Yet Another Febrile Infant Rule

The Holy Grail in the evaluation of infants of less than 60 days remains safe discharge without a lumbar puncture. Boston, Philadelphia, Rochester, Step-by-Step and others have tried to achieve this noble goal over the years. And now, the Febrile Young Infant Research Collaborative has tossed their hat into the ring.

In this retrospective query of their Pediatric Health Information System and other electronic medical records, these authors identified 181 non-ill appearing patients across 11 Emergency Departments with invasive bacterial infection, defined as bacteremia in either blood or cerebrospinal fluid. Using 362 matched controls as a comparison cohort, these authors used the typical logistic regression route to tease out the strongest predictors of IBI – age in days, observed temperature, absolute neutrophil count, and urinalysis result. Subsequently, they condensed the continuous variables into cut-offs maximizing area under the curve. These cut-offs were then incorporated into a scoring system based on the strength of their adjusted odds ratio, and then the final output was validated on the derivation set using k-fold cross-validation with 10 sets.

The final result using their best cumulative score cut-off: sensitivity of 98.8% (95% CI 95.7-99.9) with 31.3% specificity. The two cases missed were that of a 3-day old and a 40-day old otherwise afebrile in the ED with normal UA and an ANC <5185. The authors ultimately conclude their score, if validated, may have best value as a one-way prediction tool primarily to reduce current routine invasive testing, owing to its poor specificity. Certainly, I agree it does not have much value in those who might otherwise not undergo testing; a more specific risk score may be better, if not clinician gestalt.

The other tidbit I might mention is whether there could be value in incorporating time-of-onset of fever into their evaluation. We’ve seen in other studies a few of the fallouts with regard to sensitivity of IBI stem from recency of illness onset, and it may be falsely reassuring to find a normal ANC early in an illness course. Furthermore, these authors do not specifically mention whether the lack of fever in the ED could have been associated with prehospital antipyretic use. Finally, their data collection does not appear to incorporate respiratory swab results; readily available respiratory viral panel results may also prove useful in ruling out IBI.

While these data are certainly alluring, considering the desire to avoid invasive procedures in young infants, substantial prospective work is still likely required.

As a sad aside, the authors state:

However, these criteria were developed >25 years ago, and the epidemiology of serious bacterial infections has changed considerably since that time.

Unfortunately, as vaccination frequency continues to decline, even since patients were enrolled for this study, our “modern” cohort may better begin to resemble that of 25 years ago.

“A Prediction Model to Identify Febrile Infants ≤60 Days at Low Risk of
Invasive Bacterial Infection”

https://www.ncbi.nlm.nih.gov/pubmed/31167938