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

被引：151

作者：

Thwaites, Guy E. ^{[1
,2
]}

Scarborough, Matthew ^{[1
]}

Szubert, Alexander ^{[3
]}

Nsutebu, Emmanuel ^{[4
]}

Tilley, Robert ^{[5
]}

Greig, Julia ^{[6
]}

Wyllie, Sarah A. ^{[7
]}

Wilson, Peter ^{[8
]}

Auckland, Cressida ^{[9
]}

Cairns, Janet ^{[3
]}

Ward, Denise ^{[3
]}

Lal, Pankaj ^{[10
]}

Guleri, Achyut ^{[11
]}

Jenkins, Neil ^{[12
]}

Sutton, Julian ^{[13
]}

Wiselka, Martin ^{[14
]}

Armando, Gonzalez-Ruiz ^{[15
]}

Graham, Clive ^{[16
]}

Chadwick, Paul R. ^{[17
]}

Barlow, Gavin ^{[18
]}

Gordon, N. Claire ^{[1
]}

Young, Bernadette ^{[1
]}

Meisner, Sarah ^{[19
]}

McWhinney, Paul ^{[20
]}

Price, David A. ^{[21
]}

Harvey, David ^{[22
]}

Nayar, Deepa ^{[23
]}

Jeyaratnam, Dakshika ^{[24
]}

Planche, Tim ^{[25
]}

Minton, Jane ^{[26
]}

Hudson, Fleur ^{[3
]}

Hopkins, Susan ^{[27
]}

Williams, John ^{[28
]}

Torok, M. Estee ^{[29
]}

Llewelyn, Martin J. ^{[30
]}

Edgeworth, Jonathan D. ^{[31
]}

Walker, A. Sarah ^{[1
,3
]}

机构：

[1] Univ Oxford, Nuffield Dept Med, Oxford, England

[2] Univ Oxford, Clin Res Unit, Ho Chi Minh City, Vietnam

[3] UCL, MRC, Clin Trials Unit, London, England

[4] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England

[5] Plymouth Hosp Natl Hlth Serv NHS Trust, Plymouth, Devon, England

[6] Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England

[7] Portsmouth Hosp NHS Trust, Portsmouth, Hants, England

[8] Univ Coll London Hosp Natl Hlth Serv Fdn Trust, London, England

[9] Royal Devon & Exeter NHS Fdn Trust, Exeter, Devon, England

[10] Aintree Univ Hosp NHS Fdn Trust, Aintree, England

[11] Blackpool Teaching Hosp NHS Fdn Trust, Blackpool, England

[12] Heart England NHS Fdn Trust, Birmingham, W Midlands, England

[13] Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England

[14] Univ Hosp Leicester NHS Trust, Dept Infect & Trop Med, Leicester, Leics, England

[15] Darent Valley Hosp, Dept Microbiol, Dartford, England

[16] North Cumbria Univ Hosp NHS Trust, Carlisle, England

[17] Salford Royal NHS Fdn Trust, Salford, Lancs, England

[18] Hull & East Yorkshire Hosp NHS Trust, Kingston Upon Hull, N Humberside, England

[19] Royal United Hosp Bath NHS Fdn Trust, Bath, Avon, England

[20] Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England

[21] Newcastle Upon Tyne Hosp NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England

[22] Wirral Univ Teaching Hosp NHS Fdn Trust, Birkenhead, Merseyside, England

[23] Cty Durham & Darlington NHS Fdn Trust, Durham, England

[24] Kings Coll Hosp NHS Fdn Trust, London, England

[25] St Georges Univ Hosp NHS Fdn Trust, London, England

[26] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England

[27] Royal Free London NHS Fdn Trust, London, England

[28] South Tees Hosp NHS Fdn Trust, Middlesbrough, Cleveland, England

[29] Univ Cambridge, Dept Med, Cambridge, England

[30] Brighton & Sussex Med Sch, Brighton, E Sussex, England

[31] Kings Coll London, London, England

来源：

LANCET | 2018年 / 391卷 / 10121期

关键词：

CLINICAL MANAGEMENT; INFECTIONS; THERAPY;

D O I：

10.1016/S0140-6736(17)32456-X

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. Copyright (c) The Author(s). Published by Elsevier Ltd.

引用

页码：668 / 678

页数：11

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