Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial
Authors: Guy E Thwaites, Matthew Scarborough, Alexander Szubert, Emmanuel Nsutebu, Robert Tilley, Julia Greig, Sarah A Wyllie, Peter Wilson, Cressida Auckland, Janet Cairns, Denise Ward, Pankaj Lal, Achyut Guleri, Neil Jenkins, Julian Sutton, Martin Wiselka, Gonzalez-Ruiz Armando, Clive Graham, Paul R Chadwick, Gavin Barlow, N Claire Gordon, Bernadette Young, Sarah Meisner, Paul McWhinney, David A Price, David Harvey, Deepa Nayar, Dakshika Jeyaratnam, Tim Planche, Jane Minton, Fleur Hudson, Susan Hopkins, John Williams, M Estee Török, Martin J Llewelyn, Jonathan D Edgeworth, A Sarah Walker, Matthew Scarborough, Musa Kamfose, Ana de Veciana, Nicola Claire Gordon, Leon Peto, Gemma Pill, Tiphanie Clarke, Laura Watson, Bernadette Young, Dai Griffiths, Ali Vaughn, Luke Anson, Elian Liu, Sanuki Perera, Lydia Rylance-Knight, Carmen Cantell, Ruth Moroney, Jonathan D Edgeworth, Guy Thwaites, Karen Bisnauthsing, Antonio Querol-Rubiera, Charlotte Gibbs, Amita Patel, Carolyn Hemsley, Anna L Goodman, Duncan Wyncoll, Jason Biswas, Jennifer Fitzpatrick, Lizzie Roberts, James Millard, Neil Stone, Angela Cape, Lisa Hurley, Chi Kai Tam, Emmanuel Nsutebu, Marie-Claire Hoyle, Kate Maitland, Leona Trainor, Helen Reynolds, Jennifer Harrison, Jim Anson, Joseph Lewis, Jonathan Folb, Lynsey Goodwin, Nicholas Beeching, Sarah Dyas, Helen Winslow, Elizabeth Foote, Paul Roberts, Pavithra Natarajan, Alex Chrdle, Manuel Fenech, Hannah Allsop, Robert Tilley, Rachel Austin-Hutchison, Louise Barrett, Karen Brookes, Leanne Carwithen, Andrew Conbeer, Richard Cunningham, Charlotte Eglinton, Rosie Fok, Hannah Gott, Shona Hughes, Lewis Jones, Maggie Kalita, Angela King, Linda March, Mike Marner, Tracey Mynes, Aiden Plant, Suzanne Price, Judy Sercombe, Alison Stolton, Mark Wallis, Marie-Claire West, Jackie Westcott, Claire Williams, Rob Wosley, Leona Yabsley, Julia Greig, Laura Butland, Julie Sorrell, Tamara Mitchell, Abiola Alli, James Meiring, Boingotlo Masake, Carlene Rowson, Lynne Smart, Laura Makey, Sarah Moll, Jane Cunningham, Kim Ryalls, Kathryn Birchall, Janet Middle, Yvonne Jackson, Diane Swift, Joby Cole, Bala Subramanian, Faith Okhuoya, Maria Edwards, Cheryl Bailey, Rebecca Warren, Gayti Islam, Michael Ankcorn, Sarah Birchall, Paul Jones, John Humphries, Stephen Booth, Cariad Evan, Sarah Wyllie, Andrew Flatt, Lenka Strakova, Maria Hayes, Stacey Valentine, Clare James, Mary Wands, Nicolas Cortes, Nisa Khan, Robert Porter, Zoe Martin, Keith Yip, Helen Preedy, Helen Chesterfield, Tracey Dobson, Colin Walker, Martin Llewelyn, Angela Dunne, Laura Latter, Alison Porges, James Price, John Paul, Laura Behar, Louise Robinson, Amy Murray, Jennifer Fitzpatrick, Tenessa Sargent, Carrie Ridley, Laura Ortiz-Ruiz de Gordoa, Deborah Gilliam, Carole McPherson, Simon Matthews, Emma Foreman, Rajesh Jarghese, Alisha Beddoe, Sebastien Martin, Sephora Shaw, Dominika Wlazly, Maggie Cole, Abraham Gihawi, Kevin Cole, M Estée Török, Theodore Gouliouris, Luke Bedford, Rebecca B Saunderson, Ilias Mariolis, Rachel Bousfield, Isobel Ramsay, Daniel Greaves, Sani Aliyu, Kim Cox, Lois Mlemba, Lynne Whitehead, Naval Vyse, Mark Bolton, John Williams, Pauline Lambert, David Chadwick, Kirsty Baillie, Martyn Cain, Richard Bellamy, Jason Wong, Jane Thompson, Helen Vassallo, Agnieszka Skotnicka, Andrea Boyce, Anthony Donnelly, Peter Wilson, Graham FitzGerald, Victoria Dean, Kristian Warnes, Anna Reyes, Saadia Rahman, Lillian Tsang, Joanne Williams, Stephen Morris-Jones, Susan Hopkins, Elen Witness, Orla Brady, Elizabeth Woodford, Teresa Pettifer, Angela McCadden, Ben Marks, Sophie Collier, Damien Mack, Simon Warren, Colin Brown, Adrian Lyons, Sara Taiyari, Stephen Mepham, Anna Sweeney, Li-An Brown, Cressida Auckland, Alison Potter, Jess Mandiza, Maxine Hough, Sue Williams, Caroline Renton, Fiona Walters, Maria Nadolski, Andree Evans, Polly Tarrant, Katherine Curley, Sophie Whiteley, Julia Halpin, Melanie Hutchings, Shirley Todd, Christop Lohan, Tamika Chapter, Emma Folland, Alaric Colville, Katy Marden, Marina Morgan, Rosie Fok, Rob Porter, Mel Baxter, Jane Minton, Sarah Rippon, Muge Cevik, Judith Chapman, Tim Kemp, Rachel Vincent, Dave Osborne, Tracey Platt, James Calderwood, Bernadette Cook, Caroline Bedford, Leanne Galloway-Browne, Nadine Abberley, Kelly Attack, Joanna Allen, Pankaj Lal, Melanie Harrison, Sarah Stevenson, Carol Brooks, Paula Harlow, Jordan Ewing, Shirley Cooper, Roderick Balancio-Tolentino, Laura O'Neil, Rebecca Tagney, Daniela Shackcloth, Tim Planche, James Fellows, Ruth Millett, Jo Studham, Cherrelle de Souza, Geoffrey Howell, Hezron Greaves, Ella Foncel, Rahul Kurup, Jack Briggs, Melody Smith, Cristina Suarez, Giordana Sorrentino, Antonia Scobie, Angela Houston, Fozia Ahmad, Aodhan Breathnach, Rakhee Chahuan, Katie Wilkins, Achyut Guleri, Natalia Waddington, Rashmi Sharma, Peter Flegg, Veenu Kollipara, Mazhar Alam, Andrew Potter, Stacey Donaldson, Charlote Armer, Julie Frudd, Dakshika Jeyaratnam, Manju Joy, Asha Mathews, Stephen K Glass, Ayodele Ajayi, Amanda Fife, Saba Qaiser, Sharon Sheehan, Sergio Muñoz-Villaverde, Noah Yogo, Ines De Abreu, Gaynor Notcheva, Joanna Flanagan, Cordelia Watson, Efisia Sais, Adetunji Adedayo, Vicky Chu, Georgina Shaw, Michelle A Graver, Rebecca Palmer, Donna Palmer, Senait Haile, Joanne Gordon, Chi Kai Tam, Kirandip Mandar, Weronika Szypura, Neil Jenkins, Josephine Marange, Vusumuzi Shabangu, Katy Moore, Jill Lyons, Melinda Munang, Mirriam Sangombe, Ed Moran, Abid Hussain, Martin Wiselka, Adam Lewszuk, Sally Batham, Kate Ellis, Leila Bahadur, Helena White, Manish Pareek, Amandip Sahota, Stephen Coleman, Hilary Pateman, Atul Kotecha, Christopher Sim, Andrew Rosser, Jill Deane, Richard Nendick, Catherine Aldridge, Anne Clarke, Michelle Wood, Adele Marshall, Lynsey Stephenson, Tracy Matheson-Smith, John Sloss, Kathryn Potts, Joanne Malkin, Lemonia Ftika, Veena Raviprakash, Julian Sutton, Ahalya Malachira, Miranda Kean, Kristine Criste, Kirsty Gladas, Caroline Andrews, Clare Hutchison, Ellen Adams, Janet Andrews, Belinda Romans, Nicola Ridley, Melanie Ekani, Julie Mitchell, Nicola Smith, Tristan Clark, Sarah Glover, Robert Reed, Tat Yam, Holly Burton, Rasha Said, David Harvey, Amy Janvier, Reni Jacob, Chris Smalley, Alison Fair, Susan Lord, Kate Ripalda, Helen Wooldridge, Luis Cotter, Gus Cardoso, Elaine Strachan, Gagan Kaler, Adam Mohamoodally, Emma Lawrence, Zoe Prime, Rachel Abrahams, David Ashley Price, Lesley Rigden, Laura Shewan, Katherine Cullen, Ingrid Emmerson, Karen Martin, Hesther Wilson, Charley Higham, Kathryn Louise Taylor, Edmund Ong, Bijal Patel, Helena Bond, Janine Gradwell, John Widdrington, Clive Graham, Sarah Thornthwaite, Scott Prentice, Una Poultney, Hannah Crowther, Helen Fairlamb, Emily Hetherington, Chris Brewer, Suryabrata Banerjee, Clare Hamson, Anna McSkeane, Paul McWhinney, Paula Sharratt, Joanne Thorpe, Sue Kimachia, Helen Wilson, Benjamin Jeffs, Leslie Masters, Jonathan Wilson, Judith Platt, Lisa Burgess, Paul Chadwick, Adam Jeans, Claire Keatley, Amanda Moran, Zoe Swann, Katherine Pagett, Alex Peel, Jason Howard, Sarah Meisner, Kate Maloney, Avril Masdin, Louise Wright, Gavin Barlow, Samantha Crossman, Vicki Lowthorpe, Emma Moore, Peter Moss, Angela Parkin, Adam Wolstencroft, Bev Warner, Clare Tarbotton, Alison Eyre, Anne Anderson, Tina Burdett, Amy Driffill, Ann Sarah Walker, Fleur Hudson, Alex Szubert, Janet Cairns, Denise Ward, Helen Webb, Charlotte Russell, Brooke Jackson, Damilola Otiko, Chiara Borg, Lindsey Masters, Zaheer Islam, Carlos Díaz-Montaña, Debbie Johnson
Journal: The Lancet (2017)

BackgroundStaphylococcus 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.MethodsIn 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.FindingsBetween 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).InterpretationAdjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.FundingUK National Institute for Health Research Health Technology Assessment.