Most international guidelines recommend lumbar punctures for all infants who have a fever at 28 days or younger to rule out bacterial meningitis. Clinical prediction tools may allow for more selective testing, but little is known about how well they perform in identifying infants at low risk for a life-threatening bacterial infection.

Researchers, led by Brett Burstein, MDCM, PhD, MPH, with the Montreal Children’s Hospital, McGill University Health Centre in Montreal, Quebec, Canada, assessed the diagnostic accuracy of the updated Pediatric Emergency Care Applied Research Network (PECARN) prediction rule and found that it had high sensitivity but lower specificity for identifying febrile infants 28 days or younger with invasive bacterial infections. There were no missed cases of bacterial meningitis, according to the paper. Findings were published online in JAMA.

Pooled Data Over 16 Years

The researchers performed a study analyzing pooled data from four published prospective international cohort studies of well-appearing, full-term infants (at least 37 weeks’ gestation) 28 days or younger who presented with fever (temperature ≥ 38.0 °C (100.4 °F) over the past 16 years.

Among 1537 infants 28 days or younger, 69 (4.5%) had invasive bacterial infections, including 11 (0.7%) with bacterial meningitis. Overall, 632 (41.1%) met low-risk criteria. The prediction tool had a sensitivity of 94.2% (95% CI, 85.6%-97.8%), specificity of 41.6% (95% CI, 36.7%-46.7%), positive predictive value of 6.9% (95% CI, 4.8%-9.9%), and negative predictive value of 99.4% (95% CI, 98.1%-99.8%) for invasive bacterial infections.

“In a secondary analysis of 2531 infants from the two US-based cohorts from which the rule was originally derived and the four validation cohorts, 96 (3.8%) had invasive bacterial infections, 22 (0.9%) had bacterial meningitis, and 1079 (42.6%) were classified as low risk; rule performance was similar,” the researchers report. “No infants with bacterial meningitis were misclassified in the primary or secondary analyses.”

They wrote that their data should inform guidelines and decisions shared between families and providers for low-risk infants aged 28 days or younger who present with fever.

Potential ‘Major Clinical Impact’

“This study has the potential for major clinical impact,” commenters wrote in an accompanying editorial. Justin B. Searns, MD, with the Sections of Hospital Medicine and Infectious Diseases at Children’s Hospital Colorado, and Sean T. O’Leary, MD, MPH, also with the Section of Pediatric Infectious Diseases at Children’s Hospital Colorado in Aurora, Colorado, wrote that “In the US, more than 70,000 infants are evaluated for fever within the first few months of life every year. If the cohorts presented here are a representative sample, close to half of these febrile infants would be considered to be at low risk for bacterial infection.”

If the sample is representative, they wrote, using the PECARN tool could mean “tens of thousands of avoided lumbar punctures, antimicrobial courses, and hospitalizations every year in the US alone.”

However, the editorialists highlighted some of the study’s limitations and potential considerations. They wrote that the high negative predictive value (99.4%) “should be taken in the context of the very low prevalence of invasive bacterial infections among well-appearing febrile neonates in the analysis.” Additionally, all infants assessed were in high-income countries, and generalizability to low- and middle-income countries is not known. Only full-term infants were included, they note, “making it difficult to translate these findings to the care of preterm infants with higher rates of invasive bacterial infections.”

While the study helps move toward refining targeted approaches for diagnosis and care, “[M]ore work is needed before guidelines are changed,” Searns and O’Leary wrote.

Guideline Change Not Yet Warranted

Nada Mallick, MD, MBA, attending physician in critical care medicine at Children’s National Hospital in Washington, DC, also said further data would be needed to change guidelines given the limitations of the study. “I think we should take this data and use it as a clinical tool,” she said.

She told Medscape Medical News that clinical judgment in each patient’s case is critical, even when tools point to low risk.

“If a patient is lethargic, still looks sick, then I would still go ahead and have them have a lumbar puncture,” Mallick said. “The consequence of missing meningitis is very high.”

The researchers looked at a very specific subset of patients, she said, and those won’t always be the patients that physicians see. “These neonates were previously healthy, but you can get neonates who may have complex heart disease or who may be at risk for other types of immunosuppression. You may get the infants predisposed to being sick coming in with frequent infections or high fevers.”

Burstein reported grants from Biomérieux Canada, speaker honorarium from Thermo Fisher Scientific, and being supported by the Quebec Health Research Fund outside the submitted work. Editorialists and Mallick reported having no relevant financial relationships.

Marcia Frellick is an independent, Chicago-based healthcare journalist and a regular contributor to Medscape Medical News.