The highly heterogeneous NSTIs require an individualized analysis approach, as different pathogenic mechanisms are likely to be involved and consequently, different individualized therapeutic approaches are warranted. Such analyses require a customized approach in which each patient is linked to its own infecting isolate.
In this WP, we will corroborate the data generated in WP1, 2, 3 and 4 and by assessment of these factors at the local site of infection (i.e. tissue from NSTI patients collected in WP2 as well as tissue from the infected mice from WP1). Also analyses of mechanistic action of specific therapies by assessment of patient samples collected pre- and post-therapy will be done. Such an approach will provide a comprehensive understanding of these infections and should provide information as to the mechanistic action/efficacy of novel therapies. An essential aspect on this project is the unique availability of tissue biopsy material and the expertise of Partner 1 in visualization and cellular imaging that allow direct assessment of host-microbe interaction at the local site of infection, i.e. the tissue milieu; thereby providing results of direct clinical relevance. Tissue biopsy material collected from NSTI patient for the bio bank include snap frozen tissue biopsies taken at the epicenter of infection and in distal areas, as well as from the surgical sites pre- and post-therapy (HBO and/or IVIG). From most patients, biopsies will be available from repeated surgical procedures during the acute phase of infection.