title: Lack of value of midregional pro-adrenomedullin and C-terminal pro-endothelin-1 for prediction of severe bacterial infections in infants with fever without a source.
abstract: The study was performed to assess the usefulness of two new biomarkers, midregional pro-adrenomedullin (MR-pro-ADM) and C-pro-endothelin-1 (CT-pro-ET-1), in predicting bacterial infection (BI) and especially invasive bacterial infection (IBI) in well-appearing infants with fever without source (FWS). For this purpose, a multicenter prospective study was conducted between February 2008 and March 2009 including well-appearing infants less than 36 months of age with FWS. MR-pro-ADM, CT-pro-ET-1, procalcitonin (PCT), CRP, and WBC were measured and compared. Among the 1,035 infants included, a bacterial infection was diagnosed in 75 patients (7.2 %), and 16 (1.54 %) had an invasive bacterial infection (bacterial meningitis, 8; occult bacteremia, 6; and sepsis, 1). MR-pro-ADM and CT-pro-ET-1 levels were less reliable for diagnosis than the other biomarkers. The area under receiver operating characteristic curve for infants with BI and IBI was 0.59 (95 % confidence interval (CI) 0.52-0.67) and 0.63 (95 % CI 0.46-0.80) for MR-pro-ADM and 0.58 (95 % CI 0.51-0.66) and 0.62 (95 % CI 0.47-0.67) for CT-pro-ET-1, respectively. Multivariate analysis showed that PCT ≥ 0.5 ng/mL, CRP ≥ 40 mg/L, and CT-pro-ET-1 ≥ 105 pmol/mL were independent risk factors for having a BI (odds ratio (OR) 6.12, 3.61, and 2.84, respectively). PCT was the only independent risk factor for having an IBI (OR 17.53 if PCT ≥ 0.5 ng/mL).
  
  
  CONCLUSIONS
  Although baseline MR-pro-ADM and CT-pro-ET-1 levels are significantly elevated in well-appearing febrile infants with a bacterial infection, their overall performance as diagnostic markers is very poor.
authors.affiliation: Pediatric Emergency Department, Department of Pediatrics, Cruces University Hospital, Plaza de Cruces s/n, E-48903 Barakaldo, Bilbao, Bizkaia, Basque Country, Spain, javier.benitof@osakidetza.net.
authors.forename: Javier
authors.initials: J
authors.lastname: Benito
authors.forename: Carlos
authors.initials: C
authors.lastname: Luaces-Cubells
authors.forename: Santiago
authors.initials: S
authors.lastname: Mintegi
authors.forename: Eider
authors.initials: E
authors.lastname: Astobiza
authors.forename: Lorea
authors.initials: L
authors.lastname: Martinez-Indart
authors.forename: Ana
authors.initials: A
authors.lastname: Valls-Lafont
authors.forename: Juan-José
authors.initials: JJ
authors.lastname: García-García
mesh_terms: D053607:Adrenomedullin / Q000097:blood*; D001424:Bacterial Infections / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D005335:Fever of Unknown Origin / Q000209:etiology*; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012372:ROC Curve; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C557077:C-terminal proendothelin-1; C000606589:CALCA protein, human; D019332:Endothelin-1; D010446:Peptide Fragments; D011498:Protein Precursors; C088633:proadrenomedullin; D053607:Adrenomedullin; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide