SummaryBackgroundStaphylococcus 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.

Objectives: To evaluate differences in bone mineral density (BMD), calcium, and vitamin D status between the Gujarati (South Asian) and white populations resident in Leicester and to determine whether this was linked to lifestyle factors. Design: An observational cross sectional study of randomly selected Gujarati and white volunteers aged from 20-40 years. Setting: City of Leicester. Participants: Subjects were randomly selected by age (20-40 years) and ethnicity. A total of 262 individuals volunteered to participate, of which 201 (51 white females, 71 Gujarati females, 37 white males, 42 Gujarati males) were eligible for the study. Main outcome measures: Results of questionnaire, BMD at the hip and lumbar spine, and measurement of serum calcium, albumin, alkaline phosphatase, and 25-hydroxyvitamin D.Results: Male and female white subjects were significantly taller and heavier than their Gujarati counterparts. There was a statistically significant difference in BMD both at the spine (p<0.001) and hip (p<0.001) between the white and Gujarati females with the Gujaratis having a lower BMD. There was a trend for Gujarati males to have a lower BMD at the hip and spine than their white counterparts but these figures did not reach statistical significance. The intensity of cigarette smoking and the amount of alcohol consumption were both higher in the white male and female subjects. Sunlight exposure (>4 hours per day) was significantly higher in white subjects compared with Gujaratis. There were no significant differences in the mean level of serum calcium or alkaline phosphatase between the Gujaratis and whites. A significantly higher proportion (p<0.001) of the Gujarati men and women had a vitamin D level that was not measurable (that is, below the lower limit of the laboratory range of normal). Of those who had a measurable level (that is, in the normal range) mean levels of vitamin D were lower (p<0.05) in the Gujarati men and women. Conclusion: The present study is the first of its kind to note a low BMD in Gujarati subjects of South Asian origin compared with their white counterparts, living in Leicester. This study also confirms the presence of low serum vitamin D levels in Gujaratis. There is a need for more research in South Asians with regard to the collection of normal BMD values. This could provide a more meaningful reference range for identifying South Asians at risk of osteoporotic fractures and may have public health implications of relevance to this ethnic group.

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Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen, and morbidity and mortality rates associated with this pathogen have increased markedly in recent years. MRSA strains are generally resistant to several classes of antibiotics and are therefore difficult and costly to treat. A major issue is to identify the sources of MRSA infections and to monitor their epidemic spread. In this study, we report the development of a typing technique for S. aureus, based on single-nucleotide polymorphism (SNP) variations in and around SmaI-restriction sites (CCCGGG). An assessment of the SmaI restriction site-based multiplex PCR (SmaI-multiplex PCR) typing (SMT) with respect to pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) revealed a high level of concordance in the clustering of the test strains. The SmaI-multiplex PCR was found to be more discriminatory than MLST/staphylococcal cassette chromosome mec (SCCmec) typing but less discriminatory than PFGE. SMT can provide real-time information for the investigation of ongoing S. aureus hospital outbreaks. SMT meets the criteria of a practical typing method: it is simple, reproducible, and highly discriminatory and does not require expensive equipment or specialist expertise. Consequently, SmaI-multiplex PCR has the potential to be used in routine clinical microbiology laboratories.