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Kathryn M Spiekerman,1 Sameer J Patel,2,3 Rupal Patel,4 Larry K Kociolek,2,3 1School of Public Health, University of Illinois at Chicago, 2Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children’s Hospital of Chicago, 3Department of Pediatrics, Northwestern University Feinberg School of Medicine, 4Department of Pharmacy, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA Abstract: Despite the enormous volume of antibiotics prescribed by pediatricians, resources to promote judicious antibiotic use are primarily limited to hospitals. The primary objective of this survey was to delineate the availability, characteristics, and perceptions of antibiograms among pediatricians. As a secondary objective, we sought to delineate the availability of other infectious diseases (ID)-related educational resources among pediatricians, the perceived need for additional resources, and their general educational preferences. We developed an anonymous electronic survey using the Research Electronic Data Capture tool, and it was sent via email to all members of the Illinois Chapter of the American Academy of Pediatrics (ICAAP). Participants were excluded if they had not completed pediatrics residency or if they had not prescribed antibiotics in the past month. Of the 1,825 ICAAP members, 294 (16%) responded; of these, 239 (81%) were eligible and completed the survey. Of the 239 respondents, 139 (58%) had access to an antibiogram and 60 (25%) had access to a pediatric-specific antibiogram. Access to a pediatric-specific antibiogram was associated with subspecialty training (P=0.007) and practice location in Chicago (P

To determine if healthcare-associated (HA)-RSV is associated with worse outcomes, this multicenter cohort study studied 26 children with HA-RSV and 78 matched non-HA-RSV patients of whom 58% and 55%, respectively, had >2 comorbidities. Overall, 39% of HA-RSV versus 18% of non-HA-RSV patients required respiratory support escalation (aOR 5.1, CI95 1.4,19.1)., (© The Journal of the Pediatric Infectious Diseases Society 2024.)

Objectives: Multiple viral respiratory epidemics occurred concurrently in 2022 but their true extent is unclear. To aid future surge planning efforts, we compared epidemiology and resource utilization with prepandemic viral respiratory seasons in 38 US children's hospitals., Methods: We performed a serial cross-sectional study from October 2017 to March 2023. We counted daily emergency department (ED), inpatient, and ICU volumes; daily surgeries; viral tests performed; the proportion of ED visits resulting in revisit within 3 days; and proportion of hospitalizations with a 30-day readmission. We evaluated seasonal resource utilization peaks using hierarchical Poisson models., Results: Peak volumes in the 2022 season were 4% lower (95% confidence interval [CI] -6 to -2) in the ED, not significantly different in the inpatient unit (-1%, 95% CI -4 to 2), and 8% lower in the ICU (95% CI -14 to -3) compared with each hospital's previous peak season. However, for 18 of 38 hospitals, their highest ED and inpatient volumes occurred in 2022. The 2022 season was longer in duration than previous seasons (P < .02). Peak daily surgeries decreased by 15% (95% CI -20 to -9) in 2022 compared with previous peaks. Viral tests increased 75% (95% CI 69-82) in 2022 from previous peaks. Revisits and readmissions were lowest in 2022., Conclusions: Peak ED, inpatient, and ICU volumes were not significantly different in the 2022 viral respiratory season compared with earlier seasons, but half of hospitals reached their highest volumes. Research on how surges impact boarding, transfer refusals, and patient outcomes is needed as regionalization reduces pediatric capacity., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Kawasaki disease (KD) is an acute febrile illness of childhood that can lead to coronary artery aneurysms (CAAs) and myocardial infarction. Intravenous immunoglobulin reduces the prevalence of CAA when given to patients with KD within 10 days of fever onset. Children with KD may undergo evaluation for other diagnoses before treatment, particularly those with incomplete KD criteria. If KD outcomes are improved with early treatment, a delay in treatment while evaluating for other causes might place these patients at risk., Methods: We performed a retrospective cohort study of children treated for KD within the first 10 days of illness at our KD center from 2014 to 2021 to determine the prevalence of CAA by day of treatment., Results: A total of 290 patients met the study criteria. No statistically significant difference was found in the odds of developing a maximum z score ≥2.5 for each day of delayed treatment within 10 days of fever onset (adjusted odds ratio, 0.87; 95% CI, .72-1.05; P = .13). Subgroup analyses by age, sex, and year of treatment did not reveal a significant association between treatment day and maximum z score ≥2.5, although the number of patients <6 months of age was small., Conclusions: Our study supports current recommendations. We found similar odds of developing adverse coronary outcomes regardless of treatment day within 10 days from fever onset., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Special pathogens are broadly defined as highly transmissible organisms capable of causing severe disease in humans. Children's hospital healthcare personnel (HCP) should be prepared to identify patients possibly infected with a special pathogen, isolate the patient to minimize transmission, and inform key infection prevention, clinical, and public health stakeholders. Effective preparedness requires resources and practice with attention to education, policies and procedures, drills and training, and supplies. Successfully preparing for special pathogens is an important measure toward keeping communities, HCP, and patients and families safe in this global age that brings pathogens from across the world to our doorstep., Competing Interests: Disclosure L.K. Kociolek reports grant support from Merck, United States and the Department of Health and Human Services, United States, Health Resources and Services Administration, United States. A.L. Shane reports grant support from the Department of Health and Human Services, Administration for Strategic Preparedness and Response, United States (BARDA). K.A. Simonsen reports grant support from Merck, Alinta, and the Department of Health and Human Services, Administration for Strategic Preparedness and Response to support her salary. D.M. Zerr reports grant from Merck and consultancy for Allovir., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Persistent SARS-CoV-2 infection in immunocompromised hosts is thought to contribute to viral evolution by facilitating long-term natural selection and viral recombination in cases of viral co-infection or superinfection. However, there are limited data on the longitudinal intra-host population dynamics of SARS-CoV-2 co-infection/superinfection, especially in pediatric populations. Here, we report a case of Delta-Omicron superinfection in a hospitalized, immunocompromised pediatric patient., Methods: We conducted Illumina whole genome sequencing (WGS) for longitudinal specimens to investigate intra-host dynamics of SARS-CoV-2 strains. Topoisomerase PCR cloning of Spike open-reading frame and Sanger sequencing of samples was performed for four specimens to validate the findings. Analysis of publicly available SARS-CoV-2 sequence data was performed to investigate the co-circulation and persistence of SARS-CoV-2 variants., Results: Results of WGS indicate the patient was initially infected with the SARS-CoV-2 Delta variant before developing a SARS-CoV-2 Omicron variant superinfection, which became predominant. Shortly thereafter, viral loads decreased below the level of detection before resurgence of the original Delta variant with no residual trace of Omicron. After 54 days of persistent infection, the patient tested negative for SARS-CoV-2 but ultimately succumbed to a COVID-19-related death. Despite protracted treatment with remdesivir, no antiviral resistance mutations emerged. These results indicate a unique case of persistent SARS-CoV-2 infection with the Delta variant interposed by a transient superinfection with the Omicron variant. Analysis of publicly available sequence data suggests the persistence and ongoing evolution of Delta subvariants despite the global predominance of Omicron, potentially indicative of continued transmission in an unknown population or niche., Conclusion: A better understanding of SARS-CoV-2 intra-host population dynamics, persistence, and evolution during co-infections and/or superinfections will be required to continue optimizing patient care and to better predict the emergence of new variants of concern., (© 2023. The Author(s).)

Since the initial publication of A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals in 2008, the prevention of healthcare-associated infections (HAIs) has continued to be a national priority. Progress in healthcare epidemiology, infection prevention, antimicrobial stewardship, and implementation science research has led to improvements in our understanding of effective strategies for HAI prevention. Despite these advances, HAIs continue to affect ∼1 of every 31 hospitalized patients, leading to substantial morbidity, mortality, and excess healthcare expenditures, and persistent gaps remain between what is recommended and what is practiced.The widespread impact of the coronavirus disease 2019 (COVID-19) pandemic on HAI outcomes in acute-care hospitals has further highlighted the essential role of infection prevention programs and the critical importance of prioritizing efforts that can be sustained even in the face of resource requirements from COVID-19 and future infectious diseases crises.The Compendium: 2022 Updates document provides acute-care hospitals with up-to-date, practical expert guidance to assist in prioritizing and implementing HAI prevention efforts. It is the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Disease Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Pediatric Infectious Disease Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), the Surgical Infection Society (SIS), and others.

Background: In adults with Clostridioides difficile infection (CDI), higher stool concentrations of toxins A and B are associated with severe baseline disease, CDI-attributable severe outcomes, and recurrence. We evaluated whether toxin concentration predicts these presentations in children with CDI., Methods: We conducted a prospective cohort study of inpatients aged 2-17 years with CDI who received treatment. Patients were followed for 40 days after diagnosis for severe outcomes (intensive care unit admission, colectomy, or death, categorized as CDI primarily attributable, CDI contributed, or CDI not contributing) and recurrence. Baseline stool toxin A and B concentrations were measured using ultrasensitive single-molecule array assay, and 12 plasma cytokines were measured when blood was available., Results: We enrolled 187 pediatric patients (median age, 9.6 years). Patients with severe baseline disease by IDSA-SHEA criteria (n = 34) had nonsignificantly higher median stool toxin A+B concentration than those without severe disease (n = 122; 3,217.2 vs 473.3 pg/mL; P = .08). Median toxin A+B concentration was nonsignificantly higher in children with a primarily attributed severe outcome (n = 4) versus no severe outcome (n = 148; 19,472.6 vs 429.1 pg/mL; P = .301). Recurrence occurred in 17 (9.4%) of 180 patients. Baseline toxin A+B concentration was significantly higher in patients with versus without recurrence: 4,398.8 versus 280.8 pg/mL ( P = .024). Plasma granulocyte colony-stimulating factor concentration was significantly higher in CDI patients versus non-CDI diarrhea controls: 165.5 versus 28.5 pg/mL ( P < .001)., Conclusions: Higher baseline stool toxin concentrations are present in children with CDI recurrence. Toxin quantification should be included in CDI treatment trials to evaluate its use in severity assessment and outcome prediction.

With the approval and development of narrow-spectrum antibiotics for the treatment of Clostridioides difficile infection (CDI), the primary endpoint for treatment success of CDI antibiotic treatment trials has shifted from treatment response at end of therapy to sustained response 30 days after completed therapy. The current definition of a successful response to treatment (three or fewer unformed bowel movements [UBMs] per day for 1-2 days) has not been validated, does not reflect CDI management, and could impair assessments for successful treatment at 30 days. We propose new definitions to optimise trial design to assess sustained response. Primarily, we suggest that the initial response at the end of treatment be defined as (1) three or fewer UBMs per day, (2) a reduction in UBMs of more than 50% per day, (3) a decrease in stool volume of more than 75% for those with ostomy, or (4) attainment of bowel movements of Bristol Stool Form Scale types 1-4, on average, by day 2 after completion of primary CDI therapy (ie, assessed on day 11 and day 12 of a 10-day treatment course) and following an investigator determination that CDI treatment can be ceased., Competing Interests: Declaration of interests AMS is supported by career development awards from the US Veteran Affairs and Institute for Translational Medicine, serves on an advisory board for Recursion Pharmaceuticals, and has accepted honoraria from the American Society of Healthcare Pharmacists and the Academy for Continued Healthcare Learning. CDA has been supported by an investigator-initiated grant from Merck; serves on advisory boards for Cidara Therapeutics, Merck, and AiCuris; and has accepted honoraria from the American Society of Healthcare Pharmacists and the Academy for Continued Healthcare Learning. OAC has grants from Amplyx, Basilea, German Federal Ministry of Education and Research, Cidara, German Center for Infection Research, Commission's Directorate-General for Research and Innovation (101037867), F2G, Gilead, Matinas, MedPace, Merck Sharp & Dohme, Mundipharma, Octapharma, Pfizer, and Scynexis, has accepted consulting fees from AbbVie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partners, Mycoses Study Group Education & Research Consortium, Noxxon, Octapharma, Pardes, Pfizer, Pharmaceutical Security Institute, Scynexis, and Seres Therapeutics; has accepted speakernhonoraria from Abbot, AbbVie, Al-Jazeera Pharmaceuticals, Astellas, Gilead, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Noscendo, Pfizer, and Shionogi; has served as an expert witness for Cidara; has participated on advisory boards for Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, PSI, Pulmocide, Shionogi, and the Prime Meridian Group; has filed for a patent with the German Patent and Trade Mark Office (Geschlossene Inkubationssysteme mit verbessertem Atemwegszugang für Untersuchungsvorrichtungen, DE 10 2021 113 007.7); has stock in CoRe Consulting; and has non-financial interests in the European Confederation of Medical Mycology, International Society for Human and Animal Mycology, Mycoses Study Group Education & Research Consortium, and Wiley Publishing. KWG is funded by investigator-initiated awards from Summit Therapeutics, Acurx, Paratek, and Seres Therapeutics. DNG has grants from the US Centers for Disease Control and Prevention and US Veteran Affairs, a licensing agreement with Destiny Pharma, and has accepted consulting fees from Destiny Pharma. SJ is funded by grants from Paratek and Destiny Pharma, has accepted consulting fees from Bio-K+, Acurx, Ferring Pharmaceuticals, and Summit Therapeutics, and serves on the data safety monitoring board for Pfizer. SAK is funded by the Crohn's and Colitis Foundation, the Mooney Family Initiative for Translational and Clinical Studies in Rare Diseases Translational Research Program, Cures Within Reach, and the National Institute of Allergy and Infectious Diseases; has accepted consulting fees from Guidepoint; has accepted honoraria from the Louisiana Academy of Nutrition & Diabetics and Boston IBD; has accepted travel support from the Crohn's and Colitis and Helmsley Foundations; serves on the Peggy Lillis Foundation advisory board; and holds Eli Lilly stock. CPK has grant funding from Milky Way Life Sciences, Pfizer, National Institutes of Health (NIH), Merck, and Takeda Pharmaceuticals; has accepted consulting fees from Artugen, Facile Therapeutics, Ferring Pharmaceuticals, Finch Therapeutics, Pfizer, Milky Way Life Sciences, RVAC Medicines, Seres Therapeutics, and Summit Therapeutics; has a patent with Quanterix; serves on the advisory board for Finch Therapeutics; is secretary for the Foundation for Celiac Disease Outcome Measures; and has stock in First Light and Cour Pharmaceuticals. CRK has grant funding from the NIH; has accepted consulting fees from Sebela Pharmaceuticals; and has accepted speakers honoraria from the American College of Gastroenterology. LKK has research funding from Merck. TL has accepted funding from Summit, Crestone, MGB Biopharma, Actelion, Cubist/Merck, Seres Therapeutics, and Vedanta Biosciences; and has accepted consulting fees from MGB Biopharma and Seres Therapeutics. MJGTV has received grants from MSD, Heel, Biontech, and Roche; has accepted consulting fees from MaaT, Tillots, MSD/Merck, FAV00B, Dr Regenold, Roche, and EUMEDICA; and has accepted honoraria from Merck/MSD, 3M, Ferring Pharmaceuticals, Astellas, Uniklinik Karlsruhe, Uniklinik Köln, Akademia für Infektionsmedizin, Klinikum Essen, Pfizer, Universitätsklinikum Heidelberg, Uniklinik Frankfurt, Landesärztekammer Hessen, Janssen, Institut Merieux, Forum für medizinische Fortildung, Universitätsklinikum Freburg, Berliner Dialy Seminar, Zertifikatskurs PTA im Krankenhaus, Falk Foundation, St Johannes Hospital, DiaLog Service, CED Service, Ärtzekammer Niedersachsen, St Josef Hospital, Limbach Grupe SE, SUMIT OZFORD, EUMDEICA Kit Kongress, Tillots Pharma, Helios Lkiniken, Lahn-Dill-Kliniken, and Gilead. MHW has research support from Almirall, Da Volterra, EnteroBiotix, GlaxoSmithKline (GSK), Merck, MicroPharm, Nabriva, Paratek, Pfizer, Seres Therapeutics, Summit Therapeutics, The European Tissue Symposium, Tillotts, IMI2 (EU Horizon 2020), and EFPIA partners; has accepted consulting fees from AiCuris, Bayer, Crestone, Da Volterra, Deinove, Destiny Pharma, EnteroBiotix, The European Tissue Symposium, Ferring, GSK, Menarini, Merck, Nestlé, Paion, Paratek, Pfizer, Phico Therapeutics, Qpex Biopharma, Seres, Surface Skins, Summit, Tillotts, and Vaxxilon/Idorsia; and has accepted speakers honoraria from Merck, Pfizer, Seres, and Tillotts. ERD is funded by grants from Synthetic Biologics and Ferring Pharmaceuticals and has accepted consulting fees from Pfizer, Merck, Ferring Pharmaceuticals, Abbott, GSK, Seres Therapeutics, and Summit Therapeutics. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To assess the effectiveness of distinct message types in promoting coronavirus disease 2019 (COVID-19) vaccination intentions for parents of children and adolescents., Methods: We collected data through the Voices of Child Health in Chicago Parent Panel Survey from October to November 2021. Parents were randomly assigned to read 1 of 4 vaccine message types and then report their intentions to vaccinate each COVID-19-unvaccinated child (0-17 years) in their household (n = 1453)., Results: The sample included 898 parents. Compared with a control group (37.5%), the proportion of parents who were very likely to vaccinate their children was higher when messages highlighted that other trusted parents have vaccinated their children (53.3%) or that the vaccine is safe and thoroughly tested (48.9%) but not when messages highlighted that the vaccine is well-tolerated (41.5%). After adjusting for parent and child characteristics, the odds of being very likely to vaccinate remained higher in the trusted parents group but not in the safe/thoroughly tested group. Unlike the control and well-tolerated groups, there were no racial/ethnic disparities in the unadjusted proportion of parents who were very likely to vaccinate in the trusted parents and safe/thoroughly tested groups. Message types affected the unadjusted proportion of COVID-19-unvaccinated parents who were very likely to vaccinate their children., Conclusions: Messages that focus on trusted parents choosing to vaccinate their children were more effective at promoting parents' COVID-19 vaccination intentions for their children than alternative messages. These findings have implications for public health messaging and pediatric providers' communications with parents., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Outbreaks of healthcare-associated respiratory syncytial virus (HA-RSV) infections in children are well described, but less is known about sporadic HA-RSV infections. We assessed the epidemiology and clinical outcomes associated with sporadic HA-RSV infections., Methods: We retrospectively identified hospitalized children ≤18 years old with HA-RSV infections in six children's hospitals in the United States during the respiratory viral seasons October-April in 2016-2017, 2017-2018, and 2018-2019 and prospectively from October 2020 through November 2021. We evaluated outcomes temporally associated with HA-RSV infections including escalation of respiratory support, transfer to the pediatric intensive care unit (PICU), and in-hospital mortality. We assessed demographic characteristics and comorbid conditions associated with escalation of respiratory support., Results: We identified 122 children (median age 16.0 months [IQR 6, 60 months]) with HA-RSV. The median onset of HA-RSV infections was hospital day 14 (IQR 7, 34 days). Overall, 78 (63.9%) children had two or more comorbid conditions; cardiovascular, gastrointestinal, neurologic/neuromuscular, respiratory, and premature/ neonatal comorbidities were most common. Fifty-five (45.1%) children required escalation of respiratory support and 18 (14.8%) were transferred to the PICU. Five (4.1%) died during hospitalization. In the multivariable analysis, respiratory comorbidities (aOR: 3.36 [CI95 1.41, 8.01]) were associated with increased odds of escalation of respiratory support., Conclusions: HA-RSV infections cause preventable morbidity and increase healthcare resource utilization. Further study of effective mitigation strategies for HA-respiratory viral infections should be prioritized; this priority is further supported by the impact of the COVID-19 pandemic on seasonal viral infections., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Intestinal bile acids play an essential role in the Clostridioides difficile lifecycle having been shown in vitro to modulate various aspects of pathogenesis, including spore germination, vegetative growth, and more recently the action of the primary virulence determinant, TcdB. Here, we investigated whether physiological levels of the total pool of intestinal bile acids in mice and humans protect against TcdB action. Small molecules extracted from the lumenal contents of the small intestine, cecum, colon, and feces were found to inhibit TcdB in accordance with the differential amounts of total bile acids in each compartment. Extracts from antibiotic-treated and germ-free mice, despite harboring dramatically altered bile acid profiles, unexpectedly also prevented TcdB-induced cell rounding to similar extents. We show that protection, however, is surmountable and can be overcome at higher doses of TcdB-typical to those seen during severe C. difficile infection-suggesting that the protective properties of intestinal bile acids are operant primarily under low to moderate toxin levels. Taken together, these findings demonstrate a role for intestinal bile acids in attenuating virulence, provide insights into asymptomatic carriage of toxigenic C. difficile , and inform strategies to manipulate bile acid levels for therapeutic benefit.

Objectives: We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients., Methods: This is a multicenter retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow-up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition., Results: Of 59 pediatric patients identified at 9 centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after 1 or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; 4 (9.5%) of which were likely treatment-related. There were no deaths or infections with multidrug resistant organisms during follow-up and all patients with a SAE fully recovered., Conclusions: The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: A recent study from Taiwan suggested that Clostridium innocuum may be an unrecognized cause of antibiotic-associated diarrhea (AAD) and clinically indistinguishable from Clostridioides difficile infection. Our objective was to compare C. innocuum prevalence and strain between those with AAD and asymptomatic controls., Methods: In this cross-sectional study, we collected stool from 200 individuals with AAD and 100 asymptomatic controls. We evaluated the association between AAD and C. innocuum in stool using anaerobic culture and quantitative polymerase chain reaction (qPCR). To identify strain-specific associations with AAD, we performed whole-genome sequencing of C. innocuum isolates using Illumina MiSeq and constructed comparative genomics analyses., Results: C. innocuum was isolated from stool of 126/300 (42%) subjects and more frequently from asymptomatic controls than AAD subjects (50/100 [50%] vs 76/200 [38%], respectively; P = .047). C. innocuum isolation frequency was not associated with AAD in either the adult or pediatric subgroups. C. innocuum and C. difficile were frequently co-prevalent in individuals with and without diarrhea. There were no phylogenetic differences or accessory genome associations between C. innocuum isolates from AAD subjects and asymptomatic controls., Conclusions: C. innocuum was frequently isolated and at a greater frequency in asymptomatic controls than those with AAD. We did not identify strain lineages or accessory genomic elements associated with AAD. These data highlight that differentiating C. innocuum-associated diarrhea from asymptomatic colonization, and differentiating diarrhea caused by C. difficile from C. innocuum, are clinical microbiology challenges that require additional investigation to identify host-specific factors and/or biomarkers that distinguish these conditions., Competing Interests: Potential conflicts of interest. L. K. K. has received research grants from Merck, unrelated to this study. M. P. A. reports lecture honoraria and development of educational content with DKBMed and participation on a Data Safety and Monitoring Board for AbbVie Pharmaceuticals. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To compare the incidence, epidemiology, testing patterns, treatment, and outcomes of Clostridioides difficile infection (CDI) among hospitalized pediatric patients from 2013 to 2019., Study Design: The Pediatric Health Information System database was queried for patient admissions (age 0-17 years) with International Classification of Diseases, 9th and 10th edition, codes for diagnoses of CDI with a billing code for a CDI-related antibiotic treatment., Results: We identified 17 142 pediatric patients, representing 23 052 admissions, with CDI. The adjusted annual CDI incidence decreased over the study period from 7.09 cases per 10 000 patient-days (95% CI, 6.15-8.18) in 2013 to 4.89 cases per 10 000 patient-days (95% CI, 4.03-5.93) in 2019 (P < .001). C difficile-specific testing also decreased during the study period (P < .001). Chronic gastrointestinal conditions (36%) and malignancy (32%) were the most common comorbidities in CDI encounters. Oral metronidazole use decreased during the study period (P < .01) and oral vancomycin use increased (P < .001)., Conclusions: Our study demonstrates a decrease in CDI incidence in hospitalized pediatric patients, a notable change from prior studies, although this may have been influenced by altered testing patterns. We found a high incidence of CDI in patients with cancer and gastrointestinal conditions: groups that warrant targeted evaluation of CDI prevention and treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Recent COVID-19 surges are attributed to emergence of more transmissible SARS-CoV-2 variants of concern (VOCs). The relative severity of VOCs in children is unknown., Methods: We performed a single-center retrospective cohort study of children ≤18 years old diagnosed with COVID-19 from October 2020-February 2022 and whose SARS-CoV-2 isolate underwent Illumina sequencing. We measured the frequency of five markers of COVID-19 severity. Logistic regression models were fitted to estimate the odds of each severity marker with each VOC., Results: Among 714 children, 471 (66.0%) were infected with a VOC: 96 (13.4%) alpha, 38 (5.3%) gamma, 119 (16.7%) delta, and 215 (30.1%) omicron. High-risk medical conditions and increasing age were independently associated with COVID-19 severity. After adjusting for age, race, ethnicity, high-risk medical conditions, and COVID-19 community incidence, neither alpha, delta, nor omicron was associated with severe COVID-19. Gamma was independently associated with hospitalization (OR 6.7, 95% CI 2.0-22.1); pharmacologic treatment (OR 5.7, 95% CI 1.2-26.8); respiratory support (OR 11.9, 95% CI 2.7-62.4); and severe disease per the WHO Clinical Progression Scale (OR 11.7, 95% CI 2.1-90.5). Upon subgroup analyses, omicron was independently associated with ICU admission and severe disease per the WHO Clinical Progression Scale in children without SARS-CoV-2 immunization or prior COVID-19 infection., Conclusions: Compared to non-VOC COVID-19, the gamma VOC was independently associated with increased COVID-19 severity, as was omicron in children without SARS-CoV-2 immunization or prior COVID-19 infection. SARS-CoV-2 vaccination and prior COVID-19 prevented severe outcomes during the omicron surge., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In a prospective cohort study, stools from children <3 years with and without diarrhea who were Clostridioides difficile nucleic acid amplification test-positive underwent ultrasensitive and quantitative toxin measurement. Among 37 cases and 46 controls, toxin concentration distributions overlapped substantially. Toxin concentration alone does not distinguish C. difficile infection from colonization in young children., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To identify the impact of universal masking on COVID-19 incidence and putative SARS-CoV-2 transmissions events among children's hospital healthcare workers (HCWs)., Design: Quasi-experimental study., Setting: Single academic free-standing children's hospital., Methods: We performed whole-genome sequencing of SARS-CoV-2- PCR-positive samples collected from HCWs 3 weeks before and 6 weeks after implementing a universal masking policy. Phylogenetic analyses were performed to identify clusters of clonally related SARS-CoV-2 indicative of putative transmission events. We measured COVID-19 incidence, SARS-CoV-2 test positivity rates, and frequency of putative transmission events before and after the masking policy was implemented., Results: HCW COVID-19 incidence and test positivity declined from 14.3 to 4.3 cases per week, and from 18.4% to 9.0%, respectively. Putative transmission events were only identified prior to universal masking., Conclusions: A universal masking policy was associated with reductions in HCW COVID-19 infections and occupational acquisition of SARS-CoV-2.

Objectives: To describe coronavirus disease 2019 (COVID-19)-related pediatric hospitalizations during a period of B.1.617.2 (Δ) variant predominance and to determine age-specific factors associated with severe illness., Methods: We abstracted data from medical charts to conduct a cross-sectional study of patients aged <21 years hospitalized at 6 United States children's hospitals from July to August 2021 for COVID-19 or with an incidental positive severe acute respiratory syndrome coronavirus 2 test. Among patients with COVID-19, we assessed factors associated with severe illness by calculating age-stratified prevalence ratios (PR). We defined severe illness as receiving high-flow nasal cannula, positive airway pressure, or invasive mechanical ventilation., Results: Of 947 hospitalized patients, 759 (80.1%) had COVID-19, of whom 287 (37.8%) had severe illness. Factors associated with severe illness included coinfection with respiratory syncytial virus (RSV) (PR 3.64) and bacteria (PR 1.88) in infants; RSV coinfection in patients aged 1 to 4 years (PR 1.96); and obesity in patients aged 5 to 11 (PR 2.20) and 12 to 17 years (PR 2.48). Having ≥2 underlying medical conditions was associated with severe illness in patients aged <1 (PR 1.82), 5 to 11 (PR 3.72), and 12 to 17 years (PR 3.19)., Conclusions: Among patients hospitalized for COVID-19, factors associated with severe illness included RSV coinfection in those aged <5 years, obesity in those aged 5 to 17 years, and other underlying conditions for all age groups <18 years. These findings can inform pediatric practice, risk communication, and prevention strategies, including vaccination against COVID-19., (Copyright © 2022 by the American Academy of Pediatrics.)

Importance: Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics., Objective: To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes., Design, Setting, and Participants: This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children's Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes., Exposures: A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative)., Main Outcomes and Measures: The primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics ≥3 days after PICU admission) and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock., Results: Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation., Conclusions and Relevance: Multidisciplinary diagnostic stewardship interventions can reduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.

Objectives: Previously considered solely an opportunistic pathogen, Clostridium innocuum (CI) was recently reported in Taiwan to be an emerging cause of antibiotic-associated diarrhea and clinically indistinguishable from Clostridioides difficile (CD) infection. We previously identified CI culture supernatant being cross-reactive with commercial CD toxin enzyme immunoassays. We aimed to identify and characterize the cross-reacting protein and determine whether it functioned as a human toxin., Methods: We performed western blots using CI culture supernatants and CD anti-toxin antibodies and identified interacting bands. We identified protein(s) using tandem mass spectrometry and evaluated them by cytotoxicity assays., Results: CI, but not CD, was isolated from stool of 12 children and adults with diarrhea. Culture supernatant from 6/12 CI isolates, and an ATCC reference strain, tested positive for CD toxins (total 7/13 isolates) by commercial EIA. Using two of these isolates, we identified two ∼40 kDa hypothetical proteins, CI&#95;01447 and CI&#95;01448, and confirmed cross-reactivity with CD anti-toxin antibodies by enzyme immunoassay and Western blot. Whole-genome sequencing confirmed all 13 isolates contained both genes, which were highly conserved. We observed no cytopathic or cytotoxic effects to HeLa cells when treated with these proteins. We identified amino acid sequence similarity to the NlpC/P60 family of proteins., Conclusions: Our findings do not suggest CI proteins CI&#95;01448 and CI&#95;01447, which cross-react with antibodies against CD toxins A and B, are toxic to HeLa cells. Further studies are needed to determine the function of these cross-reacting proteins and the potential virulence factors that could be responsible for CI diarrheal disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Abstract: Hepatic involvement in coronavirus disease 2019 (COVID-19) is typically characterized as mild hepatitis with preserved synthetic function in children. Severe hepatitis is a rare complication of COVID-19 infection that has not been extensively described in the pediatric population. We report a case series of four previously healthy children who presented with significant hepatitis as the primary manifestation of COVID-19 infection. Two of these patients met criteria for acute liver failure. None of the patients had respiratory symptoms. One patient was found to have complement dysfunction resulting in microangiopathic features and was treated successfully with eculizumab. This case is in line with adult post-mortem data showing that more severe cases of hepatic dysfunction secondary to COVID-19 infection may be associated with complement activation and microangiopathic features. Liver function should be evaluated in cases of severe COVID-19, and severe acute respiratory syndrome coronavirus 2 infection should be considered as a cause of acute severe hepatitis even in patients without significant respiratory or other systemic symptoms., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background/objectives: Antibiotic indication documentation at the time of order entry is mandated by the Joint Commission. Inclusion of indication at order entry may have an impact on the time to administration. Our primary objective was to evaluate agreement between indication selected during order entry and clinical notes. Our secondary objective was to observe if there was a change in time to administration after indications were required during order entry., Methods: Patients ≤18 years old who received ≥1 dose of vancomycin or ceftriaxone during a preintervention period and 3 postintervention periods were included. Indication for use, agreement between order and clinical note, and timing of antibiotic administration were collected., Results: Most common indication for vancomycin (total: 789) was sepsis (26%, n = 204). Common indications for ceftriaxone (total: 1071) were sepsis (12%, n = 127), perforated appendicitis (12%, n = 125), and urinary tract infection (10%, n = 107). Postintervention, agreement between the indication selected during order entry and indication documented in clinical note for ceftriaxone and vancomycin orders were 41% and 46%, respectively. Median time to administration decreased among patients who received ceftriaxone ( P < .01) but had no significant impact on time to administration of vancomycin ( P = .49)., Conclusions: Indication for ceftriaxone and vancomycin selected during order entry and reported in clinical notes inconsistently matched. Inclusion of antibiotic indication may impact time to administration.

During June 2021, the highly transmissible † B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating strain in the United States. U.S. pediatric COVID-19-related hospitalizations increased during July-August 2021 following emergence of the Delta variant and peaked in September 2021. § As of May 12, 2021, CDC recommended COVID-19 vaccinations for persons aged ≥12 years, ¶ and on November 2, 2021, COVID-19 vaccinations were recommended for persons aged 5-11 years.** To date, clinical signs and symptoms, illness course, and factors contributing to hospitalizations during the period of Delta predominance have not been well described in pediatric patients. CDC partnered with six children's hospitals to review medical record data for patients aged <18 years with COVID-19-related hospitalizations during July-August 2021. †† Among 915 patients identified, 713 (77.9%) were hospitalized for COVID-19 (acute COVID-19 as the primary or contributing reason for hospitalization), 177 (19.3%) had incidental positive SARS-CoV-2 test results (asymptomatic or mild infection unrelated to the reason for hospitalization), and 25 (2.7%) had multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition associated with COVID-19. §§ Among the 713 patients hospitalized for COVID-19, 24.7% were aged <1 year, 17.1% were aged 1-4 years, 20.1% were aged 5-11 years, and 38.1% were aged 12-17 years. Approximately two thirds of patients (67.5%) had one or more underlying medical conditions, with obesity being the most common (32.4%); among patients aged 12-17 years, 61.4% had obesity. Among patients hospitalized for COVID-19, 15.8% had a viral coinfection ¶¶ (66.4% of whom had respiratory syncytial virus [RSV] infection). Approximately one third (33.9%) of patients aged <5 years hospitalized for COVID-19 had a viral coinfection. Among 272 vaccine-eligible (aged 12-17 years) patients hospitalized for COVID-19, one (0.4%) was fully vaccinated.*** Approximately one half (54.0%) of patients hospitalized for COVID-19 received oxygen support, 29.5% were admitted to the intensive care unit (ICU), and 1.5% died; of those requiring respiratory support, 14.5% required invasive mechanical ventilation (IMV). Among pediatric patients with COVID-19-related hospitalizations, many had severe illness and viral coinfections, and few vaccine-eligible patients hospitalized for COVID-19 were vaccinated, highlighting the importance of vaccination for those aged ≥5 years and other prevention strategies to protect children and adolescents from COVID-19, particularly those with underlying medical conditions., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Ila R. Singh reports funding from the National Institutes of Health (NIH) as a coinvestigator for grant no. R61HD105593 to characterize pediatric COVID-19. Roberta L. DeBiasi reports grant support and contracts for COVID-19 and MIS-C, unrelated to the current work; consulting fees from I-ACT for Children; honoraria from the Infectious Diseases in Children Conference (NYC) and Children’s Hospital Colorado Infectious Diseases Conference (Denver); and unpaid membership on the board of the Pediatric Infectious Diseases Society. Larry K. Kociolek reports a grant from the Walder Foundation Chicago Coronavirus Assessment Network Initiative, institutional support from Merck and NIH/NIAID; and honoraria for educational events at Northwest Community Hospital and Nemours/duPont Children’s Hospital. Jessica Snowden reports institutional support from NIH Office of the Director–ECHO program and NIH/NHLBI–RECOVER program, unrelated to the current work. Frederick E. Barr reports application of patent 17364280 with Asklepion Pharmaceuticals for L-citrulline to prevent or treat endothelial dysfunction. Sapna Bamrah Morris and Sophia K. Chiu report membership on a data safety monitoring board in a study of ivermectin for treatment of severe COVID-19 in Ghana. Sophia Hsu reports ownership of 5 shares of Moderna stock and 7 shares of Novavax stock, and ownership within the past 36 months (but no current ownership) of stock in BioNTech, Gilead Sciences, and Pfizer. Theresa M. Dulski reports that her husband receives restricted stock units as part of his compensation from his employer, a cancer diagnostics company that also performs COVID-19 testing. No other potential conflicts of interest were disclosed.

Clostridioides difficile has become the most common healthcare-associated pathogen in the United States, leading the US Centers for Disease Control and Prevention (CDC) to classify C. difficile as an "urgent" public health threat that requires "urgent and aggressive action." This call to action has led to new discoveries that have advanced our understanding of Clostridioides difficile infection (CDI) immunology and clinical development of immunologic-based therapies for CDI prevention. However, CDI immunology research has been limited in pediatric populations, and several unanswered questions remain regarding the function of host immune response in pediatric CDI pathogenesis and the potential role of immunologic-based therapies in children. This review summarizes the innate and adaptive immune responses previously characterized in animals and humans and provides a current update on clinical development of immunologic-based therapies for CDI prevention in adults and children. These data inform the future research needs for children., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Clostridium innocuum is an anaerobic, gram-positive, spore-forming bacterium identified by Smith and King in 1962 after being isolated from a patient with an appendiceal abscess. Its name, C. innocuum, reflected its clinically "innocuous" nature based on observed lack of virulence in animal models of infection. Since that time, C. innocuum has been identified as both part of the normal intestinal flora and the cause of a rare, intrinsically vancomycin-resistant opportunistic infection in immunocompromised patients. More recently, reports from Taiwan suggest that C. innocuum, in addition to being a known extraintestinal pathogen, may also be a diarrheal pathogen that causes a C. difficile infection-like antibiotic-associated diarrheal illness. However, unanswered questions about the clinical relevance of C. innocuum remain. Here we review the microbiological and clinical characteristics of this emerging pathogen., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: The US Centers for Disease Control and Prevention (CDC) classified Clostridioides difficile as an 'urgent' public health threat that requires 'urgent and aggressive action'. This call to action has led to new discoveries that have advanced C. difficile infection (CDI) epidemiology, diagnosis and treatment, albeit predominantly in adults. In 2017, the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America published clinical practice guidelines for both adults and children. At that time, recommendations in children were generally limited to relatively low-quality evidence., Recent Findings: Since publication of this guidance, there have been many advancements in the understanding of CDI in children. These include better understanding of healthcare settings as uncommon sources of C. difficile acquisition in children; risk factors for recurrent and community-associated CDI; performance of diagnostic tests in children and strategies for optimizing their use; and a more rigorous evidence base for CDI treatment in children, including the first-ever randomized controlled trial of CDI treatment in children and the largest study of fecal microbiota transplantation in children., Summary: This review highlights the most recent salient advancements in paediatric CDI knowledge and practice that supplement published clinical guidance provided prior to these advancements., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

A quasi-experimental study performed in a pediatric hematology-oncology unit demonstrated that whole-room ultraviolet-C disinfection was associated with a significant reduction in hospital-onset Clostridioides difficile infection (P< .01, trend and level), but not healthcare-associated viral respiratory infections (P= .06 for trend, P= .36 for level) or central line-associated bloodstream infections (P> 0.75, trend and level)., (Copyright © 2021. Published by Elsevier Inc.)

Young children will ultimately need to be vaccinated to stop the spread of coronavirus disease 2019 (COVID-19). Initial studies of vaccine were performed in adults. Randomized controlled trials are the gold standard. In the COVID-19 pandemic, many questions need to be answered about the ethics and feasibility of these trials. Given the harms of the COVID-19 pandemic and the now-known efficacy of the vaccines in adults and teens, the question of whether clinical equipoise exists for a placebo-controlled trial of vaccines in younger children remains. Parents may be reluctant to enroll children in these trials because they want their child to receive the vaccine or because they are worried about vaccines or clinical trials in general. One option for gathering data on tolerability and efficacy in children would be to use a nonrandomized trial to enroll parents willing to vaccinate their children and those who are hesitant. We discuss the advantages and disadvantages of such an open-label trial that could provide guidance for future pandemics. (Clin Ther., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health., Participants: The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification)., Methods: Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings., Results: A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level "harm index" for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions., Conclusions: We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.

Background: Postoperative infections can occur during surgical replacement of pulse generators for pacemakers and implantable cardioverter-defibrillators. The incidence of infection is poorly documented in children and patients with adult congenital heart disease. The utility of surveillance cultures obtained from device pocket swabs is unknown in this group., Methods: We reviewed surgical replacements of cardiovascular implantable pulse generators from 2010 to 2017. Two cohorts were defined. In a surveillance cohort (123 patients), aerobic and anaerobic culture swabs of the device pocket were obtained at the time of generator change. In a nonsurveillance cohort (107 patients), generator change occurred without obtaining cultures., Results: During 230 generator changes (mean patient age 19 years; 77% with structural congenital heart disease), two clinical infections occurred at the surgical site (0.9% incidence). Neither infection occurred in the surveillance cohort. Cultures were positive in 12 (9.8%) of 123 patients in the surveillance cohort, but 11 of 12 were likely contaminants and none were subsequently associated with clinical disease. There was no association between clinical infection or positive surveillance cultures and the location of pulse generator, the presence of other concurrent surgeries, or a history of prior pocket infection., Conclusions: Clinical infection was rare after pulse generator change in children and young adults. No cases required reintervention on the pocket. Surveillance cultures did not improve clinical care. These data extend current recommendations that surveillance cultures are not required during generator change to the pediatric and young adult population.

Background: The CNS manifestations of COVID-19 in children have primarily been described in case reports, which limit the ability to appreciate the full spectrum of the disease in paediatric patients. We aimed to identify enough cases that could be evaluated in aggregate to better understand the neuroimaging manifestations of COVID-19 in the paediatric population., Methods: An international call for cases of children with encephalopathy related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and abnormal neuroimaging findings was made. Clinical history and associated plasma and cerebrospinal fluid data were requested. These data were reviewed by a central neuroradiology panel, a child neurologist, and a paediatric infectious diseases expert. The children were categorised on the basis of their time of probable exposure to SARS-CoV-2. In addition, cases were excluded when a direct link to SARS-CoV-2 infection could not be established or an established alternate diagnostic cause could be hypothesised. The accepted referral centre imaging data, from ten countries, were remotely reviewed by a central panel of five paediatric neuroradiologists and a consensus opinion obtained on the imaging findings., Findings: 38 children with neurological disease related to SARS-CoV-2 infection were identified from France (n=13), the UK (n=8), the USA (n=5), Brazil (n=4), Argentina (n=4), India (n=2), Peru (n=1), and Saudi Arabia (n=1). Recurring patterns of disease were identified, with neuroimaging abnormalities ranging from mild to severe. The most common imaging patterns were postinfectious immune-mediated acute disseminated encephalomyelitis-like changes of the brain (16 patients), myelitis (eight patients), and neural enhancement (13 patients). Cranial nerve enhancement could occur in the absence of corresponding neurological symptoms. Splenial lesions (seven patients) and myositis (four patients) were predominantly observed in children with multisystem inflammatory syndrome. Cerebrovascular complications in children were less common than in adults. Significant pre-existing conditions were absent and most children had favourable outcomes. However, fatal atypical CNS co-infections developed in four previously healthy children infected with SARS-CoV-2., Interpretation: Acute-phase and delayed-phase SARS-CoV-2-related CNS abnormalities are seen in children. Recurring patterns of disease and atypical neuroimaging manifestations can be found and should be recognised being as potentially due to SARS-CoV-2 infection as an underlying aetiological factor. Studies of paediatric specific cohorts are needed to better understand the effects of SARS-CoV-2 infection on the CNS at presentation and on long-term follow-up in children., Funding: American Society of Pediatric Neuroradiology, University of Manchester (Manchester, UK). VIDEO ABSTRACT., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 asymptomatic versus 197 symptomatic children aged 0 to 4 years, 79 asymptomatic versus 97 symptomatic children aged 5 to 9 years, 69 asymptomatic versus 75 symptomatic children aged 10 to 13 years, 73 asymptomatic versus 109 symptomatic children aged 14 to 17 years) were compared. The median adjusted Ct value for asymptomatic children was 10.3 cycles higher than for symptomatic children ( P < 0.0001), and VL were 3 to 4 logs lower than for symptomatic children ( P  < 0.0001); differences were consistent ( P  < 0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (odds ratio [OR], 6.5; P  = 0.01), a recent contact (OR, 2.3; P  = 0.02), and testing for surveillance (OR, 2.7; P  = 0.005) had higher estimated risks of having a Ct value in the lowest quartile than children without, while an immunocompromised status had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in their nasopharynx/oropharynx than symptomatic children, but the timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children., (Copyright © 2020 American Society for Microbiology.)

Asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carriage among hospitalized children and risk of transmission to healthcare workers (HCWs) was evaluated by point prevalence survey. We estimated 1-2% prevalence of SARS-CoV-2 among children without coronavirus disease 2019 symptoms. There was no secondary transmission among HCWs exposed to these patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)