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 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
Subedi, Shrada
et al.
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2016
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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.

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Clinical Infectious Diseases

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62

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2

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© 2016 Oxford University Press. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Clinical Infectious Diseases following peer review. The definitive publisher-authenticated version Combination of Vancomycin and β-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial , Clinical Infectious Diseases, Volume 62, Issue 2, Pages 173–180, 2020 is available online at: https://doi.org/10.1093/cid/civ808

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Biological sciences

Biomedical and clinical sciences

MRSA

Staphylococcus aureus

bacteremia

clinical trial

vancomycin

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Davis, JS; Sud, A; O'Sullivan, MVN; Robinson, JO; Ferguson, PE; Foo, H; van Hal, SJ; Ralph, AP; Howden, BP; Binks, PM; Kirby, A; Tong, SYC; Combination Antibiotics for MEthicillin Resistant Staphylococcus aureus (CAMERA) study group; Subedi, S; et al., Combination of Vancomycin and β-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial., Clin Infect Dis, 2016, 62 (2), pp. 173-180

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