Procalcitonin in Serious Bacterial Infection: Spoiler Alert – It Doesn’t Help Here Either

A guest post by Anand Swaminathan (@EMSwami) of EM Lyceum and Essentials of EM fame.

Over the years, numerous studies have been published attempting to show the benefit for serum markers in diagnosing sepsis or other infections. These markers include ESR, CRP and more recently, procalcitonin (PCT). Despite the reams of literature published, no study has shown a true patient centered outcome benefit to using these markers. Instead of doing an in depth review here of the literature on PCT, I recommend reading Rory Spiegel’s post here.

This recent article from Academic Emergency Medicine attempts to use PCT as an indicator of serious bacterial infection (SBI) in children under 3 years of age. They basically compared PCT with WBC, absolute neutrophil count (ANC) and absolute band count. PCT had the largest area under the curve (0.80 vs. 0.76 for WBC, 0.73 for ANC and 0.67 for absolute band count). Overall, the study found that all of these tests suffered from poor sensitivities but that specificity for PCT (92.7% at a cutoff of 0.6 ng/ml) coupled with its sensitivity (51.6% at the same cutoff) yielded the best positive likelihood ratio of any of these tests (+LR = 7.04). Based on this finding, the investigators conclude that PCT is a “more accurate marker than white blood count, absolute neutrophil count or absolute band count in identifying young febrile infants and children with serious bacterial infections.”
But, are we asking the right question? This study, as with many of the others, tries to use PCT to identify patients that we would otherwise miss as having a serious infection. However, they don’t compare PCT to physician clinical judgment. Or, more importantly, they do not investigate if PCT adds to clinical judgment. Instead, they compare it to markers we know are seriously lacking in their ability to predict (WBC, ANC and absolute band count).
Additionally, the investigators focus on the positive likelihood ratio and the high specificity. But we aren’t concerned about overworkup in febrile kids. As with all bad diseases, we want high sensitivity to make sure we miss as few SBIs as possible and a low negative likelihood ratio to aid in risk stratification. With a strong negative likelihood ratio (-LR < 0.10) we could use a PCT < 0.5 ng/ml to risk stratify patients to a low or very low risk of SBI and potentially send them home with follow up. Here, a PCT < 0.5 ng/ml had a – LR = 0.52. In this study, 13.3% (30/226) patients ultimately had an SBI. If you started with a pretest probability of 13.3% and apply a – LR of 0.52 using the Fagan Nomogram (below) you’d get a post-test probability of around 10%. This is nowhere near low enough for us to stop our workup.
Where does this leave us? Biomarkers will continue to be pushed since there are strong industry interests. Additionally, we want something concrete, objective and tangible to help us with our clinical decision-making. Future studies, though should focus on the additional benefit of markers to the clinician’s assessment and gestalt instead of looking at the biomarker in a vacuum. Show us this and we’ll all sit up and take notice. Until then, procalcitonin is simply another test without a clear indication.

Special thanks to Rory Spiegel (@CaptainBasilEM) and Mike Mojica for the help with this post.