title: Immunomodulatory adjuvant therapy in severe community-acquired pneumonia.
abstract: Severe pneumonia has a high mortality (38.2%) despite evidence-based therapy. Rising rates of antimicrobial resistance increase the urgency to develop new treatment strategies. Multiple adjuvant therapies for pneumonia have been investigated but none are currently licensed. Profound immune dysregulation occurs in patients with severe infection. An initial hyper-inflammatory response is followed by a secondary hypo-inflammatory response with 'immune-paralysis'. There is focus on the development of immunostimulatory agents to improve host ability to combat primary infection and reduce secondary infections. Successful treatments must be targeted to immune response; promising biomarkers exist but have not yet reached common bedside practice. We explore evidence for adjuvant therapies in community-acquired pneumonia. We highlight novel potential treatment strategies using a broad-based search strategy to include publications in pneumonia and severe sepsis. We explore reasons for the failure to develop effective adjuvant therapies and highlight the need for targeted therapy specific to immune activity.
authors.affiliation: Liverpool School of Tropical Medicine - Clinical Sciences, Pembroke Place, Liverpool L3 5QA, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Morton
authors.forename: Shaun Harry
authors.initials: SH
authors.lastname: Pennington
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D011014:Pneumonia / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D007155:Immunologic Factors
keywords: GM-CSF; IFN-γ; IL-7; augmented passive immunotherapy; critical care; macrolides; statin; thymosin-α1