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Viruses LOWER Procalcitonin? Impact of Viral Infection on PCT in Febrile Infants

December 7, 2023

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Written by Clay Smith

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Procalcitonin (PCT) is suppressed in young febrile infants in the presence of confirmed viral infection (CVI), which lowers its sensitivity to detect bacterial infection (BI). Infants meeting the AAP cutoff of 0.5 ng/mL, even in the presence of CVI, should undergo full diagnostic workup for BI.

Is it just a virus?
Febrile infants 22-60 days may undergo risk stratification to forgo invasive diagnostic workup and possibly hospitalization. The AAP recommends a PCT level of >0.5 ng/mL as the threshold for further workup for BI, though my institution has chosen 0.3 ng/mL as the cutoff, based on the Milcent et al study. Acute viral infection may lead to lower PCT, via immune suppression from cytokines such as interferon-gamma. This single-center retrospective study included 663 febrile infants 8-60 days. Key findings are listed in the Table. PCT was indeed lower among infants who were BI+/CVI+ compared to BI+/CVI-*; median PCT 0.36 vs 0.89 ng/mL, respectively. If BI-/CVI- or BI-/CVI+, PCT was ~0.1 ng/mL. Sensitivity for PCT dropped in those who were CVI+, but specificity remained essentially unchanged. Of note, the PCT 25th percentile among those BI+/CVI+ was 0.12, indicating that 25% of these infants had PCT of ≤0.12 ng/mL.

*BI+/- = bacterial infection present/absent; CVI+/- = confirmed viral infection present/absent

From cited article

How will this change my practice?
This is a single center study with a relatively small sample size and very few patients (N=48) in some subgroups, such as the BI+/CVI+ group. But it confirms that viral infection suppresses PCT in BI+ infants, and this changes my thinking. My hospital clinical practice guideline says that infants 29-60 days old with CVI on respiratory pathogen panel PCR may be excluded from additional workup, which is reasonable. But I usually order the respiratory viral PCR and inflammatory markers concurrently. Previously, I may have been tempted to discount the inflammatory markers in infants with a positive respiratory PCR. However, this study makes me think about this differently. A CVI actually suppresses PCT levels in BI+ infants. So, I will strongly consider a full workup, with LP, even in CVI+ infants, if the PCT is >0.3 ng/mL – and certainly if it is >0.5 ng/mL, the AAP cutoff. In febrile CVI+ infants 29-60 days with PCT <0.3 ng/mL, I probably won’t do a LP, but I will at least consider it and have an open discussion with the parents about the small risk, ensuring close follow up of the infant.

Special thanks to Don Arnold for pointing this important article out to me and for reviewing and editing this post.

Effect of Viral Illness on Procalcitonin as a Predictor of Bacterial Infection in Febrile Infants. Hosp Pediatr. 2023 Nov 1;13(11):961-966. doi: 10.1542/hpeds.2022-007070.

What are your thoughts?