title: The systemic inflammatory response to Clostridium difficile infection.
abstract: BACKGROUND
  The systemic inflammatory response to Clostridium difficile infection (CDI) is incompletely defined, particularly for patients with severe disease.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  A broad systemic inflammatory response occurs during CDI and severe cases appear to differ from non-severe infections.
authors.affiliation: Division of Infectious Diseases, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Department of Internal Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Division of Infectious Diseases, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, United States of America.
authors.forename: Krishna
authors.initials: K
authors.lastname: Rao
authors.affiliation: Division of Pulmonary and Critical Care Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Department of Internal Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: John R
authors.initials: JR
authors.lastname: Erb-Downward
authors.affiliation: Division of Infectious Diseases, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Department of Internal Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Seth T
authors.initials: ST
authors.lastname: Walk
authors.affiliation: Department of Internal Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Dejan
authors.initials: D
authors.lastname: Micic
authors.affiliation: Division of Pulmonary and Critical Care Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Department of Internal Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Nicole
authors.initials: N
authors.lastname: Falkowski
authors.affiliation: Division of Infectious Diseases, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Department of Internal Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Santhosh
authors.affiliation: Division of Infectious Diseases, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Department of Internal Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Mogle
authors.affiliation: Division of Infectious Diseases, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Department of Internal Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Ring
authors.affiliation: Division of Infectious Diseases, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Department of Internal Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Department of Microbiology and Immunology, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Young
authors.affiliation: Division of Pulmonary and Critical Care Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Department of Internal Medicine, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America; Department of Microbiology and Immunology, the University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Gary B
authors.initials: GB
authors.lastname: Huffnagle
authors.affiliation: Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Aronoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016360:Clostridioides difficile / Q000276:immunology*; D003015:Clostridium Infections / Q000097:blood / Q000276:immunology*; D003967:Diarrhea / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005759:Gastroenteritis / Q000097:blood / Q000276:immunology / Q000382:microbiology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins