OBJECTIVES:  Clinical decision support (CDS) has promise for the implementation of antimicrobial stewardship programs (ASPs) in the emergency department (ED). We sought to assess the usability of a newly developed automated CDS to improve guideline-adherent antibiotic prescribing for pediatric community-acquired pneumonia (CAP) and urinary tract infection (UTI).

METHODS:  We conducted comparative usability testing between an automated, prototype CDS-enhanced discharge order set and standard order set, for pediatric CAP and UTI antibiotic prescribing. After an extensive user-centered design process, the prototype CDS was integrated into the electronic health record, used passive activation, and embedded locally adapted prescribing guidelines. Participants were randomized to interact with three simulated ED scenarios of children with CAP or UTI, across both systems. Measures included task completion, decision-making and usability errors, clinical actions (order set use and correct antibiotic selection), as well as objective measures of system usability, utility, and workload using the National Aeronautics and Space Administration Task Load Index (NASA-TLX). The prototype CDS was iteratively refined to optimize usability and workflow.

RESULTS:  Usability testing in 21 ED clinical providers demonstrated that, compared to the standard order sets, providers preferred the prototype CDS, with improvements in domains such as explanations of suggested antibiotic choices ( < 0.001) and provision of additional resources on antibiotic prescription ( < 0.001). Simulated use of the CDS also led to overall improved guideline-adherent prescribing, with a 31% improvement for CAP. A trend was present toward absolute workload reduction. Using the NASA-TLX, workload scores for the current system were median 26, interquartile ranges (IQR): 11 to 41 versus median 25, and IQR: 10.5 to 39.5 for the CDS system ( = 0.117).

CONCLUSION:  Our CDS-enhanced discharge order set for ED antibiotic prescribing was strongly preferred by users, improved the accuracy of antibiotic prescribing, and trended toward reduced provider workload. The CDS was optimized for impact on guideline-adherent antibiotic prescribing from the ED and end-user acceptability to support future evaluative trials of ED ASPs.

BACKGROUND: The absence of consensus for outcomes in pediatric antibiotic trials is a major barrier to research harmonization and clinical translation. We sought to develop expert consensus on study outcomes for clinical trials of children with mild community-acquired pneumonia (CAP).

METHODS: Applying the Delphi method, a multispecialty expert panel ranked the importance of various components of clinical response and treatment failure outcomes in children with mild CAP for use in research. During Round 1, panelists suggested additional outcomes in open-ended responses that were added to subsequent rounds of consensus building. For Rounds 2 and 3, panelists were provided their own prior responses and summary statistics for each item in the previous round. The consensus was defined by >70% agreement.

RESULTS: The expert panel determined that response to and failure of treatment should be addressed at a median of 3 days after initiation. Complete or substantial improvement in fever, work of breathing, dyspnea, tachypnea when afebrile, oral intake, and activity should be included as components of adequate clinical response outcomes. Clinical signs and symptoms including persistent or worsening fever, work of breathing, and reduced oral intake should be included in treatment failure outcomes. Interventions including receipt of parenteral fluids, supplemental oxygen, need for high-flow nasal cannula oxygen therapy, and change in prescription of antibiotics should also be considered in treatment failure outcomes.

CONCLUSIONS: Clinical response and treatment failure outcomes determined by the consensus of this multidisciplinary expert panel can be used for pediatric CAP studies to provide objective data translatable to clinical practice.

OBJECTIVE: To determine the prevalence of bacteremia and/or bacterial meningitis in febrile infants ≤60 days of age with positive urinalysis (UA) results.

METHODS: Secondary analysis of a prospective observational study of noncritical febrile infants ≤60 days between 2011 and 2019 conducted in the Pediatric Emergency Care Applied Research Network emergency departments. Participants had temperatures ≥38°C and were evaluated with blood cultures and had UAs available for analysis. We report the prevalence of bacteremia and bacterial meningitis in those with and without positive UA results.

RESULTS: Among 7180 infants, 1090 (15.2%) had positive UA results. The risk of bacteremia was higher in those with positive versus negative UA results (63/1090 [5.8%] vs 69/6090 [1.1%], difference 4.7% [3.3% to 6.1%]). There was no difference in the prevalence of bacterial meningitis in infants ≤28 days of age with positive versus negative UA results (∼1% in both groups). However, among 697 infants aged 29 to 60 days with positive UA results, there were no cases of bacterial meningitis in comparison to 9 of 4153 with negative UA results (0.2%, difference -0.2% [-0.4% to -0.1%]). In addition, there were no cases of bacteremia and/or bacterial meningitis in the 148 infants ≤60 days of age with positive UA results who had the Pediatric Emergency Care Applied Research Network low-risk blood thresholds of absolute neutrophil count <4 × 103 cells/mm3 and procalcitonin <0.5 ng/mL.

CONCLUSIONS: Among noncritical febrile infants ≤60 days of age with positive UA results, there were no cases of bacterial meningitis in those aged 29 to 60 days and no cases of bacteremia and/or bacterial meningitis in any low-risk infants based on low-risk blood thresholds in both months of life. These findings can guide lumbar puncture use and other clinical decision making.

Although neonatal herpes simplex virus (HSV) causes significant morbidity, utilization of the cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) test remains variable. Our objective was to examine the association of CSF HSV PCR testing with length of stay (LOS) in a 20-center retrospective cohort of hospitalized infants aged ≤60 days undergoing evaluation for meningitis after adjustment for patient-level factors and clustering by center. Of 20,496 eligible infants, 7,399 (36.1%) had a CSF HSV PCR test performed, and 46 (0.6% of those tested) had a positive test. Infants who had a CSF HSV PCR test performed had a 23% longer hospital LOS (incident rate ratio 1.23; 95% CI: 1.14-1.33). Targeted CSF HSV PCR testing may mitigate the impact on LOS for low-risk infants.

<p><strong>OBJECTIVES: </strong>To determine the prevalence of invasive bacterial infections (IBIs) and adverse events in afebrile infants with acute otitis media (AOM).</p>

<p><strong>METHODS: </strong>We conducted a 33-site cross-sectional study of afebrile infants ≤90 days of age with AOM seen in emergency departments from 2007 to 2017. Eligible infants were identified using emergency department diagnosis codes and confirmed by chart review. IBIs (bacteremia and meningitis) were determined by the growth of pathogenic bacteria in blood or cerebrospinal fluid (CSF) culture. Adverse events were defined as substantial complications resulting from or potentially associated with AOM. We used generalized linear mixed-effects models to identify factors associated with IBI diagnostic testing, controlling for site-level clustering effect.</p>

<p><strong>RESULTS: </strong>Of 5270 infants screened, 1637 met study criteria. None of the 278 (0%; 95% confidence interval [CI]: 0%-1.4%) infants with blood cultures had bacteremia; 0 of 102 (0%; 95% CI: 0%-3.6%) with CSF cultures had bacterial meningitis; 2 of 645 (0.3%; 95% CI: 0.1%-1.1%) infants with 30-day follow-up had adverse events, including lymphadenitis (1) and culture-negative sepsis (1). Diagnostic testing for IBI varied across sites and by age; overall, 278 (17.0%) had blood cultures, and 102 (6.2%) had CSF cultures obtained. Compared with infants 0 to 28 days old, older infants were less likely to have blood cultures ( &lt; .001) or CSF cultures ( &lt; .001) obtained.</p>

<p><strong>CONCLUSION: </strong>Afebrile infants with clinician-diagnosed AOM have a low prevalence of IBIs and adverse events; therefore, outpatient management without diagnostic testing may be reasonable.</p>

<p><strong>OBJECTIVES: </strong>To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection.</p>

<p><strong>METHODS: </strong>In this 23-center nested case-control study, we matched 149 infants with HSV to 1340 controls; all were ≤60 days old and had cerebrospinal fluid obtained within 24 hours of presentation or had HSV detected. The primary and secondary outcomes were invasive (disseminated or central nervous system) or any HSV infection, respectively.</p>

<p><strong>RESULTS: </strong>Of all infants included , 90 (60.4%) had invasive and 59 (39.6%) had skin, eyes, and mouth disease. Predictors independently associated with invasive HSV included younger age (adjusted odds ratio [aOR]: 9.1 [95% confidence interval (CI): 3.4-24.5] &lt;14 and 6.4 [95% CI: 2.3 to 17.8] 14-28 days, respectively, compared with &gt;28 days), prematurity (aOR: 2.3, 95% CI: 1.1 to 5.1), seizure at home (aOR: 6.1, 95% CI: 2.3 to 16.4), ill appearance (aOR: 4.2, 95% CI: 2.0 to 8.4), abnormal triage temperature (aOR: 2.9, 95% CI: 1.6 to 5.3), vesicular rash (aOR: 54.8, (95% CI: 16.6 to 180.9), thrombocytopenia (aOR: 4.4, 95% CI: 1.6 to 12.4), and cerebrospinal fluid pleocytosis (aOR: 3.5, 95% CI: 1.2 to 10.0). These variables were transformed to derive the HSV risk score (point range 0-17). Infants with invasive HSV had a higher median score (6, interquartile range: 4-8) than those without invasive HSV (3, interquartile range: 1.5-4), with an area under the curve for invasive HSV disease of 0.85 (95% CI: 0.80-0.91). When using a cut-point of ≥3, the HSV risk score had a sensitivity of 95.6% (95% CI: 84.9% to 99.5%), specificity of 40.1% (95% CI: 36.8% to 43.6%), and positive likelihood ratio 1.60 (95% CI: 1.5 to 1.7) and negative likelihood ratio 0.11 (95% CI: 0.03 to 0.43).</p>

<p><strong>CONCLUSIONS: </strong>A novel HSV risk score identified infants at extremely low risk for invasive HSV who may not require routine testing or empirical treatment.</p>

<p><strong>BACKGROUND: </strong>A "champagne tap" is a lumbar puncture with no cerebrospinal fluid (CSF) red blood cells (RBCs). Clinicians disagree whether the absence of CSF white blood cells (WBCs) is also required.</p>

<p><strong>AIMS: </strong>As supervising providers frequently reward trainees after a champagne tap, we investigated how varying the definition impacted the frequency of trainee accolades.</p>

<p><strong>MATERIALS &amp; METHODS: </strong>We performed a secondary analysis of a retrospective cross-sectional study of infants ≤60&nbsp;days of age who had a CSF culture performed in the emergency department (ED) at one of 20 centers participating in a Pediatric Emergency Medicine Collaborative Research Committee (PEM CRC) endorsed study. Our primary outcomes were a champagne tap defined by either a CSF RBC count of 0&nbsp;cells/mm regardless of CSF WBC count or both CSF RBC and WBC counts of 0&nbsp;cells/mm .</p>

<p><strong>RESULTS: </strong>Of the 23,618 eligible encounters, 20,358 (86.2%) had both a CSF RBC and WBC count obtained. Overall, 3,147 (13.3%) had a CSF RBC count of 0&nbsp;cells/mm and 377 (1.6%) had both CSF WBC and RBC counts of 0&nbsp;cells/mm (relative rate 8.35, 95% confidence interval 7.51 to 9.27).</p>

<p><strong>CONCLUSIONS: </strong>In infants, a lumbar puncture with a CSF RBC count of 0&nbsp;cells/mm regardless of the CSF WBC count occurred eight-times more frequently than one with both CSF WBC and RBC counts of 0&nbsp;cells/mm . A broader champagne tap definition would allow more frequent recognition of procedural success, with the potential to foster a supportive community during medical training, potentially protecting against burnout.</p>

<p><strong>OBJECTIVES: </strong>To determine age-specific reference values and quantify age-related changes for cerebrospinal fluid (CSF) white blood cell (WBC) counts and protein and glucose concentrations in infants ≤60 days of age.</p>

<p><strong>METHODS: </strong>This multicenter, cross-sectional study included infants ≤60 days old with CSF cultures and complete CSF profiles obtained within 24 hours of presentation. Those with conditions suspected or known to cause abnormal CSF parameters (eg, meningitis) and those with a hospital length of stay of &gt;72 hours were excluded. Reference standards were determined for infants ≤28 days of age and 29 to 60 days of age by using the third quartile +1.5 interquartile range for WBC and protein and the first quartile -1.5 interquartile range for glucose. CSF parameter centile curves based on age were calculated by using the LMST method.</p>

<p><strong>RESULTS: </strong>A total of 7766 patients were included. CSF WBC counts were higher in infants ≤28 days of age (upper bound: 15 cells/mm) than in infants 29 to 60 days of age (upper bound: 9 cells/mm;&lt; .001). CSF protein concentrations were higher in infants ≤28 days of age (upper bound: 127 mg/dL) than in infants 29 to 60 days of age (upper bound: 99 mg/dL;&lt; .001). CSF glucose concentrations were lower in infants ≤28 days of age (lower bound: 25 mg/dL) than in infants 29 to 60 days of age (lower bound: 27 mg/dL;&lt; .001).</p>

<p><strong>CONCLUSIONS: </strong>The age-specific CSF WBC count, protein concentration, and glucose concentration reference values identified in this large, multicenter cohort of infants can be used to interpret the results of lumbar puncture in infants ≤60 days of age.</p>

<p><strong>BACKGROUND: </strong>Although neonatal herpes simplex virus (HSV) is a potentially devastating infection requiring prompt evaluation and treatment, large-scale assessments of the frequency in potentially infected infants have not been performed.</p>

<p><strong>METHODS: </strong>We performed a retrospective cross-sectional study of infants ≤60 days old who had cerebrospinal fluid culture testing performed in 1 of 23 participating North American emergency departments. HSV infection was defined by a positive HSV polymerase chain reaction or viral culture. The primary outcome was the proportion of encounters in which HSV infection was identified. Secondary outcomes included frequency of central nervous system (CNS) and disseminated HSV, and HSV testing and treatment patterns.</p>

<p><strong>RESULTS: </strong>Of 26 533 eligible encounters, 112 infants had HSV identified (0.42%, 95% confidence interval [CI]: 0.35%-0.51%). Of these, 90 (80.4%) occurred in weeks 1 to 4, 10 (8.9%) in weeks 5 to 6, and 12 (10.7%) in weeks 7 to 9. The median age of HSV-infected infants was 14 days (interquartile range: 9-24 days). HSV infection was more common in 0 to 28-day-old infants compared with 29- to 60-day-old infants (odds ratio 3.9; 95% CI: 2.4-6.2). Sixty-eight (0.26%, 95% CI: 0.21%-0.33%) had CNS or disseminated HSV. The proportion of infants tested for HSV (35%; range 14%-72%) and to whom acyclovir was administered (23%; range 4%-53%) varied widely across sites.</p>

<p><strong>CONCLUSIONS: </strong>An HSV infection was uncommon in young infants evaluated for CNS infection, particularly in the second month of life. Evidence-based approaches to the evaluation for HSV in young infants are needed.</p>

<p>Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T&nbsp;cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T&nbsp;cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for&nbsp;different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection. Network analysis linked changes to severity of infection, asthma, sex, and age. An influenza pediatric signature (IPS) distinguished acute influenza from other ARTIs and outperformed other influenza prediction gene lists. The IPS allowed a deeper investigation of the connection between transcriptional alterations and clinical characteristics of acute illness, including age-based differences in circuits connecting the STAT1/2 pathway to ISGs. A CD8 T&nbsp;cell-focused systems immunology approach in pediatrics identified age-based alterations in ARTI host response pathways.</p>