CRPs; are they CRaP?

I was taught before asking for a test to always ask myself 2 questions.

What will I do if the result is negative?

What will I do if the result is positive?

The counsel was that if the 2 answers are the same: don’t do the test!

In neonatology we have for many years been trying to find accurate predictive tests for sepsis. In a child with possible clinical signs for sepsis, or a clinical situation that puts them at high risk, then an accurate test that could reduce antibiotic use, might be helpful. At present about 0.8% of cultures taken to rule out early onset sepsis, and 10% for late onset sepsis, are positive. So 99.2% and 90% of antibiotic courses do not help the infant, but select out resistant organisms. What we really need is a test which is rapidly positive, and specific for sepsis. A test which becomes positive the day after the antibiotics are already started, and which is sensitive but not specific is not much use to us.

It seems to be not much use in older children either. A publication in BMC Pediatrics reviewed the use of CRPs in neonates and older children in an acute care hospital. They showed that most of the tests did not have any impact on clinical management, and they cost a great deal of money.

They did not mention the blood loss, but in tiny preterm babies this can be a significant issue for any test we do. A blood test needing 0.6 mL of blood for example (such as the CRP requirement for the lab in our hospital) will often lead to the baby having substantially more than 0.6 mL taken, say 1 mL. And if repeated 10 times during a hospitalisation, lead to a substantial blood loss.

The Health Technology Assessment program in the UK is amazingly productive in many different areas of medicine. They have just published a systematic review of predictive tests for serious infections in children. Unfortunately for my purposes they excluded neonatal studies and patients under 1 month of age. But I am convinced they would find the same thing that they note in their discussion. ‘Both CRP and PCT offer similar diagnostic performance and are superior to WBCs. However, neither CRP nor PCT has sufficient diagnostic value to either confirm or exclude a serious infection, and thus their results must be interpreted in the light of clinical findings’.

Very often when CRP is requested, the answer to the 2 questions posed above will be ‘I will  start antibiotics and wait until the cultures are negative before stopping them’. If that is the case, save the money and reduce the blood loss!

About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research and tagged , . Bookmark the permalink.

3 Responses to CRPs; are they CRaP?

  1. CRP is reasonably sensitive for early onset sepsis by about 12 to 18 hours (Benitz et al Peds 1998), and could be used to accelerate the decision to stop antibiotics prior to the 24 hour dose in conjunction with a (so far) negative blood culture and a reassuring clinical course, noting that 95% of postive cultures in EOS are positive by 24 hours (Jardine et al. J Paeds Child Health 2006). We found that many infants we treated for ? EOS ended up getting 3 days (50% of infants) , 4 days (15%) or 5 days (20%) of antibiotics so there seems to be plenty of room to cut antibiotic exposure at the back end of the courses. CRP can help provide some moral support!

    • I certainly agree that if the CRP is going to alter your clinical management, then by all means you should go ahead. I”m not sure how often that is what actually happens, often a CRP is taken at the same time as the septic work up, and then the result is ignored as it was too early anyway! The proportion of positive cultures when screening for early onset sepsis is somewhere round 1%, so if you take a CRP at 24 hours (with a sensitivity of about 90%) and it is negative the post-test likelihood if sepsis drops to about 0.1%. If you get the result instantly you could avoid the 24 hour dose of ampicillin in some babies. But if you are going to stop after a negative culture at 36 hours anyway (which I think you should almost always do) then you really don’t get much bang for your buck.
      But what about the converse? The specificity of CRPs is not great, around 75%, so 25% of the babies will have an elevated concentration, but no proven sepsis, you could easily end up continuing the antibiotics for false positive CRPs more often than stopping them early because of a reassuring negative.
      I do occasionally do CRPs, usually if I am not sure about a baby who had a septic workup and is on antibiotics, but I wonder if there is culture negative sepsis or pneumonia, or stage 1 NEC, by 24 hours after treatment you can be reassured by a very low value. But I often find myself even more unsure when we get back a raised value in a baby who is doing well. Should you continue the antibiotics? Do you need to treat ‘culture-negative sepsis’ with antibiotics at all?
      I well remember a pair of monozygotic preterm twins who both presented with early septic shock. One had E Coli in the blood stream, the other didn’t. The 2nd clearly had culture-negative sepsis, but was it just due to transfer of cytokines from the other baby who was truly infected? I don’t know, we gave both a full course of antibiotics anyway!

  2. Pingback: They really are CRAP! C-ReActive Protein: “Hazardous Waste”. | Neonatal Research

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