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A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial
Nathan Kuppermann1, Peter S Dayan2, Deborah A Levine3
1Departments of Emergency Medicine and Pediatrics, University of California, Davis School of Medicine, Sacramento.
Insights
A new prediction rule accurately identifies febrile infants at low risk for serious bacterial infections (SBIs) using urinalysis, absolute neutrophil count (ANC), and procalcitonin. This may reduce unnecessary tests and hospitalizations for infants.
Area of Science:
- Pediatrics
- Infectious Diseases
- Clinical Diagnostics
Background:
- Serious bacterial infections (SBIs) in young febrile infants can lead to severe complications.
- Current diagnostic methods like lumbar punctures and hospitalizations carry risks and costs.
- Biomarkers beyond white blood cell count (WBC) may improve risk stratification for SBIs in infants.
Purpose of the Study:
- To develop and validate a clinical prediction rule for identifying febrile infants aged 60 days or younger who are at low risk for SBIs.
- To establish a reliable tool to potentially avoid invasive procedures and reduce healthcare costs.
Main Methods:
- Prospective observational study involving 1821 febrile infants (≤60 days old) across 26 emergency departments.
- Data collected included clinical findings, WBC, absolute neutrophil count (ANC), serum procalcitonin, and urinalysis.
- Binary recursive partitioning analysis was used to derive and validate the prediction rule.
Main Results:
- The prediction rule identified low-risk infants using a negative urinalysis, ANC ≤4090/µL, and procalcitonin ≤1.71 ng/mL.
- In the validation cohort, the rule demonstrated high sensitivity (97.7%) and negative predictive value (99.6%) for SBIs.
- The rule correctly identified most infants at low risk, with only a few misclassifications and no missed cases of bacterial meningitis.
Conclusions:
- A validated prediction rule incorporating urinalysis, ANC, and procalcitonin can accurately identify febrile infants at low risk for SBIs.
- Clinical implementation of this rule could significantly decrease unnecessary lumbar punctures, antibiotic use, and hospitalizations.
- Further validation in independent cohorts is recommended before widespread clinical adoption.
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 Measures:
Serious bacterial infection, defined as urinary tract infection, bacteremia, or bacterial meningitis.
Results:
We 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 ×109 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 Relevance:
We 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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