C-Reactive Protein As a Predictor Of Bacterial Disease In Children With Sickle Cell Disease and Fever

Children with sickle cell disease (SCD) are at increased risk of serious bacterial disease compared to children without SCD. Children with SCD and fever are recommended to undergo prompt evaluation, including a physical exam, complete blood count, blood culture, and sometimes chest x-ray. These children often receive empiric parenteral antibiotics until blood cultures show no bacteremia for forty-eight hours. Studies in this population have identified clinical and laboratory features that are associated with low rates of bacteremia or that predict bacteremia. C-reactive protein is an acute phase reactant that has been studied as a predictor for bacteremia in a variety of clinical situations. Crp, however, has not been evaluated as a predictor of serious bacterial disease in children with SCD.

Retrospective chart review of children age 0 – 18.9 year old admitted to Baystate Children’s Hospital with a diagnosis of SCD and fever who had crp and blood culture drawn between January 1, 2009 and December 31, 2011. SCD included homozygous SS disease, SC disease, or Sβ-thalassemia. Bacterial disease was defined as bacteremia, osteomyelitis, pneumonia/ acute chest syndrome, pyelonephritis. Parental report of fever was accepted. Age, maximum temperature, white blood count (WBC), absolute neutrophil count (ANC), percent of neutrophils (ANC/WBC), and crp were evaluated.

80 cases met inclusion criteria. 18 cases had bacterial disease. Compared to children without bacterial disease, those with bacterial disease were older (mean age 11 vs. 4.8 yr, p < 0.001), had higher mean crp (5.7 vs. 1.6 mg/dL, p <0.001), higher mean WBC (20.9 vs. 15.6 x 10³/mm³, p = 0.004), and higher mean ANC (13.5 vs. 8.7 x 10³/mm³, p = 0.002). There were no significant differences between maximum temperature and percent neutrophils between the two groups. After regression analysis for all variables, age and crp remained significant between the two groups (p = 0.001 for both). A receiver operator characteristic (ROC) curve using crp and age produced an area under the curve of 0.87.

Children with SCD hospitalized for fever and diagnosed with bacterial illnesses are older and have higher crp compared to those without bacterial illness. The ROC curve based age and crp has characteristics of a good screening test. Because children with SCD and fever will usually receive empiric antibiotics regardless and the repercussions of a missed bacterial illness are great, using crp to determine antibiotic administration is likely limited. Rather, a low crp, especially in a younger child, may be helpful to determine patients who are candidates for early discharge or those who can be managed as an outpatient. Prospective use of crp for fever in this population, including outpatients, is warranted in order to identify the best sensitivity and specificity.

No relevant conflicts of interest to declare.