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.

unlabelledThe 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).

conclusionAlthough 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.