A National Quality Improvement Collaborative to Improve Antibiotic Use in Pediatric Infections.

BACKGROUND: Nearly 25% of antibiotics prescribed to children are inappropriate or unnecessary, subjecting patients to avoidable adverse medication effects and cost. METHODS: We conducted a quality improvement initiative across 118 hospitals participating in the American Academy of Pediatrics Value in Inpatient Pediatrics Network 2020 to 2022. We aimed to increase the proportion of children receiving appropriate: (1) empirical, (2) definitive, and (3) duration of antibiotic therapy for community-acquired pneumonia, skin and soft tissue infections, and urinary tract infections to ≥85% by Jan 1, 2022. Sites reviewed encounters of children >60 days old evaluated in the emergency department or hospital. Interventions included monthly audit with feedback, educational webinars, peer coaching, order sets, and a mobile app containing site-specific, antibiogram-based treatment recommendations. Sites submitted 18 months of baseline, 2-months washout, and 10 months intervention data. We performed interrupted time series (analyses for each measure. RESULTS: Sites reviewed 43 916 encounters (30 799 preintervention, 13 117 post). Overall median [interquartile range] adherence to empirical, definitive, and duration of antibiotic therapy was 67% [65% to 70%]; 74% [72% to 75%] and 61% [58% to 65%], respectively at baseline and was 72% [71% to 72%]; 79% [79% to 80%] and 71% [69% to 73%], respectively, during the intervention period. Interrupted time series revealed a 13% (95% confidence interval: 1% to 26%) intercept change at intervention for empirical therapy and a 1.1% (95% confidence interval: 0.4% to 1.9%) monthly increase in adherence per month for antibiotic duration above baseline rates. Balancing measures of care escalation and revisit or readmission did not increase. CONCLUSIONS: This multisite collaborative increased appropriate antibiotic use for community-acquired pneumonia, skin and soft tissue infections, and urinary tract infection among diverse hospitals.

COVID-19 Vaccine Hesitancy Among Parents: A Qualitative Study.

OBJECTIVES: Addressing parental/caregivers' coronavirus disease 2019 (COVID-19) vaccine hesitancy is critical to improving vaccine uptake in children. Common concerns have been previously reported through online surveys, but qualitative data from KII and focus groups may add much-needed context. Our objective was to examine factors impacting pediatric COVID-19 vaccine decision-making in Black, Spanish-speaking, and rural white parents/caregivers to inform the content design of a mobile application to improve pediatric COVID-19 vaccine uptake. METHODS: Parents/caregivers of children aged 2 to 17 years from groups disproportionately affected by COVID-19-related vaccine hesitancy (rural-dwelling persons of any race/ethnicity, urban Black persons, and Spanish-speaking persons) were included on the basis of their self-reported vaccine hesitancy and stratified by race/ethnicity. Those expressing vaccine acceptance or refusal participated in KII, and those expressing hesitancy in focus groups. Deidentified transcripts underwent discourse analysis and thematic analysis, both individually and as a collection. Themes were revised until coders reached consensus. RESULTS: Overall, 36 participants completed the study: 4 vaccine acceptors and 4 refusers via KIIs, and the remaining 28 participated in focus groups. Participants from all focus groups expressed that they would listen to their doctor for information about COVID-19 vaccines. Infertility was a common concern, along with general concerns about vaccines. Vaccine decision-making was informed by the amount of information available to parents/caregivers, including scientific research; possible positive and negative long-term effects; and potential impacts of vaccination on preexisting medical conditions. CONCLUSIONS: Parents/caregivers report numerous addressable vaccine concerns. Our results will inform specific, targeted interventions for improving COVID-19 vaccine confidence.

An assessment of information needs and workflows for emergency service providers and caregivers of children with medical complexity.

BACKGROUND: The goal of Project Austin, an initiative to improve emergency care for rural children who are medically complex (CMC), is to provide an Emergency Information Form (EIF) to their parents/caregivers, to local Emergency Medical Services, and Emergency Departments. EIFs are standard forms recommended by the American Academy of Pediatrics that provide pre-planned rapid response instructions, including medical conditions, medications, and care recommendations, for emergency providers. Our objective is to describe the workflows and perceived utility of the provided emergency information forms (EIFs) in the acute medical management of CMC. METHODS: We sampled from two key stakeholder groups in the acute management of CMC: four focus groups with emergency medical providers from rural and urban settings and eight key informant interviews with parents/caregivers enrolled in an emergency medical management program for CMC. Transcripts were thematically analyzed in NVivo© by two coders using a content analysis approach. The thematic codes were combined into a codebook and revised the themes present through combining relevant themes and developing of sub-themes until they reached consensus. RESULTS: All parents/caregivers interviewed were enrolled in Project Austin and had an EIF. Emergency medical providers and parents/caregivers supported the usage of EIFs for CMC. Parents/caregivers also felt EIFs made emergency medical providers more prepared for their child. Providers identified that EIFs helped provide individualized care, however they were not confident the data was current and so felt unsure they could rely on the recommendations on the EIF. CONCLUSION: EIFs are an easy way to engage parents, caregivers, and emergency medical providers about the specifics of a care for CMC during an emergency. Timely updates and electronic access to EIFs could improve their value for medical providers.

Active vs Traditional Methods of Recruiting Children for a Clinical Trial in Rural Primary Care Clinics: A Cluster-Randomized Clinical Trial.

Importance: To our knowledge, there are no published randomized clinical trials of recruitment strategies. Rigorously evaluated successful recruitment strategies for children are needed. Objective: To evaluate the feasibility of 2 recruitment methods for enrolling rural children through primary care clinics to assess whether either or both methods are sufficiently effective for enrolling participants into a clinical trial of a behavioral telehealth intervention for children with overweight or obesity. Design, Setting, and Participants: This cluster-randomized clinical trial of 2 recruitment methods was conducted at 4 primary care clinics in 4 separate states. Each clinic used both recruitment methods in random order. Clinic eligibility criteria included at least 40% pediatric patients with Medicaid coverage and at least 100 potential participants. Eligibility criteria for children included a rural home address, age 6 to 11 years, and body mass index at or above the 85th percentile. Recruitment began February 3, 2020, and randomization of participants occurred on August 17, 2020. Data were analyzed from October 3, 2021, to April 21, 2022. Interventions: Two recruitment methods were assessed: the active method, for which a list of potential participants seen within the past year at each clinic was generated through the electronic health record and consecutively approached by research staff based on visit date to the clinic, and the traditional method, for which recruitment included posters, flyers, social media, and press release. Clinics were randomized to the order in which the 2 methods were implemented in 4-week periods, followed by a 4-week catch-up period using the method found most effective in previous periods. Main Outcomes and Measures: For each recruitment method, the number and proportion of randomized children among those who were approached was calculated. Results: A total of 104 participants were randomized (58 girls [55.8%]; mean age, 9.3 [95% CI, 9.0-9.6] years). Using the active method, 535 child-parent dyads were approached and 99 (18.5% [95% CI, 15.3%-22.1%]) were randomized. Using the traditional method, 23 caregivers expressed interest, and 5 (21.7% [95% CI, 7.5%-43.7%]) were randomized. All sites reached full enrollment using the active method and no sites achieved full enrollment using the traditional method. Mean time to full enrollment was 26.3 (range, 21.0-31.0) days. Conclusions and Relevance: This study supports the use of the active approach with local primary care clinics to recruit children with overweight and obesity from rural communities into clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04142034.

Duration of Antibiotic Therapy for Bacterial Meningitis in Young Infants: A Systematic Review.

BACKGROUND AND OBJECTIVES: Recommendations for parenteral antibiotic therapy duration in bacterial meningitis in young infants are based predominantly on expert consensus. Prolonged durations are generally provided for proven and suspected meningitis and are associated with considerable costs and risks. The objective of the study was to review the literature on the duration of parenteral antibiotic therapy and outcomes of bacterial meningitis in infants <3 months old. METHODS: We searched PubMed, Embase, and the Cochrane Library for publications until May 31, 2021. Eligible studies were published in English and included infants <3 months old with bacterial meningitis for which the route and duration of antibiotic therapy and data on at least 1 outcome (relapse rates, mortality, adverse events, duration of hospitalization, or neurologic sequelae) were reported. RESULTS: Thirty-two studies were included: 1 randomized controlled trial, 25 cohort studies, and 6 case series. The randomized controlled trial found no difference in treatment failure rates between 10 and 14 days of therapy. One cohort study concluded that antibiotic courses >21 days were not associated with improved outcomes as compared with shorter courses. The remaining studies had small sample sizes and/or did not stratify outcomes by therapy duration. Meta-analysis was not possible because of the heterogeneity of the treatments and reported outcomes. CONCLUSIONS: Rigorous, prospective clinical trial data are lacking to determine the optimal parenteral antibiotic duration in bacterial meningitis in young infants. Given the associated costs and risks, there is a pressing need for high-quality comparative effectiveness research to further study this question.

Improving pediatric COVID-19 vaccine uptake using an mHealth tool (MoVeUp): study protocol for a randomized, controlled trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccines demonstrate excellent effectiveness against infection, severe disease, and death. However, pediatric COVID-19 vaccination rates lag among individuals from rural and other medically underserved communities. The research objective of the current protocol is to determine the effectiveness of a vaccine communication mobile health (mHealth) application (app) on parental decisions to vaccinate their children against COVID-19. METHODS: Custodial parents/caregivers with ≥ 1 child eligible for COVID-19 vaccination who have not yet received the vaccine will be randomized to download one of two mHealth apps. The intervention app will address logistical and motivational barriers to pediatric COVID-19 vaccination. Participants will receive eight weekly push notifications followed by two monthly push notifications (cues to action) regarding vaccinating their child. Through branching logic, users will access customized content based on their locality, degree of rurality-urbanicity, primary language (English/Spanish), race/ethnicity, and child's age to address COVID-19 vaccine knowledge and confidence gaps. The control app will provide push notifications and information on general pediatric health and infection prevention and mitigation strategies based on recommendations from the American Academy of Pediatrics (AAP) and the Centers for Disease Control and Prevention (CDC). The primary outcome is the proportion of children who complete COVID-19 vaccination series. Secondary outcomes include the proportion of children who receive ≥ 1 dose of COVID-19 vaccine and changes in parent/caregiver scores from baseline to immediately post-intervention on the modified WHO SAGE Vaccine Hesitancy Scale adapted for the COVID-19 vaccine. DISCUSSION: The COVID-19 pandemic inflicts disproportionate harm on individuals from underserved communities, including those in rural settings. Maximizing vaccine uptake in these communities will decrease infection rates, severe illness, and death. Given that most US families from these communities use smart phones, mHealth interventions hold the promise of broad uptake. Bundling multiple mHealth vaccine uptake interventions into a single app may maximize the impact of deploying such a tool to increase COVID-19 vaccination. The new knowledge to be gained from this study will directly inform future efforts to increase COVID-19 vaccination rates across diverse settings and provide an evidentiary base for app-based vaccine communication tools that can be adapted to future vaccine-deployment efforts. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT05386355 . Registered on May 23, 2022.

Perceived Barriers to Clinical Trials Participation: A Survey of Pediatric Caregivers.

Introduction: Pediatric clinical trials are difficult to conduct, leading to off-label use of medication in children based on results of trials with adults. As a unique population, children deserve to have appropriately tested therapies. The purpose of this study was to evaluate pediatric caregivers' beliefs and perceived barriers to participation in clinical trials. Methods: The study was completed within the Sunflower Pediatric Clinical Trials Research Extension (SPeCTRE), an affiliate of the IDeA States Pediatric Clinical Trials Network (ISPCTN). This was a cross-sectional survey, adapted from the Pediatric Research Participation Questionnaire. A convenience sample of pediatric caregivers was recruited in three areas of a highly rural Midwestern state between 2017 and 2018. Results: A total of 159 caregivers completed surveys; the majority (72.3%) were previously familiar with clinical trials, but less than 20% had ever been invited to participate. Caregivers were willing to consider enrolling their child if a physician in whom they had high trust recommended the trials (H = 10.1, p = 0.04) and if there were perceived benefits, such as access to tests and medications not covered by insurance (correlation coefficient [CC] = 0.4, p < 0.01) and compensation for time and travel (CC = 0.3, p = 0.04). Conclusions: Trust in their physician highly influences likelihood of a caregiver consenting to have their child participate in a clinical trial. Therefore, to facilitate opportunities for children to participate in clinical trials, physicians need to be trained so they can offer trials locally. In addition, trials need to offer benefits, such as increased access to tests and medications as well as appropriate compensation.

Inhaled Corticosteroid Exposure in Hospitalized Infants with Bronchopulmonary Dysplasia.

OBJECTIVE: The objective of this paper was to determine inhaled corticosteroid (IC) use in infants with bronchopulmonary dysplasia (BPD), define the interhospital variation of IC administration to infants with BPD, and compare clinical, demographic, and hospital factors associated with IC use. STUDY DESIGN: Using the Pediatric Health Information System database, a retrospective multicenter cohort of 4,551 infants born at <32 weeks of gestation with developing BPD was studied. The clinical, demographic, and hospital characteristics of infants exposed and not exposed to ICs were compared. RESULTS: IC use varied markedly between hospitals, ranging from 0 to 66% of infants with BPD exposed to ICs. Increased annual BPD census was not associated with IC use. In total, 25% (1,144 out of 4,551) of patients with BPD and 43% (536 out of 1,244) of those with severe BPD received ICs. Increased IC exposure was associated with lower birth weight and gestational age, days on respiratory support, need for positive pressure ventilation at 36-week postmenstrual age, need for tracheostomy, and increased use of systemic steroids, bronchodilators, and diuretics. CONCLUSION: IC exposure is common in infants with BPD, with substantial interhospital variability. IC use was associated with more severe disease. Hospital experience did not account for the wide variability in IC use by the hospital. Further research into the effects of ICs use is urgently needed to help guide their use in this vulnerable population. KEY POINTS: · The risks and benefits of IC use in infants with BPD are incompletely understood.. · IC use is common in infants with BPD (25%) and severe BPD (43%) varies widely by hospital (0-66% of patients with BPD received an IC).. · Hospital experience did not account for the wide interhospital variation in IC use..

Prevalence of Invasive Bacterial Infections in Well-Appearing, Febrile Infants.

BACKGROUND AND OBJECTIVES: Data on invasive bacterial infection (IBI), defined as bacteremia and/or bacterial meningitis, in febrile infants aged <60 days old primarily derive from smaller, dated studies conducted at large, university-affiliated medical centers. Our objective with the current study was to determine current prevalence and epidemiology of IBI from a contemporary, national cohort of well-appearing, febrile infants at university-affiliated and community-based hospitals. PATIENTS AND METHODS: Retrospective review of well-appearing, febrile infants aged 7 to 60 days was performed across 31 community-based and 44 university-affiliated centers from September 2015 to December 2017. Blood and cerebrospinal fluid bacterial culture results were reviewed and categorized by using a priori criteria for pathogenic organisms. Prevalence estimates and subgroup comparisons were made by using descriptive statistics. RESULTS: A total of 10 618 febrile infants met inclusion criteria; cerebrospinal fluid and blood cultures were tested from 6747 and 10 581 infants, respectively. Overall, meningitis prevalence was 0.4% (95% confidence interval [CI]: 0.2-0.5); bacteremia prevalence was 2.4% (95% CI: 2.1-2.7). Neonates aged 7 to 30 days had significantly higher prevalence of bacteremia, as compared with infants in the second month of life. IBI prevalence did not differ between community-based and university-affiliated hospitals (2.7% [95% CI: 2.3-3.1] vs 2.1% [95% CI: 1.7-2.6]). Escherichia coli and Streptococcus agalactiae were the most commonly identified organisms. CONCLUSIONS: This contemporary study of well-appearing, febrile infants supports previous epidemiological estimates of IBI prevalence and suggests that the prevalence of IBI may be similar among community-based and university-affiliated hospitals. These results can be used to aid future clinical guidelines and prediction tool development.

Best Practices for Conducting Clinical Trials With Indigenous Children in the United States.

We provide guidance for conducting clinical trials with Indigenous children in the United States. We drew on extant literature and our experience to describe 3 best practices for the ethical and effective conduct of clinical trials with Indigenous children. Case examples of pediatric research conducted with American Indian, Alaska Native, and Native Hawaiian communities are provided to illustrate these practices. Ethical and effective clinical trials with Indigenous children require early and sustained community engagement, building capacity for Indigenous research, and supporting community oversight and ownership of research. Effective engagement requires equity, trust, shared interests, and mutual benefit among partners over time. Capacity building should prioritize developing Indigenous researchers. Supporting community oversight and ownership of research means that investigators should plan for data-sharing agreements, return or destruction of data, and multiple regulatory approvals. Indigenous children must be included in clinical trials to reduce health disparities and improve health outcomes in these pediatric populations. Establishment of the Environmental Influences on Child Health Outcomes Institutional Development Award States Pediatric Clinical Trials Network (ECHO ISPCTN) in 2016 creates a unique and timely opportunity to increase Indigenous children's participation in state-of-the-art clinical trials.

Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities: A Randomized Clinical Trial.

Importance: Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19. Objective: To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. Design, Setting, and Participants: Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57. Interventions: Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200 mg (n = 588), or placebo (n = 587). Main Outcomes and Measures: The primary outcome was incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection. Results: The prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years; 722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5% vs 15.2%; odds ratio, 0.43 [95% CI, 0.28-0.68]; P < .001; absolute risk difference, -6.6 [95% CI, -10.7 to -2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57; all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo). Conclusions and Relevance: Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT04497987.

Rationale and protocol for a cluster randomized, cross-over trial of recruitment methods of rural children in primary care clinics: A feasibility study of a pediatric weight control trial in the IDeA States Pediatric Clinical Trials Network.

A significant percentage of clinical trials fail due to poor recruitment. Despite this, few studies exist to evaluate clinical trial recruitment strategies using a randomized approach in any population, and none exist to test recruitment strategies for trials involving children or rural populations. For clinical trials focused on weight control, evaluating retention and dose are extremely important, as poor retention can lead to biased samples and existing research shows that dose (i.e. contact hours) is directly related to patient outcome. Finally, adequacy of blinding of assessment teams is rarely reported in pediatric trials, and unblinded staff may be more likely to inadvertently bias findings. Therefore, in this feasibility trial we aim to use rigorous clinical trial methodology to assess the effectiveness of two different recruitment strategies, as well as test retention, dose, and blinding. Specifically, we describe the rationale, design, and planned implementation of a feasibility study of a rural pediatric obesity treatment trial that will be implemented in four medical clinics in four states affiliated with the Environmental influences on Child Health Outcomes IDeA States Pediatric Clinical Trials Network (ECHO ISPCTN). The primary objective is to assess recruitment rate for consecutive recruitment (approaching recently seen eligible patients in consecutive order by date seen) compared to traditional recruitment (such as posters, flyers, tear-offs), as well as to assess retention, dose, and blinding. If successful, this trial will support the implementation of a large multi-state trial directed at addressing obesity in rural children and their families recruited from their primary care clinics. Registered with ClinicalTrials.gov NCT ID NCT04142034.

Racial and ethnic disparities in bronchiolitis management in freestanding children's hospitals.

OBJECTIVE: Variation in bronchiolitis management by race and ethnicity within emergency departments (EDs) has been described in single-center and prospective studies, but large-scale assessments across EDs and inpatient settings are lacking. Our objective is to describe the association between race and ethnicity and bronchiolitis management across 37 U.S. freestanding children's hospitals from 2015 to 2018. METHODS: Using the Pediatric Health Information System, we analyzed ED and inpatient visits from November 2015 to November 2018 of children with bronchiolitis 3 to 24 months old. Rates of use for specific diagnostic tests and therapeutic measures were compared across the following race/ethnicity categories: 1) non-Hispanic White (NHW), 2) non-Hispanic Black (NHB), 3) Hispanic, and 4) other. The subanalyses of ED patients only and children < 1 year old were performed. Mixed-effect logistic regression was performed to compare the adjusted odds of receiving specific test/treatment using NHW children as the reference group. RESULTS: A total of 134,487 patients met inclusion criteria (59% male, 28% NHB, 26% Hispanic). Adjusted analysis showed that NHB children had higher odds of receiving medication associated with asthma (odds ratio [OR] = 1.27, 95% confidence interval [CI] = 1.22 to 1.32) and lower odds of receiving diagnostic tests (blood cultures, complete blood counts, viral testing, chest x-rays; OR = 0.78, 95% CI = 0.75 to 0.81) and antibiotics (OR = 0.58, 95% CI = 0.52 to 0.64) than NHW children. Hispanic children had lower odds of receiving diagnostic testing (OR = 0.94, 95% CI = 0.90 to 0.98), asthma-associated medication (OR = 0.92, 95% CI = 0.88 to 0.96), and antibiotics (OR = 0.74, 95% CI = 0.66 to 0.82) compared to NHW children. CONCLUSION: NHB children more often receive corticosteroid and bronchodilator therapies; NHW children more often receive antibiotics and chest radiography. Given that current guidelines generally recommend supportive care with limited diagnostic testing and medical intervention, these findings among NHB and NHW children represent differing patterns of overtreatment. The underlying causes of these patterns require further investigation.

Comparing Patterns of Care for Febrile Infants at Community and University-Affiliated Hospitals.

OBJECTIVES: Most children in the United States receive treatment in community hospitals, but descriptions of clinical practice patterns in pediatric care in this setting are lacking. Our objectives were to compare clinical practice patterns primarily between community and university-affiliated hospitals and secondarily by number of pediatric beds before and during participation in a national practice standardization project. METHODS: We performed a retrospective secondary analysis on data from 126 hospitals that participated in the American Academy of Pediatrics' Value in Inpatient Pediatrics Reducing Excessive Variability in the Infant Sepsis Evaluation project, a national quality improvement project conducted to improve care for well-appearing febrile infants aged 7 to 60 days. Four use measures were compared by hospital type and by number of non-ICU pediatric beds. RESULTS: There were no differences between community and university-affiliated hospitals in the odds of hospital admission, average length of stay, or odds of cerebrospinal fluid culture. The odds of chest radiograph at community hospitals were higher only during the baseline period. There were no differences by number of pediatric beds in odds of admission or average length of stay. For hospitals with ≤30 pediatric beds, the odds of chest radiograph were higher and the odds of cerebrospinal fluid culture were lower compared with hospitals >50 beds during both study periods. CONCLUSIONS: In many key aspects, care for febrile infants does not differ between community and university-affiliated hospitals. Clinical practice may differ more by number of pediatric beds.

Antibiotic Regimens and Associated Outcomes in Children Hospitalized With Staphylococcal Scalded Skin Syndrome.

BACKGROUND: Controversy exists regarding the optimal antibiotic regimen for use in hospitalized children with staphylococcal scalded skin syndrome (SSSS). Various regimens may confer toxin suppression and/or additional coverage for methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant S aureus (MRSA). OBJECTIVES: To describe antibiotic regimens in hospitalized children with SSSS and examine the association between antistaphylococcal antibiotic regimens and patient outcomes. DESIGN/METHODS: Retrospective cohort study of children hospitalized with SSSS using the Pediatric Health Information System database (2011-2016). Children who received clindamycin monotherapy, clindamycin plus MSSA coverage (eg, nafcillin), or clindamycin plus MRSA coverage (eg, vancomycin) were included. The primary outcome was hospital length of stay (LOS); secondary outcomes were treatment failure and cost. Generalized linear mixed-effects models were used to compare outcomes among antibiotic groups. RESULTS: Of 1,259 children included, 828 children received the most common antistaphylococcal antibiotic regimens: clindamycin monotherapy (47%), clindamycin plus MSSA coverage (33%), and clindamycin plus MRSA coverage (20%). Children receiving clindamycin plus MRSA coverage had higher illness severity (44%) compared with clindamycin monotherapy (28%) and clindamycin plus MSSA (32%) (P =.001). In adjusted analyses, LOS and treatment failure did not differ among the 3 regimens (P =.42 and P =.26, respectively). Cost was significantly lower for children receiving clindamycin monotherapy and highest in those receiving clindamycin plus MRSA coverage (mean, $4,839 vs $5,348, respectively; P <.001). CONCLUSIONS: In children with SSSS, the addition of MSSA or MRSA coverage to clindamycin monotherapy was associated with increased cost and no incremental difference in clinical outcomes.

Effect of Combined Clinical Practice Guideline and Electronic Order Set Implementation on Febrile Infant Evaluation and Management.

OBJECTIVE: Management of febrile infants 60 days and younger for suspected serious infection varies widely. Clinical practice guidelines (CPGs) are intended to improve clinician adherence to evidence-based practices. In 2011, a CPG for managing febrile infants was implemented in an urban children's hospital with simultaneous release of an electronic order set and algorithm to guide clinician decisions for managing infants for suspected serious bacterial infection. The objective of the present study was to determine the association of CPG implementation with order set use, clinical practices, and clinical outcomes. METHODS: Records of febrile infants 60 days and younger from February 1, 2009, to January 31, 2013, were retrospectively reviewed. Clinical documentation, order set use, clinical management practices, and outcomes were compared pre-CPG and post-CPG release. RESULTS: In total, 1037 infants pre-CPG and 930 infants post-CPG implementation were identified. After CPG release, more infants 29 to 60 days old underwent lumbar puncture (56% vs 62%, P = 0.02). Overall antibiotic use and duration of antibiotic use decreased for infants 29 to 60 days (57% vs 51%, P = 0.02). Blood culture and urine culture obtainment remained unchanged for older infants. Diagnosed infections, hospital readmissions, and length of stay were unchanged. Electronic order sets were used in 80% of patient encounters. CONCLUSIONS: Antibiotic use and lumbar puncture performance modestly changed in accordance with CPG recommendations provided in the electronic order set and algorithm, suggesting that the presence of embedded prompts may affect clinician decision-making. Our results highlight the potential usefulness of these decision aids to improve adherence to CPG recommendations.

Inhaled bronchodilator exposure in the management of bronchopulmonary dysplasia in hospitalized infants.

OBJECTIVE: To determine clinical, demographic, and hospital factors associated with inhaled bronchodilator (IB) use in infants with bronchopulmonary dysplasia (BPD) and specifically severe BPD. STUDY DESIGN: Retrospective multicenter cohort study of 4986 infants born <32 weeks gestation with developing BPD at 28 days of life. We used the Pediatric Health Information System database to compare hospital experience and the demographic and clinical characteristics of infants exposed and not exposed to IBs. RESULTS: Twenty-five percent of BPD patients (1224/4986) and 48% of severe BPD patients (664/1390) received IBs. IB exposure was higher in infants with the tracheostomy, prolonged steroid and diuretic exposure, and longer duration of respiratory support. IB use varied markedly between hospitals (0-59%). Average annual BPD census was not associated with IB use. CONCLUSION: Bronchodilator exposure is common in BPD patients with substantial variability in its use. Hospital experience did not account for the between-hospital variation in practice.

Targeted Amino Acid Substitution Overcomes Scale-Up Challenges with the Human C5a-Derived Decapeptide Immunostimulant EP67.

EP67 is a second-generation, human C5a-derived decapeptide agonist of C5a receptor 1 (C5aR1/CD88) that selectively activates mononuclear phagocytes over neutrophils to potentiate protective innate and adaptive immune responses while potentially minimizing neutrophil-mediated toxicity. Pro7 and N-methyl-Leu8 (Me-Leu8) amino acid residues within EP67 likely induce backbone structural changes that increase potency and selective activation of mononuclear phagocytes over neutrophils versus first-generation EP54. The low coupling efficiency between Pro7 and Me-Leu8 and challenging purification by HPLC, however, greatly increase scale-up costs of EP67 for clinical use. Thus, the goal of this study was to determine whether replacing Pro7 and/or Me-Leu8 with large-scale amenable amino acid residues predicted to induce similar structural changes (cyclohexylalanine7 and/or leucine8) sufficiently preserves EP67 activity in primary human mononuclear phagocytes and neutrophils. We found that EP67 analogues had similar potency, efficacy, and selective activation of mononuclear phagocytes over neutrophils. Thus, replacing Pro7 and/or Me-Leu8 with large-scale amenable amino acid residues predicted to induce similar structural changes is a suitable strategy to overcome scale-up challenges with EP67.