Combination of Vancomycin and β-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial.
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Davis Joshua S, Sud Archana, O'Sullivan Matthew V N, Robinson James O, Ferguson Patricia E, Foo Hong, van Hal Sebastiaan J, Ralph Anna P, Howden Benjamin P, Binks Paula M, Kirby Adrienne, Tong Steven Y C, Combination Antibiotics for MEthicillin Resistant Staphylococcus aureus (CAMERA) study group, Combination Antibiotics for MEthicillin Resistant Staphylococcus aureus (CAMERA) study group, Tong Steven, Davis Joshua, Binks Paula, Majumdar Suman, Ralph Anna, Baird Rob, Gordon Claire, Jeremiah Cameron, Leung Grace, Brischetto Anna, Crowe Amy, Dakh Farshid, Whykes Kelly, Kirkwood Maria, Sud Archana, Menon Mahesh, Somerville Lucy, Subedi Shrada, Owen Shirley, O'Sullivan Matthew, Liu Eunice, Zhou Fei, Robinson Owen, Coombs Geoffrey, Ferguson Patrician, Ralph Anna, Liu Eunice, Pollet Simon, Van Hal Sebastian, Foo Hong, Van Hal Sebastian, Davis Rebecca
Аннотация
METHODS: In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days.
RESULTS: We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P = .06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity.
CONCLUSIONS: Combining an antistaphylococcal β-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au).