OBJECTIVE:The COVID-19 pandemic may have affected the care of patients with influenza. We investigated influenza antiviral use and associated factors in children hospitalized with influenza before and during the late COVID-19 pandemic. METHODS:We conducted active surveillance among US children with acute respiratory illness at 7 sites in the New Vaccine Surveillance Network before the COVID-19 pandemic (December 1, 2016 to March 31, 2020) and during the late pandemic period (July 1, 2021 to June 30, 2023). We included children hospitalized within 10 days of symptom onset who had positive test results for influenza by clinical or research testing. Research swabs were collected from all enrolled children; clinical testing was provider-directed. We used mixed-effects Poisson regression to compare incidence proportions of influenza antiviral use in the late pandemic with those of the prepandemic period. We determined factors associated with antiviral use during the late pandemic period using a mixed-effects logistic regression model. RESULTS:Among 1560 children hospitalized with influenza, antiviral use ranged between 48.3% and 56.8% prepandemic but declined to 38.1% in 2021 to 2022 and 46.1% in 2022 to 2023. The estimated antiviral use was 23% lower in the late pandemic (incidence proportion ratio, 0.77; 95% CI, 0.68-0.87) compared with the prepandemic period. During the late pandemic, factors associated with higher odds of antiviral use included an underlying medical condition presence, current season influenza vaccination, clinical influenza testing, intensive care unit admission, and site. CONCLUSIONS:Influenza antiviral use in children hospitalized with influenza remained suboptimal following the COVID-19 pandemic. Our study highlights the need to improve antiviral use in children hospitalized with influenza.

Management and prevention of thromboembolism (TE) in pediatric acute myeloid leukemia (AML) are challenging because of prolonged periods of thrombocytopenia and associated bleeding. There are no guidelines for prophylactic or therapeutic anticoagulation for children with AML. This study aimed to understand the use of anticoagulation and its association with bleeding events (BEs) during index hospitalization in children with AML, both with and without thromboses. A retrospective cohort study was performed using the Pediatric Health Information System administrative database of index hospitalizations for patients aged 1 to 21 years from 2016 to 2024 with the diagnosis of AML across 49 children's hospitals. Demographic data, diagnosis of TE, anticoagulation use, and BE were extracted. A total of 3768 patients with AML were included, with 167 (4.4%) experiencing a TE. A total of 171 patients (4.5%) received anticoagulation, with almost half receiving anticoagulation in the absence of a TE diagnosis (presumed prophylaxis). Of patients with a TE, 88 (52.3%) received anticoagulation, with the remainder receiving no anticoagulation. Enoxaparin was the most frequently used anticoagulant, followed by rivaroxaban, but wide institutional variation was observed in the choice of anticoagulant. A total of 750 patients (20%) experienced ≥1 BE. Most patients (705/750 [94%]) with BE received no anticoagulation. Prospective research is needed to determine the safest and most effective use of prophylactic and therapeutic anticoagulation in this patient population.

ABSTRACT:Ketamine is recommended as an opioid-sparing adjunct for sickle cell disease (SCD)-related pain management. Little is known regarding its use in hospitalized youth with SCD. We aimed to describe trends in ketamine administration and examine associations between ketamine administration and outcomes in hospitalized youth with SCD. We conducted a cross-sectional, multicenter study examining hospital admissions for youth with SCD from 44 children's hospitals in the United States from 2016 to 2023. Youth aged ≥6 months with SCD were identified using International Classification of Diseases tenth revision codes. Exposures included age, sex, race, payor, childhood opportunity index, hydroxyurea administration, and concomitant methadone, buprenorphine, or gabapentinoid administration. The primary outcome was ketamine administration during admission. Secondary outcomes included length of stay, days on IV opioids, all-cause 14-day readmission rates, and intensive care unit stays during admissions with ketamine administered during the first 3 days of hospitalization (early) and hospital day 4 or later (late). From 2016 to 2023, 4.5% (n = 3391) of admissions for patients with SCD included ketamine administration, with prevalence increasing from 2.3% in 2016 to 5.7% in 2023 (P< .001). Age groups ≥12 years and the year ≥2019 was associated with increased odds of ketamine administration. Admissions with ketamine administration were also more likely to have administration of methadone and hydroxyurea. Early vs late ketamine administration was associated with shorter length of stay and fewer parental opioid days, indicating randomized controlled studies are needed to determine not only which patients benefit from ketamine but also the impact of early administration.

Reports of neuropsychiatric events related to oseltamivir use have led to public health concerns. Oseltamivir is transported out of the CSF by the P-glycoprotein (P-gp) system. We explored whether concurrent use of oseltamivir and P-gp inhibitors, which would increase CSF concentrations of oseltamivir, is associated with neuropsychiatric events. Notes: 1.Person-time accrued for each subject beginning on the first day of the influenza season and continuing through the earliest occurrence of an incident neuropsychiatric outcome event (see definition below), loss of enrollment, death, age 18 years, or end of the study. 2. Characterization of study exposures and covariates was conducted throughout follow-up for all individuals, began at cohort entry and was measured at the person-day level, allowing exposures and covariates to be time-dependent. Importantly, the start date for all influenza episodes (both treated and untreated) began on the same date, i.e., the date of influenza diagnosis. 3. Other exposure includes other influenza antivirals other than oseltamivir (e.g. baloxavir, zanamivir, peramivir) alone or in combination with influenza, oseltamivir + P-gp modifiers without influenza exposure and P-gp modifiers alone. 4. Outcome definition: The outcome definition includes both neurologic (seizures, encephalitis, altered mental status, ataxia/movement disorders, vision changes, dizziness, headache, sleeping disorders) and psychiatric (suicidal or self-harm behaviors, mood disorders, psychosis/hallucination) eventsFigure 1.Forest plot of incidence-rate ratios for serious neuropsychiatric events We assembled a retrospective cohort of children 5-17 years and followed them during the 2016-2020 influenza seasons in the Marketscan database. Each person-day of follow-up was assigned to one of six cohorts: 1) untreated influenza (10 day period after influenza diagnosis), 2) treated influenza (influenza + oseltamivir dispensing plus days supply) 3) post-treatment influenza (period between completion of oseltamivir and 10 days after influenza diagnosis), 4) treated influenza+P-gp inhibitor, 5) other (other antivirals or P-gp modifiers) or 6) no exposure. The outcome was serious neuropsychiatric events resulting in hospitalization and identified using a validated algorithm (PPV ∼90%) (Table 1). Incidence-rate ratios (IRRs) with 95% CI were estimated using Poisson regression model adjusting for relevant confounders. Sensitivity analyses were performed including alternative exposure and outcome definitions as well as unmeasured confounding. A total of 5,481,906 children contributed 125,029,135 person-weeks of follow-up, encompassing 400,031 person-weeks of influenza and 15,098 neuropsychiatric events. Median age was 13.0 (IQR 9, 16) years (Table 1). Compared with untreated influenza, episodes of influenza treated with oseltamivir had lower risk of neuropsychiatric events (treated influenza IRR 0.34, 95% CI 0.21-0.55; post-treatment influenza IRR 0.52, 95% CI 0.35-0.76; treated influenza+P-gp inhibitor 0.18, 95% CI 0.0.3-1.30) (Figure 1). Alternate analyses suggest misclassification (Figure 2) or unmeasured confounding (measured E-value 5.33) would not explain the findings. Oseltamivir use was associated with a reduced risk of serious pediatric neuropsychiatric events, even when used concurrently with medications that would theoretically increase CSF concentrations of the drug. These findings provide reassurance to patients and providers as to the safety of oseltamivir use. James W. Antoon, MD, PhD, MPH, AstraZeneca: Advisor/Consultant|NIH: Grant/Research Support Carlos G. Grijalva, MD MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|GSK: Advisor/Consultant|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support

ABSTRACT Rare adverse drug reactions (ADRs) are underrecognized and underreported in the electronic medical record (EMR). These events often require clinical review, making systematic identification challenging. The study aim was to develop an approach to prioritize identification and validation of a rare ADR to trimethoprim‐sulfamethoxazole causing acute respiratory distress syndrome (TMP‐SMX ARDS) across medical institutions. We developed a clinical phenotype based on 2 local TMP‐SMX ARDS cases mapped to standardized elements of a national comparative healthcare database (PHIS). We validated identification of TMP‐SMX ARDS at scale across medical institutions. A set of scoring criteria was created to prioritize cases and generate a center‐specific top 10 list of candidate encounters. External validation at 3 PHIS contributing hospitals with a known TMP‐SMX ARDS case was performed by reviewing the top 10 candidate list for the known case. The review period was January 1, 2012–January 1, 2025. EMR data extracted from 2 TMP‐SMX ARDS cases included patients that both required extracorporeal membrane oxygenation for > 100 days, experienced air leak early in hospital presentation, required tracheostomy placement, and were hospitalized for > 440 days. Based on the TMP‐SMX ARDS phenotype, the local cases ranked 1st and 3rd on the PHIS generated top 10 candidate list for internal validation. For external validation, known cases were identified on their respective hospital top 10 lists, ranking 3rd, 3rd, and 5th. Applying a TMP‐SMX ARDS phenotype to a national health care database paired with clinical review of candidate cases may be an effective approach to identify underrecognized ADRs.

Background and Purpose: Children with acute asthma exacerbations are frequently hospitalized due to insufficient response to inhaled β-agonist and systemic corticosteroid potentially due to leukotriene mediated airway inflammation. Montelukast is a potent leukotriene receptor antagonist approved for chronic asthma treatment. We performed a randomized dose-escalation trial of high-dose oral montelukast to identify the dose of oral montelukast suitable for future efficacy studies. Experimental Approach: We performed a Phase 2, adaptive, double-masked randomized controlled trial comparing high-dose oral montelukast plus standard treatment versus standard alone in children with exacerbations moderate-to-severe exacerbations after initial inhaled albuterol treatment. Three sequential groups received escalating weight-based dose levels (2.0, 2.5, and 3.0 mg/kg) with maximum plasma concentration (Cmax) used as the pharmacokinetic target for dose escalation. We hypothesized that at least one dose level would achieve a target Cmax of 1,700 ng/ml in > 86% of dose-level participants. Key Results: Among 45 participants randomized to montelukast and 44 to placebo, median [IQR] ages were 6.6 [5.4, 10] and 6.7 [5.3, 9.9] years, with high-moderate pre-treatment exacerbation severity. The target Cmax was reached in 67%, 80%, and 90% of participants at doses of 2.0, 2.5, and 3.0 mg/kg, respectively. Adverse events were infrequent and mild. Conclusion and Implications: Among children with moderate or severe acute asthma exacerbations not responsive to initial inhaled albuterol, oral montelukast at a dose of 3.0 mg/kg reliably achieves a potentially therapeutic Cmax. These findings support dose selection for an adequately powered efficacy trial of montelukast in this population.

Summary Paediatric penicillin allergy prevalence declined from 7.57% to 6.65% (2018–2024), especially in youngest children. An overall decrease in new PAL and an increase in institutional penicillin allergy delabelling was observed.

OBJECTIVE: The objective of this study was to determine the population-based incidence of influenza-associated serious neurologic events in children < 5 years of age. METHODS: We conducted a retrospective cohort of children < 5 years of age enrolled in a Medicaid program during the 2016 to 2017 through 2019 to 2020 influenza seasons. Serious influenza-associated neurologic events were defined as a neurologic event resulting in hospitalization. Population-based incidence of serious influenza-associated neurologic events was calculated by dividing the number of events by the total accrued follow-up time and expressed per 100,000 influenza person-weeks. Incidence estimates were stratified by neurologic event category, age, sex, neurologic comorbidity, influenza season, and antiviral use. RESULTS: A total of 79,727 influenza cases among 70,258 unique children were included. The overall incidence of serious influenza-associated neurologic events was 38.0 (95% confidence interval [CI] 27.5-51.2) per 100,000 person-weeks of influenza. The most common serious neurologic event was seizure (34.5 per 100,000 influenza person-weeks of influenza, 95% CI 24.5-47.1) whereas encephalitis and ataxia/movement disorders were least common (0.9 per 100,000 influenza person-weeks of influenza, 95% CI 0.02-4.9). Incidence rates were generally higher in children < 2 years and significantly more common in children with neurologic conditions compared to those without neurologic conditions. Incidence rates were similar among those with and without influenza antiviral use. CONCLUSIONS: Our findings reveal that serious neurologic complications are uncommon in young children with influenza but markedly higher in those with underlying neurologic conditions. These data emphasize the importance of preventing, identifying, and treating influenza in this vulnerable population.

Importance:Despite national recommendations, antiviral prescribing in emergency departments (EDs) for children at higher risk of severe influenza, such as those younger than 5 years and those with specific underlying conditions, remains low. Objective:To assess whether there were changes in antiviral prescribing for children at higher risk of severe influenza in academic pediatric EDs before the COVID-19 pandemic (2016-2020) vs the late pandemic period (2021-2023). Design, Setting, and Participants:This multicenter, cross-sectional study included influenza-positive children younger than 18 years presenting to the ED at 1 of 7 US pediatric academic hospitals participating in the Centers for Disease Control and Prevention's New Vaccine Surveillance Network. The analysis focused on children at higher risk of severe influenza seen in the ED from December 1, 2016, to June 30, 2023. Exposure:High risk of severe influenza. Main Outcomes and Measures:The primary outcome was antiviral prescribing. Children with influenza who met the criteria for higher risk of severe influenza were included. Antiviral prescribing practices were compared across the prepandemic and late pandemic periods. Mixed-effects logistic regression was used to identify factors associated with prescribing during the late pandemic period. Results:Of 3378 influenza-positive children (median [IQR] age, 3.9 [1.8-7.2] years), 2514 (74.4%; 1363 male [40.3%]) were classified as having higher risk of severe influenza during the prepandemic and late pandemic periods. Antiviral prescriptions decreased from 32.2% (622 of 1931 children) before the pandemic to 15.6% (91 of 583 children) in the late pandemic period, representing a 53% relative decrease. In the late pandemic period, symptom duration less than 2 days (adjusted odds ratio, 4.08; 95% CI, 2.49-6.71) and clinical influenza testing (adjusted odds ratio, 17.20; 95% CI, 4.08-72.37) were significantly associated with antiviral prescribing. Conclusions and Relevance:This multicenter, cross-sectional study of children with influenza in EDs found that, for children at higher risk of severe influenza illness, influenza antiviral prescribing decreased during the COVID-19 pandemic compared with prepandemic levels, despite unchanged treatment guidelines. Interventions are needed to support guideline-concordant prescribing in this population.

BACKGROUND:Influenza contributes to a high burden of pediatric emergency department (ED) visits annually. Guidelines recommend outpatient antiviral treatment for children at higher risk of severe influenza and recommend considering treatment for those who present within 2 days of symptom onset. We describe antiviral prescription in children with influenza presenting to the ED. METHODS:We analyzed data from the New Vaccine Surveillance Network (2016-2020), including children presenting to the ED and enrolled with confirmed influenza at one of seven pediatric academic centers. We compared characteristics of children prescribed antivirals to those who were not, using generalized estimating equations models to identify predictors of antiviral prescription. Children were considered at higher risk of severe influenza if they were < 5 years old or had an underlying condition. RESULTS:Overall, 2472 (15%) of 16,915 enrolled children tested positive for influenza virus. Among these, 1931 (78%) were at higher risk of severe influenza; only 622 (32%) received an antiviral. Among 233 (9%) children not at high risk with symptom onset ≤ 2 days, 62 (27%) were prescribed an antiviral. Children prescribed an antiviral had a shorter duration of illness prior to presenting to the ED. For children at higher risk of severe influenza, odds of antiviral prescription were higher for those clinically tested for influenza and with underlying conditions. CONCLUSION:Clinical testing and having an underlying condition were associated with antiviral prescription in children at higher risk of severe influenza. However, only 1/3 of those at higher risk were prescribed an antiviral. Strategies to increase antiviral use for children at higher risk for influenza in the ED are needed.

Importance Reports of pediatric neuropsychiatric events during influenza treatment with oseltamivir have prompted public concerns. However, whether oseltamivir or influenza infection is associated with increased risk of neuropsychiatric events remains unclear. Objective To determine the association between influenza, oseltamivir, and serious neuropsychiatric events. Design, Setting, and Participants This retrospective cohort study was conducted in a population-based ambulatory setting during the 2016 to 2017 and 2019 to 2020 influenza seasons. Follow-up began on the first day of the influenza season and continued through the earliest occurrence of an outcome event, loss of enrollment, death, age 18 years, or end of the season or study. Children aged 5 to 17 years enrolled in Tennessee Medicaid were for eligible for inclusion. Data analysis was completed from July 2023 to March 2025. Exposures Each person-day of follow-up was assigned to 1 of the following 5 mutually exclusive exposure groups: (1) untreated influenza; (2) treated influenza; (3) posttreatment period (period between oseltamivir completion and end of influenza period); (4) influenza prophylaxis; and (5) no exposure. Main Outcomes and Measures The primary outcome was a neuropsychiatric event requiring hospitalization, and events were identified using a validated algorithm. Poisson regression estimated incidence rate ratios (IRRs) while accounting for relevant covariates measured on each person-day. Sensitivity analyses examined robustness of findings to alternate exposure and outcome definitions, time-varying outcome risk, negative control outcome, and unmeasured confounding. Results Among 692 975 eligible children, a total of 692 295 children (median [IQR] age, 11 [7-14] years; 50.3% female) experienced 1230 serious neuropsychiatric events (898 neurologic and 332 psychiatric) during 19 688 320 person-weeks of follow-up. Among the 151 401 influenza episodes, 66.7% (95% CI, 66.5%-67.0%) were dispensed oseltamivir (60.1% [95% CI, 59.6%-60.6%] among those at high risk for influenza complications). The most common events overall were mood disorders (36.3%) and suicidal or self-harm behaviors (34.2%). Compared with untreated influenza, event rates were lower during oseltamivir-treated influenza periods (IRR, 0.53; 95% CI, 0.33-0.88) and posttreatment periods (IRR, 0.42; 95% CI, 0.24-0.74). Subanalyses suggest that this finding is driven more by a reduction in neurologic events (IRR, 0.45; 95% CI, 0.25-0.82) than psychiatric events (IRR, 0.80; 95% CI, 0.34-1.88). Sensitivity analyses suggest misclassification or unmeasured confounding would not explain these findings. Conclusions and Relevance In this cohort study, oseltamivir treatment during influenza episodes was associated with a reduced risk of serious neuropsychiatric events. These findings support oseltamivir use for prevention of these influenza-related complications.

Background. Guidelines state that all hospitalized children with suspected or confirmed influenza receive prompt treatment with influenza-specific antivirals. We sought to determine the frequency of, and factors associated with, antiviral receipt among hospitalized children. Methods. We conducted active surveillance of children presenting with fever or respiratory symptoms from 1 December 2016 to 31 March 2020 at 7 pediatric medical centers in the New Vaccine Surveillance Network. The cohort consisted of children hospitalized with influenza A or B confirmed by clinical or research testing. The primary outcome was frequency of antiviral receipt during hospitalization. We used logistic regression to obtain adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with antiviral receipt. Results. A total of 1213 children with laboratory-confirmed influenza were included. Overall, 652 children (53.8%) received an antiviral. Roughly 63.0% of children received clinical influenza testing. Among those with clinical testing, 67.4% received an antiviral. Factors associated with higher odds of antiviral receipt included hematologic (aOR = 1.76; 95% CI = 1.03-3.02) or oncologic/immunocompromising (aOR = 2.41; 95% CI = 1.13-5.11) disorders, prehospitalization antiviral receipt (aOR = 2.34; 95% CI = 1.49-3.67), clinical influenza testing (aOR = 3.07; 95% CI = 2.28-4.14), and intensive care unit admission (aOR = 1.53; 95% CI = 1.02-2.29). Symptom duration >2 days was associated with lower odds of antiviral treatment (aOR = 0.40; 95% CI = .30-.52). Antiviral receipt varied by site with a 5-fold difference across sites. Conclusions. Almost half of children hospitalized with influenza did not receive antivirals. Additional efforts to understand barriers to guideline adherence are crucial for optimizing care in children hospitalized with influenza.

Abstract Background Despite recommendations from CDC and ACIP, antiviral prescription for children who are at higher risk of severe influenza (including those < 5 years and those with certain underlying conditions) in emergency departments (EDs) remains suboptimal. This study assessed changes in antiviral prescription for children at higher risk of severe influenza in EDs from the pre-COVID-19-pandemic period to the COVID-19 pandemic period. Demographic and clinical characteristics of children at higher risk of severe influenza(1) enrolled in the ED with laboratory confirmed influenza, stratified by pandemic periods (N=2,5001). (1) Defined as children <5 years old and/or those with any underlying medical condition. Methods Data from NVSN, a 7-site, prospective surveillance study of acute respiratory illnesses, were analyzed. Children at higher risk for severe influenza in EDs with confirmed influenza by research or clinical testing were included. We compared children who received antiviral prescriptions with those who did not. The study period was categorized into pre-pandemic (12/01/2016 to 03/31/2020) and late pandemic (07/01/2021 to 03/31/2023) periods. We used mixed-effects Poisson regression to compare antiviral prescription incidence proportions before the pandemic and during the late pandemic period. Mixed-effects logistic regression was used to evaluate factors associated with antiviral prescription during the late pandemic period among children at higher risk. Incidence proportion ratios from mixed-effects Poisson model(1) among children at higher risk of severe influenza (N=2,500). (1) The estimates presented are from a mixed-effects Poisson model with a log link and random intercepts for study sites, with outcome as number of children with an antiviral prescription. Results A total of 3,436 children in the ED tested positive for influenza, of whom 2,500 (73%) were classified as higher risk for severe influenza. Pre-pandemic, 31% were prescribed antivirals compared to 12% during the late pandemic among those at higher risk (Table 1). Prescription of antivirals for children at higher risk decreased by 69% in 2021-2022 and by 55% in 2022-2023 compared to the pre-pandemic (Table 2, Figure 1). Symptom duration and clinical influenza testing were significantly associated with antiviral prescription among children at higher risk during the late pandemic period (Figure 2). Percent of antiviral prescriptions among children at higher risk of severe influenza illness presenting to the emergency departments of seven children’s hospitals, stratified by clinical influenza testing (N=2,500). Conclusion Influenza antiviral prescription among children at higher risk for severe influenza in EDs decreased significantly during the COVID-19 pandemic compared to the pre-pandemic, despite treatment recommendations. While clinical testing has increased during the COVID-19 pandemic and is associated with prescription of influenza antivirals, prescription remains low. Efforts are needed to improve antiviral prescriptions for children at higher risk for severe influenza in EDs. Adjusted odds ratios of antiviral prescription among children at higher risk of severe influenza illness presenting to the emergency departments of seven children’s hospitals during the pandemic period (2021-2023; N=459). We used logistic regression to compare the odds of antiviral prescription, adjusting for age, symptom duration, clinical influenza testing (rapid antigen or PCR), influenza season, peak influenza season, and study site as a random effect. Disclosures James W. Antoon, MD, PhD, MPH, AstraZeneca: Advisor/Consultant|NIH: Grant/Research Support James Chappell, MD, PhD, Merck: Grant/Research Support Janet A. Englund, MD, Abbvie: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Speaker at meeting|SanofiPasteur: Advisor/Consultant|Shinogi: Advisor/Consultant Geoffrey A. Weinberg, MD, Inhalon: Advisor/Consultant|Merck & Company: Honoraria for textbook chapter preparation Mary A. Staat, MD, MPH, Cepheid: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria Elizabeth P. Schlaudecker, MD, MPH, Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, FAAM, Abbott: Grant/Research Support|Abbott: Honoraria|BioMerieux: Grant/Research Support|Cepheid: Grant/Research Support|Diasorin: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Luminex: Grant/Research Support|Qiagen: Grant/Research Support Christopher J. Harrison, MD, GSK: Grant/Research Support|Medscape: Honoraria|Merck: Grant/Research Support|Pfizer: Grant/Research Support|UpToDate: Honoraria Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support

BACKGROUND:Despite national guidelines on appropriate antibiotic therapy, there is wide variation in antibiotic decision-making for children with community-acquired pneumonia. This study sought to determine prevalence and factors associated with guideline-concordant antibiotic use in children presenting with pneumonia to the emergency department (ED). METHODS:We enrolled children aged younger than 18 years presenting to the ED at 2 US children's hospitals between September 2017 and May 2019 with clinical and radiographic pneumonia. The primary outcome was guideline-concordant antibiotic use as defined by the 2011 Infectious Diseases Society of America pediatric pneumonia guideline and local expert consensus. Outcomes included proportion of antibiotic use and proportion of guideline-concordant treatment. We used multivariable logistic regression models to determine associations of comorbidities and functional limitations, clinical findings, and radiographic characteristics with overall antibiotic use and guideline-concordant treatment. RESULTS:Among 772 included children, 573 received antibiotics (74.2%), and 441 (57.1%) received guideline-concordant antibiotic treatment. Antibiotic initiation was less likely in those with interstitial findings on chest radiograph (adjusted odds ratio [aOR], 0.14; 95% CI, 0.07-0.25) and negative results or nonperformance of viral testing (aOR, 0.39; 95% CI, 0.24-0.65). Guideline-concordant treatment was more likely in those with chest indrawing (aOR, 2.22; 95% CI, 1.34-3.66) and less likely in those with clinically significant effusion (aOR, 0.21; 95% CI, 0.06-0.76). CONCLUSIONS:Among children presenting to the ED with pneumonia, more than 40% received treatment inconsistent with guideline recommendations. These observations underscore opportunities to improve appropriate antibiotic use in this population.

Abstract Background Influenza-specific antivirals are recommended for all hospitalized children with suspected or confirmed influenza. However, antiviral use remains suboptimal. We investigated antiviral use in children hospitalized with influenza before the COVID-19 pandemic and during the late pandemic period, as well as factors associated with antiviral use. Methods We conducted active surveillance on children < 18 years old with acute respiratory illness at seven pediatric centers in the New Vaccine Surveillance Network before the COVID-19 pandemic (12/01/2016–03/31/2020) and during the late pandemic period (07/01/2021–03/31/2023). We included children hospitalized within 10 days of symptom onset who tested positive for influenza A or B viruses by clinical or research testing. We used mixed-effects Poisson regression to compare incidence proportions of antiviral use in the 2021–22 and 2022–23 seasons to before the pandemic. In addition, we fit a mixed-effects logistic regression model with the study site as a random effect to determine factors associated with antiviral use during the late pandemic period. Results Among 1,549 children hospitalized with influenza, antiviral use ranged between 48.3% and 57.0% pre-pandemic but declined to 38.1% in 2021–22 and 45.7% in 2022–23 (Table 1; Figure 1). Influenza-specific antiviral use was estimated to be 31% lower in 2021–22 (p=0.064) and 20% lower in 2022–23 (p< 0.001) compared to the pre-pandemic period (Table 2), despite an increase in clinical testing. During the late pandemic, factors associated with higher odds of antiviral use included an underlying medical condition, influenza vaccination, clinical influenza testing, intensive care unit (ICU) admission, admission during the peak of influenza season, and some study sites (Figure 2).Figure 1.Children hospitalized within 10 days of onset of fever or a respiratory symptom who were positive for influenza A or B by clinical or research testing, disaggregated by clinical testing status, New Vaccine Surveillance Network (12/01/2016–03/31/2023; N=1,545). (A) Absolute frequencies of children hospitalized during each time period. (B) Relative frequency of antiviral use among all these children. Conclusion Influenza-specific antiviral use in hospitalized children remained suboptimal, with a significant decline during the late COVID-19 pandemic. Our study highlights the need for enhanced efforts to improve antiviral use in this population at increased risk of severe influenza illness. Multiple factors were associated with antiviral use, underscoring the importance of considering these factors when developing interventions to optimize pediatric influenza management.Figure 2.Factors associated with antiviral use among children hospitalized with influenza during the late COVID-19 pandemic period (07/01/2021–03/31/2023) in the New Vaccine Surveillance Network. All results are from a single generalized linear mixed-effects model with the study site as a random effect. Red denotes lower odds of antiviral use, and green denotes higher odds of antiviral use. Abbreviations: aOR, adjusted odds ratio; CI, confidence interval. Disclosures James W. Antoon, MD, PhD, MPH, AstraZeneca: Advisor/Consultant|NIH: Grant/Research Support Janet A. Englund, MD, Abbvie: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Speaker at meeting|SanofiPasteur: Advisor/Consultant|Shinogi: Advisor/Consultant Geoffrey A. Weinberg, MD, Inhalon: Advisor/Consultant|Merck & Company: Honoraria for textbook chapter preparation Mary A. Staat, MD, MPH, Cepheid: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria Elizabeth P. Schlaudecker, MD, MPH, Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, FAAM, Abbott: Grant/Research Support|Abbott: Honoraria|BioMerieux: Grant/Research Support|Cepheid: Grant/Research Support|Diasorin: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Luminex: Grant/Research Support|Qiagen: Grant/Research Support Christopher J. Harrison, MD, GSK: Grant/Research Support|Medscape: Honoraria|Merck: Grant/Research Support|Pfizer: Grant/Research Support|UpToDate: Honoraria James Chappell, MD, PhD, Merck: Grant/Research Support Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support

In January 2025, CDC received several reports of deaths among children aged <18 years with a severe form of influenza-associated encephalopathy (IAE) termed acute necrotizing encephalopathy (ANE). Because no national surveillance for IAE currently exists, CDC requested notification of U.S. pediatric IAE cases from clinicians and health departments during the 2024-25 influenza season, a high-severity season with a record number of pediatric influenza-associated deaths. Among 192 reports of suspected IAE submitted to CDC, 109 (57%) were categorized as IAE, 37 (34%) of which were subcategorized as ANE, and 72 (66%) as other IAE; 82 reports did not meet IAE criteria and were categorized as other influenza-associated neurologic disease. The median age of children with IAE was 5 years and 55% were previously healthy, 74% were admitted to an intensive care unit, and 19% died; 41% of children with ANE died. Only 16% of children with IAE who were vaccination-eligible had received the 2024-25 influenza vaccine. Health care providers should consider IAE in children with encephalopathy or altered level of consciousness and a recent or current febrile illness when influenza viruses are circulating. Annual influenza vaccination is recommended for all children aged ≥6 months to prevent influenza and associated complications, potentially including severe neurologic disease such as IAE and ANE.

OBJECTIVES:To evaluate the prevalence of antiviral drug use in children in the US with influenza at high risk for complications and to identify factors associated with dispensing. STUDY DESIGN:We conducted a retrospective cohort study of outpatient visits for individuals < 18 years during the 2016-2020 influenza seasons using the Merative MarketScan Commercial Claims and Encounter database. High-risk status was defined using Infectious Disease Society of America definitions and included: age, specific comorbidities, pregnancy or postpartum status, and living in a long-term care facility. The primary outcome was antiviral (oseltamivir, zanamivir, baloxavir) dispensing within 2 days of influenza diagnosis. We determined clinical factors associated with antiviral dispensing using modified Poisson regression. RESULTS:A total of 372 372 influenza episodes were identified among 331 389 children at high risk for influenza complications and included in this study. The median (IQR) age was 4.0 years (2.0, 9.0). Overall, during 201 638 (54.1%) episodes of the influenza, antiviral treatment was dispensed. Factors associated with increased antiviral use included asthma, West and South US geographic regions, urgent care settings, and specific health insurance plans. Factors associated with decreased antiviral use include younger age, emergency department setting, Midwest and Northeast geographic regions, and health insurance plans. CONCLUSION:Despite national guidelines recommending that all children at high risk for influenza complications receive antiviral treatment, nearly half of these children at high-risk did not receive an antiviral in our study. We identify several factors associated with decreased antiviral treatment that may serve to inform future interventions aiming to improve the care of vulnerable children with influenza.