title: Intestinal inflammatory biomarkers and outcome in pediatric Clostridium difficile infections.
abstract: OBJECTIVE
  To identify specific fecal biomarkers for symptomatic Clostridium difficile infection and predictors of poor outcomes.
  
  
  METHODS
  We enrolled 65 children with positive C difficile testing (cases) and 37 symptomatic controls. We also analyzed stool samples from colonized and non-colonized asymptomatic children. We performed enzyme immunoassays to determine fecal interleukin (IL)-8, lactoferrin, and phosphorylated-p38 protein concentrations, and quantitative polymerase chain reaction to determine IL-8 and chemokine ligand (CXCL)-5 RNA relative transcript abundances, and C difficile bacterial burden.
  
  
  RESULTS
  Of 68 asymptomatic controls, 16 were colonized with C difficile. Phosphorylated-p38 was specific for C difficile infection but lacked sensitivity. Fecal cytokines were elevated in samples from symptomatic children, whether cases or controls. In children with C difficile infection, fecal CXCL-5 and IL-8 messenger RNA abundances at diagnosis correlated with persistent diarrhea after 5 days of C difficile infection therapy and with treatment with vancomycin. When children with concomitant viral gastroenteritis were excluded, these correlations persisted. Time-to-diarrhea resolution was significantly longer in patients with elevated fecal cytokines at diagnosis. A logistic regression model identified high CXCL-5 messenger RNA abundance as the only predictor of persistent diarrhea. Conversely, fecal C difficile bacterial burden was not different in symptomatic and asymptomatic children and did not correlate with any clinical outcome measure.
  
  
  CONCLUSIONS
  Fecal inflammatory cytokines may be useful in distinguishing C difficile colonization from disease and identifying children with C difficile infection likely to have prolonged diarrhea.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
authors.forename: Rana E
authors.initials: RE
authors.lastname: El Feghaly
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Stauber
authors.forename: Phillip I
authors.initials: PI
authors.lastname: Tarr
authors.forename: David B
authors.initials: DB
authors.lastname: Haslam
mesh_terms: D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D004761:Enterocolitis, Pseudomembranous / Q000175:diagnosis / Q000276:immunology; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis*; D007781:Lactoferrin / Q000032:analysis*; D008297:Male; D011446:Prospective Studies; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis*
chemical_list: D015415:Biomarkers; D016209:Interleukin-8; D048051:p38 Mitogen-Activated Protein Kinases; D007781:Lactoferrin
keywords: CT; CXCL; Chemokine ligand; Cycle threshold; Difference of CT between cytokines and internal control, representing cytokine relative abundance; EIA; Enzyme immunoassay; HR; Hazard ratio; IBD; IL; Inflammatory bowel disease; Interleukin; MD; Median difference; Messenger RNA; PCR; Phosphorylated-p38; Polymerase chain reaction; RR; RT; Relative risk; Reverse-transcription; SLCH; St. Louis Children's Hospital; WBC; White blood cell; mRNA; pp38; ΔCT