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Does Leukopenia or Neutropenia Predict Bacterial Infection in Febrile Infants?

June 24, 2024

Written by Joshua Belfer

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In a cohort of febrile infants, leukopenia ≤2500 cells/µL was associated with invasive bacterial infections; neutropenia was not predictive.

Can we be even better about screening febrile infants for bacterial infection?
Using the PECARN dataset of febrile infants ≤60 days old, a secondary analysis on 6,865 infants assessed for an association between leukopenia or neutropenia and invasive bacterial infections (IBI, bacteremia or bacterial meningitis). Overall, 8.6% were leukopenic (<5000 cells/µL) and 4.5% neutropenic ( <1000 cells/µL); the frequency of IBI in the leukopenia group was 2.7% (16/593) and 1.3% (4/311) in the neutropenia group.

Multivariable logistic regression analysis found that WBC counts of ≤2500 cells/µL were associated with increased odds (aOR 13.48) of IBI. Neither leukopenia 2501-5000 cells/µL nor any degree of neutropenia showed increased risk of IBI. Importantly, all patients with leukopenia ≤2500 cells/µL with IBI had elevated procalcitonin (PCT) levels.

One important limitation is that HSV infection was not evaluated in this study; we know that procalcitonin is suppressed in febrile infants with a viral infection, and it is not known from this study if leukopenia or neutropenia can help risk assess those infants with a normal PCT who have HSV infection. Additionally, the overall small number of infants with leukopenia contributed to a very wide 95% confidence interval of the associations with IBI.

How will this change my practice?
You’ll remember the 2021 AAP Febrile Infant Guidelines that recognized PCT as the most accurate inflammatory marker for risk stratification. I work in a hospital that has PCT testing, so this study likely will not change my practice considerably. If you don’t have PCT readily available, this provides you with an additional inflammatory marker to help identify at-risk febrile infants. While the addition of another biomarker will increase sensitivity (and thus may lead to more lumbar punctures) being done in this population, with the serious consequences of missing bacteremia or meningitis, I welcome the additional biomarker that can help identify these infants.     

Source
Leukopenia, neutropenia, and procalcitonin levels in young febrile infants with invasive bacterial infections. Acad Emerg Med. 2024 Apr 25. doi: 10.1111/acem.14921. Epub ahead of print. PMID: 38661246.

What are your thoughts?