Urinary Tract Infection, Bacteremia, and Meningitis Among Febrile Young Infants With SARS-CoV-2 and Non–SARS-CoV-2 Viral Infections

This cohort study assesses the prevalence of urinary tract infections (UTIs), bacteremia, and bacterial meningitis among infants systematically tested for SARS-CoV-2 and non–SARS-CoV-2 viruses, with a focus on invasive bacterial infections.


Introduction
Guidelines from the American Academy of Pediatrics (AAP) have been published to evaluate febrile infants aged 8 to 60 days for urinary tract infections (UTIs), bacteremia, and bacterial meningitis. 1 Studies 2 suggest that the presence of a respiratory virus is associated with decreased risk of these infections; however, it remains unclear how viral testing should guide laboratory evaluation and management. 1 Moreover, the emergence of SARS-CoV-2 and changing epidemiology since the COVID-19 pandemic present further challenges to risk stratification. 3This study sought to assess the prevalence of UTIs, bacteremia, and bacterial meningitis among infants systematically tested for SARS-CoV-2 and non-SARS-CoV-2 viruses, with a focus on invasive bacterial infections (IBIs; ie, bacteremia and bacterial meningitis collectively). 1

Methods
This was a secondary analysis of prospectively collected quality improvement data for all infants aged 60 days and younger evaluated for fever at an urban tertiary pediatric emergency department between March 2020 and December 2022. 4Standardized clinical, laboratory, and telephone follow-up data were collected for all infants.Only previously healthy, full-term infants aged 8 to 60 days with a documented rectal temperature of 38.0 °C or higher meeting AAP inclusion and exclusion criteria were included for analysis. 1All infants underwent multiplex respiratory testing that included SARS-CoV-2 (eTable in Supplement 1).Cerebrospinal fluid testing was at the discretion of the treating physician.Final infection status was confirmed for all infants by microbiologic culture results and telephone follow-up 14 to 28 days after discharge.UTI, bacteremia, and bacterial meningitis were defined according to current definitions. 2,3Infants with SARS-CoV-2 plus any other non-SARS-CoV-2 virus detected were analyzed in the SARS-CoV-2 group.
Prevalences of any infection (UTI, bacteremia, and bacterial meningitis) and IBI specifically were compared between infants with no virus detected and SARS-CoV-2 or non-SARS-CoV-2 infections by χ 2 testing using Stata statistical software version 14.1 (StataCorp).A 2-tailed P < .05 was considered statistically significant.This cohort study received approval from the McGill University Heath Centre research ethics board, with a waiver of informed consent because the data were collected prospectively for quality improvement purposes.The study followed Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

Results
There were 931 infants included for analysis.Their median (IQR) age was 38 (25-49) days, 547 (58.8%) were male, and 428 (46.0%) were hospitalized (Table ).Almost all infants had culture results available for blood (871 infants [93.6%]) and urine (875 infants [94.0%]).Overall, 107 infants (11.5%) had UTI, bacteremia, or bacterial meningitis, and 20 (2.2%) had IBIs.Viruses were detected among 611 infants (65.6%), including 163 (17.5%) with SARS-CoV-2.The prevalence of UTI, bacteremia, and    A limitation of this study is that it was conducted at a single center.SARS-CoV-2 variant testing was uncommon, and variants may not be equally associated with lower infection risk.Multiplex testing does not distinguish between human rhinovirus and enterovirus, which could underestimate the difference between virus-negative and non-SARS-CoV-2 groups. 6Only 20 infants had IBIs, but the study cohort was similarly large compared with prospective cohorts informing AAP guidelines. 1

Figure .
Figure.Prevalence of Any Infection and Invasive Bacterial Infections (IBIs) Specifically Among Febrile Infants According to Viral Status
1TI, Bacteremia, and Meningitis Among Febrile Young Infants With Viral InfectionsDiscussionTo our knowledge, this cohort study is the first to assess the prevalence of UTI, bacteremia, and bacterial meningitis among febrile young infants systematically tested for viral infections including SARS-CoV-2.Findings are similar to previous studies with selective viral testing, suggesting a significantly lower but nonnegligible risk of UTI and IBI among infants non-SARS-CoV-2 infections 1,2 and very low risk of IBI among those with SARS-CoV-2.5These findings support AAP recommendations that a confirmed non-SARS-CoV-2 virus should not affect the initial evaluation for young infants with fever.1However,findings demonstrating the very low risk of IBIs among infants with SARS-CoV-2 may assist clinicians individualize management and inform shared decision-making with parents, particularly when rapid COVID-19 testing results are known or available at the point of care.