TY - JOUR
T1 - Intestinal inflammatory biomarkers and outcome in pediatric clostridium difficile infections
AU - El Feghaly, Rana E.
AU - Stauber, Jennifer L.
AU - Tarr, Phillip I.
AU - Haslam, David B.
N1 - Funding Information:
Supported by a Washington University-Pfizer Biomedical Agreement . D.H. received funds from the Midwest Regional Centers of Excellence in Biodefense ( U54-AI057160 ). P.T. is supported by the Melvin E. Carnahan Professorship in Pediatrics , Washington University Digestive Diseases Research Core Center , Biobank ( 5P30 DK052574 ), and the National Institutes of Health ( AI47499 ), and received an honorarium for a lecture at Cepheid in 2012. The authors declare no conflicts of interest.
PY - 2013/12
Y1 - 2013/12
N2 - Objectives To identify specific fecal biomarkers for symptomatic Clostridium difficile infection and predictors of poor outcomes. Study design 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.
AB - Objectives To identify specific fecal biomarkers for symptomatic Clostridium difficile infection and predictors of poor outcomes. Study design 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.
UR - http://www.scopus.com/inward/record.url?scp=84888325292&partnerID=8YFLogxK
U2 - 10.1016/j.jpeds.2013.07.029
DO - 10.1016/j.jpeds.2013.07.029
M3 - Article
C2 - 24011765
AN - SCOPUS:84888325292
SN - 0022-3476
VL - 163
SP - 1697-1704.e2
JO - Journal of Pediatrics
JF - Journal of Pediatrics
IS - 6
ER -