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

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.