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

The molecular epidemiology of Giardiasis in South-west London

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The molecular epidemiology of Giardiasis in South-west London

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Cutaneous Mycobacterium kansasii Infection: Case Report and Review

A case of cutaneous Mycobacterium kansasii infection is reported, and 28 similar cases are reviewed. Cutaneous infection may resemble sporotrichosis and is often associated with systemic illness, immunosuppression, skin pathology, or contact with contaminated water. Immunosuppressed patients with M. kansasii infection may present with atypical clinical features (such as cellulitis and seroma) and atypical histology (absence of granulomas), which may delay diagnosis and effective treatment. The incidence of disseminated M. kansasii infection, which has a worse prognosis, is higher among immunosuppressed patients. When M. kansasii infection is confined to the skin, the disease is usually indolent. Chemotherapy with a variety of agents, including traditional antituberculous agents as well as erythromycin, minocycline, and doxycycline, has been successful, although in vitro resistance to isoniazid and p-aminosalicylic acid is common. Reducing the dose of corticosteroids may be a beneficial adjunct to therapy for M. kansasii infection

Multiple drug-resistant mycobacterium tuberculosis:Evidence for changing fitness following passage through human hosts

Recent studies have shown a difference in the genotype of resistant bacteria following passage in animals compared to those passaged in vitro. This suggests that organisms rapidly adapt to their environment of growth. We sought to investigate whether this phenomenon occurred in human infection and whether changes could be detected in the fitness (growth velocity) of isolates transmitted between human hosts. Isogenic strains of Mycobacterium tuberculosis were obtained from a well-documented hospital outbreak. The subjects included those who were HIV seropositive and immunocompromised. The relative fitness of each sample was measured using growth competition in vitro. The results confirmed that our method of measuring fitness was not influenced by the storage conditions of the isolates, and demonstrated that the fitness of genetically similar isolates obtained from different patients in the outbreak differed significantly, as reflected in the growth velocity of the strains. This study provides the first evidence that multiple drug resistant M. tuberculosis strains adapt to the environment of their human host