The Systemic Inflammatory Response to Clostridium difficile Infection

• Published in: PloS one Vol. 9; no. 3; p. e92578
• Main Authors: Rao, Krishna, Erb-Downward, John R., Walk, Seth T., Micic, Dejan, Falkowski, Nicole, Santhosh, Kavitha, Mogle, Jill A., Ring, Cathrin, Young, Vincent B., Huffnagle, Gary B., Aronoff, David M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.03.2014; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies; Biology and Life Sciences; Biomarkers; Case-Control Studies; Chemokines; Clostridioides difficile - immunology; Clostridium difficile; Clostridium Infections - blood; Clostridium Infections - immunology; Colorectal surgery; Critical care; Cytokines; Diarrhea; Diarrhea - blood; Diarrhea - immunology; Diarrhea - microbiology; Eotaxin; Epidermal growth factor; Female; Fibroblast growth factor 2; Gastroenteritis - blood; Gastroenteritis - immunology; Gastroenteritis - microbiology; Health aspects; Hepatocyte growth factor; Hospital patients; Humans; Immunology; Infection; Infections; Infectious diseases; Inflammation; Inflammation Mediators - blood; Inflammatory response; Intercellular Signaling Peptides and Proteins - blood; Interleukin 6; Interleukin 8; Internal medicine; Male; Medicine; Medicine and Health Sciences; Middle Aged; Multivariate analysis; Nosocomial infections; Ostomy; Principal components analysis; Proteins; Regression analysis; Rodents; Studies; Variance analysis; Young Adult; Montana; Ann Arbor Michigan; United States > US; Michigan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0092578

The systemic inflammatory response to Clostridium difficile infection (CDI) is incompletely defined, particularly for patients with severe disease. Analysis of 315 blood samples from 78 inpatients with CDI (cases), 100 inpatients with diarrhea without CDI (inpatient controls), and 137 asymptomatic outpatient controls without CDI was performed. Serum or plasma was obtained from subjects at the time of CDI testing or shortly thereafter. Severe cases had intensive care unit admission, colectomy, or death due to CDI within 30 days after diagnosis. Thirty different circulating inflammatory mediators were quantified using an antibody-linked bead array. Principal component analysis (PCA), multivariate analysis of variance (MANOVA), and logistic regression were used for analysis. Based on MANOVA, cases had a significantly different inflammatory profile from outpatient controls but not from inpatient controls. In logistic regression, only chemokine (C-C motif) ligand 5 (CCL5) levels were associated with cases vs. inpatient controls. Several mediators were associated with cases vs. outpatient controls, especially hepatocyte growth factor, CCL5, and epithelial growth factor (inversely associated). Eight cases were severe and associated with elevations in IL-8, IL-6, and eotaxin. A broad systemic inflammatory response occurs during CDI and severe cases appear to differ from non-severe infections.