A pilot study of the predictive value of plasma tumor necrosis factor alpha and interleukin 1 beta for Streptococcus pneumoniae bacteremia in febrile children.

Abstract

To determine the value of tumor necrosis factor alpha (TNF) and interleukin 1 beta (IL1) levels in predicting Streptococcus pneumoniae bacteremia in nontoxic-appearing, febrile children who do not have a bacterial source for their fever on physical examination. A prospective, nested case-control study was conducted in a children's hospital ED. All febrile children < 3 years old who were believed to be immunocompetent and not in shock, had no obvious bacterial source for their fever on physical examination, and had a blood culture obtained were eligible. Plasma obtained at the time of the blood culture was available for analysis by enzyme-linked immunosorbent assays for TNF and IL1. Children who had positive blood cultures for Streptococcus pneumoniae were the cases. The controls were selected from children who had negative blood cultures. During a 1-year period, 12 cases and 65 controls were identified. There was no significant difference in age, height or duration of fever, or illness acuity between the groups. The following were used as threshold values for positive test: white blood cell (WBC) count > 15.0 x 10(9) cells/L, TNF > 21.5 ng/mL, and IL1 > 9.0 ng/mL. Using an estimated prior probability of bacteremia of 4%, the positive predictive value (PPV) and the negative predictive value (NPV) for bacteremia were 11.7% and 98.6% using the WBC count, 11.1% and 98.6% using the IL1 level, and 9.0% and 98.9% using the TNF level. The combination of WBC count with either TNF or IL1 gave an NPV of 100%, with PPVs of 8.5% for TNF and 9.9% for IL1. Like the WBC count, TNF and IL1 are good negative but poor positive predictors of Streptococcus pneumoniae bacteremia in nontoxic-appearing, febrile children. At present, the addition of plasma TNF or IL1 levels would add little to emergency physicians' ability to predict Streptococcus pneumoniae bacteremia. However, as the quantification of these cytokines becomes more rapid, available, and standardized, and more knowledge of TNF and IL1 levels during various illnesses is gained, their utility in the clinical setting for ruling out bacteremia should be further assessed.