Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

Thwaites, Guy E and Scarborough, Matthew and Szubert, Alexander and Nsutebu, Emmanuel and Tilley, Robert and Greig, Julia and Wyllie, Sarah A and Wilson, Peter and Auckland, Cressida and Cairns, Janet and Ward, Denise and Lal, Pankaj and Guleri, Achyut and Jenkins, Neil and Sutton, Julian and Wiselka, Martin and Armando, Gonzalez-Ruiz and Graham, Clive and Chadwick, Paul R and Barlow, Gavin and Gordon, N Claire and Young, Bernadette and Meisner, Sarah and McWhinney, Paul and Price, David A and Harvey, David and Nayar, Deepa and Jeyaratnam, Dakshika and Planche, Tim and Minton, Jane and Hudson, Fleur and Hopkins, Susan and Williams, John and Török, M Estee and Llewelyn, Martin J and Edgeworth, Jonathan D and Walker, A Sarah (2018) Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet (London, England), 391 (10121). pp. 668-678. ISSN 1474-547X. This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs

Full text not available from this repository.
Official URL: https://www.clinicalkey.com/#!/content/playContent...

Abstract

BACKGROUND

Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.

METHODS

In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants.

FINDINGS

Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005).

INTERPRETATION

Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.

FUNDING

UK National Institute for Health Research Health Technology Assessment.

Item Type: Article
Additional Information: This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs
Subjects: WC Communicabable diseases
Divisions: Clinical Support > Infectious Diseases
Related URLs:
Depositing User: Mrs Yolande Brookes
Date Deposited: 03 Oct 2018 12:37
Last Modified: 03 Oct 2018 12:37
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1752

Actions (login required)

View Item View Item