Sepsis: a roadmap for future research.
Sepsis is a common and lethal syndrome: although outcomes have improved, mortality remains high. No specific anti-sepsis treatments exist; as such, management of patients relies mainly on early recognition allowing correct therapeutic measures to be started rapidly, including administration of appropriate antibiotics, source control measures when necessary, and resuscitation with intravenous fluids and vasoactive drugs when needed. Although substantial developments have been made in the understanding of the basic pathogenesis of sepsis and the complex interplay of host, pathogen, and environment that affect the incidence and course of the disease, sepsis has stubbornly resisted all efforts to successfully develop and then deploy new and improved treatments. Existing models of clinical research seem increasingly unlikely to produce new therapies that will result in a step change in clinical outcomes. In this Commission, we set out our understanding of the clinical epidemiology and management of sepsis and then ask how the present approaches might be challenged to develop a new roadmap for future research.
Brighton and Sussex Medical School, Brighton, UK. Electronic address: j.cohen@bsms.ac.uk.
Jonathan
J
Cohen
University of Brussels, Erasme University Hospital, Brussels, Belgium.
Jean-Louis
JL
Vincent
Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and University of Toronto, Toronto, ON, Canada.
Neill K J
NK
Adhikari
Department of Anesthesiology and Intensive Care, Federal University of São Paulo, São Paulo, Brazil.
Flavia R
FR
Machado
Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Derek C
DC
Angus
Infectious Diseases Service and Institute of Microbiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Thierry
T
Calandra
Infectious Diseases Service and Institute of Microbiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Katia
K
Jaton
Infectious Diseases Service and Institute of Microbiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Stefano
S
Giulieri
Infectious Diseases Service and Institute of Microbiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Julie
J
Delaloye
Infectious Disease Division, Alpert Medical School of Brown University, Providence, RI, USA.
Steven
S
Opal
Feinstein Institute for Medical Research, Manhasset, NY, USA.
Kevin
K
Tracey
Centre of Experimental and Molecular Medicine, Academic Medical Centre, University of Amsterdam, Netherlands; Division of Infectious Diseases, Academic Medical Centre, University of Amsterdam, Netherlands.
Tom
T
van der Poll
Office of Anti-infectives and Vaccines, Human Medicines Evaluation Division, European Medicines Agency, London, UK.
Eric
E
Pelfrene
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D035843:Biomedical Research / Q000639:trends*; D002986:Clinical Trials as Topic; D019468:Disease Management; D005544:Forecasting; D054884:Host-Pathogen Interactions; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D015994:Incidence; D058990:Molecular Targeted Therapy; D057285:Precision Medicine; D018805:Sepsis / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology
D000900:Anti-Bacterial Agents; D007155:Immunologic Factors