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.

BACKGROUND: Despite the increased availability of diagnostic tests for respiratory viruses, their clinical utility for children with community-acquired pneumonia (CAP) remains uncertain.

OBJECTIVE: To identify patterns of respiratory virus testing across children's hospitals prior to the COVID-19 pandemic and to determine whether hospital-level rates of viral testing were associated with clinical outcomes.

DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective cohort study of children hospitalized for CAP at 19 children's hospitals in the United States from 2010-2019.

MAIN OUTCOMES AND MEASURES: Using a novel method to identify the performance of viral testing, we assessed time trends in the use of viral tests, both overall and stratified by testing method. Adjusted proportions of encounters with viral testing were compared across hospitals and were correlated with length of stay, antibiotic and oseltamivir use, and performance of ancillary laboratory testing.

RESULTS: There were 46,038 hospitalizations for non-severe CAP among children without complex chronic conditions. The proportion with viral testing increased from 38.8% to 44.2% during the study period (p < .001). Molecular testing increased (27.2% to 40.0%, p < .001) and antigen testing decreased (33.2% to 7.8%, p < .001). Hospital-specific adjusted proportions of testing ranged from 10.0% to 83.5% and were not associated with length of stay, antibiotic use, or antiviral use. Hospitals that performed more viral testing did not have lower rates of ancillary laboratory testing.

CONCLUSIONS: Viral testing practices varied widely across children's hospitals and were not associated with clinically important process or outcome measures. Viral testing may not influence clinical management for many children hospitalized with CAP.

BACKGROUND: Limited data exist to inform antibiotic selection among people with cystic fibrosis (CF) with airway infection by multiple CF-related microorganisms. This study aimed to determine among children with CF co-infected with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (Pa) if the addition of anti-MRSA antibiotics to antipseudomonal antibiotic treatment for pulmonary exacerbations (PEx) would be associated with improved clinical outcomes compared with antipseudomonal antibiotics alone.

METHODS: Retrospective cohort study using data from the CF Foundation Patient Registry-Pediatric Health Information System linked dataset. The odds of returning to baseline lung function and having a subsequent PEx requiring intravenous antibiotics were compared between PEx treated with anti-MRSA and antipseudomonal antibiotics and those treated with antipseudomonal antibiotics alone, adjusting for confounding by indication using inverse probability of treatment weighting.

RESULTS: 943 children with CF co-infected with MRSA and Pa contributed 2,989 PEx for analysis. Of these, 2,331 (78%) PEx were treated with both anti-MRSA and antipseudomonal antibiotics and 658 (22%) PEx were treated with antipseudomonal antibiotics alone. Compared with PEx treated with antipseudomonal antibiotics alone, the addition of anti-MRSA antibiotics to antipseudomonal antibiotic therapy was not associated with a higher odds of returning to ≥90% or ≥100% of baseline lung function or a lower odds of future PEx requiring intravenous antibiotics.

CONCLUSIONS: Children with CF co-infected with MRSA and Pa may not benefit from the addition of anti-MRSA antibiotics for PEx treatment. Prospective studies evaluating optimal antibiotic selection strategies for PEx treatment are needed to optimize clinical outcomes following PEx treatment.

OBJECTIVES: To help guide empiric treatment of infants ≤60 days old with suspected invasive bacterial infection by describing pathogens and their antimicrobial susceptibilities.

STUDY DESIGN: Cross-sectional study of infants ≤60 days old with invasive bacterial infection (bacteremia and/or bacterial meningitis) evaluated in the emergency departments of 11 children's hospitals between July 1, 2011 and June 30, 2016. Each site's microbiology laboratory database or electronic medical record system was queried to identify infants from whom a bacterial pathogen was isolated from either blood or cerebrospinal fluid. Medical records of these infants were reviewed to confirm the presence of a pathogen and to obtain demographic, clinical, and laboratory data.

RESULTS: Of the 442 infants with invasive bacterial infection, 353 (79.9%) had bacteremia without meningitis, 64 (14.5%) had bacterial meningitis with bacteremia, and 25 (5.7%) had bacterial meningitis without bacteremia. The peak number of cases of invasive bacterial infection occurred in the second week of life; 364 (82.4%) infants were febrile. Group B streptococcus was the most common pathogen identified (36.7%), followed by Escherichia coli (30.8%), Staphylococcus aureus (9.7%), and Enterococcus spp (6.6%). Overall, 96.8% of pathogens were susceptible to ampicillin plus a third-generation cephalosporin, 96.0% to ampicillin plus gentamicin, and 89.2% to third-generation cephalosporins alone.

CONCLUSIONS: For most infants ≤60 days old evaluated in a pediatric emergency department for suspected invasive bacterial infection, the combination of ampicillin plus either gentamicin or a third-generation cephalosporin is an appropriate empiric antimicrobial treatment regimen. Of the pathogens isolated from infants with invasive bacterial infection, 11% were resistant to third-generation cephalosporins alone.

OBJECTIVES: We sought to determine the time to pathogen detection in blood and cerebrospinal fluid (CSF) for infants ≤60 days old with bacteremia and/or bacterial meningitis and to explore whether time to pathogen detection differed for non-ill-appearing and ill-appearing infants.

METHODS: We included infants ≤60 days old with bacteremia and/or bacterial meningitis evaluated in the emergency departments of 10 children's hospitals between July 1, 2011, and June 30, 2016. The microbiology laboratories at each site were queried to identify infants in whom a bacterial pathogen was isolated from blood and/or CSF. Medical records were then reviewed to confirm the presence of a pathogen and to extract demographic characteristics, clinical appearance, and the time to pathogen detection.

RESULTS: Among 360 infants with bacteremia, 316 (87.8%) pathogens were detected within 24 hours and 343 (95.3%) within 36 hours. A lower proportion of non-ill-appearing infants with bacteremia had a pathogen detected on blood culture within 24 hours compared with ill-appearing infants (85.0% vs 92.9%, respectively; = .03). Among 62 infants with bacterial meningitis, 55 (88.7%) pathogens were detected within 24 hours and 59 (95.2%) were detected within 36 hours, with no difference based on ill appearance.

CONCLUSIONS: Among infants ≤60 days old with bacteremia and/or bacterial meningitis, pathogens were commonly identified from blood or CSF within 24 and 36 hours. However, clinicians must weigh the potential for missed bacteremia in non-ill-appearing infants discharged within 24 hours against the overall low prevalence of infection.

BACKGROUND: Differences among febrile infant institutional clinical practice guidelines (CPGs) may contribute to practice variation and increased healthcare costs.

OBJECTIVE: Determine the association between pediatric emergency department (ED) CPGs and laboratory testing, hospitalization, ceftriaxone use, and costs in febrile infants.

DESIGN: Retrospective cross-sectional study in 2013.

SETTING: Thirty-three hospitals in the Pediatric Health Information System.

PATIENTS: Infants aged ≤56 days with a diagnosis of fever.

EXPOSURES: The presence and content of ED-based febrile infant CPGs assessed by electronic survey.

MEASUREMENTS: Using generalized estimating equations, we evaluated the association between CPG recommendations and rates of urine, blood, cerebrospinal fluid (CSF) testing, hospitalization, and ceftriaxone use at ED discharge in 2 age groups: ≤28 days and 29 to 56 days. We also assessed CPG impact on healthcare costs.

RESULTS: We included 9377 ED visits; 21 of 33 EDs (63.6%) had a CPG. For neonates ≤28 days, CPG recommendations did not vary and were not associated with differences in testing, hospitalization, or costs. Among infants 29 to 56 days, CPG recommendations for CSF testing and ceftriaxone use varied. CSF testing occurred less often at EDs with CPGs recommending limited testing compared to hospitals without CPGs (adjusted odds ratio: 0.5, 95% confidence interval: 0.3-0.8). Ceftriaxone use at ED discharge varied significantly based on CPG recommendations. Costs were higher for admitted and discharged infants 29 to 56 days old at hospitals with CPGs.

CONCLUSIONS: CPG recommendations for febrile infants 29 to 56 days old vary across institutions for CSF testing and ceftriaxone use, correlating with observed practice variation. CPGs were not associated with lower healthcare costs.

: media-1vid110.1542/5840460609001PEDS-VA_2018-1879 OBJECTIVES: To evaluate the Rochester and modified Philadelphia criteria for the risk stratification of febrile infants with invasive bacterial infection (IBI) who do not appear ill without routine cerebrospinal fluid (CSF) testing.

METHODS: We performed a case-control study of febrile infants ≤60 days old presenting to 1 of 9 emergency departments from 2011 to 2016. For each infant with IBI (defined as a blood [bacteremia] and/or CSF [bacterial meningitis] culture with growth of a pathogen), controls without IBI were matched by site and date of visit. Infants were excluded if they appeared ill or had a complex chronic condition or if data for any component of the Rochester or modified Philadelphia criteria were missing.

RESULTS: Overall, 135 infants with IBI (118 [87.4%] with bacteremia without meningitis and 17 [12.6%] with bacterial meningitis) and 249 controls were included. The sensitivity of the modified Philadelphia criteria was higher than that of the Rochester criteria (91.9% vs 81.5%; = .01), but the specificity was lower (34.5% vs 59.8%; < .001). Among 67 infants >28 days old with IBI, the sensitivity of both criteria was 83.6%; none of the 11 low-risk infants had bacterial meningitis. Of 68 infants ≤28 days old with IBI, 14 (20.6%) were low risk per the Rochester criteria, and 2 had meningitis.

CONCLUSIONS: The modified Philadelphia criteria had high sensitivity for IBI without routine CSF testing, and all infants >28 days old with bacterial meningitis were classified as high risk. Because some infants with bacteremia were classified as low risk, infants discharged from the emergency department without CSF testing require close follow-up.

OBJECTIVES: To determine across and within hospital differences in the predictors of 365-day admission frequency for diabetic ketoacidosis (DKA) in children at US children's hospitals.

STUDY DESIGN: Multicenter retrospective cohort analysis of 12 449 children 2-18 years of age with a diagnosis of DKA in 42 US children's hospitals between 2004 and 2012. The main outcome of interest was the maximum number of DKA admissions experienced by each child within any 365-day interval during a 5-year follow-up period. The association between patient characteristics and the maximum number of DKA admissions within a 365-day interval was examined across and within hospitals.

RESULTS: In the sample, 28.3% of patients admitted for DKA experienced at least 1 additional DKA admission within the following 365 days. Across hospitals, patient characteristics associated with increasing DKA admission frequency were public insurance (OR 1.97, 95% CI 1.71-2.26), non-Hispanic black race (OR 2.40, 95% CI 2.02-2.85), age ≥12 (OR 1.98, 95% CI 1.7-2.32), female sex (OR 1.41, 95% CI 1.29-1.55), and mental health comorbidity (OR 1.36, 95% CI 1.13-1.62). Within hospitals, non-Hispanic black race was associated with higher odds of 365-day admission in 59% of hospitals, and public insurance was associated with higher odds in 56% of hospitals. Older age, female sex, and mental health comorbidity were associated with higher odds of 365-day admission in 42%, 29%, and 15% of hospitals, respectively.

CONCLUSIONS: Across children's hospitals, certain patient characteristics are associated with more frequent DKA admissions. However, these factors are not associated with increased DKA admission frequency for all hospitals.

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.

OBJECTIVES: To derive and internally validate a prediction model for the identification of febrile infants ≤60 days old at low probability of invasive bacterial infection (IBI).

METHODS: We conducted a case-control study of febrile infants ≤60 days old who presented to the emergency departments of 11 hospitals between July 1, 2011 and June 30, 2016. Infants with IBI, defined by growth of a pathogen in blood (bacteremia) and/or cerebrospinal fluid (bacterial meningitis), were matched by hospital and date of visit to 2 control patients without IBI. Ill-appearing infants and those with complex chronic conditions were excluded. Predictors of IBI were identified with multiple logistic regression and internally validated with 10-fold cross-validation, and an IBI score was calculated.

RESULTS: We included 181 infants with IBI (155 [85.6%] with bacteremia without meningitis and 26 [14.4%] with bacterial meningitis) and 362 control patients. Twenty-three infants with IBI (12.7%) and 138 control patients (38.1%) had fever by history only. Four predictors of IBI were identified (area under the curve 0.83 [95% confidence interval (CI): 0.79-0.86]) and incorporated into an IBI score: age <21 days (1 point), highest temperature recorded in the emergency department 38.0-38.4°C (2 points) or ≥38.5°C (4 points), absolute neutrophil count ≥5185 cells per μL (2 points), and abnormal urinalysis results (3 points). The sensitivity and specificity of a score ≥2 were 98.8% (95% CI: 95.7%-99.9%) and 31.3% (95% CI: 26.3%-36.6%), respectively. All 26 infants with meningitis had scores ≥2.

CONCLUSIONS: Infants ≤60 days old with fever by history only, a normal urinalysis result, and an absolute neutrophil count <5185 cells per μL have a low probability of IBI.