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

© 2015 The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com. Background. In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin...

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Main Authors: Davis, J., Sud, A., O'Sullivan, M., Robinson, James, Ferguson, P., Foo, H., Van Hal, S., Ralph, A., Howden, B., Binks, P., Kirby, A., Tong, S., Majumdar, S., Baird, R., Gordon, C., Jeremiah, C., Leung, G., Brischetto, A., Crowe, A., Dakh, F., Whykes, K., Kirkwood, M., Menon, M., Somerville, L., Subedi, S., Owen, S., Liu, E., Zhou, F., Robinson, O., Coombs, G., Pollet, S., Davis, R.
Format: Journal Article
Published: Oxford University Press 2016
Online Access:http://hdl.handle.net/20.500.11937/25614
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author Davis, J.
Sud, A.
O'Sullivan, M.
Robinson, James
Ferguson, P.
Foo, H.
Van Hal, S.
Ralph, A.
Howden, B.
Binks, P.
Kirby, A.
Tong, S.
Tong, S.
Davis, J.
Binks, P.
Majumdar, S.
Ralph, A.
Baird, R.
Gordon, C.
Jeremiah, C.
Leung, G.
Brischetto, A.
Crowe, A.
Dakh, F.
Whykes, K.
Kirkwood, M.
Menon, M.
Somerville, L.
Subedi, S.
Owen, S.
O'Sullivan, M.
Liu, E.
Zhou, F.
Robinson, O.
Coombs, G.
Ferguson, P.
Pollet, S.
Van Hal, S.
Davis, R.
author_facet Davis, J.
Sud, A.
O'Sullivan, M.
Robinson, James
Ferguson, P.
Foo, H.
Van Hal, S.
Ralph, A.
Howden, B.
Binks, P.
Kirby, A.
Tong, S.
Tong, S.
Davis, J.
Binks, P.
Majumdar, S.
Ralph, A.
Baird, R.
Gordon, C.
Jeremiah, C.
Leung, G.
Brischetto, A.
Crowe, A.
Dakh, F.
Whykes, K.
Kirkwood, M.
Menon, M.
Somerville, L.
Subedi, S.
Owen, S.
O'Sullivan, M.
Liu, E.
Zhou, F.
Robinson, O.
Coombs, G.
Ferguson, P.
Pollet, S.
Van Hal, S.
Davis, R.
author_sort Davis, J.
building Curtin Institutional Repository
collection Online Access
description © 2015 The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com. Background. In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal ß-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 ß-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).
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spelling curtin-20.500.11937-256142017-09-13T15:17:10Z Combination of Vancomycin and ß-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial Davis, J. Sud, A. O'Sullivan, M. Robinson, James Ferguson, P. Foo, H. Van Hal, S. Ralph, A. Howden, B. Binks, P. Kirby, A. Tong, S. Tong, S. Davis, J. Binks, P. Majumdar, S. Ralph, A. Baird, R. Gordon, C. Jeremiah, C. Leung, G. Brischetto, A. Crowe, A. Dakh, F. Whykes, K. Kirkwood, M. Menon, M. Somerville, L. Subedi, S. Owen, S. O'Sullivan, M. Liu, E. Zhou, F. Robinson, O. Coombs, G. Ferguson, P. Pollet, S. Van Hal, S. Davis, R. © 2015 The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com. Background. In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal ß-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 ß-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). 2016 Journal Article http://hdl.handle.net/20.500.11937/25614 10.1093/cid/civ808 Oxford University Press unknown
spellingShingle Davis, J.
Sud, A.
O'Sullivan, M.
Robinson, James
Ferguson, P.
Foo, H.
Van Hal, S.
Ralph, A.
Howden, B.
Binks, P.
Kirby, A.
Tong, S.
Tong, S.
Davis, J.
Binks, P.
Majumdar, S.
Ralph, A.
Baird, R.
Gordon, C.
Jeremiah, C.
Leung, G.
Brischetto, A.
Crowe, A.
Dakh, F.
Whykes, K.
Kirkwood, M.
Menon, M.
Somerville, L.
Subedi, S.
Owen, S.
O'Sullivan, M.
Liu, E.
Zhou, F.
Robinson, O.
Coombs, G.
Ferguson, P.
Pollet, S.
Van Hal, S.
Davis, R.
Combination of Vancomycin and ß-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial
title Combination of Vancomycin and ß-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial
title_full Combination of Vancomycin and ß-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial
title_fullStr Combination of Vancomycin and ß-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial
title_full_unstemmed Combination of Vancomycin and ß-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial
title_short Combination of Vancomycin and ß-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial
title_sort combination of vancomycin and ß-lactam therapy for methicillin-resistant staphylococcus aureus bacteremia: a pilot multicenter randomized controlled trial
url http://hdl.handle.net/20.500.11937/25614