The role of the innate immune response in hospital- versus community-acquired infection in febrile medical patients

Objectives: To study the role of the innate immune response in the higher mortality of hospital-than of community-acquired infections, in febrile medical patients. Methods: We studied presumably immunocompetent patients with new-onset fever and a clinically presumed focus of infection (N = 212) at a university department of internal medicine. Clinical and microbiological data were collected for 2 days from inclusion, and circulating complement activation product C3a, secretory phospholipase A(2), interleukin (IL)-6, procalcitonin, and elastase-alpha(1)-antitrypsin were measured. Patients were followed for septic shock and outcome, up to a maximum of 7 and 28 days after inclusion, respectively. Infection was considered hospital-acquired if it developed at least 72 h after admission. Results: Fifty-four patients had hospital-acquired infections and 158 had community-acquired infections, with septic shock and mortality rates of 15% and 24%, and 4% and 6% (p = 0.001), respectively. Bloodstream infection predisposed to septic shock and the latter predisposed to death. Bloodstream infection was relatively more common in septic shock originating from community-acquired infection and was associated with an innate immune response in both hospital- and community-acquired infection, as judged from circulating immune variables. In contrast, circulating C3a, IL-6, and procalcitonin were more elevated when septic shock developed following hospital- than community-acquired infection, independent of infectious focus. The levels of C3a, secretory phospholipase A(2), IL-6, and elastase-alpha(1)-antitrypsin were more elevated in ultimate non-survivors than in survivors in both infection groups. Conclusions: The data suggest that rates of septic shock and mortality from hospital- vs. community-acquired infections in febrile medical patients are not increased by impaired innate immunity. In contrast, proinflammatory factors may be particularly useful to predict a downhill, course in hospital- acquired infections. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.