PEDIATRICS Vol. 104 No. 6 December 1999, pp. 1321-1326
Tumor Necrosis Factor-
, Interleukin-1
, and Interleukin-6
Levels in Febrile, Young Children With and Without Occult Bacteremia
Received Apr 5, 1999; accepted Jun 4, 1999.
, and
From the * Department of Pediatrics, University of Cincinnati
and Children's Hospital Medical Center, Cincinnati, Ohio; and the
Departments of Pediatrics and Medicine (Allergy/Immunology), Medical
College of Wisconsin, Milwaukee, Wisconsin.
Objective. To determine the utility
of plasma levels of tumor necrosis factor-
(TNF), interleukin
1
(IL-1), and interleukin 6 (IL-6) in the prediction of occult
bacteremia in febrile, young children.
Study Design. Prospective, case-control study conducted in a large, urban, children's hospital emergency department. Eligibility criteria were: 0 to 36 months of age, febrile, nontoxic appearing, immunocompetent, no apparent bacterial source for fever on physical examination, and blood culture obtained. Additional blood, procured at the time of the blood culture, was analyzed by enzyme-linked immunosorbent assay for TNF, IL-1, and IL-6. Children with positive blood cultures for pathogenic bacteria served as cases. Two age-matched controls for each case were selected from the children with negative cultures.
Results. Out of 1329 enrollees, 33 cases and 66 controls
were evaluated. IL-6 levels were significantly higher for the cases
than controls but with moderate overlap in their ranges. TNF and
IL-1 levels were not significantly different between cases and
controls. Height of fever, duration of fever, acute illness observation
score, absolute band count, and white blood cell count were all much less predictive of bacteremia than either IL-6 or absolute neutrophil count (ANC). The optimum IL-6 threshold value had a sensitivity of
88%, a specificity of 70%, a positive predictive value (PPV) of
7.0%, a negative predictive value (NPV) of 99.6%, and an odds ratio
(OR) of 16.7 (95% confidence interval [CI], 4.8-71.6). The optimum
ANC threshold value had a sensitivity of 82%, a specificity of 74%, a
PPV of 7.5%, a NPV of 99.4%, and an OR of 12.8 (95% CI, 3.2-59.7).
The best predictor was a combination of IL-6 and ANC. It had a
sensitivity of 100%, a specificity of 78%, a PPV of 10.4%, a NPV
of 100%, and an OR which is undefined because of the 100%
sensitivity (95% CI, 33.0-
). For comparison, a WBC >15 × 109 cells/L had a sensitivity of 48%, a specificity of
79%, a PPV of 5.5%, a NPV of 98.3%, and an OR of 3.5 (95% CI,
1.1-10.7).
Conclusions. In febrile children 0 to 36 months of age, IL-6 levels may be helpful in the prediction of occult bacteremia, but TNF and IL-1 levels are not. IL-6 levels alone or notably when combined with an ANC were more predictive of occult bacteremia than traditional tests and clinical criteria. The wide range in the IL-6 values for cases and controls detracts from the precision of the findings. The lack of rapid processing and clinical availability of IL-6 assays hampers its present application. However, despite these drawbacks and given the poor ability of traditional clinical and laboratory criteria to predict occult bacteremia, these results suggest a possible future role for IL-6 in predicting occult bacteremia when rapid assays become available. Key words: bacteremia, tumor necrosis factor, interleukin 1, interleukin 6, test performance, cytokine, fever.
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