Outcomes of Fever in Infants and Young Children with SCD Presenting to the Emergency Room
Authors: Sirigaddi Krishnaveni , Aban Inmaculada , Bemrich-Stolz Christina J. , Howard Thomas H. , Hilliard Lee , Lebensburger Jeffrey D. 
Published: October 2019

Abstract
The introduction of antibiotic prophylaxis and vaccinations has reduced the incidence of bacteremia and sepsis in pediatric patients with sickle cell disease (SCD). Due to concern of mortality from sepsis, SCD patients with fever require admission for IV antibiotics until bacteremia is ruled out. The 2014 NIH Evidence-Based Management of Sickle Cell Disease guidelines recommends hospitalization for patients with temperature ≥ 39.5 C and who appear ill. Prior pediatric research has defined "high risk patients" as those with temperature ≥ 40 C, WBC >30,000 or <5,000/mcl, appear ill, or have pulmonary infiltrates on chest x-ray (CXR). (Wilimas NEJM 1993) We reviewed all Emergency Room (ER) visits for febrile patients <6 years of age with HbSS or HbSB0 thalassemia to evaluate these predictive models for bacteremia.
Methods: In a 16 year IRB approved cohort, we identified 609 ER visits to Children's of Alabama for fever among 169 children < 6 years old with HbSS or SB0 thalassemia. All patients receive standard of care penicillin prophylaxis and vaccination. We reviewed every blood culture obtained during their ER visit and admission to determine the incidence of bacteremia including pneumococcal bacteremia. We recorded vital signs, blood counts, and CXR findings during the ER visit. We compared differences in these variables among patients with and without bacteremia. We created categorical variables (yes/no) to evaluate NIH fever guidelines (Temp >39.5C and ill appearance) and "high risk patient" recommendations (Temp >40C, ill appearance, abnormal white blood cell count (>30,000 or <5,000//mcl), or pulmonary infiltrates on CXR). Descriptive statistics, t-test for normally distributed data and Wilcoxon for non-normally distributed data, and Fisher's exact test were performed in JMP12. Sensitivity and specificity were calculated from 2x2 tables. To examine the predictive models for bacteremia, we utilized multiple logistic regression to develop the receiving operating characteristics curves and area under the curve (AUC).
Results: Among the 169 patients (0-5.99yrs) with HbSS or SB0 thalassemia that were evaluated in the Children's of Alabama ER for fever, 95 (56%) were female. Five hundred and twelve (84%) admissions were identified among the 609 ER visits including all patients with bacteremia. Fourteen patients (2.3%) evaluated in the ER for fever were subsequently diagnosed with bacteremia including 9 (1.5%) positive for pneumococcus. The incidence of bacteremia among young patients presenting to the ER for fever was 1.4 events per 100 patient years and the rate of pneumococcus was 0.9 events per 100 patient years. Patients with bacteremia had higher WBC (27.0 ±7.8 vs 17.2 ±8.5, p<0.0001) than patients without bacteremia. No statistical differences were noted for patients with and without bacteremia for temperature (p=0.06) or heart rate (p=0.3). The sensitivity and specificity of individual variables for bacteremia were: Temp ≥ 39.5 (Sen: 57%, Specificity: 65%), Temp ≥ 40 (sensitivity: 29%, specificity 90%), Ill appearing (sensitivity: 43%, specificity: 86%), abnormal WBC (sensitivity: 36%, specificity 91%) abnormal CXR (appearing (sensitivity: 57%, specificity: 72%). To evaluate models for bacteremia, the AUC for NIH admission guidelines and "high risk patients" were 0.68 and 0.80 respectively.
Conclusion: While the incidence of bacteremia is low, young children with SCD are frequently admitted for IV antibiotics until bacteremia is ruled out. Our data suggests using the "high risk model" for admission criteria in febrile children with SCD. Developing models that can accurately predict bacteremia are limited due to the low incidence of bacteremia.

Disclosures
Lebensburger: NHLBI: Research Funding; American Society of Hematology, Scholar Award: Research Funding.