CAMERA2 - combination antibiotic therapy for methicillin-resistant Staphylococcus aureus infection: study protocol for a randomised controlled trial.

Tong, Steven YC

Nelson, Jane

Paterson, David L

Fowler, Vance G

Howden, Benjamin P

Cheng, Allen C

Chatfield, Mark

Lipman, Jeffrey

Van Hal, Sebastian

O'Sullivan, Matthew

Robinson, James O

Yahav, Dafna

Lye, David

Davis, Joshua S

CAMERA2 study group and the Australasian Society for Infectious Diseases Clinical Research Network

England

2017-01-01T19:56:04Z

2016-03-31

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a serious infection resulting in 20-50 % 90-day mortality. The limitations of vancomycin, the current standard therapy for MRSA, make treatment difficult. The only other approved drug for treatment of MRSA bacteraemia, daptomycin, has not been shown to be superior to vancomycin. Surprisingly, there has been consistent in-vitro and in-vivo laboratory data demonstrating synergy between vancomycin or daptomycin and an anti-staphylococcal β-lactam antibiotic. There is also growing clinical data to support such combinations, including a recent pilot randomised controlled trial (RCT) that demonstrated a trend towards a reduction in the duration of bacteraemia in patients treated with vancomycin plus flucloxacillin compared to vancomycin alone. Our aim is to determine whether the addition of an anti-staphylococcal penicillin to standard therapy results in improved clinical outcomes in MRSA bacteraemia. METHODS/DESIGN: We will perform an open-label, parallel-group, randomised (1:1) controlled trial at 29 sites in Australia, New Zealand, Singapore, and Israel. Adults (aged 18 years or older) with MRSA grown from at least one blood culture and able to be randomised within 72 hours of the index blood culture collection will be eligible for inclusion. Participants will be randomised to vancomycin or daptomycin (standard therapy) given intravenously or to standard therapy plus 7 days of an anti-staphylococcal β-lactam (flucloxacillin, cloxacillin, or cefazolin). The primary endpoint will be a composite outcome at 90 days of (1) all-cause mortality, (2) persistent bacteraemia at day 5 or beyond, (3) microbiological relapse, or (4) microbiological treatment failure. The recruitment target of 440 patients is based on an expected failure rate for the primary outcome of 30 % in the control arm and the ability to detect a clinically meaningful absolute decrease of 12.5 %, with a two-sided alpha of 0.05, a power of 80 %, and assuming 10 % of patients will not be evaluable for the primary endpoint. DISCUSSION: Key potential advantages of adding anti-staphylococcal β-lactams to standard therapy for MRSA bacteraemia include their safety profile, low cost, and wide availability. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02365493 . Registered 24 February 2015.

http://www.ncbi.nlm.nih.gov/pubmed/27029920

10.1186/s13063-016-1295-3

1745-6215

https://hdl.handle.net/10161/13303

eng

Springer Science and Business Media LLC

Trials

10.1186/s13063-016-1295-3

Cefazolin

Cloxacillin

Combination

Daptomycin

Flucloxacillin

MRSA

Methicillin-resistant

Nafcillin

Randomised controlled trial

Staphylococcus aureus

Vancomycin

Anti-Bacterial Agents

Australia

Cefazolin

Clinical Protocols

Cloxacillin

Daptomycin

Drug Therapy, Combination

Floxacillin

Humans

Israel

Methicillin Resistance

Methicillin-Resistant Staphylococcus aureus

New Zealand

Research Design

Singapore

Staphylococcal Infections

Time Factors

Treatment Outcome

Vancomycin

beta-Lactams

CAMERA2 - combination antibiotic therapy for methicillin-resistant Staphylococcus aureus infection: study protocol for a randomised controlled trial.

Journal article

http://www.ncbi.nlm.nih.gov/pubmed/27029920

170

Basic Science Departments

Clinical Science Departments

Duke

Duke Clinical Research Institute

Institutes and Centers

Medicine

Medicine, Infectious Diseases

Molecular Genetics and Microbiology

School of Medicine

Published online

17