title: Therapeutic Targets in Sepsis: Past, Present, and Future.
abstract: Antibiotics and fluids have been standard treatment for sepsis since World War II. Many molecular mediators of septic shock have since been identified. In models of sepsis, blocking these mediators improved organ injury and decreased mortality. Clinical trials, however, have failed. The absence of new therapies has been vexing to clinicians, clinical researchers, basic scientists, and the pharmaceutical industry. This article examines the evolution of sepsis therapy and theorizes about why so many well-reasoned therapies have not worked in human trials. We review new molecular targets for sepsis and examine trial designs that might lead to successful treatments for sepsis.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, 400 Parnassus Avenue, 5th Floor ACC, San Francisco, CA 94143, USA. Electronic address: eric.seeley@ucsf.edu.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Seeley
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Bernard
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D006801:Humans; D018805:Sepsis / Q000188:drug therapy*; D012772:Shock, Septic / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents
keywords: Antibiotics; Sepsis; Therapeutic targets; Treatment