The CSCC coordinates and supports translational and clinical research on life-threatening infections, in particular on sepsis and its sequelae. Advancing translation from results of basic research to improved prevention, diagnosis and therapy is crucial in this connection. Accordingly, transdisciplinary exchange and collaboration are central elements of the research activities.
Four research areas shape the scientific profile of the CSCC:
Bugs – difficult-to-treat infections
Prevention of infections and optimized treatment are core topics in sepsis prevention. The spectrum of microbes causing invasive infection and sepsis has been changing markedly over the last decades. With the demographic change and consequently growing numbers of prosthetic implants, systemic infections increasingly emerge from biofilms that are poorly accessible for standard antibiotic regimens. Multi-resistant bacteria and fungi, not covered by the commonly used empiric antibiotic treatment, are on the rise and associated with increased mortality. Translational projects and clinical studies within this research area specifically focus on difficult-to-treat infections, aiming to improve our understanding of their biology and to optimize diagnosis, treatment, and clinical management. Moreover, microbial strategies for persistence in host organisms and cells are investigated in the research area Bugs. Thus, this section builds bridges to research topics of the excellence cluster of the Friedrich Schiller University.
Drugs – novel strategies for antimicrobial therapy
Numerous studies have shown that inappropriate antimicrobial treatment, e.g. due to antimicrobial resistance, underdosing, and / or delayed initiation, dramatically increases mortality in sepsis. The research area Drugs therefore investigates strategies for optimizing therapies of sepsis and infectious diseases. This includes strategies for rapid therapy initiation, optimized use of antibiotics as well as pharmacological approaches to targeted therapies of organ and tissue damage as well as sepsis sequelae. The research area, thus, contributes to strengthen connections between the CSCC research areas and between collaborative research consortia at the Friedrich Schiller University and clinical research at the Jena University Hospital.
Damage – targeted strategies in organ failure
Sepsis is the predominant cause of multi-organ failure, which determines prognosis in the critically ill. The current concept assumes that end organ failure results from an uncontrolled inflammatory response; yet, strategies to neutralize mediators of inflammation have failed to improve outcome in numerous trials. Mounting evidence suggests that cell type-specific activation and control of signaling events mediate development or resolution of organ dysfunction. Projects in the research area Damage address sepsis-induced remote organ failure with the long-term goals to cell- and tissue-specifically interfere with the underlying pathophysiology and to identify and explore potential novel “drugable” targets. Further, strategies are devised to quickly transfer promising results to preclinical testing. The concomitant development of diagnostic and theranostic strategies will help us to avoid the common discrepancy between success in animal testing and failure of adjunctive interventions in clinical trials.
In view of current developments of microbiome research and the recent success of the Friedrich Schiller University in the German Excellence Initiative, the research field increasingly opens to the investigation of interactions of commensal and pathogenic microbiota with the human host. In addition to strengthened collaboration with institutions of the University, the research area thus also tightens connections to the research area Bugs, which amongst others investigates the molecular interactions between microbiome, immune system and host parenchymal tissues.
Repair – post-acute care and (long-term) outcome research
Beside prevention, early diagnosis, and rapid treatment, mid- and long-term care of sepsis survivors eminently impact overall outcome and quality of life of patients suffering from sepsis. Whereas recent data show that sepsis-related mortality in ICUs and hospitals has steadily decreased over the last decade, detailed epidemiological data on sepsis morbidity in the mid- and long-term are lacking. Despite the high clinical relevance, biological mechanisms causing characteristic disease symptoms of patients in the long-term outcome are only rudimentarily understood and treatment options are missing. The lowered sepsis-related mortality has resulted in a larger number of patients and their relatives, who face mid- and long-term consequences of sepsis, thus leading to an increasing burden of disease, which is also becoming continuously more important in public health care.
The research area Repair addresses current knowledge gaps and medical need regarding mid- and long-term consequences of sepsis. The questions are addressed, on the one hand, from a clinical point of view and in close connection to the research area Damage. On the other hand, possibilities are explored to reduce social and mental problems of sepsis survivors. Moreover, the research area continuously opens to approaches of health services research. Based on the results of the Mid-German Sepsis Cohort, questions relevant to this end are expected to arise. Repair thus covers a broad spectrum ranging sepsis prevention to improved care for sepsis survivors.