Recent developments in the identification of novel therapeutic targets for the treatment of patients with sepsis and septic shock.

The overall mortality in patients with sepsis is approximately 30%; this figure increases to 50% or higher in patients with septic shock, and sepsis continues to be seen as a major clinical challenge. The recent success of several important trials has fuelled interest in further therapeutic developments. Here, I review the many different strategies that are being investigated, focusing in particular on those that are in late pre-clinical or early clinical development. These can be broadly divided into three groups: strategies aimed at bacterial targets, strategies aimed at disorders of immune regulation in the host, and finally, other novel strategies based on modifying host response; which, if any, of these will prove successful in large clinical trials is unknown. Nevertheless, the fact that sepsis has finally proved tractable as a target for new drug development lends support to those who believe that at least some of the compounds identified in this paper will prove to have clinical benefit.