Boston, Philadelphia Criteria Misclassify Many Infants With Invasive Bacterial Infections

By Lisa Rapaport

March 25, 2020

(Reuters Health) - The decades-old Boston and Philadelphia criteria for identifying infants at risk for serious bacterial infections misclassify many babies as low-risk, a new study suggests.

"In the era of widespread conjugate vaccination and maternal antibiotic prophylaxis, the bacterial epidemiology has changed, potentially changing the performance of these criteria," said coauthor Dr. Todd Lyons of Harvard Medical School and Boston Children's Hospital.

"In our large validation study, these rules missed approximately one-third of infants with bacterial meningitis," Lyons said by email.

The researchers assembled a multicenter cohort of infants, 29 to 60 days old, who had cerebrospinal fluid (CSF) and blood cultures obtained within 24 hours of arrival in the emergency department.

They examined the performance of the modified Boston criteria (peripheral white blood cell count of at least 20,000 cells per mm3, CSF WBC of at least 10 cells per mm3, and urinalysis with at least 10 WBC per high-power field or positive urine dip result) and the modified Philadelphia criteria (peripheral WBC of at least 15,000 cells per mm3, CSF WBC of at least 8 cells per mm3, positive CSF Gram-stain, and urinalysis with at least 10 WBC per high-power field or positive urine dip result) for the identification of invasive bacterial infections (IBI).

Specifically, they focused on growth of pathogenic bacteria from CSF culture (bacterial meningitis) or from blood culture (bacteremia).

The study team applied the modified Boston criteria to 8,344 infants and the modified Philadelphia criteria to 8,131 babies.

Overall, the modified Boston criteria identified 133 of the 212 infants with IBI (sensitivity 62.7% (95% confidence interval (CI) 55.9% to 69.3%) and specificity 59.2% (95% CI 58.1% to 60.2%)). The modified Philadelphia criteria identified 157 of the 219 infants with IBI (sensitivity 71.7% (95% CI 65.2% to 77.6%) and specificity 46.1% (95% CI 45.0% to 47.2%)).

The modified Boston and Philadelphia criteria misclassified 17 of 53 (32.1%) and 13 of 56 (23.3%) infants with bacterial meningitis, respectively.

Better risk-stratification tools, likely including novel biomarkers, are needed to enable the rapid and accurate identification of infants at low risk of IBI who may be safely managed as outpatients, the study team concludes.

One limitation of the analysis is that the sample cohort only included infants who had a CSF culture obtained. Researchers were also unable to obtain data on infants' clinical appearance, comorbidities, or indication for undergoing evaluation for IBI. And they didn't know whether babies developed a fever at home or during the course of their ED visit.

Despite the limitations, this study obtained results very similar to previous studies, many of which were also retrospective and had similar methodological drawbacks, said Dr. Jefferson Antonio Buendia, a pediatric pulmonologist at Children's Hospital Council of Medellin, in Colombia.

"Using a scale that is wrong in a third of patients is not helpful," Buendia, who wasn't involved in the study, said by email.

Incorrect results might classify an infant as low-risk who actually has a potentially life-threatening bacterial infection, Buendia said, or it might lead to unnecessary treatment with antibiotics and invasive tests that carry a risk of contamination or infection.

"The message is very clear that vaccination remains the most effective strategy to reduce the likelihood of severe bacterial infection in children with fever with no apparent focus," Buendia said. "These scales were very useful in the before the introduction of the pneumococcal and influenza vaccine, however at this time given the infrequency of the event they are only useful in the population with low health resources or low vaccination rates."

SOURCE: Pediatrics, online March 23, 2020.