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Title: Combination of Vancomycin and β-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial.
Authors: 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
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
Citation: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2016-01-15; 62(2): 173-180
Abstract: In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal β-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. 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. 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. 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 (
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Journal title: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Publication Date: 2016-01-15
Type: Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
DOI: 10.1093/cid/civ808
Appears in Collections:(a) NT Health Research Collection

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