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The Pros and Cons of Viral Testing: How to Risk-Stratify the Febrile Infant When Procalcitonin Is Not Available

May 21, 2024

Editor's Note: Dr. Claire Castellano (she/her/hers) is a resident physician in pediatrics at the Children’s Hospital of Philadelphia. In addition to her MD, Claire has a Master’s in Public Health, focusing on global epidemiology. Claire hopes to combine her interests in medical education and global health in her career as a pediatrician-Rachel Y. Moon, MD, Associate Editor, Digital Media, Pediatrics

Parents of newborns are given lots of anticipatory guidance, including the seriousness of fevers in the first few weeks of life. Infants 60 days old or younger with temperatures ≥38 degrees C (100.4 degrees F) are at high risk for bacterial infections, including bacteremia and meningitis. 

The AAP recently updated their guidelines for this group of babies, the febrile neonate, in a clinical practice guideline, “Evaluation and Management of Well-Appearing Febrile Infants 8-60 days Old,” which distinguishes low- versus high-risk infants. It is crucial to make this distinction when weighing risks and benefits of a sepsis work-up: although the risk of missing bacterial meningitis is not one to take lightly, a lumbar puncture is also not an entirely benign procedure. The guidelines recommend using an absolute neutrophil count (ANC) and procalcitonin (PCT) level to distinguish low- from high-risk infants. 

However, PCT testing is not easily accessible in all settings. In these situations, the AAP guidelines recommend using ANC, C-reactive protein (CRP), and maximum temperature to risk-stratify infants. 

Caroline Wolek, BSc, and colleagues at McGill University, University of British Columbia, and University of California-Davis acknowledge that rapid multiplex viral testing is often more accessible than PCT testing and investigated the role of viral testing to aid in identifying invasive bacterial infections (IBIs) in febrile neonates. Their article, entitled “Viral Testing for Febrile Infants without Procalcitonin Measurement,” is being released early in Pediatrics this week (10.1542/peds.2024-065689). 

The authors analyzed data from 1104 previously healthy, term, febrile infants who were evaluated at a pediatric emergency department from January 2018 to December 2022. Definitions were used from the AAP guidelines to define febrile infants (8–60 days old with fever ≥ 38 C) and low-risk for IBI (CRP < 20 mg/L, ANC < 5200/mm3, maximum temperature < 38.5).

In this group of febrile infants: 

  • 9% had an invasive bacterial infection
  • 1% had a virus detected 
  • 8% met low risk criteria
  • Of these, 0 had an IBI
  • 2% met high-risk criteria (all IBI were in this group) 
  • 2% were virus-negative
  • 8% were virus-positive
  • 9% of high-risk, virus-negative had IBI
  • 2% of high-risk, virus-positive had IBI

These data suggest that the AAP guidelines using ANC, CRP, and maximum temperature to classify low-risk for IBI do a good job ruling out IBI: none of the low-risk infants had an IBI! 

However, these three data points alone have poor specificity, with a high false positive rate, meaning that many infants who are categorized as “high-risk” will not have IBI. 

By including viral testing as an additional data point, the authors were better able to distinguish true high-risk infants. The high-risk, virus-negative infants had the highest rates of IBI. 

But viral testing isn’t perfect! In this study with only 25 cases of IBI, there were 5 infants who had a co-infection of virus and bacteria (a viral-positive infant who also had IBI), 4 of whom happened to have a rhinovirus/enterovirus infection. 

This study highlights the potential benefit from thoughtful use of viral testing as an affordable, easy way for institutions without access to PCT testing to aid in their risk-stratification of febrile infants.

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