Combination of vancomycin and beta-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, Combination Antibiotics for MEthicillin Resistant Staphylococcus aureus (CAMERA) study group, Australasian Society for Infectious Diseases Clinical Research Network

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Abstract

BACKGROUND: In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and anti-staphylococcal beta-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 1.5g intravenously (IV) twice daily and were randomly assigned (1:1) to flucloxacillin 2g IV 6 hourly for seven 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 [CI] 41 , 102 ; P=0.06) of that in the standard therapy group. There was no difference in the secondary endpoints of 28 and 90 day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. CONCLUSIONS: Combining an anti-staphylococcal beta-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant endpoints are warranted.
Original languageEnglish
Pages (from-to)173-180
Number of pages8
JournalClinical Infectious Diseases
Volume62
Issue number2
DOIs
Publication statusPublished - 2016

Keywords

  • Staphylococcus aureus
  • bacteremia
  • MRSA
  • clinical trial
  • vancomycin
  • β-lactam

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