TY - JOUR
T1 - A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections
AU - Kuppermann, Nathan
AU - Dayan, Peter S.
AU - Levine, Deborah A.
AU - Vitale, Melissa
AU - Tzimenatos, Leah
AU - Tunik, Michael G.
AU - Saunders, Mary
AU - Ruddy, Richard M.
AU - Roosevelt, Genie
AU - Rogers, Alexander J.
AU - Powell, Elizabeth C.
AU - Nigrovic, Lise E.
AU - Muenzer, Jared
AU - Linakis, James G.
AU - Grisanti, Kathleen
AU - Jaffe, David M.
AU - Hoyle, John D.
AU - Greenberg, Richard
AU - Gattu, Rajender
AU - Cruz, Andrea T.
AU - Crain, Ellen F.
AU - Cohen, Daniel M.
AU - Brayer, Anne
AU - Borgialli, Dominic
AU - Bonsu, Bema
AU - Browne, Lorin
AU - Blumberg, Stephen
AU - Bennett, Jonathan E.
AU - Atabaki, Shireen M.
AU - Anders, Jennifer
AU - Alpern, Elizabeth R.
AU - Miller, Benjamin
AU - Casper, T. Charles
AU - Dean, J. Michael
AU - Ramilo, Octavio
AU - Mahajan, Prashant
N1 - Funding Information:
part by grant H34MCO8509 from Health Resources and Services Administration, Emergency Services for Children and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (grant R01HD062477). This project was also supported in part by the Health Resources and Services Administration, Maternal and Child Health Bureau, Emergency Medical Services for ChildrenNetwork Development Demonstration Program under cooperative agreements U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684, and U03MC22685.
PY - 2019/4
Y1 - 2019/4
N2 - 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/;L 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 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..
AB - 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/;L 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 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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U2 - 10.1001/jamapediatrics.2018.5501
DO - 10.1001/jamapediatrics.2018.5501
M3 - Article
C2 - 30776077
AN - SCOPUS:85061647823
VL - 173
SP - 342
EP - 351
JO - JAMA Pediatrics
JF - JAMA Pediatrics
SN - 2168-6203
IS - 4
ER -