Barriers to the effective treatment of sepsis: Antimicrobial agents, sepsis definitions, and host-directed therapies

Ngan H. Lyle, Olga M. Pena, John H. Boyd, Robert E.W. Hancock

Research output: Contribution to journalArticle

39 Citations (Scopus)


Sepsis is a complex clinical syndrome involving both infection and a deleterious host immune response. Antimicrobial agents are key elements of sepsis treatment, yet despite great strides in antimicrobial development in the last decades, sepsis continues to be associated with unacceptably high mortality (∼30%). This is the result, on one hand, of the rise of antimicrobial resistant organisms and, on the other hand, of the dearth of effective host-directed immune therapies. A major obstacle to the development of good host-directed therapies is the lack of understanding of the host immune response. The problem is exacerbated by poor nonspecific clinical definitions of disease. Poor definitions have had a profound impact on sepsis research, from epidemiologic studies to the failed clinical trials of host-directed therapies. Therefore, better definitions must be developed to enable advancement in the field.

Original languageEnglish
Pages (from-to)101-114
Number of pages14
JournalAnnals of the New York Academy of Sciences
Issue number1
Publication statusPublished - 1 Sep 2014
Externally publishedYes


  • Antimicrobial resistance
  • Host-directed therapies
  • Immunology
  • Sepsis
  • Sepsis definitions

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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