{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:06:45Z","timestamp":1787026005915,"version":"build-2736575974"},"reference-count":76,"publisher":"National Institute for Health and Care Research","issue":"59","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["10\/104\/25"],"award-info":[{"award-number":["10\/104\/25"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"\n Background<\/jats:title>\n \n Staphylococcus aureus<\/jats:italic>\n bacteraemia is a common and frequently fatal infection. Adjunctive rifampicin may enhance early\n S. aureus<\/jats:italic>\n killing, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To determine whether or not adjunctive rifampicin reduces bacteriological (microbiologically confirmed) failure\/recurrence or death through 12 weeks from randomisation. Secondary objectives included evaluating the impact of rifampicin on all-cause mortality, clinically defined failure\/recurrence or death, toxicity, resistance emergence, and duration of bacteraemia; and assessing the cost-effectiveness of rifampicin.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Parallel-group, randomised (1\u2009:\u20091), blinded, placebo-controlled multicentre trial.<\/jats:p>\n <\/jats:sec>\n \n Setting<\/jats:title>\n UK NHS trust hospitals.<\/jats:p>\n <\/jats:sec>\n \n Participants<\/jats:title>\n \n Adult inpatients (\u2265\u200918 years) with meticillin-resistant or susceptible\n S. aureus<\/jats:italic>\n grown from one or more blood cultures, who had received <\u200996 hours of antibiotic therapy for the current infection, and without contraindications to rifampicin.\n <\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Adjunctive rifampicin (600\u2013900\u2009mg\/day, oral or intravenous) or placebo for 14 days in addition to standard antibiotic therapy. Investigators and patients were blinded to trial treatment. Follow-up was for 12 weeks (assessments at 3, 7, 10 and 14 days, weekly until discharge and final assessment at 12 weeks post randomisation).<\/jats:p>\n <\/jats:sec>\n \n Main outcome measures<\/jats:title>\n The primary outcome was all-cause bacteriological (microbiologically confirmed) failure\/recurrence or death through 12 weeks from randomisation.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Between December 2012 and October 2016, 758 eligible participants from 29 UK hospitals were randomised: 370 to rifampicin and 388 to placebo. The median age was 65 years [interquartile range (IQR) 50\u201376 years]. A total of 485 (64.0%) infections were community acquired and 132 (17.4%) were nosocomial; 47 (6.2%) were caused by meticillin-resistant\n S. aureus<\/jats:italic>\n . A total of 301 (39.7%) participants had an initial deep infection focus. Standard antibiotics were given for a median of 29 days (IQR 18\u201345 days) and 619 (81.7%) participants received flucloxacillin. By 12 weeks, 62 out of 370 (16.8%) patients taking rifampicin versus 71 out of 388 (18.3%) participants taking the placebo experienced bacteriological (microbiologically confirmed) failure\/recurrence or died [absolute risk difference \u20131.4%, 95% confidence interval (CI) \u20137.0% to 4.3%; hazard ratio 0.96, 95% CI 0.68 to 1.35;\n p<\/jats:italic>\n \u2009=\u20090.81]. There were 4 (1.1%) and 5 (1.3%) bacteriological failures (\n p<\/jats:italic>\n \u2009=\u20090.82) in the rifampicin and placebo groups, respectively. There were 3 (0.8%) versus 16 (4.1%) bacteriological recurrences (\n p<\/jats:italic>\n \u2009=\u20090.01), and 55 (14.9%) versus 50 (12.9%) deaths without bacteriological failure\/recurrence (\n p<\/jats:italic>\n \u2009=\u20090.30) in the rifampicin and placebo groups, respectively. Over 12 weeks, there was no evidence of differences in clinically defined failure\/recurrence\/death (\n p<\/jats:italic>\n \u2009=\u20090.84), all-cause mortality (\n p<\/jats:italic>\n \u2009=\u20090.60), serious (\n p<\/jats:italic>\n \u2009=\u20090.17) or grade 3\/4 (\n p<\/jats:italic>\n \u2009=\u20090.36) adverse events (AEs). However, 63 (17.0%) participants in the rifampicin group versus 39 (10.1%) participants in the placebo group experienced antibiotic or trial drug-modifying AEs (\n p<\/jats:italic>\n \u2009=\u20090.004), and 24 (6.5%) participants in the rifampicin group versus 6 (1.5%) participants in the placebo group experienced drug-interactions (\n p<\/jats:italic>\n \u2009=\u20090.0005). Evaluation of the costs and health-related quality-of-life impacts revealed that an episode of\n S. aureus<\/jats:italic>\n bacteraemia costs an average of \u00a312,197 over 12 weeks. Rifampicin was estimated to save 10% of episode costs (\n p<\/jats:italic>\n \u2009=\u20090.14). After adjustment, the effect of rifampicin on total quality-adjusted life-years (QALYs) was positive (0.004 QALYs), but not statistically significant (standard error 0.004 QALYs).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with\n S. aureus<\/jats:italic>\n bacteraemia.\n <\/jats:p>\n <\/jats:sec>\n \n Future work<\/jats:title>\n Given the substantial mortality, other antibiotic combinations or improved source management should be investigated.<\/jats:p>\n <\/jats:sec>\n \n Trial registrations<\/jats:title>\n Current Controlled Trials ISRCTN37666216, EudraCT 2012-000344-10 and Clinical Trials Authorisation 00316\/0243\/001.<\/jats:p>\n <\/jats:sec>\n \n Funding<\/jats:title>\n \n This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in\n Health Technology Assessment<\/jats:italic>\n ; Vol. 22, No. 59. See the NIHR Journals Library website for further project information.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3310\/hta22590","type":"journal-article","created":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T05:54:42Z","timestamp":1541051682000},"page":"1-148","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia: the ARREST RCT"],"prefix":"10.3310","volume":"22","clinical-trial-number":[{"clinical-trial-number":"isrctn37666216","registry":"10.18810\/isrctn","type":"results"},{"clinical-trial-number":"2012-000344-10","registry":"10.18810\/euctr","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2858-2087","authenticated-orcid":true,"given":"Guy E","family":"Thwaites","sequence":"first","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford, Oxford, UK"},{"name":"Oxford University Clinical 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