A blood test to avoid a spinal tap in an infant? Yes please. / by Methods Man

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For the video version of this post, click here. Here’s a secret for any non-clinicians watching this. Docs are terrified of fevers in very young infants - not because they turn out so horribly - most are benign viral infections - but because fever in an infant of less than 4 weeks requires a spinal tap to rule out meningitis. It would be great to have a test that could reliably and quickly tell us if a baby’s fever was due to a bacterial infection that needs prompt and aggressive treatment, or a virus, that can be managed at home.

Enter procalcitonin. It’s pretty much undetectable in the blood of healthy kids, but goes up in the setting of inflammation.  Interestingly, it seems to go up much more in the setting of bacterial infection than viral infection.  Could we use procalcitonin level to triage infants with fevers? Could we avoid blood cultures and spinal taps?

An article appearing in JAMA pediatrics suggests that we could, but I’m not sure the evidence is so clear. Here are the basics:  researchers in France enrolled around 2000 babies from 7 - 91 days of life who presented to the emergency room with fever. The workup done was left to the discretion of the treating physician, but a blood sample for procalcitonin was taken and blindly measured later.

As you might expect, only about 10% of the babies had bacterial infections (which included urinary tract infections).  Bacteremia or meningitis were found in less than 1%. I want to focus on that last group, as UTIs can be pretty easily diagnosed by urine dipstick. Could procalcitonin rule out blood or cerebrospinal fluid infection? Well, using a cut-off of 0.3 ng/ml, babies with high procalcitonin levels were 31 times more likely to have bacterial meningitis or bacteremia than kids without those levels.  That sounds pretty good.

But to really evaluate this test, we have to look at the sensitivity, which was reported at 90%.  That means that you’ll capture 90% of those terrible infections if you use a 0.3ng/ml cutoff.  That’s good, but not great. And as a parent of a one month old myself, not a risk I’d be willing to take.  Lowering the threshold to 0.12ng/ml apparently would capture all the bad infections, but at that point, the false-positive rate would be really high.

The manuscript did demonstrate that procalcitonin is better than some alternatives like c-reactive protein and white blood cell count. But one thing they don’t report? Clinician’s suspicion.  They mention in the methods section that the treating physician classified each infant as well, minimally, moderately, or very ill.  How did those assessments perform?  We aren’t told.

It basically boils down to how many spinal taps we can avoid without missing any cases of meningitis. It may be reasonable to feel comfortable sending the baby home when the procalcitonin level is extremely low, but I suspect in those cases the physicians were pretty comfortable anyway. For me to push for the broad adoption of this test, I want to see that it tells us something physicians don’t already know - and this manuscript came up short on that front. But if that data does finally arrive, well, we’ll all be thankful.