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.

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This large multicenter study validates the Bacterial Meningitis Score prediction rule in the era of conjugate pneumococcal vaccine as an accurate decision support tool. The risk of bacterial meningitis is very low (0.1%) in patients with none of the criteria. The Bacterial Meningitis Score may be helpful to guide clinical decision making for the management of children presenting to emergency departments with CSF pleocytosis.

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In patients with bacterial meningitis, antibiotic pretreatment is associated with higher cerebrospinal fluid glucose levels and lower cerebrospinal fluid protein levels, although pretreatment does not modify cerebrospinal fluid white blood cell count or absolute neutrophil count results.

IMPORTANCE Clinicians often risk stratify young febrile infants for invasive bacterial infections (IBIs), defined as bacteremia and/or bacterial meningitis, using complete blood cell count parameters.OBJECTIVE To estimate the accuracy of individual complete blood cell count parameters to identify febrile infants with IBIs. DESIGN, SETTING, AND PARTICIPANTSPlanned secondary analysis of a prospective observational cohort study comprising 26 emergency departments in the Pediatric Emergency Care Applied Research Network from 2008 to 2013. We included febrile (Ն38°C), previously healthy, full-term infants younger than 60 days for whom blood cultures were obtained. All infants had either cerebrospinal fluid cultures or 7-day follow-up. MAIN OUTCOMES AND MEASURESWe tested the accuracy of the white blood cell count, absolute neutrophil count, and platelet count at commonly used thresholds for IBIs. We determined optimal thresholds using receiver operating characteristic curves. RESULTSOf 4313 enrolled infants, 1340 (31%; 95% CI, 30% to 32%) were aged 0 to 28 days, 2412 were boys (56%), and 2471 were white (57%). Ninety-seven (2.2%; 95% CI, 1.8% to 2.7%) had IBIs. Sensitivities were low for common complete blood cell count parameter thresholds: white blood cell count less than 5000/μL, 10% (95% CI, 4% to 16%) (to convert to 10 9 per liter, multiply by 0.001); white blood cell count Ն15 000/μL, 27% (95% CI, 18% to 36%); absolute neutrophil count Ն10 000/μL, 18% (95% CI, 10% to 25%) (to convert to × 10 9 per liter, multiply by 0.001); and platelets <100 × 10 3 /μL, 7% (95% CI, 2% to 12%) (to convert to × 10 9 per liter, multiply by 1). Optimal thresholds for white blood cell count (11 600/μL), absolute neutrophil count (4100/μL), and platelet count (362 × 10 3 /μL) were identified in models that had areas under the receiver operating characteristic curves of 0.57 (95% CI, 0.50-0.63), 0.70 (95% CI, 0.64-0.76), and 0.61 (95% CI, 0.55-0.67), respectively. CONCLUSIONS AND RELEVANCENo complete blood cell count parameter at commonly used or optimal thresholds identified febrile infants 60 days or younger with IBIs with high accuracy. Better diagnostic tools are needed to risk stratify young febrile infants for IBIs.

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