A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections

Abstract

for the Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN) IMPORTANCE In young febrile infants, serious bacterial infections (SBIs), including urinary tract infections, bacteremia, and meningitis, may lead to dangerous complications. However, lumbar punctures and hospitalizations involve risks and costs. Clinical prediction rules using biomarkers beyond the white blood cell count (WBC) may accurately identify febrile infants at low risk for SBIs.OBJECTIVE To derive and validate a prediction rule to identify febrile infants 60 days and younger at low risk for SBIs. DESIGN, SETTING, AND PARTICIPANTS Prospective, observational study between March 2011 and May 2013 at 26 emergency departments. Convenience sample of previously healthy febrile infants 60 days and younger who were evaluated for SBIs. Data were analyzed between April 2014 and April 2018.EXPOSURES Clinical and laboratory data (blood and urine) including patient demographics, fever height and duration, clinical appearance, WBC, absolute neutrophil count (ANC), serum procalcitonin, and urinalysis. We derived and validated a prediction rule based on these variables using binary recursive partitioning analysis. MAIN OUTCOMES AND MEASURESSerious bacterial infection, defined as urinary tract infection, bacteremia, or bacterial meningitis. RESULTSWe derived the prediction rule on a random sample of 908 infants and validated it on 913 infants (mean age was 36 days, 765 were girls [42%], 781 were white and non-Hispanic [43%], 366 were black [20%], and 535 were Hispanic [29%]). Serious bacterial infections were present in 170 of 1821 infants (9.3%), including 26 (1.4%) with bacteremia, 151 (8.3%) with urinary tract infections, and 10 (0.5%) with bacterial meningitis; 16 (0.9%) had concurrent SBIs. The prediction rule identified infants at low risk of SBI using a negative urinalysis result, an ANC of 4090/μL or less (to convert to ×10 9 per liter, multiply by 0.001), and serum procalcitonin of 1.71 ng/mL or less. In the validation cohort, the rule sensitivity was 97.7% (95% CI, 91.3-99.6), specificity was 60.0% (95% CI, 56.6-63.3), negative predictive value was 99.6% (95% CI, 98.4-99.9), and negative likelihood ratio was 0.04 (95% CI, 0.01-0.15). One infant with bacteremia and 2 infants with urinary tract infections were misclassified. No patients with bacterial meningitis were missed by the rule. The rule performance was nearly identical when the outcome was restricted to bacteremia and/or bacterial meningitis, missing the same infant with bacteremia. CONCLUSIONS AND RELEVANCEWe derived and validated an accurate prediction rule to identify febrile infants 60 days and younger at low risk for SBIs using the urinalysis, ANC, and procalcitonin levels. Once further validated on an independent cohort, clinical application of the rule has the potential to decrease unnecessary lumbar punctures, antibiotic administration, and hospitalizations.

Comparison of Clinical and Epidemiologic Characteristics of Young Febrile Infants with and without Severe Acute Respiratory Syndrome Coronavirus-2 Infection

“…The first case of the novel coronavirus disease 2019 (COVID- 19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),was diagnosed in December of 2019 in Wuhan, China and was designated as a worldwide pandemic in March 2020. 1,2 In January 2020, J o u r n a l P r e -p r o o f the first case in the United States (US) was identified, and in March 2020 a national emergency was declared.…”

Role of Viral Molecular Panels in Diagnosing the Etiology of Fever in Infants Younger Than 3 Months

“…25 Other authors have focused on detecting infants at low risk of SBI using clinical scores. 26 Documenting a viral infection has also been shown to contribute to identify febrile infants at low risk of SBI. [9][10][11][12][13] However, as having a proven viral infection does not fully rule out the risk of SBI (especially UTI), [15][16][17] viral tests cannot replace blood or urine analysis but must be seen as additional tools in the management of these patients.…”

Diagnosis and Management of UTI in Febrile Infants Age 0–2 Months: Applicability of the AAP Guideline

“…Multiple risk stratification algorithms for febrile infants aged ≤60 days categorize infants with a positive UA (and therefore likely UTI) as high-risk for having concomitant bacteremia or meningitis, for which lumbar puncture (LP) is typically recommended. [43][44][45] The risk of not testing CSF is the potential to insufficiently treat meningitis because treatment for UTIs and meningitis differ in dosing, route, and duration. Recent studies have challenged the practice of routine LPs for infants aged 1-2 months with a suspected UTI due to the low prevalence (0%-0.3%) of concomitant meningitis.…”