title: The failure of biologics in sepsis: where do we stand?
abstract: The failure of the PROWESS-SHOCK study of recombinant human activated protein C (drotrecogin alfa) has generated much scepticism about the future of immunomodulatory interventions in sepsis. This review presents a summary of the few remaining promising strategies for immunointervention. These comprise intravenous clarithromycin, haemoperfusion through a polymyxin B-embedded fibre device (PMX-B), recombinant thrombomodulin (rTM) and intravenous immunoglobulin preparations enriched in IgM and IgA (IgMA). The great heterogeneity in the pathophysiology of sepsis mandates a highly individualised approach. This approach comprises: septic shock and multiple organ dysfunction syndrome arising in the field of ventilator-associated pneumonia as an indication for intravenous clarithromycin; abdominal severe sepsis/shock for PMX-B haemoperfusion; sepsis and acute coagulopathy for rTM; and early septic shock for IgMA. However, specific diagnostic tools should be developed to make this personalised approach more robust.
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece. egiamarel@med.uoa.gr
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
mesh_terms: D001688:Biological Products / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D018805:Sepsis / Q000628:therapy*; D017211:Treatment Failure
chemical_list: D001688:Biological Products; D007155:Immunologic Factors