No mortality benefit, increased risk of acute kidney injury with addition of beta-lactam to usual therapy for MRSA bacteremia

Référence

Tong SYC, Lye DC, Yahav D, et al, for the Australasian Society for Infectious Diseases Clinical Research Network. Effect of vancomycin or daptomycin with vs. without an antistaphylococcal beta-lactam on mortality, bacteremia, relapse, or treatment failure in patients with MRSA bacteremia. JAMA 2020;323(6):527-537.

Sommaire

Although the current standard therapy for MRSA bacteremia is vancomycin or daptomycin, prior retrospective studies have shown improved outcomes with the addition of beta-lactams. In this study, investigators randomized hospitalized patients with positive blood cultures for MRSA to receive standard therapy (n = 178) or combination therapy with an added beta-lactam for 7 days (n = 174). The beta-lactams used were either flucloxacillin or cloxacillin; cefazolin was used for those with penicillin allergy. The 2 groups had similar baseline characteristics (median age 65 years; 60%-70% men) and 99% of the study population received vancomycin. For the primary composite endpoint of all-cause mortality, persistent bacteremia, microbiological relapse, or microbiological treatment failure at 90 days, there was no significant difference between the 2 groups (35% with combination therapy vs 39% with standard therapy; P = .42). The study was stopped early because of a significantly higher incidence of acute kidney injury in the combination therapy group (23% vs 6%; P < .001). This led to an underpowered study that did not reach the target study population of 440 patients to detect a 12.5% difference in the primary outcome.