Archive for January 16, 2018

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

Lancet. 2017 Dec 14. pii: S0140-6736(17)32456-X. [Epub ahead of print]

Thwaites GE1, Scarborough M2, Szubert A3, Nsutebu E4, Tilley R5, Greig J6, Wyllie SA7, Wilson P8, Auckland C9, Cairns J3, Ward D3, Lal P10, Guleri A11, Jenkins N12, Sutton J13, Wiselka M14, Armando GR15, Graham C16, Chadwick PR17, Barlow G18, Gordon NC2, Young B2, Meisner S19, McWhinney P20, Price DA21, Harvey D22, Nayar D23, Jeyaratnam D24, Planche T25, Minton J26, Hudson F3, Hopkins S27, Williams J28, Török ME29, Llewelyn MJ30, Edgeworth JD31, Walker AS32; United Kingdom Clinical Infection Research Group (UKCIRG).

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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.


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.


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).


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


UK National Institute for Health Research Health Technology Assessment.



January 16, 2018 at 11:05 am

Predictors of pneumonia in lower respiratory tract infections: 3C prospective cough complication cohort study.

European Respiratory Journal November 22, 2017 V.50 N.5   

Moore M1, Stuart B2, Little P2, Smith S3, Thompson MJ4, Knox K3, van den Bruel A3, Lown M2, Mant D3.

Author information

1 University of Southampton, Primary Care Medical Group, Aldermoor Health Centre, Southampton, UK

2 University of Southampton, Primary Care Medical Group, Aldermoor Health Centre, Southampton, UK.

3 Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK.

4 Dept of Family Medicine, University of Washington, Seattle, WA, USA.


The aim was to aid diagnosis of pneumonia in those presenting with lower respiratory tract symptoms in routine primary care.A cohort of 28 883 adult patients with acute cough attributed to lower respiratory tract infections (LRTIs) was recruited from 5222 UK practices in 2009-13. Symptoms, signs and treatment were recorded at presentation and subsequent events followed-up for 30 days by chart review. The predictive value of patient characteristics, presenting symptoms and clinical findings for the diagnosis of pneumonia in the first 7 days was established.Of the 720 out of 28 883 (2.5.%) radiographed within 1 week of the index consultation, 115 (16.0%; 0.40% of 28 883) were assigned a definite or probable pneumonia diagnosis. The significant independent predictors of radiograph-confirmed pneumonia were temperature >37.8°C (RR 2.6; 95% CI 1.5-4.8), crackles on auscultation (RR 1.8; 1.1-3.0), oxygen saturation <95% (RR 1.7; 1.0-3.1) and pulse >100·min-1 (RR 1.9; 1.1-3.2). Most patients with pneumonia (99/115, 86.1%) exhibited at least one of these four clinical signs; the positive predictive value of having at least one of these signs was 20.2% (95% CI 17.3-23.1).In routine practice, radiograph-confirmed pneumonia as a short-term complication of LRTI is very uncommon (one in 270). Pulse oximetry may aid the diagnosis of pneumonia in this setting.


January 16, 2018 at 11:01 am


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