title: Interleukin-27: a novel biomarker in predicting bacterial infection among the critically ill.
abstract: BACKGROUND
  A continued need exists for effective diagnostic biomarkers in bacterial sepsis among critically ill patients, despite increasing use of available biomarkers such as procalcitonin (PCT). Interleukin-27 (IL-27) has shown early promise in a recent preliminary study, exhibiting high specificity and positive predictive values for bacterial infection in critically ill children. This validation study was performed to assess the value of IL-27 in predicting bacterial infection among patients admitted to the pediatric intensive care unit and to compare its performance with that of PCT.
  
  
  METHODS
  A single-center (n = 702) prospective study was performed comparing both IL-27 and PCT levels between bacterially infected and uninfected cohorts in the pediatric intensive care unit. Infected status was determined by a chart review by an intensivist blinded to biomarker results. Formal performance comparisons included calculations of receiver operating characteristic (ROC) curves for IL-27 and PCT individually in addition to a combination strategy using a decision tree generated by classification and regression tree (CART) methodology. Secondary analysis focusing on subjects with documented bloodstream infections was performed.
  
  
  RESULTS
  The overall infection rate was 27 %. ROC curves for the primary analysis yielded areas under the curve (AUCs) of 0.64 (0.59 to 0.68) for IL-27 and 0.61 (0.56 to 0.65) for PCT. Secondary analysis defining infected status exclusively through positive blood cultures yielded AUCs of 0.75 (0.68 to 0.81) for IL-27 and 0.64 (0.57 to 0.71) for PCT, with a specificity of 95 % (92 % to 97 %) for the prior established IL-27 cut-point value of at least 5.0 ng/ml. Similar AUCs were found for the subset of immunocompromised patients. In a CART-derived analysis taking immunocompromised status into consideration, a combination of IL-27 and PCT yielded an AUC of 0.81 (0.75 to 0.86), statistically improved from either IL-27 or PCT alone.
  
  
  CONCLUSIONS
  Despite having a modest predictive value for infection independent of source, IL-27 may serve as a useful biomarker in estimating risk of bacterial infection among critically ill pediatric patients with bloodstream infections. In particular, among immunocompromised subjects, this diagnostic biomarker may be helpful either alone or using a combination strategy with other available biomarkers.
authors.affiliation: Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA. william.hanna@sickkids.ca.
authors.forename: William J
authors.initials: WJ
authors.lastname: Hanna
authors.affiliation: Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA. zachary.berrens@cchmc.org.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Berrens
authors.affiliation: Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA. travis.langner@cchmc.org.
authors.forename: Travis
authors.initials: T
authors.lastname: Langner
authors.affiliation: Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA. patrick.lahni@cchmc.org.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lahni
authors.affiliation: Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA. hector.wong@cchmc.org.|Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA. hector.wong@cchmc.org.
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
mesh_terms: D000293:Adolescent; D001424:Bacterial Infections / Q000097:blood / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D005260:Female; D006801:Humans; D007223:Infant; D007378:Interleukins / Q000097:blood*; D008297:Male; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D012372:ROC Curve; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000097:blood / Q000175:diagnosis
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D007378:Interleukins; C464565:MYDGF protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide