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This series of 28 infants with group B streptococcal (GBS) cellulitis-adenitis from a single institution over 24 years offers insights important to the early recognition, spectrum of findings, and optimal management of this rare manifestation of invasive GBS disease.

Background Kingella kingae is a recognized cause of bone and joint infections (BJI) in infants. The diagnosis of Kingella kingae BJI can be challenging due to its fastidious growth with conventional culturing methods even when infected tissue is obtained. Kingella kingae spinal infections are likely an underdiagnosed entity given the limitations of culture-based methods and the reluctance to biopsy spinal locations of infection (in favor of empiric treatment). This approach often necessitates MRSA coverage. A sensitive, rapid, noninvasive diagnostic approach to pediatric vertebral infections would enable targeted therapy. Detection of circulating microbial cell-free DNA (mcfDNA) in the plasma originating from areas of sequestered infection through next-generation sequencing (NGS) has shown utility in pediatric pneumonia (Farnaes et al. DMID 2019) and a wide variety of infections in the immunocompromised host (Rossoff et al. OFID 2019) and potentially offers promise in resolving the etiology of pediatric vertebral infections. Methods The Karius test is a CLIA-certified/CAP-accredited NGS plasma test that detects circulating mcfDNA in the blood. After mcfDNA is extracted and NGS performed, human sequences are removed and remaining sequences are aligned to a curated pathogen database of >1400 organisms. Organisms present above a statistical threshold are reported and quantified. The time to result reporting is on average 24 hours from sample receipt. Karius Test results over the prior 2 years were reviewed for detections of Kingella kingae in the context of spinal infections. Clinical chart review was performed by the treating pediatric infectious diseases physicians at each participating institution after IRB notification and approval. Results Six cases of Kingella kingae pediatric vertebral infections were identified across five institutions; clinical data were available for five cases across four institutions (see Table). Four cases were male; the average age was 15.3 months. Four of five cases had an antecedent URI. The clinical presentations were characterized by decreased mobility and relatively bland inflammatory response (lack of fever, bland inflammatory markers). The lumbar region was the most commonly affected vertebral location (80%). Blood cultures were negative in all cases; empiric anti-MRSA therapy was initiated in all cases. The time to result of Kingella kingae mcfDNA detection in the plasma was one day from sample receipt in all cases. McfDNA from co-pathogens were detected in 66.7% of cases (Haemophilus influenzae was the most common). The detection of Kingella kingae by the Karius test influenced a decision to narrow coverage in 80% of cases and a decision to forego biopsy in 60% of cases. Conclusion Plasma NGS for circulating mcfDNA offers a rapid, noninvasive means of detecting Kingella kingae pediatric vertebral infection. This culture-independent approach may enable specific diagnosis despite antibiotic pretreatment and obviate the need for an invasive procedure. Accurate identification of Kingella kingae has important implications on antibiotic stewardship enabling targeted therapy without the reliance on empiric MRSA coverage. Given the capacity to detect over 1400 organisms from a single sample NGS for mcfDNA offers a means to detect a broad variety of pathogens known to have predilection to cause pediatric spine infection.

In this retrospective study, we aimed to evaluate the performance of dried-blood-spot (DBS) testing as a diagnostic method for the congenital cytomegalovirus (cCMV). We reviewed the medical records and DBS test results of 89 patients who had also undergone diagnostic cCMV testing within the first 21 days of life. The DBS test had a sensitivity of 83.9%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 73%. Patients with a true-positive DBS had a higher median level of CMV in blood according to PCR than those with a false-negative result. Additionally, all patients with cCMV and hearing loss had a positive DBS test, with higher median viremia levels observed in those with hearing loss compared to those without a CMV PCR blood test. These results suggest that DBS-based testing is useful in the diagnosis of cCMV, and its performance may be related to levels of CMV viremia. DBS testing accurately identified those patients with congenital/early onset hearing loss and those at risk of developing late-onset hearing loss.