First name
Mark
Middle name
I
Last name
Neuman

Title

Developing Consensus on Clinical Outcomes for Children with Mild Pneumonia: A Delphi Study.

Year of Publication

2023

Date Published

01/2023

ISSN Number

2048-7207

Abstract

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.

DOI

10.1093/jpids/piac123

Alternate Title

J Pediatric Infect Dis Soc

PMID

36625856

Title

Respiratory virus testing and clinical outcomes among children hospitalized with pneumonia.

Year of Publication

2022

Number of Pages

693-701

Date Published

06/2022

ISSN Number

1553-5606

Abstract

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.

DOI

10.1002/jhm.12902

Alternate Title

J Hosp Med

PMID

35747928

Title

Post-COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection.

Year of Publication

2022

Number of Pages

e2223253

Date Published

07/2022

ISSN Number

2574-3805

Abstract

Importance: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children.

Objectives: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs.

Design, Setting, and Participants: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls.

Exposure: SARS-CoV-2 detected via nucleic acid testing.

Main Outcomes and Measures: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey.

Results: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]).

Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.

DOI

10.1001/jamanetworkopen.2022.23253

Alternate Title

JAMA Netw Open

PMID

35867061

Title

Antibiotics and outcomes of CF pulmonary exacerbations in children infected with MRSA and Pseudomonas aeruginosa.

Year of Publication

2022

Date Published

08/2022

ISSN Number

1873-5010

Abstract

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.

DOI

10.1016/j.jcf.2022.08.001

Alternate Title

J Cyst Fibros

PMID

35945130

Title

Risk Stratification of Febrile Infants ≤60 Days Old Without Routine Lumbar Puncture.

Year of Publication

2018

Date Published

2018 Nov 13

ISSN Number

1098-4275

Abstract

: 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.

DOI

10.1542/peds.2018-1879

Alternate Title

Pediatrics

PMID

30425130

Title

A Prediction Model to Identify Febrile Infants ≤60 Days at Low Risk of Invasive Bacterial Infection.

Year of Publication

2019

Date Published

2019 Jun 05

ISSN Number

1098-4275

Abstract

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.

DOI

10.1542/peds.2018-3604

Alternate Title

Pediatrics

PMID

31167938

Title

Association of clinical practice guidelines with emergency department management of febrile infants ≤56 days of age.

Year of Publication

2015

Number of Pages

358-65

Date Published

06/2015

ISSN Number

1553-5606

Abstract

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.

DOI

10.1002/jhm.2329

Alternate Title

J Hosp Med

PMID

25684689

Title

Febrile Infants ≤60 Days Old With Positive Urinalysis Results and Invasive Bacterial Infections.

Year of Publication

2020

Date Published

2020 Nov 25

ISSN Number

2154-1671

Abstract

OBJECTIVES: We aimed to describe the clinical and laboratory characteristics of febrile infants ≤60 days old with positive urinalysis results and invasive bacterial infections (IBI).

METHODS: We performed a planned secondary analysis of a retrospective cohort study of febrile infants ≤60 days old with IBI who presented to 11 emergency departments from July 1, 2011, to June 30, 2016. For this subanalysis, we included infants with IBI and positive urinalysis results. We analyzed the sensitivity of high-risk past medical history (PMH) (prematurity, chronic medical condition, or recent antimicrobial receipt), ill appearance, and/or abnormal white blood cell (WBC) count (<5000 or >15 000 cells/μL) for identification of IBI.

RESULTS: Of 148 febrile infants with positive urinalysis results and IBI, 134 (90.5%) had bacteremia without meningitis and 14 (9.5%) had bacterial meningitis (11 with concomitant bacteremia). Thirty-five infants (23.6%) with positive urinalysis results and IBI did not have urinary tract infections. The presence of high-risk PMH, ill appearance, and/or abnormal WBC count had a sensitivity of 53.4% (95% confidence interval: 45.0-61.6) for identification of IBI. Of the 14 infants with positive urinalysis results and concomitant bacterial meningitis, 7 were 29 to 60 days old. Six of these 7 infants were ill-appearing or had an abnormal WBC count. The other infant had bacteremia with cerebrospinal fluid pleocytosis after antimicrobial pretreatment and was treated for meningitis.

CONCLUSIONS: The sensitivity of high-risk PMH, ill appearance, and/or abnormal WBC count is suboptimal for identifying febrile infants with positive urinalysis results at low risk for IBI. Most infants with positive urinalysis results and bacterial meningitis are ≤28 days old, ill-appearing, or have an abnormal WBC count.

DOI

10.1542/hpeds.2020-000638

Alternate Title

Hosp Pediatr

PMID

33239319

Title

Characteristics of Afebrile Infants ≤60 Days of Age With Invasive Bacterial Infections.

Year of Publication

2021

Number of Pages

100-105

Date Published

2021 Jan

ISSN Number

2154-1671

Abstract

OBJECTIVES: To describe the characteristics and outcomes of afebrile infants ≤60 days old with invasive bacterial infection (IBI).

METHODS: We conducted a secondary analysis of a cross-sectional study of infants ≤60 days old with IBI presenting to the emergency departments (EDs) of 11 children's hospitals from 2011 to 2016. We classified infants as afebrile if there was absence of a temperature ≥38°C at home, at the referring clinic, or in the ED. Bacteremia and bacterial meningitis were defined as pathogenic bacterial growth from a blood and/or cerebrospinal fluid culture.

RESULTS: Of 440 infants with IBI, 78 (18%) were afebrile. Among afebrile infants, 62 (79%) had bacteremia without meningitis and 16 (20%) had bacterial meningitis (10 with concomitant bacteremia). Five infants (6%) died, all with bacteremia. The most common pathogens were (35%), (16%), and (16%). Sixty infants (77%) had an abnormal triage vital sign (temperature <36°C, heart rate ≥181 beats per minute, or respiratory rate ≥66 breaths per minute) or a physical examination abnormality (ill appearance, full or depressed fontanelle, increased work of breathing, or signs of focal infection). Forty-three infants (55%) had ≥1 of the following laboratory abnormalities: white blood cell count <5000 or >15 000 cells per μL, absolute band count >1500 cells per μl, or positive urinalysis. Presence of an abnormal vital sign, examination finding, or laboratory test result had a sensitivity of 91% (95% confidence interval 82%-96%) for IBI.

CONCLUSIONS: Most afebrile young infants with an IBI had vital sign, examination, or laboratory abnormalities. Future studies should evaluate the predictive ability of these criteria in afebrile infants undergoing evaluation for IBI.

DOI

10.1542/hpeds.2020-002204

Alternate Title

Hosp Pediatr

PMID

33318052

Title

Epidemiology and Etiology of Invasive Bacterial Infection in Infants ≤60 Days Old Treated in Emergency Departments.

Year of Publication

2018

Date Published

2018 May 18

ISSN Number

1097-6833

Abstract

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.

DOI

10.1016/j.jpeds.2018.04.033

Alternate Title

J. Pediatr.

PMID

29784512

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