycoside/β-lactam combination was not associated with a beneficial effect on the development of antimicrobial resistance among initially antimicrobial-susceptible isolates.

Journal Article.  5514 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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