Video Abstract Video Abstract Determining infection etiology can be difficult because viral and bacterial diseases often manifest similarly. A host protein test that computationally integrates the circulating levels of TNF-related apoptosis-induced ligand, interferon γ-induced protein-10, and C-reactive protein to differentiate between bacterial and viral infection (called MMBV) demonstrated high performance in multiple prospective clinical validation studies. Here, MMBV’s diagnostic accuracy is evaluated in febrile children for whom physicians were uncertain about etiology when applied at the physician’s discretion. Patients aged 3 months to 18 years were retrospectively recruited (NCT03075111; SPIRIT study; 2014–2017). Emergency department physician's etiological suspicion and certainty level were recorded in a questionnaire at blood-draw. MMBV results are based on predefined score thresholds: viral/non-bacterial etiology (0 ≤ score <35), equivocal (35 ≤ score ≤65), and bacterial or coinfection (65 < score ≤100). Reference standard etiology (bacterial/viral/indeterminate) was adjudicated by 3 independent experts based on all available patient data. Experts were blinded to MMBV. MMBV and physician’s etiological suspicion were assessed against the reference standard. Of 3003 potentially eligible patients, the physicians were uncertain about infection etiology for 736 of the cases assigned a reference standard (128 bacterial, 608 viral). MMBV performed with sensitivity 89.7% (96/107; 95% confidence interval 82.4–94.3) and specificity 92.6% (498/538; 95% confidence interval 90.0–94.5), significantly outperforming physician's etiological suspicion (sensitivity 49/74 = 66.2%, specificity 265/368 = 72.0%; P < .0001). MMBV equivocal rate was 12.4% (91/736). MMBV was more accurate in determining etiology compared with physician's suspicion and had high sensitivity and specificity according to the reference standard.

Background and objectives: Adenovirus causes acute respiratory illness that can mimic bacterial infection, making it challenging to differentiate adenoviral infection from adenoviral-bacterial co-infection. A host-protein score (BV score) for differentiating bacterial from viral infection that combines the expression levels of TNF-related apoptosis-induced ligand, interferon gamma-induced protein-10, and C-reactive protein exhibited a negative predictive value (NPV) of 98% in prior studies. Here we evaluate BV score's diagnostic accuracy in pediatrics with adenovirus PCR detection.Methods: This is a sub-analysis of children aged 3 months to 20 years with adenovirus PCR-positive infection recruited prospectively in two previous cohort studies. Reference standard diagnosis (bacterial, viral or indeterminate) was based on expert adjudication. BV score ranges from 0 to 100 and provides three results based on predefined cutoffs: viral or other non-bacterial etiology (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65), and bacterial or co-infection (65 < score ≤ 100). Experts were blinded to BV results.Results: Out of 1,779 children, 142 had an adenovirus PCR-positive nasopharyngeal swab. Median age was 1.2 years (interquartile range 0.6–1.8), 50.7% were male and 52.8% were hospitalized. 12 cases were reference standard bacterial, 115 reference standard viral and 15 were indeterminate. BV score attained sensitivity of 100.0% (no false negatives), specificity of 89.5% (95% confidence interval: 83.2–95.8), and NPV of 100.0% (92.6–100.0). Equivocal rate was 19.7%.Conclusions: BV score accurately differentiated between adenoviral and bacterial-adenoviral co-infection in this cohort of children with PCR-positive adenovirus detection. This performance supports a potential to improve appropriate antibiotic use.

Background: Identifying infectious etiology in pediatric emergency medicine can be challenging, often leading to antibiotic misuse. MeMed BV (MMBV) is a host-protein test that accurately differentiates bacterial from viral infections, but real-world utility data in children are limited. Methods: We performed a single-center retrospective study of preschool-aged children enrolled in two pragmatic cohort studies, where MMBV was ordered at physician discretion. In the “pre” study, MMBV results were not available (standard of care, SC arm), whereas in the “post” study, MMBV results were available in a timely manner (MMBV arm). The primary endpoint was change in antibiotic prescribing rate among outpatients with viral MMBV results. Secondary endpoints included prescribing rate changes in a lower respiratory tract infection (LRTI) subcohort and changes in hospital length of stay (LOS). Results: The study cohort included 1,022 children in the SC arm and 474 in the MMBV arm. Antibiotic prescribing in outpatients with viral MMBV results decreased from 20.3% in the SC arm to 7.5% in the MMBV arm ( p = 0.007). Prescribing increased in outpatients with bacterial MMBV results ( p = 0.111), resulting in a net decline across outpatients in the SC versus MMBV arms (25.0% vs. 16.8%; p = 0.071). In the LRTI subcohort, there was a prescribing decreased (84.0% to 67.9%; p = 0.002) irrespective of patient disposition. Despite more severe clinical presentation, patients in the MMBV arm had a shorter length of stay (LOS) compared with patients in the SC arm (3.1 ± 1.9 vs. 3.6 ± 1.9 days; p < 0.001). Conclusions: Implementation of MMBV in routine pediatric emergency care was associated with optimized antibiotic use and shorter hospital LOS.

Background: Kingella kingae is a primary cause of pediatric osteoarticular infections. Diagnosis is challenging due to mild clinical presentations and fastidious culture growth, often mimicking viral illnesses. The MeMed BV™ assay measures C-reactive protein (CRP), interferon gamma-induced protein 10 (IP-10), and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) to differentiate bacterial from viral infections, but its utility in K. kingae has not been evaluated. Objectives: To characterize the CRP, IP-10, and TRAIL profiles in pediatric patients with confirmed K. kingae infections compared to viral and classical bacterial cohorts. Methods: This retrospective study analyzed 19 children with microbiologically confirmed K. kingae. Controls included viral (n = 20), pneumococcal (n = 17) and Gram-negative (n = 7) cohorts. Serum concentrations of the three host-response proteins were compared. Results: The median age of the K. kingae cohort was 11.0 months (IQR, 9.0–12.0 months). Compared to viral controls, K. kingae elicited significantly lower IP-10 levels (median: 100.0 pg/mL [IQR, <100.0–399.0] vs. 632.5 pg/mL [IQR, 346.3–1375.8]; p = 0.004) and a downward trend in TRAIL levels (median: 75.0 pg/mL [IQR, 66.0–95.0] vs. 169.5 pg/mL [IQR, 76.5–205.0]; p = 0.066), aligning with a bacterial profile. Conversely, K. kingae induced significantly lower inflammatory and host-response markers than typical bacterial infections; its median CRP (18.8 mg/L [IQR, 10.0–50.0]) and MeMed BV™ score (28 [IQR, 11–61]) were markedly lower than those observed in the pneumococcal cohort (CRP: 94.0 mg/L [IQR, 39.5–182.5]; MeMed BV: 89 [IQR, 51–98.5]) and the alternative bacterial cohort (CRP: 106.0 mg/L [IQR, 32.0–250.0]; MeMed BV: 73.0 [IQR, 67.0–99.0]). Conclusions: Kingella kingae infections elicit a distinct host-response fingerprint characterized by mild CRP elevation, leukocytosis, and uniquely suppressed IP-10 levels. Utilizing this three-protein signature may help distinguish K. kingae from viral mimics, preventing diagnostic delays and optimizing antibiotic stewardship.