The Lancet Infectious Diseases CommissionSepsis: a roadmap for future research
Section snippets
Introduction: facing the challenge of sepsis
Patients with sepsis—a severe infection associated with organ dysfunction1—constitute a large proportion of the critically ill population and, although outcomes have improved,2 mortality remains higher than 25–30%, and even 40–50% when shock is present.3 No effective specific anti-sepsis treatments exist, therefore management of patients with sepsis relies mainly on early recognition allowing correct therapeutic measures to be started rapidly, including administration of appropriate
An unresolved issue
An important difference exists between a definition that is used to identify an individual who has a specific disorder and a definition that is used for epidemiological purposes. The former definition might have therapeutic, prognostic, or sociological implications for the patient and will need to be pragmatic and easy to apply. By contrast, an epidemiological definition will often be used for clinical trials or for public health surveillance reasons and will need to be as robust and rigorous
The global epidemiology of sepsis
Sepsis is both one of the best known yet most poorly understood medical disorders. First recognised by Hippocrates, sepsis can be described as the state in which a host mounts an inflammatory response to an invading pathogen with poor results. The lay definition states that sepsis is a life-threatening disorder that arises when the body's response to an infection injures its own tissues and organs. Sepsis leads to shock, multiple organ failure, and death, especially if not recognised early and
Diagnostic microbiology
Diagnostic microbiology stands at the epicentre of the tests for sepsis in patients. Nowadays, microbiological studies for the detection of bacteria or fungi in blood, body fluids, or relevant tissues continue to rely for the most part on conventional culture-based systems, which remain the gold standard. Blood cultures are positive in 30–40% of patients with severe sepsis and septic shock.123 In most instances bloodstream infections are intermittent and the circulating microbial loads are low,
Molecular targets and experimental therapies for sepsis
Conventional management principles with timely administration of intravenous fluids, oxygen, and antimicrobials combined with so-called source control, drainage of infectious foci, and advanced organ support in an intensive-care setting have reduced the overall mortality of severe sepsis to historically low rates (<20%).2, 7 Regrettably, long-term outcomes suggest that substantial residual morbidity and excess mortality risks persist for survivors after initial treatment for septic shock. The
Failure of clinical sepsis trials
As we have noted earlier, although the outcome of patients with sepsis has improved substantially in recent years,2, 51 this improvement in outcome has not been accomplished by any of the many adjuvant therapies tested in more than 100 phase 2 and phase 3 clinical sepsis trials.308, 309 Rather, the improved sepsis prognosis is probably mainly caused by an increased recognition and faster intervention by health-care services for cases of sepsis than was previously achieved, possibly due to
Sepsis: a call to action
In conceiving and writing this Commission, our intent has been two fold. The first was to describe the present status of what is one of those most challenging medical disorders in routine clinical practice, and the second, to identify those areas in which we think research is most crucial in driving forward transformational change. This second intent, what we have called the roadmap for the future, has informed this call to action (panel 2). We acknowledge that we have intentionally left
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