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Clinical Question
Does the addition of an antistaphylococcal beta-lactam to standard therapy improve outcomes for patients with methicillin-resistant Staphyloccous aureus bacteremia?
Bottom line
Adding an antistaphyloccal beta-lactam to standard antibiotic therapy for methicillin-resistant Staphyloccous aureus (MRSA) bacteremia had no effect on a composite outcome of mortality, persistent bacteremia, relapse, and treatment failure. However, this trial was terminated early because of an increased incidence of acute kidney injury in patients who received combination therapy with vancomycin and a beta-lactam. Ultimately, the study was underpowered to detect a difference in the primary outcome if one truly exists. 1b-
Reference
Study design: Randomized controlled trial (nonblinded)
Funding: Government
Setting: Inpatient (any location) with outpatient follow-up
Synopsis
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.
Reviewer
Nita Shrikant Kulkarni, MD
Assistant Professor in Hospital Medicine
Northwestern University
Chicago, IL