Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children: The SCOUT-CAP Randomized Clinical Trial.

2022

2022 Jan 18

2168-6211

<p><strong>Importance: </strong>Childhood community-acquired pneumonia (CAP) is usually treated with 10 days of antibiotics. Shorter courses may be effective with fewer adverse effects and decreased potential for antibiotic resistance.</p>

<p><strong>Objective: </strong>To compare a short (5-day) vs standard (10-day) antibiotic treatment strategy for CAP in young children.</p>

<p><strong>Design, Setting, and Participants: </strong>Randomized double-blind placebo-controlled clinical trial in outpatient clinic, urgent care, or emergency settings in 8 US cities. A total of 380 healthy children aged 6 to 71 months with nonsevere CAP demonstrating early clinical improvement were enrolled from December 2, 2016, to December 16, 2019. Data were analyzed from January to September 2020.</p>

<p><strong>Intervention: </strong>On day 6 of their originally prescribed therapy, participants were randomized 1:1 to receive 5 days of matching placebo or 5 additional days of the same antibiotic.</p>

<p><strong>Main Outcomes and Measures: </strong>The primary end point was the end-of-treatment response adjusted for duration of antibiotic risk (RADAR), a composite end point that ranks each child's clinical response, resolution of symptoms, and antibiotic-associated adverse effects in an ordinal desirability of outcome ranking (DOOR). Within each DOOR rank, participants were further ranked by the number of antibiotic days, assuming that shorter antibiotic durations were more desirable. Using RADAR, the probability of a more desirable outcome was estimated for the short- vs standard-course strategy. In a subset of children, throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora.</p>

<p><strong>Results: </strong>A total of 380 children (189 randomized to short course and 191 randomized to standard course) made up the study population. The mean (SD) age was 35.7 (17.2) months, and 194 participants (51%) were male. Of the included children, 8 were Asian, 99 were Black or African American, 234 were White, 32 were multiracial, and 7 were of unknown or unreported race; 33 were Hispanic or Latino, 344 were not Hispanic or Latino, and 3 were of unknown or unreported ethnicity. There were no differences between strategies in the DOOR or its individual components. Fewer than 10% of children in either strategy had an inadequate clinical response. The short-course strategy had a 69% (95% CI, 63-75) probability of a more desirable RADAR outcome compared with the standard-course strategy. A total of 171 children were included in the resistome analysis. The median (range) number of antibiotic resistance genes per prokaryotic cell (RGPC) was significantly lower in the short-course strategy compared with the standard-course strategy for total RGPC (1.17 [0.35-2.43] vs 1.33 [0.46-11.08]; P = .01) and β-lactamase RGPC (0.55 [0.18-1.24] vs 0.60 [0.21-2.45]; P = .03).</p>

<p><strong>Conclusions and Relevance: </strong>In this study, among children responding to initial treatment for outpatient CAP, a 5-day antibiotic strategy was superior to a 10-day strategy. The shortened approach resulted in similar clinical response and antibiotic-associated adverse effects, while reducing antibiotic exposure and resistance.</p>

<p><strong>Trial Registration: </strong>ClinicalTrials.gov Identifier: NCT02891915.</p>

10.1001/jamapediatrics.2021.5547

JAMA Pediatr

35040920

Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of COVID-19 in Children and Adolescents.

2021

2021 Jan 03

2048-7207

<p><strong>BACKGROUND: </strong>In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for two novel virus-neutralizing monoclonal antibody therapies, bamlanivimab, and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate COVID-19 in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products.</p>

<p><strong>METHODS: </strong>A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion.</p>

<p><strong>RESULTS: </strong>The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis.</p>

<p><strong>CONCLUSIONS: </strong>Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence, and ensure implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.</p>

10.1093/jpids/piaa175

J Pediatric Infect Dis Soc

33388760

Development of a Quality Improvement Learning Collaborative to Improve Pediatric Sepsis Outcomes.

2021

2021 Jan

1098-4275

<p>Pediatric sepsis is a major public health problem. Published treatment guidelines and several initiatives have increased adherence with guideline recommendations and have improved patient outcomes, but the gains are modest, and persistent gaps remain. The Children's Hospital Association Improving Pediatric Sepsis Outcomes (IPSO) collaborative seeks to improve sepsis outcomes in pediatric emergency departments, ICUs, general care units, and hematology/oncology units. We developed a multicenter quality improvement learning collaborative of US children's hospitals. We reviewed treatment guidelines and literature through 2 in-person meetings and multiple conference calls. We defined and analyzed baseline sepsis-attributable mortality and hospital-onset sepsis and developed a key driver diagram (KDD) on the basis of treatment guidelines, available evidence, and expert opinion. Fifty-six hospital-based teams are participating in IPSO; 100% of teams are engaged in educational and information-sharing activities. A baseline, sepsis-attributable mortality of 3.1% was determined, and the incidence of hospital-onset sepsis was 1.3 cases per 1000 hospital admissions. A KDD was developed with the aim of reducing both the sepsis-attributable mortality and the incidence of hospital-onset sepsis in children by 25% from baseline by December 2020. To accomplish these aims, the KDD primary drivers focus on improving the following: treatment of infection; recognition, diagnosis, and treatment of sepsis; de-escalation of unnecessary care; engagement of patients and families; and methods to optimize performance. IPSO aims to improve sepsis outcomes through collaborative learning and reliable implementation of evidence-based interventions.</p>

10.1542/peds.2020-1434

Pediatrics

33328337

Pediatric research priorities in healthcare-associated infections and antimicrobial stewardship.

2020

1-4

2020 Nov 26

1559-6834

<p><strong>OBJECTIVE: </strong>To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.</p>

<p><strong>PARTICIPANTS: </strong>The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).</p>

<p><strong>METHODS: </strong>Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings.</p>

<p><strong>RESULTS: </strong>A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level "harm index" for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions.</p>

<p><strong>CONCLUSIONS: </strong>We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.</p>

10.1017/ice.2020.1267

Infect Control Hosp Epidemiol

33239122

Evaluating Pediatric Sepsis Definitions Designed for Electronic Health Record Extraction and Multicenter Quality Improvement.

2020

e916-e926

2020 Oct

1530-0293

<p><strong>OBJECTIVES: </strong>To describe the Children's Hospital Association's Improving Pediatric Sepsis Outcomes sepsis definitions and the identified patients; evaluate the definition using a published framework for evaluating sepsis definitions.</p>

<p><strong>DESIGN: </strong>Observational cohort.</p>

<p><strong>SETTING: </strong>Multicenter quality improvement collaborative of 46 hospitals from January 2017 to December 2018, excluding neonatal ICUs.</p>

<p><strong>PATIENTS: </strong>Improving Pediatric Sepsis Outcomes Sepsis was defined by electronic health record evidence of suspected infection and sepsis treatment or organ dysfunction. A more severely ill subgroup, Improving Pediatric Sepsis Outcomes Critical Sepsis, was defined, approximating septic shock.</p>

<p><strong>INTERVENTIONS: </strong>Participating hospitals identified patients, extracted data, and transferred de-identified data to a central data warehouse. The definitions were evaluated across domains of reliability, content validity, construct validity, criterion validity, measurement burden, and timeliness.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>Forty hospitals met data quality criteria across four electronic health record platforms. There were 23,976 cases of Improving Pediatric Sepsis Outcomes Sepsis, including 8,565 with Improving Pediatric Sepsis Outcomes Critical Sepsis. The median age was 5.9 years. There were 10,316 (43.0%) immunosuppressed or immunocompromised patients, 4,135 (20.3%) with central lines, and 2,352 (11.6%) chronically ventilated. Among Improving Pediatric Sepsis Outcomes Sepsis patients, 60.8% were admitted to intensive care, 26.4% had new positive-pressure ventilation, and 19.7% received vasopressors. Median hospital length of stay was 6.0 days (3.0-13.0 d). All-cause 30-day in-hospital mortality was 958 (4.0%) in Improving Pediatric Sepsis Outcomes Sepsis; 541 (6.3%) in Improving Pediatric Sepsis Outcomes Critical Sepsis. The Improving Pediatric Sepsis Outcomes Sepsis definitions demonstrated strengths in content validity, convergent construct validity, and criterion validity; weakness in reliability. Improving Pediatric Sepsis Outcomes Sepsis definitions had significant initial measurement burden (median time from case completion to submission: 15 mo [interquartile range, 13-18 mo]); timeliness improved once data capture was established (median, 26 d; interquartile range, 23-56 d).</p>

<p><strong>CONCLUSIONS: </strong>The Improving Pediatric Sepsis Outcomes Sepsis definitions demonstrated feasibility for large-scale data abstraction. The patients identified provide important information about children treated for sepsis. When operationalized, these definitions enabled multicenter identification and data aggregation, indicating practical utility for quality improvement.</p>

10.1097/CCM.0000000000004505

Crit. Care Med.

32931197

Central line-associated bloodstream infections in neonates with gastrointestinal conditions: developing a candidate definition for mucosal barrier injury bloodstream infections.

2014

1391-9

2014 Nov

1559-6834

<p><strong>OBJECTIVE: </strong>To develop a candidate definition for central line-associated bloodstream infection (CLABSI) in neonates with presumed mucosal barrier injury due to gastrointestinal (MBI-GI) conditions and to evaluate epidemiology and microbiology of MBI-GI CLABSI in infants.</p>

<p><strong>DESIGN: </strong>Multicenter retrospective cohort study.</p>

<p><strong>SETTING: </strong>Neonatal intensive care units from 14 US children's hospitals and pediatric facilities.</p>

<p><strong>METHODS: </strong>A multidisciplinary focus group developed a candidate MBI-GI CLABSI definition based on presence of an MBI-GI condition, parenteral nutrition (PN) exposure, and an eligible enteric organism. CLABSI surveillance data from participating hospitals were supplemented by chart review to identify MBI-GI conditions and PN exposure.</p>

<p><strong>RESULTS: </strong>During 2009-2012, 410 CLABSIs occurred in 376 infants. MBI-GI conditions and PN exposure occurred in 149 (40%) and 324 (86%) of these 376 neonates, respectively. The distribution of pathogens was similar among neonates with versus without MBI-GI conditions and PN exposure. Fifty-nine (16%) of the 376 initial CLABSI episodes met the candidate MBI-GI CLABSI definition. Subsequent versus initial CLABSIs were more likely to be caused by an enteric organism (22 of 34 [65%] vs 151 of 376 [40%]; P = .009) and to meet the candidate MBI-GI CLABSI definition (19 of 34 [56%] vs 59 of 376 [16%]; P &lt; .01).</p>

<p><strong>CONCLUSIONS: </strong>While MBI-GI conditions and PN exposure were common, only 16% of initial CLABSIs met the candidate definition of MBI-GI CLABSI. The high proportion of MBI-GI CLABSIs among subsequent infections suggests that infants with MBI-GI CLABSI should be a population targeted for further surveillance and interventional research.</p>

10.1086/678410

Infect Control Hosp Epidemiol

25333434

Evaluating application of the National Healthcare Safety Network central line-associated bloodstream infection surveillance definition: a survey of pediatric intensive care and hematology/oncology units.

2013

663-70

2013 Jul

1559-6834

<p><strong>OBJECTIVE: </strong>To evaluate the application of the National Healthcare Safety Network (NHSN) central line-associated bloodstream infection (CLABSI) definition in pediatric intensive care units (PICUs) and pediatric hematology/oncology units (PHOUs) participating in a multicenter quality improvement collaborative to reduce CLABSIs; to identify sources of variability in the application of the definition.</p>

<p><strong>DESIGN: </strong>Online survey using 18 standardized case scenarios. Each described a positive blood culture in a patient and required a yes- or-no answer to the question "Is this a CLABSI?" NHSN staff responses were the reference standard.</p>

<p><strong>SETTING: </strong>Sixty-five US PICUs and PHOUs.</p>

<p><strong>PARTICIPANTS: </strong>Staff who routinely adjudicate CLABSIs using NHSN definitions.</p>

<p><strong>RESULTS: </strong>Sixty responses were received from 58 (89%) of 65 institutions; 78% of respondents were infection preventionists, infection control officers, or infectious disease physicians. Responses matched those of NHSN staff for 78% of questions. The mean (SE) percentage of concurring answers did not differ for scenarios evaluating application of 1 of the 3 criteria ("known pathogen," 78% [1.7%]; "skin contaminant, &gt;1 year of age," 76% [SE, 2.5%]; "skin contaminant, ≤1 year of age," 81% [3.8%]; [Formula: see text]). The mean percentage of concurring answers was lower for scenarios requiring respondents to determine whether a CLABSI was present or incubating on admission (64% [4.6%]; [Formula: see text]) or to distinguish between primary and secondary bacteremia (65% [2.5%]; [Formula: see text]).</p>

<p><strong>CONCLUSIONS: </strong>The accuracy of application of the CLABSI definition was suboptimal. Efforts to reduce variability in identifying CLABSIs that are present or incubating on admission and in distinguishing primary from secondary bloodstream infection are needed.</p>

10.1086/671005

Infect Control Hosp Epidemiol

23739069