Combination of Vancomycin and β-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial

Joshua S. Davis, Archana Sud, Matthew V N O'Sullivan, James O. Robinson, Patricia E. Ferguson, Hong Foo, Sebastiaan J. Van Hal, Anna P. Ralph, Benjamin P. Howden, Paula M. Binks, Adrienne Kirby, Steven Y C Tong, Steven Tong, Paula Binks, Suman Majumdar, Anna Ralph, Rob Baird, Claire Gordon, Cameron Jeremiah, Grace LeungAnna Brischetto, Amy Crowe, Farshid Dakh, Kelly Whykes, Maria Kirkwood, Mahesh Menon, Lucy Somerville, Shrada Subedi, Shirley Owen, Matthew O'Sullivan, Eunice Liu, Fei Zhou, Owen Robinson, Geoffrey Coombs, Patrician Ferguson, Simon Pollet, Sebastian Van Hal, Rebecca Davis, CAMERA Study Group, CAMERA Study Group, CAMERA Study Group, CAMERA Study Group, CAMERA Study Group, CAMERA Study Group, CAMERA Study Group

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    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 (www.anzctr.org.au).

    Original languageEnglish
    Pages (from-to)173-180
    Number of pages8
    JournalClinical Infectious Diseases
    Volume62
    Issue number2
    DOIs
    Publication statusPublished - 15 Jan 2016

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