Emerging drugs for the treatment of sepsis.
BACKGROUND
Despite improvement in medical care, severe sepsis and septic shock remain an unmet medical need. Their incidence is steadily increasing and the worldwide mortality ranges between 30% and 50%. This generates the need for agents that modulate the immune function of the host.


METHODS
Available agents can be divided into three categories according to their mechanism of action: i) agents that block bacterial products and inflammatory mediators. Hemoperfusion with polymyxin B embedded fiber device that blocks bacterial lipopolysaccharides (LPS) has given promising clinical results. Blockade of TNF-α with afelimomab and CytoFab appears promising; ii) modulators of immune function. Hydrocortisone stress replacement, intravenous infusion of clarithromycin and immunonutrition with omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) have all yielded positive clinical results. Recombinant thrombomodulin for patients with disseminated intravascular coagulation appears a promising alternative; and iii) immunostimulation. Meta-analysis of conducted trials disclosed the decrease of mortality in septic shock after administration of immunoglobulin preparations enriched with IgM.


CONCLUSIONS
The underlying pathophysiologic mechanisms in septic patients are highly individualized. As such, specific tools should be developed in the near future to define these differences and tailor therapeutic strategies accordingly.
University of Athens, Medical School, 4th Department of Internal Medicine, Athens, Greece.
Antigone
A
Kotsaki
Evangelos J
EJ
Giamarellos-Bourboulis
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D005938:Glucocorticoids; D007155:Immunologic Factors