Oral Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

The INFECT-project; a multicentre prospective study on necrotizing soft tissue infections: from clinics to pathogenesis to intervention. (#69)

Anna Norrby-Teglund 1 , Mattias Svensson 1 , Ole Hyldegaard 2 , Michael Nekludov 3 , Ylva Karlsson 4 , Per Arnell 5 , Malak Kotb 6 , Dietmar Pieper 7 , Vitor Martins dos Santos 8 , Francois Vandenesch 9 , Christoph Reschreiter 10 , Doreen Marsden 11 , Eytan Ruppin 12 , INFECT study group 1
  1. Karolinska Institutet, Stockholm, STOCKHOLM, Sweden
  2. Rigshospitalet, Copenhagen, Denmark
  3. Karolinska University Hospital, Stockholm, Sweden
  4. Blekinge Hospital , Karlskrona, Sweden
  5. Sahlgrenska University Hospital, Gothenburg, Sweden
  6. University of North Dakota, grand Forks, USA
  7. Helmholtz Institute for Infection Research, Braunschweig, Germany
  8. Wageningen University, Wageningen, The Netherlands
  9. University of Lyon, Lyon, France
  10. CUBE, St Valentin, Austria
  11. The Lee Spark Foundation, Preston, UK
  12. University of Tel Aviv , Tel Aviv, Israel

The INFECT-project focuses on necrotizing soft tissue infections (NSTIs), which are rapidly spreading life-threatening infections. Diagnosis and management are difficult due to heterogeneity in clinical presentation, in co-morbidities and in microbiological aetiology. The project builds on eight work packages (WPs) including: WP2, recruitment of NSTI patients and patient samples, and experimental models; a murine NSTI model (WP1) and a human tissue model (WP6). Samples from infected individuals/models are analysed for host and pathogen traits by genomics, transcriptomics, proteomics and metabolomics (WP3-6). All data are analyzed in relation to clinical parameters by integrated computational modelling (WP4) to identify involved pathways/networks and disease traits that are used for development of novel diagnostic tests (WP7). WP8 aims to disseminate and exploit the results through implementation of improved guidelines and novel diagnostics and therapeutics. In INFECT, >400 NSTI patients have been enrolled and >6000 biobank samples collected. Beta-hemolytic streptococcus was the most common cause of infection. Through a forward systems genetics approach using BXD mice, the IL1β network was identified as a key network involved in modulating the susceptibility to infection. This was further supported by analysis of patient plasma and tissue biopsies as well as infected human skin tissue model. Other key findings of INFECT include, among others, identification of 1) bacterial biofilm in infected tissue which can contribute to reduced antibiotic efficacy, and 2) bacterial pore-forming toxins as central mediators of tissue necrosis.