In vitro bactericidal activity of amoxicillin combined with different cephalosporins against endocarditis-associated Enterococcus faecalis clinical isolates

International audienceBackground - The combination of amoxicillin with cefazolin could be an interesting regimen for the empirical therapy of severe infective endocarditis, but its activity against enterococci is unknown. Objectives - To evaluate in vitro the bactericidal activity of the combination of amoxicillin with different cephalosporins including cefazolin. Methods - Combinations of amoxicillin (at MIC×¼) with cefazolin, cefotaxime, ceftriaxone, cefepime, ceftaroline or ceftobiprole (at the mean free plasma concentration) were studied using time-kill experiments for 10 endocarditis-associated Enterococcus faecalis strains and 2 reference strains. Results - The combinations amoxicillin/cefazolin, amoxicillin/cefotaxime, amoxicillin/ceftriaxone and amoxicillin/cefepime were synergistic at 12 and 24 h against 12/12 strains and amoxicillin/ceftobiprole and amoxicillin/ceftaroline against 10/12 strains. The combination amoxicillin/cefepime was bactericidal at 24 h against 9/12 strains, the combination amoxicillin/cefazolin against 8/12 strains, the combinations amoxicillin/ceftaroline, amoxicillin/cefotaxime and amoxicillin/ceftobiprole against 7/12 strains and the combination amoxicillin/ceftriaxone against 6/12 strains. Conclusions - The combination amoxicillin/cefazolin is as synergistic and bactericidal in vitro as amoxicillin/cefotaxime or amoxicillin/ceftriaxone against E. faecalis

D7.1 First Data Management Plan

This first version of the Data Management Plan (DMP) follows in its core the template structure for an Open Research Data Pilot (ORDP) (section 3). The ORDP launched for all H2020 project has two functions: developing a DMP and providing open access to research data, this way to foster openness and re-use. Polifonia is a project operating between various humanities fields and content providers, relying on knowledge engineering and semantic web technologies as its primary mode of operation. From the specific features of Polifonia, specific requirements1 for the Data Management follow. To address this specificity, we have extended the formal template of the DMP with two sections. Section 1, the introduction, summarises the specific approach of Polifonia in the creation of a knowledge graph which incorporates various aspects of musical heritage (introducing the Polifonia Pilots). Section 2 reflects how the DMP is used to coordinate the collaboration inside of Polifonia. As we show, the process towards the DMP complements other cross-Work package activities, such as working on the Roadmap towards the Polifonia Portal (WP1) and the activities of the Technical Board. The interdisciplinary character of Polifonia and its envisioned mode of working (as described in the Description of Actions) has influenced what we eventually choose to document in this first version of the DMP. The core of the deliverable is section 3, the ORDP, which zooms into the Pilots as primary sources for data, even though not all of them are organized around a specific set of data. In other words, this DMP version maps out the legacy from which Polifonia starts. In later iterations of the Data Management Plan the focus will be shifted to components inherently use and produced in Polifonia. How this shift will be accompanied by the next two iterations of the Data Management Planning we discuss in the conclusion

D7.2 Data Management Plan (Second Version)

This second version of the Data Management Plan (DMP) follows the template structure for an Open Research Data Pilot (ORDP) (section 2). As elaborated in the first version of the DMP (Admiraal et al. 2021), we see data management planning as inherent part of the overall knowledge exchange coordination in the project, and therefore closely related to the development of the socio-technical roadmap (Guillotel-Nothmann et al. 2022). In the first section Introduction we summarise Polifonia’s approach towards data management planning. We further detail the progress made from the DMP version 1 to 2, and by which methods those were achieved. In section 2 Polifonia Data Management Plan, we use the ORDP template, to document the achievements of data management in Polifonia, and discuss main achievements of Polifonia such as the Polifonia Ecosystem, the Polifonia Knowledge Graph, and Polifonia Ontology and the Polifonia Portal from the point of view of best practices in data management. A short Outlook section summarises tasks and steps toward the DMP version 3

A new SARS-CoV-2 variant poorly detected by RT-PCR on nasopharyngeal samples, with high lethality: an observational study

International audienceObjectives - In early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a 'variant under investigation' (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant. Methods - Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown. Results - From 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73-88 versus 73 years, IQR 67-82, p < 0.05) and their first RT-PCR tests were rarely positive (6/39, 15% versus 31/32, 97%, p < 0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0, 95%CI 1.5-10.9) and increased lethality (28-day mortality 18/39 (46%) for B.1.616 versus 5/32 (16%) for VOC, p = 0.006). Conclusion - We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality