Genetics in the Prevention and Treatment of Sepsis

Abstract

Sepsis, the systemic response to acute infection, continues to be a leading cause of hospitalization, intensive care unit admission, and mortality in the United States despite significant advances in our understanding of sepsis pathogenesis and improvements in hospital-provided medical care [1, 2]. Modern hospital and intensive care unit practices, including early administration of antibiotics, fluid resuscitation, hemodynamic support, and mechanical ventilation, appear to be improving outcomes among patients with sepsis and septic shock [2, 3]. However, despite decades of research, the majority of clinic trials evaluating pharmacologic therapies targeting the host response to infection have demonstrated inconsistent or negative results [4--14]. The potential of genetics to improve the prevention and treatment of sepsis lies in furthering our understanding of the heterogeneity in host responses to infection, identifying those infected individuals at highest risk of incident sepsis, multi-organ system failure, or death, and selecting patients most likely to benefit from therapies targeted at sepsis pathogenesis.