I have railed against the use of C-Reactive Protein, CRP, on this blog previously, it was my analysis that the CRP is sensitive, but with very poor specificity, both for early-onset sepsis, and for late-onset sepsis. A new systematic review in JAMA Pediatrics (Brown JVE, et al. Assessment of C-Reactive Protein Diagnostic Test Accuracy for Late-Onset Infection in Newborn Infants: A Systematic Review and Meta-analysis. JAMA Pediatr. 2020)
suggests that I was wrong (gasp!), CRP is not very sensitive either.
Analyzing 22 publications including over 2000 infants using CRP to diagnose culture-positive sepsis among mostly preterm infants after 72 hours of age. Among the infants in the studies who presented with clinical signs suggestive of sepsis, the systematic review overall included articles where positive cultures were found in 40%.
The results show a test that is of virtually no value at all, whatever threshold was used for deciding that a CRP result was positive. After analysis of the results, they found: “At the reported median specificity (0.74), sensitivity was 0.62 (95% CI, 0.50-0.72); at the reported lower quartile specificity (0.61), sensitivity was 0.76 (95% CI, 0.66-0.83); at the reported upper quartile specificity (0.84), sensitivity was 0.45 (95% CI, 0.34-0.57)”.
Sensitivity and specificity refer to the performance of the test, the meaning and usefulness of a test depend on the prevalence of the condition among those tested, which will then lead to the positive and negative predictive values. This is illustrated by the great editorial, with a Barrington-esque subtitle, which accompanies the systematic review, (Cantey JB, Bultmann CR. C-Reactive Protein Testing in Late-Onset Neonatal Sepsis: Hazardous Waste. JAMA Pediatr. 2020)
If a baby presents with signs suggestive of sepsis you could do one of 2 things, send 0.4 mL of precious blood to the lab for a CRP when you do the blood culture, or save the baby’s blood (or add it to the blood in the culture bottle to increase the yield) and flip a coin instead. This table from the editorial shows the relative value of a CRP test and a coin flip.
Flipping a coin saves blood, saves money, and is just as useful as performing a CRP!
One adverse consequence of measuring CRP is that there is sometimes an assumption that, even when the culture is negative, if the baby had an elevated CRP they must have “culture-negative sepsis” and they then receive multiple days of unnecessary antibiotics. I think the argument on rounds that we should continue the antibiotics “because it was a ‘heads'” would be laughed at, we should do the same thing when someone says we should continue antibiotics because the CRP was elevated.
Measuring CRP in the evaluation of late-onset sepsis should be abandoned. The big question to answer now is whether we consider ‘heads’ or ‘tails’ to be a positive test!