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BackgroundIn November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for 2 novel virus-neutralizing monoclonal antibody therapies, bamlanivimab and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate coronavirus disease 2019 (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.MethodsA 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.ResultsThe 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.ConclusionsBased 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 the implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.

BackgroundAlthough coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children.MethodsA panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion.ResultsGiven the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children.ConclusionsAntiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.

BackgroundAlthough coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics.MethodsA panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion.ResultsGiven the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available.ConclusionsAntiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.

Background Discontinuation of inappropriate antimicrobial therapy is an important target for stewardship intervention. The drug and duration-dependent effects of antibiotics on the developing neonatal gut microbiota needs to be precisely quantified. Methods In this retrospective, cross-sectional study, we performed 16S rRNA sequencing on stool swab samples collected from neonatal intensive care unit patients within 7 days of discontinuation of therapy who received ampicillin and tobramycin (AT), ampicillin and cefotaxime (AC), or ampicillin, tobramycin, and metronidazole (ATM). We compared taxonomic composition within term and preterm infant groups between treatment regimens. We calculated adjusted effect estimates for antibiotic type and duration of therapy on the richness of obligate anaerobes and known butyrate-producers in all infants. Results A total of 72 infants were included in the study. Term infants received AT (20/28; 71%) or AC (8/28; 29%) with median durations of 3 and 3.5 days, respectively. Preterm infants received AT (32/44; 73%) or ATM (12/44; 27%) with median durations of 4 and 7 days, respectively. Compositional analyses of 67 stool swab samples demonstrated low diversity and dominance by potential pathogens. Within 1 week of discontinuation of therapy, each additional day of antibiotics was associated with lower richness of obligate anaerobes (adjusted risk ratio [aRR], 0.84; 95% confidence interval [CI],.73–.95) and butyrate-producers (aRR, 0.82; 95% CI,.67–.97). Conclusions Each additional day of antibiotics was associated with lower richness of anaerobes and butyrate-producers within 1 week after therapy. A longitudinally sampled cohort with preexposure sampling is needed to validate our results. [ABSTRACT FROM AUTHOR]

BACKGROUND: Antimicrobial stewardship programs (ASPs) are targeted to optimize antimicrobial use. However, pediatric metrics used to measure outcomes of ASPs are not well established. Our aim for this project was to identify, refine, and develop consensus on standard metrics for pediatric ASPs. METHODS: By using a modified Delphi process, 2 surveys were sent to experts and stakeholders to establish consensus on the utility of metrics. These were subdivided into 4 ASP domains: (1) antimicrobial consumption, (2) microbiologic outcomes, (3) clinical outcomes, and (4) process measures. Respondents were asked to rank the scientific merit, impact, feasibility, and accountability of each metric. Metrics with ≥75% agreement for scientific merit were included and metrics with ≤25% agreement were discarded. Consensus was finalized with a face-to-face meeting and final survey. RESULTS: Thirty-eight participants from 15 pediatric hospitals across Canada completed all 3 rounds of the Delphi survey. In the domain of antimicrobial consumption, the 2 selected metrics were (1) days of therapy per 1000 patient-days and (2) total antimicrobial days. The clinical and process outcomes chosen were (1) 30-day readmission rate and (2) adherence to ASP recommendations, respectively. A microbiologic outcome was felt to be important and feasible, but consensus could not be obtained on a measure. Several barriers to implementation of the metrics were identified, including information technology limitations at various centers. CONCLUSIONS: We obtained consensus on 4 metrics to evaluate pediatric antimicrobial stewardship activities in Canada. Adoption of these metrics by pediatric ASPs will facilitate measurement of outcomes nationally and internationally. [ABSTRACT FROM AUTHOR]

Background: Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children., Methods: A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion., Results: Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children., Conclusions: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)