REVIEW
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Emerging therapies for the treatment of sepsis.

PURPOSE OF REVIEW: Sepsis affects patients of all ages with multiple comorbidities and underlying diagnoses, and is the result of infection by many potential pathogens infecting various organs or sites. Many molecules have been clinically tested in recent years for their potential immunomodulatory effects, but have been shown to have no beneficial effects on outcomes in heterogeneous populations of patients with sepsis. There are, therefore, no specific antisepsis therapies and mortality and morbidity rates remain high despite improved overall management of these patients. This review covers promising agents currently used in clinical trials.

RECENT FINDINGS: There are several candidates currently undergoing early and later phase of clinical testing, including thrombomodulin, alkaline phosphatase, interferon-beta, and selepressin. Other approaches including immunoglobulins, extracorporeal therapies, and pharmaconutrients will also be discussed.

SUMMARY: Despite multiple trials of potential therapies for sepsis, no strategies have yet been persistently shown to have beneficial effects on outcomes. The main reason for the disappointing results is that patient populations in these studies have been too heterogeneous. Selecting patients on the basis of general symptoms is not enough. Rather patients should be selected according to the likely action of the drug in question. To achieve this, improved biomarkers of sepsis and of the immune response are needed and the activities of the individual agents need to be carefully characterized. New candidates are being developed and the results of ongoing and recent clinical trials of immunomodulatory therapies are eagerly awaited as new therapies for sepsis are urgently needed.

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