Balanced on the Biggest Wave: Nirsevimab for Newborns.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization in infancy in the United States. Nearly all infants are infected by 2 years of age, with bronchiolitis requiring hospitalization often occurring in previously healthy children and long-term consequences of severe disease including delayed speech development and asthma. Incomplete passage of maternal immunity and a high degree of genetic variability within the virus contribute to morbidity and have also prevented successful neonatal vaccine development. Monoclonal antibodies reduce the risk of hospitalization from severe RSV disease, with palivizumab protecting high-risk newborns with comorbidities including chronic lung disease and congenital heart disease. Unfortunately, palivizumab is costly and requires monthly administration of up to five doses during the RSV season for optimal protection.Rapid advances in the past two decades have facilitated the identification of antibodies with broad neutralizing activity and allowed manipulation of their genetic code to extend half-life. These advances have culminated with nirsevimab, a monoclonal antibody targeting the Ø antigenic site on the RSV prefusion protein and protecting infants from severe disease for an entire 5-month season with a single dose. Four landmark randomized controlled trials, the first published in July 2020, have documented the efficacy and safety of nirsevimab in healthy late-preterm and term infants, healthy preterm infants, and high-risk preterm infants and those with congenital heart disease. Nirsevimab reduces the risk of RSV disease requiring medical attention (number needed to treat [NNT] 14-24) and hospitalization (NNT 33-63) with rare mild rash and injection site reactions. Consequently, the Centers for Disease Control and Prevention has recently recommended nirsevimab for all infants younger than 8 months of age entering or born during the RSV season and high-risk infants 8-19 months of age entering their second season. Implementing this novel therapy in this large population will require close multidisciplinary collaboration. Equitable distribution through minimizing barriers and maximizing uptake must be prioritized.

Assessment of COVID-19 Messaging Strategies to Increase Testing for Students With Intellectual and Developmental Disabilities.

BACKGROUND: Students with intellectual and developmental disabilities (IDD) were disproportionately impacted by the COVID-19 pandemic. This study's goal was to assess the effectiveness of 2 messaging strategies on participation in SARS-CoV-2 weekly testing. METHODS: Cluster randomized trials were conducted at 2 school systems, the special school district (SSD) and Kennedy Krieger Institute (Kennedy) to assess messaging strategies, general versus enhanced, to increase weekly screening for SARS-CoV-2. Testing was offered to staff and students from November 23, 2020 to May 26, 2022. The primary outcomes were percentage of students and staff consented weekly and percentage of study participants who had a test performed weekly. Generalized estimating equation models were utilized to evaluate the primary outcomes. RESULTS: Increases in enrollment and testing occurred during study start up, the beginning of school years, and following surges in both systems. No statistical difference was observed in the primary outcomes between schools receiving standard versus enhanced messaging. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Frequent and consistent communication is vital for families and staff. Weekly screening testing within schools is possible and highlighted the importance of utilizing equitable protocols to provide important testing to students with IDD. CONCLUSION: Enhanced messaging strategies did not increase the number of participants enrolled or the percentage of enrolled participants being tested on a weekly basis.

Practice Versus Potential: The Impact of the BioFire FilmArray Pneumonia Panel on Antibiotic Use in Children.

BACKGROUND: The BioFire FilmArray Pneumonia Panel (BFPP), a multiplex PCR panel for the diagnosis of lower respiratory tract infections, has been proposed as a tool for antimicrobial stewardship. Few studies evaluate real-world implementation of the BFPP and no studies focus exclusively on children. Our institution implemented BFPP testing without restrictions. METHODS: We conducted a retrospective cohort study in children hospitalized at St. Louis Children's Hospital to (1) characterize the use of the BFPP in pediatric patients and (2) assess how results impacted antibiotic use. We included all BFPP tests obtained during the first year after the introduction of the test, September 2021 through August 2022. The primary outcome was change in antibiotic therapy within 24 hours of results, which was compared to the potential change in antibiotic therapy determined by two infectious diseases clinicians. RESULTS: One hundred sixty-nine tests from 126 patients were included. Nine patients were immunocompromised and 19 had chronic tracheostomy. The majority of tests were sent from tracheal aspirate specimens (92%) and from patients in an intensive care unit (94%). Only 51% of tests were obtained due to respiratory failure or suspected pneumonia. For 80% of test results, there was potential to change antibiotics, but change occurred in only 46% of tests in practice. Antibiotic escalation was more common (26%) than de-escalation (15%) or discontinuation (4.1%). CONCLUSIONS: In a cohort of pediatric patients tested with the BFPP, the majority of tests were sent from tracheal aspirates and less than half of tests were associated with a change in antibiotics.

COVID-19 Related Facilitators and Barriers to In-Person Learning for Children With Intellectual and Development Disabilities: A Follow-Up.

BACKGROUND: Students with intellectual and developmental disabilities (IDD) and the staff who support them were largely in-person during the 2021-2022 school year, despite their continued vulnerability to infection with SARS-CoV-2. This qualitative study aimed to understand continued perceptions of weekly SARS-CoV-2 screening testing of students and staff amidst increased availability of vaccinations. METHODS: Twenty-three focus groups were held with school staff and parents of children with IDD to examine the perceptions of COVID-19 during the 2021-2022 school year. Responses were analyzed using a directed thematic content analysis approach. RESULTS: Four principal themes were identified: strengths and opportunities of school- and district-level mitigation policies; experience at school with the return to in-person learning; facilitators and barriers to participation in SARS-CoV-2 screening testing; and perceptions of SARS-CoV-2 testing in light of vaccine availability. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Despite the increased availability of vaccines, school staff and families agreed that saliva-based SARS-CoV-2 screening testing helped increase comfort with in-person learning as long as the virus was present in the community. CONCLUSION: To keep children with IDD in school during the pandemic, families found SARS-CoV-2 screening testing important. Clearly communicating school policies and mitigation strategies facilitated peace of mind and confidence in the school district.

Erratum: Perspectives on research needs in healthcare epidemiology, infection prevention, and antimicrobial stewardship: what's on the horizon-Part I - CORRIGENDUM.

[This corrects the article DOI: 10.1017/ash.2023.473.].

Perspectives on research needs in healthcare epidemiology, infection prevention, and antimicrobial stewardship: what's on the horizon-Part II.

In this overview, we articulate research needs and opportunities in the field of infection prevention that have been identified from insights gained during operative infection prevention work, our own research in healthcare epidemiology, and from reviewing the literature. The 10 areas of research need are: 1) Transmissions and interruptions, 2) personal protective equipment and other safety issues in occupational health, 3) climate change and other crises, 4) device, diagnostic, and antimicrobial stewardship, 5) implementation and deimplementation, 6) healthcare outside the acute care hospital, 7) low- and middle-income countries, 8) networking with the "neighbors," 9) novel research methodologies, and 10) the future state of surveillance. An introduction and chapters 1-5 are presented in part I of the article and chapters 6-10 and the discussion in part II. There are many barriers to advancing the field, such as finding and motivating the future IP workforce including professionals interested in conducting research, a constant confrontation with challenges and crises, the difficulty of performing studies in a complex environment, the relative lack of adequate incentives and funding streams, and how to disseminate and validate the often very local quality improvement projects. Addressing research gaps now (i.e., in the post-pandemic phase) will make healthcare systems more resilient when facing future crises.

Perspectives on research needs in healthcare epidemiology and antimicrobial stewardship: what's on the horizon - Part I.

In this overview, we articulate research needs and opportunities in the field of infection prevention that have been identified from insights gained during operative infection prevention work, our own research in healthcare epidemiology, and from reviewing the literature. The 10 areas of research need are: 1) transmissions and interruptions, 2) personal protective equipment and other safety issues in occupational health, 3) climate change and other crises, 4) device, diagnostic, and antimicrobial stewardship, 5) implementation and de-implementation, 6) health care outside the acute care hospital, 7) low- and middle-income countries, 8) networking with the "neighbors", 9) novel research methodologies, and 10) the future state of surveillance. An introduction and chapters 1-5 are presented in part I of the article, and chapters 6-10 and the discussion in part II. There are many barriers to advancing the field, such as finding and motivating the future IP workforce including professionals interested in conducting research, a constant confrontation with challenges and crises, the difficulty of performing studies in a complex environment, the relative lack of adequate incentives and funding streams, and how to disseminate and validate the often very local quality improvement projects. Addressing research gaps now (i.e., in the postpandemic phase) will make healthcare systems more resilient when facing future crises.

Appropriateness of antibiotic prescribing varies by clinical services at United States children's hospitals.

OBJECTIVE: To describe patterns of inappropriate antibiotic prescribing at US children's hospitals and how these patterns vary by clinical service. DESIGN: Serial, cross-sectional study using quarterly surveys. SETTING: Surveys were completed in quarter 1 2019-quarter 3 2020 across 28 children's hospitals in the United States. PARTICIPANTS: Patients at children's hospitals with ≥1 antibiotic order at 8:00 a.m. on institution-selected quarterly survey days. METHODS: Antimicrobial stewardship physicians and pharmacists collected data on antibiotic orders and evaluated appropriateness of prescribing. The primary outcome was percentage of inappropriate antibiotics, stratified by clinical service and antibiotic class. Secondary outcomes included reasons for inappropriate use and association of infectious diseases (ID) consultation with appropriateness. RESULTS: Of 13,344 orders, 1,847 (13.8%) were inappropriate; 17.5% of patients receiving antibiotics had ≥1 inappropriate order. Pediatric intensive care units (PICU) and hospitalists contributed the most inappropriate orders (n = 384 and n = 314, respectively). Surgical subspecialists had the highest percentage of inappropriate orders (22.5%), and 56.8% of these were for prolonged or unnecessary surgical prophylaxis. ID consultation in the previous 7 days was associated with fewer inappropriate orders (15% vs 10%; P < .001); this association was most pronounced for hospitalist, PICU, and surgical and medical subspecialty services. CONCLUSIONS: Inappropriate antibiotic use for hospitalized children persists and varies by clinical service. Across 28 children's hospitals, PICUs and hospitalists contributed the most inappropriate antibiotic orders, and surgical subspecialists' orders were most often judged inappropriate. Understanding service-specific prescribing patterns will enable antimicrobial stewardship programs to better design interventions to optimize antibiotic use.

Reducing length of antibiotics for children with ear infections: protocol for a cluster-randomized trial in the USA.

Aim: Preventing unnecessarily long durations of antibiotic therapy is a key opportunity to reduce antibiotic overuse in children 2 years of age and older with acute otitis media (AOM). Pragmatic interventions to reduce durations of therapy that can be effectively scaled and sustained are urgently needed. This study aims to fill this gap by evaluating the effectiveness and implementation outcomes of two low-cost interventions of differing intensities to increase guideline-concordant antibiotic durations in children with AOM. Methods: The higher intensity intervention will consist of clinician education regarding guideline-recommended short durations of antibiotic therapy; electronic health record (EHR) prescription field changes to promote prescribing of recommended short durations; and individualized clinician audit and feedback on adherence to recommended short durations of therapy in comparison to peers, while the lower intensity intervention will consist only of clinician education and EHR changes. We will explore the differences in implementation effectiveness by patient population served, clinician type, clinical setting and organization as well as intervention type. The fidelity, feasibility, acceptability and perceived appropriateness of the interventions among different clinician types, patient populations, clinical settings and intervention type will be compared. We will also conduct formative qualitative interviews with clinicians and administrators and focus groups with parents of patients to further inform the interventions and study. The formative evaluation will take place over 1.5 years, the interventions will be implemented over 2 years and evaluation of the interventions will take place over 1.5 years. Discussion: The results of this study will provide a framework for other healthcare systems to address the widespread problem of excessive durations of therapy for AOM and inform national antibiotic stewardship policy development. Clinical Trial Registration: NCT05608993 (ClinicalTrials.gov).

Clusters of SARS-CoV-2 Infection Across Six Schools for Students with Intellectual and Developmental Disabilities.

INTRODUCTION: Individuals with intellectual and developmental disabilities are at increased risk for adverse outcomes from coronavirus disease 2019. Clusters of COVID-19 infections can be used to track SARS-CoV-2 transmission. This is particularly important in environments frequently used for individuals with intellectual and developmental disabilities, such as schools. The objective of this study was to compare the number of clusters of student and staff cases identified during three distinct periods (pre-Delta, Delta, and Omicron) of the COVID-19 pandemic. METHODS: Weekly COVID-19 testing occurred from November 23, 2020 to May 27, 2022 during three phases of the COVID-19 pandemic: pre-Delta, Delta, and Omicron. Structured interviews were conducted with positive cases to determine if they contracted COVID-19 in the school environment, and interviews with school administrators responsible for contact tracing determined school-based clusters. RESULTS: 160 cases of COVID-19 were identified and 55 cluster positives were recorded during the study period. 0 (0%) cluster positives were recorded during the pre-Delta variant wave, 3 (5%) cluster positives were recorded during the Delta variant wave, and 52 (95%) cluster positives were recorded during the Omicron variant wave. Additionally, 23 (85%) of all positives during pre-Delta, 12 (50%) of all positives during Delta, 66 (61%) of all positives during Omicron, and 36 (69%) of cluster positives during Omicron did not receive CDC-recommended dosages of the COVID-19 vaccine. CONCLUSION: The Omicron variant led to an increase in cluster-based transmission, and staying up to date with vaccination guidelines was crucial in limiting transmission. CLINICAL TRIAL REGISTRATION: Prior to enrollment, this study was registered at ClinicalTrials.gov on September 25, 2020 (identifier NCT04565509; titled "Supporting the Health and Well-being of Children with Intellectual and Developmental Disability During COVID-19 Pandemic").

Principles and Practice of Antimicrobial Stewardship Program Resource Allocation.

Antimicrobial Stewardship Programs (ASP) improve individual patient outcomes and clinical care processes while reducing antimicrobial-associated adverse events, optimizing operational priorities, and providing institutional cost savings. ASP composition, resources required, and priority focuses are influenced by myriad factors. Despite robust evidence and broad national support, individual ASPs still face challenges in obtaining appropriate resources. Though understanding the current landscape of ASP resource allocation, factors influencing staffing needs, and strategies required to obtain desired resources is important, acceptance of recommended staffing levels and appropriate ASP resource allocation are much needed to facilitate ASP sustainability and growth across the complex and diverse health care continuum.

Common Data Element Collection in Underserved School Communities: Challenges and Recommendations.

OBJECTIVES: To provide recommendations for future common data element (CDE) development and collection that increases community partnership, harmonizes data interpretation, and continues to reduce barriers of mistrust between researchers and underserved communities. METHODS: We conducted a cross-sectional qualitative and quantitative evaluation of mandatory CDE collection among Rapid Acceleration of Diagnostics-Underserved Populations Return to School project teams with various priority populations and geographic locations in the United States to: (1) compare racial and ethnic representativeness of participants completing CDE questions relative to participants enrolled in project-level testing initiatives and (2) identify the amount of missing CDE data by CDE domain. Additionally, we conducted analyses stratified by aim-level variables characterizing CDE collection strategies. RESULTS: There were 15 study aims reported across the 13 participating Return to School projects, of which 7 (47%) were structured so that CDEs were fully uncoupled from the testing initiative, 4 (27%) were fully coupled, and 4 (27%) were partially coupled. In 9 (60%) study aims, participant incentives were provided in the form of monetary compensation. Most project teams modified CDE questions (8/13; 62%) to fit their population. Across all 13 projects, there was minimal variation in the racial and ethnic distribution of CDE survey participants from those who participated in testing; however, fully uncoupling CDE questions from testing increased the proportion of Black and Hispanic individuals participating in both initiatives. CONCLUSIONS: Collaboration with underrepresented populations from the early study design process may improve interest and participation in CDE collection efforts.

Utilization and Impact of Symptomatic and Exposure SARS-CoV-2 Testing in K-12 Schools.

OBJECTIVES: The Centers for Disease Control and Prevention recommend that schools can offer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic (on-demand) testing for students and staff with coronavirus disease 2019 symptoms or exposures. Data related to the uptake, implementation, and effect of school-associated on-demand diagnostic testing have not been described. METHODS: The Rapid Acceleration of Diagnostics Underserved Populations Return to School program provided resources to researchers to implement on-demand SARS-CoV-2 testing in schools. This study describes the strategies used and uptake among the different testing programs. Risk of positivity was compared for symptomatic and exposure testing during the δ and ο variant periods. We estimated the number of school absence days saved with school-based diagnostic testing. RESULTS: Of the 16 eligible programs, 7 provided school-based on-demand testing. The number of persons that participated in these testing programs is 8281, with 4134 (49.9%) receiving >1 test during the school year. Risk of positivity was higher for symptomatic testing compared with exposure testing and higher during the ο variant predominant period compared with the δ variant predominant period. Overall, access to testing saved an estimated 13 806 absent school days. CONCLUSIONS: School-based on-demand SARS-CoV-2 testing was used throughout the school year, and nearly half the participants accessed testing on more than 1 occasion. Future studies should work to understand participant preferences around school-based testing and how these strategies can be used both during and outside of pandemics.

Recommendations for SARS-CoV-2 Testing in Children With Disabilities and Medical Complexity.

Schools provide important services that cannot be provided virtually to children with medical complexity and children with intellectual and developmental disabilities, yet these children are among the most at risk from coronavirus disease 2019 (COVID-19). To keep schools open for children with medical complexity and/or intellectual and developmental disabilities during the COVID-19 pandemic, we implemented severe acute respiratory syndrome coronavirus 2 testing at 3 sites across the United States. We evaluated testing strategies for staff and students at each site, including specimen source (nasopharyngeal or saliva), test type (polymerase chain reaction or rapid antigen), and frequency and type (screening versus exposure/symptomatic) of testing provided. Among the greatest barriers to severe acute respiratory syndrome coronavirus 2 testing in these schools was the engagement of caregivers and challenges navigating legal guardianship for consenting adult students. Additionally, variability in testing strategies nationally and in the community, as well as surges in viral transmission across the United States during the course of the pandemic, led to testing hesitancy and variable participation rates. Essential to the successful implementation of testing programs is building a trusted relationship with school administrators and guardians. Leveraging our experiences with COVID-19 and forming lasting school partnerships can help keep schools for vulnerable children safe in future pandemics.

Building School-Academic Partnerships to Implement COVID-19 Testing in Underserved Populations.

OBJECTIVE: In April 2021, the US government made substantial investments in students' safe return to school by providing resources for school-based coronavirus disease 2019 (COVID-19) mitigation strategies, including COVID-19 diagnostic testing. However, testing uptake and access among vulnerable children and children with medical complexities remained unclear. METHODS: The Rapid Acceleration of Diagnostics Underserved Populations program was established by the National Institutes of Health to implement and evaluate COVID-19 testing programs in underserved populations. Researchers partnered with schools to implement COVID-19 testing programs. The authors of this study evaluated COVID-19 testing program implementation and enrollment and sought to determine key implementation strategies. A modified Nominal Group Technique was used to survey program leads to identify and rank testing strategies to provide a consensus of high-priority strategies for infectious disease testing in schools for vulnerable children and children with medical complexities. RESULTS: Among the 11 programs responding to the survey, 4 (36%) included prekindergarten and early care education, 8 (73%) worked with socioeconomically disadvantaged populations, and 4 focused on children with developmental disabilities. A total of 81 916 COVID-19 tests were performed. "Adapting testing strategies to meet the needs, preferences, and changing guidelines," "holding regular meetings with school leadership and staff," and "assessing and responding to community needs" were identified as key implementation strategies by program leads. CONCLUSIONS: School-academic partnerships helped provide COVID-19 testing in vulnerable children and children with medical complexities using approaches that met the needs of these populations. Additional work is needed to develop best practices for in-school infectious disease testing in all children.

Staphylococcus aureus Bacteremia in Pediatric Patients: Uncovering a Rural Health Challenge.

Background: Staphylococcus aureus bacteremia poses significant risk for morbidity and mortality. This may be exacerbated in rural populations facing unique health challenges. Methods: To investigate factors influencing S. aureus bacteremia outcomes, we conducted a retrospective cohort study of children admitted to St. Louis Children's Hospital (SLCH) from 2011 to 2019. Exposures included rurality (defined by the Rural-Urban Continuum Code), Area Deprivation Index, and outside hospital (OSH) admission before SLCH admission. The primary outcome was treatment failure, a composite of 90-day all-cause mortality and hospital readmission. Results: Of 251 patients, 69 (27%) were from rural areas; 28 (11%) were initially admitted to an OSH. Treatment failure occurred in 39 (16%) patients. Patients from rural areas were more likely to be infected with methicillin-resistant S. aureus (45%) vs urban children (29%; P = .02). Children initially admitted to an OSH, vs those presenting directly to SLCH, were more likely to require intensive care unit-level (ICU) care (57% vs 29%; P = .002), have an endovascular source of infection (32% vs 12%; P = .004), have a longer duration of illness before hospital presentation (4.1 vs 3.0 days; P = .04), and have delayed initiation of targeted antibiotic therapy (3.9 vs 2.6 days; P = .01). Multivariable analysis revealed rural residence (adjusted odds ratio [aOR], 2.3; 95% CI, 1.1-5.0), comorbidities (aOR, 2.9; 95% CI, 1.3-6.2), and ICU admission (aOR, 3.9; 95% CI, 1.9-8.3) as predictors of treatment failure. Conclusions: Children from rural areas face barriers to specialized health care. These challenges may contribute to severe illness and worse outcomes among children with S. aureus bacteremia.

The incidence, duration, risk factors, and age-based variation of missed opportunities to diagnose pertussis: A population-based cohort study.

OBJECTIVE: To estimate the incidence, duration and risk factors for diagnostic delays associated with pertussis. DESIGN: We used longitudinal retrospective insurance claims from the Marketscan Commercial Claims and Encounters, Medicare Supplemental (2001-2020), and Multi-State Medicaid (2014-2018) databases. SETTING: Inpatient, emergency department, and outpatient visits. PATIENTS: The study included patients diagnosed with pertussis (International Classification of Diseases [ICD] codes) and receipt of macrolide antibiotic treatment. METHODS: We estimated the number of visits with pertussis-related symptoms before diagnosis beyond that expected in the absence of diagnostic delays. Using a bootstrapping approach, we estimated the number of visits representing a delay, the number of missed diagnostic opportunities per patient, and the duration of delays. Results were stratified by age groups. We also used a logistic regression model to evaluate potential factors associated with delay. RESULTS: We identified 20,828 patients meeting inclusion criteria. On average, patients had almost 2 missed opportunities prior to diagnosis, and delay duration was 12 days. Across age groups, the percentage of patients experiencing a delay ranged from 29.7% to 37.6%. The duration of delays increased considerably with age from an average of 5.6 days for patients aged <2 years to 13.8 days for patients aged ≥18 years. Factors associated with increased risk of delays included emergency department visits, telehealth visits, and recent prescriptions for antibiotics not effective against pertussis. CONCLUSIONS: Diagnostic delays for pertussis are frequent. More work is needed to decrease diagnostic delays, especially among adults. Earlier case identification may play an important role in the response to outbreaks by facilitating treatment, isolation, and improved contact tracing.

Procedure-Level Misutilization of Antimicrobial Prophylaxis in Pediatric Surgery: Implications for Improved Stewardship and More Effective Infection Prevention.

BACKGROUND: The objective of this study was to quantify prophylaxis misutilization to identify high-priority procedures for improved stewardship and SSI prevention. METHODS: This was a multicenter analysis including 90 hospitals participating in the NSQIP-Pediatric Antibiotic Prophylaxis Collaborative from 6/2019 to 6/2020. Prophylaxis data were collected from all hospitals and misutilization measures were developed from consensus guidelines. Overutilization included use of overly broad-spectrum agents, continuation of prophylaxis >24 h after incision closure, and use in clean procedures without implants. Underutilization included omission (clean-contaminated cases), use of inappropriately narrow-spectrum agents, and administration post-incision. Procedure-level misutilization burden was estimated by multiplying NSQIP-derived misutilization rates by case volume data obtained from the Pediatric Health Information System database. RESULTS: 9861 patients were included. Overutilization was most commonly associated with overly broad-spectrum agents (14.0%), unindicated utilization (12.6%), and prolonged duration (8.4%). Procedure groups with the greatest overutilization burden included small bowel (27.2%), cholecystectomy (24.4%), and colorectal (10.7%). Underutilization was most commonly associated with post-incision administration (6.2%), inappropriate omission (4.4%), and overly narrow-spectrum agents (4.1%). Procedure groups with the greatest underutilization burden included colorectal (31.2%), gastrostomy (19.2%), and small bowel (11.1%). CONCLUSION: A relatively small number of procedures account for a disproportionate burden of antibiotic misutilization in pediatric surgery. TYPE OF STUDY: Retrospective Cohort. LEVEL OF EVIDENCE: III.

Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection.

BACKGROUND: Ceftolozane/tazobactam, a cephalosporin-ß-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed. METHODS: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points. RESULTS: The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, drug-related AEs occurred in 18.6% and 14.3% and serious AEs occurred in 11.4% and 0% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, respectively. No drug-related serious AEs or discontinuations due to drug-related AEs occurred. Rates of the clinical cure for ceftolozane/tazobactam+metronidazole and meropenem at EOT were 80.0% and 95.2% (difference: -14.3; 95% confidence interval: -26.67 to 4.93) and at TOC were 80.0% and 100.0% (difference: -19.1; 95% confidence interval: -30.18 to -2.89), respectively; 6 of the 14 clinical failures for ceftolozane/tazobactam+metronidazole at TOC were indeterminate responses imputed as failures per protocol. CONCLUSION: Ceftolozane/tazobactam+metronidazole was well tolerated in pediatric participants with cIAI and had a safety profile similar to the established safety profile in adults. In this descriptive efficacy analysis, ceftolozane/tazobactam+metronidazole appeared efficacious.

Psychosocial work environment stressors for school staff during the COVID-19 pandemic: Barriers and facilitators for supporting wellbeing.

Introduction: After periods of remote and/or hybrid learning as a result of the COVID-19 global pandemic, the return to in-person learning has been beneficial for both students and teachers, but it has not been without challenges. This study was designed to assess the impact of the return to in-person learning on the school experience, and efforts made to ease the transition in furthering a positive in-person learning environment. Materials and methods: We conducted a series of listening sessions with 4 stakeholder groups: students (n = 39), parents (n = 28), teachers/school staff (n = 41), and a combination of listening sessions and semi-structured interviews with building level and district administrators (n = 12), focusing on in-school experiences during the 2021-2022 school year amidst the COVID-19 pandemic. A primarily deductive qualitative analysis approach was employed to code the data followed by a primarily inductive thematic analysis, followed by thematic aggregation, thus providing depth and identification of nuances in the data. Results: Three main themes emerged around school staff experiences: (1) increased levels of stress and anxiety manifested in key ways, including students' challenges with personal behavior management contributing to increased aggression and staff shortages; (2) school staff described key contributors to stress and anxiety, including feeling excluded from decision making and challenges with clear and consistent communication; and (3) school staff described key facilitators that supported their management of anxiety and stress, including adaptability, heightened attention and resources to wellbeing, and leveraging interpersonal relationships. Discussion: School staff and students faced significant stress and anxiety during the 2021-2022 school year. Further exploration and identification of approaches to mitigate key contributors to increased stress and anxiety for school staff, along with increased opportunities for implementing key facilitators that were identified as important in managing and navigating the increased stress and anxiety offer valuable opportunities for helping to create a supportive work environment for school staff in the future.