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

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

Non-Nutritive Sweeteners in the Packaged Food Supply—An Assessment across 4 Countries

Increased interest among consumers in the reduction of dietary sugar intake has led to the wider availability of food products containing non-nutritive sweeteners (NNS). However, the extent to which NNS are currently being used by manufacturers to sweeten processed food and beverage products, and how NNS may be displacing added sugars as a sweetener is unknown. The current study utilized branded food composition databases from Australia, Mexico, New Zealand and the US to determine the percentage of processed food and beverage products for which there are nutrition data containing NNS and to compare total sugar density (g per 100 mL for beverages and g per 100 g for foods) between products with and without NNS. Ordinary least squares regression at the country-product level was performed to examine associations between presence of NNS and total sugar. Across all countries, 5% of products contained at least one NNS, with the highest prevalence among beverages (22%). Mexico had the highest percentage of products with NNS (11%), as compared to the United States (US) (4%), New Zealand (1%), and Australia (<1%). The presence of NNS was associated with lower mean total sugar density among beverages (range across countries: 7.5 to 8.7 g per 100 mL) and among foods (23.2 to 25.5 g per 100 g). Products with both added sugar ingredients and NNS had a lower overall mean total sugar density when compared to products containing only added sugar ingredients. Due to paucity of data on sales and market shares across these countries, our results do not reflect the extent to which consumers purchase NNS containing products. Continued monitoring of NNS in the food supply, extension of work from these data, and inclusion of market shares of products will be important as more countries introduce policies to reduce sugar