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Title: Combination of vancomycin and β-lactam therapy for methicillin-resistant staphylococcus aureus bacteremia: a pilot multicenter randomized controlled trial
Austin Authors: Davis, Joshua S;Sud, Archana;O'Sullivan, Matthew VN;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 YC;Combination Antibiotics for MEthicillin Resistant Staphylococcus aureus (CAMERA) study group;Australasian Society for Infectious Diseases Clinical Research Network
Affiliation: Global and Tropical Health Division, Menzies School of Health Research, Casuarina, Northern Territory, Australia
Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory, Australia
Department of Infectious Diseases, John Hunter Hospital, Newcastle, NSW, Australia
Department of Infectious Diseases, Nepean Hospital and University of Sydney, Kingswood, NSW, Australia
Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia
National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, NSW, Australia
Department of Infectious Diseases, Blacktown Hospital, Blacktown, NSW, Australia
Department of Microbiology and Infectious Diseases, Liverpool Hospital, Liverpool, NSW, Australia
Department Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Sydney, NSW, Australia
Department of Microbiology and Infectious Diseases, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital, Perth, Western Australia, Australia
Australian Collaborating Centre for Enterococcus and Staphylococcus Species (ACCESS) Typing and Research, School of Veterinary and Life Sciences, Murdoch University, Perth, Western Australia, Australia
School of Biomedical Sciences, Curtin University, Perth, Western Australia, Australia
Department of Microbiology and Immunology, Microbiological Diagnostic Unit, The University of Melbourne at the Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
Departments of Microbiology and Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia
Department of Microbiology, Monash University, Melbourne, Victoria, Australia
Issue Date: 15-Jan-2016 2015-09-08
Publication information: Clinical Infectious Diseases 2016; 62(2): 173-180
Abstract: BACKGROUND: 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. 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 (
DOI: 10.1093/cid/civ808
PubMed URL:
Type: Journal Article
Subjects: Anti-bacterial agents
Floxacillin - pharmacology
Staphylococcal infections - drug therapy
Vancomycin - pharmacology
Methicillin-resistant staphylococcus aureus - isolation & purification
Type of Clinical Study or Trial: Multicentre Studies
Appears in Collections:Journal articles

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