DNA fingerprinting analysis of coagulase negative staphylococci implicated in catheter related bloodstream infections

AIMS: The epidemiological assessment of cases of coagulase negative staphylococcal catheter related bloodstream infection. METHODS: Two hundred and thirty patients with suspected catheter related bloodstream infection were evaluated over a two year period. Central venous catheters were cultured both endoluminally and extraluminally. Peripheral blood, catheter hubs, skin entry, and skin control sites were also cultured. Pulsed field gel electrophoresis (PFGE) was used to DNA fingerprint coagulase negative staphylococci isolated from patients with presumptive catheter related bloodstream infection. RESULTS: Sixty cases of catheter related bloodstream infection were identified, 21 of which were attributed to coagulase negative staphylococci. Two hundred and ninety four separate isolates of coagulase negative staphylococci from the 21 cases of catheter related bloodstream infection were subjected to PFGE (mean of 14 for each case). Catheter related bloodstream infection was only confirmed by PFGE analysis in 16 of the 21 cases because in the remaining five cases peripheral blood and central venous catheter coagulase negative staphylococci isolates were different. Skin entry, control skin, and central venous catheter hub isolates matched peripheral blood isolates in six, four, and seven cases, respectively. Coagulase negative staphylococci isolates could not be cultured from the patients’ own skin in seven cases of catheter related bloodstream infection. Central venous catheter lumens were colonised in all cases of catheter related bloodstream infection compared with 44–81% of cases that had positive external surface catheter tip cultures, depending on the threshold used to define significant growth. CONCLUSIONS: Catheter related bloodstream infection as a result of coagulase negative staphylococci may be over stated in about a quarter of cases, unless a discriminatory technique is used to fingerprint isolates. No single, simplistic route of bacterial contamination of central venous catheters was identified, but endoluminal catheter colonisation is invariably present in cases of catheter related bloodstream infection. The use of central venous catheters as a means of access for monitoring and as a route of administration of drugs has become almost mandatory in patients with serious illnesses. Infections of central venous catheters are common and coagulase negative staphylococci remain the most frequent pathogens—for example, 37% of 1267 isolates in one meta-analysis.Controversy remains over the source of, and route of access by, these bacteria to the central venous catheters. Recent developments, such as catheters with antimicrobial properties, are an important advance, but until such issues are resolved it remains unclear how best to reduce the risk of catheter related bloodstream infection. “Pulsed field gel electrophoresis is well recognised as the gold standard for fingerprinting coagulase negative staphylococci” Because there are at least 33 distinct coagulase negative staphylococci species that have been identified, and because methods that use phenotyping alone cannot accurately distinguish between strains of coagulase negative staphylococci, DNA fingerprinting is required to clarify the epidemiology of coagulase negative staphylococci catheter related bacterial bloodstream infection. Despite the accepted difficulties in determining the relatedness of coagulase negative staphylococci, diagnostic laboratories routinely rely on limited information from phenotypic tests to compare isolates fro

Drug-like antagonists of P2Y receptors — from lead identification to drug development

P2Y receptors are expressed in virtually all cells and tissue types and mediate an astonishing array of biological functions, including platelet aggregation, smooth muscle cell proliferation, and immune regulation. The P2Y receptors belong to the G protein-coupled receptor superfamily and are composed of eight members encoded by distinct genes that can be subdivided into two groups on the basis of their coupling to specific G-proteins. Extensive research has been undertaken to find modulators of P2Y receptors, although to date only a limited number of small-molecule P2Y receptor antagonists have been approved by drug/medicines agencies. This Perspective reviews the known P2Y receptor antagonists, highlighting oral drug-like receptor antagonists, and considers future opportunities for the development of small molecules for clinical evaluation

Christianity, Calamity, and Culture: The Involvement of Christian Churches in the 1998 Aitape Tsunami Disaster Relief

This paper considers the links between religion and disaster relief through a detailed case study of the activities of Christian churches following the Aitape tsunami of 1998 in northwest Papua New Guinea. Based on primary fieldwork data, we argue that Christian religion was central to the way in which the Combined Churches Organization conducted its relief work and to why it sought to undertake it in the first place. A comparison of the perspectives of this organization and of other religious and governmental organizations as to the causes of this disaster and what remedies they should undertake suggests that greater attention should be paid—both by aid and development researchers and practitioners—to aspects of religious belief and the way they inform theory and practice. Much remains to explore concerning the ways religion informs the theory and practice of aid and development, particularly in the Pacific. Through the detailed case study offered here, this paper adds to the fledgling debate engaging with the links between religion and development and calls for the initiation of an agenda toward that end

Learning for life: A case study on the development of online community radio

In a context of social disaffection and economic crisis, acquiring the skills that promote employability and social participation is an increasing priority. RadioActive Europe is a project that addresses these issues, offering non-formal learning through Internet radio. This article analyzes the implementation of the project in Portugal amongst groups of young people in vulnerable contexts. Our findings suggest that participatory action-research and media education are valuable ways of empowering youngsters from deprived contexts, complementing the constraints of formal schooling.En un contexto de disgregación y crisis social, la adquisición de competencias que permitan aumentar las oportunidades de empleo y promuevan una ciudadanía más involucrada se ha ido haciendo cada vez más prioritaria. El proyecto RadioActive Europe surge en este contexto, proponiendo un aprendizaje no formal a partir de una radio ubicada en Internet. Este artículo examina la implantación del proyecto en Portugal, como una iniciativa dirigida a jóvenes en situaciones vulnerables. Se debate el potencial de proyectos de investigación-acción participativa y de la educación para los medios como forma de empoderar a jóvenes en contextos desfavorecidos, como com

Inviting backchat: how schools and communities in Ghana, Swaziland and Kenya support children to contextualize knowledge and create agency through sexuality education

Education about sex, relationships and HIV and AIDS in African contexts is riddled with socio-cultural complexity. In this paper the authors argue that in extreme contexts education can lead change further by developing young people as significant actors in their own lives and in the lives of the community by bringing bring about change in attitudes in the community, as well as practices in schools. A qualitative study was undertaken in eight primary schools of the use of student knowledge and voice to change attitudes, impact upon socio cultural beliefs, adult-child dialogue and drive changes in practice in AIDS education. Drawing on a contextual framework that includes a socio-cultural approach to education, Basil Bernstein’s well established theories of everyday and school knowledge and Catherine Campbell’s notion of AIDS competent communities, it shows how this initiative variably unfolded in six sub-Saharan countries (Botswana, Ghana, Kenya, South Africa, Swaziland and Tanzania, – although only the latter three are discussed in detail) and analyses the potential of schools to operate for the benefit of children in difficult circumstances, especially with regard to poverty, gender, sexual violence and health. Participation, dialogue and agency were the key factors

Exploring the use of new school buildings through post-occupancy evaluation and participatory action research

This paper presents the results of the development and testing of an integrated post-occupancy evaluation (POE) approach for teachers, staff, pupils and community members using newly constructed school buildings. It focusses on three cases of UK secondary schools, demonstrating how users can be inspired to engage with the problems of school design and energy use awareness. The cases provided new insights into the engagement of school teachers, staff and young people regarding issues of sustainability, management, functional performance and comfort. The integrative approach adopted in these cases provided a more holistic understanding of these buildings’ performance than could have been achieved by either observational or more traditional questionnaire-based methods. Moreover, the whole-school approach, involving children in POE, provided researchers with highly contextualised information about how a school is used, how to improve the quality of school experiences (both socially and educationally) and how the school community is contributing to the building's energy performance. These POE methods also provided unique opportunities for children to examine the social and cultural factors impeding the adoption of energy-conscious and sustainable behaviours

Synthesis and evaluation of the first fluorescent antagonists of the human P2Y2 receptor based on AR-C118925

The human P2Y2 receptor (hP2Y2R) is a G protein-coupled receptor that shows promise as a therapeutic target for many important conditions including anti-metastatic cancer therapy and more recently for the treatment of idiopathic pulmonary fibrosis. As such, there is a need for new hP2Y2R antagonists and molecular probes to study this receptor. Herein, we report the development of a new series of non-nucleotide hP2Y2R antagonists leading to the discovery of a series of fluorescent ligands containing different linkers and fluorophores based on the known, non-nucleotide hP2Y2R antagonist AR-C118925 (1). One of these conjugates 98 displayed micromolar affinity for the hP2Y2R (pKd = 6.32 ± 0.10; n=17) using a bioluminescence energy transfer (BRET) assay. Confocal microscopy with this ligand revealed displaceable membrane labeling of astrocytoma cells expressing un-tagged hP2Y2R. These properties, make 98 one of the first tools for studying hP2Y2R distribution and organization