Gaensbauer, James

Abstract Background Identification of the microorganisms causing infection in children with central nervous system infection is important. Conventional cerebrospinal fluid (CSF) tests may provide limited pathogen detection. CSF metagenomic next-generation sequencing (mNGS) may provide broader pathogen detection in a single assay. Methods Results of CSF mNGS testing performed at Mayo Clinic on patients and nonpatients between January 2024 and June 2025 were retrospectively analyzed. The subcohort of children treated at Mayo Clinic was analyzed to assess test performance as compared with conventional CSF diagnostics and potential clinical impact. Results In total 134 patients (138 CSF mNGS tests) from 22 US states and 2 international sites were included. Overall positivity was 16% with viruses representing most (59%) detections. In the Mayo Clinic subcohort (n = 15), test positivity was 27%: organisms included single detections of Streptococcus mitis group and HIV type 1, as well as 2 detections of Epstein-Barr virus, all confirmed by conventional tests. Positive results were associated with CSF pleocytosis (P = .026). Higher yield was observed in participants whose care was overseen by pediatric infectious diseases (PID) specialists (P = .026) and when a specimen hold strategy was applied (P = .033). Most results (87%) did not alter antimicrobial therapy, with 2 negative results contributing to antimicrobial de-escalation. Conclusions CSF mNGS demonstrated higher diagnostic yield in patients whose specimens showed CSF pleocytosis and in those who had PID consultation. Diagnostic stewardship strategies were applied, including specimen hold approaches and PID consultation.

Abstract Background Revaccination is required for patients who receive a hematopoietic cell transplant (HCT) to reduce vaccine preventable illness. Revaccination requires an individualized plan due to differences in immunosuppressive therapy, immune reconstitution, age, and other challenges such as graft versus host disease. A structured approach is required to ensure prompt initiation of re-vaccinations and completion of the re-vaccination schedule. This study sought to evaluate the re-vaccination process at our center as a baseline for quality improvement. Methods We conducted a retrospective chart review of pediatric patients who received an autologous or allogeneic HCT between January 2019 and March 2024 to assess time to starting re-vaccination after post-HCT medical clearance and percentage of patients up to date within each series of vaccinations per internal protocol. Results A total of 64 patients were evaluated, of whom 23 were female and 35 underwent allogeneic stem cell transplant. For analysis, 13 were excluded due to death prior to clearance for vaccination. Among those included, 42 patients were cleared for restarting vaccines, and 37 (88%) of those have received at least one vaccine, while only 25 (59%) have completed the first series of recommended vaccines. The average time from transplant to administration of the first vaccine was 431 days for autologous HCT and 459 days for allogeneic HCT. The average time from medical clearance to the first vaccine was 66 days. The mean interval between the first and second vaccine doses was 97 days. Conclusion The majority of eligible patients initiated re-vaccination after transplant, but rates for the receipt of full recommended initial series remained suboptimal, with notable delays with notable delays between transplant and the day of clearance as well as clearance and the first vaccine administered. These findings highlight significant gaps in post-transplant immunization practices and underscore the need for targeted interventions to optimize protection for this vulnerable population. Disclosures All Authors: No reported disclosures

Abstract Background 16S ribosomal RNA (rRNA) gene PCR and sequencing may serve as an adjunctive diagnostic tool in complex infections, identifying bacteria in patients on antibiotics whose cultures may be negative. Data on the optimal clinical settings for utilizing this type of testing are limited. This study reviews a single center's 16S rRNA PCR/sequencing experience in children to identify clinical syndromes and optimize specimen choice for higher yield, leading to testing of appropriate patients. Methods A retrospective study was performed at Mayo Clinic, Rochester involving children aged 0 to 18 years whose normally sterile tissue or fluid samples underwent 16S rRNA gene PCR/sequencing. The assay involved an up-front real-time PCR assay, reported as negative or submitted to Sanger or next-generation sequencing depending on Ct values. Data was collected on patient characteristics and results of 16S rRNA gene PCR/sequencing and conventional tests. Impact on clinical decision-making was assessed as to whether the advanced molecular diagnostic changed antimicrobial therapy. Results A total of 162 tests were performed on 124 patients, including 47% females (58/124) with a median age of 9.6 (range, 2.2-15.0) years. Overall, 33/162 (20%) of tests were positive in 24/124 (19%) patients. 58% of positive tests (19/33) were from samples with negative bacterial cultures. Cerebrospinal fluid was the most common specimen tested (n=38; 31%). Positive results were more likely from fluid compared to tissue samples (OR [95% CI]: 3.1 [1.3, 7.1], p=.007; OR [95% CI]: 0.3 [0.1, 0.8], p=.007, respectively). Testing was positive in 5/10 (50%) pleural fluids tested, a higher positivity rate than any other specimen type (OR [95% CI]: 5 [1.3, 19.0], p=.011). No significant changes in antibiotics were made within 24 hours of reporting positive 16S rRNA gene PCR/sequencing results. Conclusion This study highlights the importance of selecting appropriate sample types for 16S rRNA gene PCR/sequencing in pediatric patients. The assay is most likely to yield positive results in children with pleural effusion and in other fluid samples such as subdural and synovial fluid. Further implementation science research is needed to achieve impact on clinical practice. Disclosures Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria

Abstract Introduction Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis (TB). Pediatric data comparing the 2 IGRAs in the United States are very limited. We compared the performance of the 2 IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cutoff values. Methods Children aged 0-15 years with both T-SPOT.TB (T-SPOT) and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests were identified from a US multicenter study enrolling people at elevated risk of TBI or progression to TB disease. Results were compared using McNemar’s Chi-square tests with stratification by age category and testing reason. Percent agreement and kappa statistics were also calculated. We characterized quantitative test results among children with discordant QFT-GIT-positive/T-SPOT-negative results. Results Among 3793 children, a higher number had positive QFT-GIT than T-SPOT (10.1% vs 7.4%, P < .001). This difference was noted for all age categories except <2 years, and for children with close-contact and non-close contact test indications. Among discordant QFT-GIT-positive/T-SPOT-negative children, lowering the positive threshold for T-SPOT to include borderline spot counts (5-7) did not eliminate the discordance, nor were QFT-GIT antigen-minus-nil results concentrated in the range just above the standard cutoff of 0.35 IU/mL. Conclusions In a large pediatric cohort tested for TBI, QFT-GIT had a higher proportion of positive results than T-SPOT, and discordance was not related to quantitative results close to the established diagnostic cutoffs.

Over the last decade, there have been widespread efforts to reduce non-evidence-based therapies for viral bronchiolitis. We question whether this change in practice has inadvertently impacted the diagnosis and management of other pediatric lower-respiratory-tract illnesses. We used the Pediatric Health Information System (PHIS) and logistic regression to describe trends in relative diagnosis frequency of bronchiolitis, viral pneumonia, and reactive airway disease (RAD)/asthma as well as systemic corticosteroid use among children of the age range 1 to 4 years over a 10-year period. Among 169,207 children, the relative frequency of asthma/RAD diagnoses declined over a 10-year period, while bronchiolitis and viral pneumonia diagnoses increased among children of the age range 1 to 3 years and 2 to 4 years, respectively. Frequency of systemic corticosteroid use declined. We question whether the observed shift in diagnosis from asthma/RAD to bronchiolitis or viral pneumonia is reflective of true disease pathophysiology or if it represents an unintended consequence of campaigns surrounding bronchiolitis.

Abstract Background Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring. Methods Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring. Results Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. Conclusions BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible.

Objective: This analysis summarizes observational epidemiologic data and transmission dynamics of SARS-CoV-2 among people aged <18 years to better characterize the pediatric COVID-19 pandemic. Methods: We conducted a retrospective study of public health surveillance data among children in Denver, Colorado, who were reported to have COVID-19 from March 1, 2020, through September 30, 2021. We used descriptive statistics and bivariate rate ratios (RRs) to describe demographic and clinical characteristics, transmission dynamics, case trends, and ecological associations. Results: A total of 9815 children and adolescents who had COVID-19 were reported during the study period. Adolescents aged 14-17 years had the highest incidence rate (IR) per 1000 people (IR = 107.5; 3021 of 28 108). Hispanic/Latino children had a 1.6 times higher rate of infection than non-Hispanic White children (RR = 1.57; 95% CI, 1.50-1.65; P < .001). Few hospitalizations (n = 138, 1.4%) and deaths (n = 3, 0%) occurred. Most children were symptomatic (4487 of 5499, 81.6%). Within household clusters, a large proportion of pediatric cases (n = 6136) were a secondary case (n = 3959, 64.5%), followed by index case (n = 1170, 19.1%) and co–index case (n = 1007, 16.4%). Non-Hispanic White children had an increased risk of being an index or co–index case (RR = 1.14; 95% CI, 1.06-1.23; P < .001), while Hispanic/Latino children had an increased risk of being a secondary case (RR = 1.07; 95% CI, 1.03-1.11; P < .001). From 2020 to 2021, the association between pediatric case rates and neighborhoods with higher poverty and households with ≥3 people decreased. Conclusions: Older children and those identifying as Hispanic/Latino had a disproportionate incidence of disease. A sizable proportion of children were considered index cases or co–index cases. Pediatric prevention strategies, especially vaccinations, are vital for pandemic control.