Background Although Coronavirus Disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data evaluating 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 non-invasive or invasive mechanical ventilation or extra-corporeal 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 non-invasive 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.

Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)-229E, HKU1, NL63 and OC43-circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined.

Background Rapid blood culture diagnostics are costly and of unclearbenefit for patients with Gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, prospective, randomized controlled trial comparing outcomes of patients with GNB BSI who had blood culture testing with standard of care (SOC) culture and antimicrobial susceptibility testing (AST) versus rapid organism identification (ID) and phenotypic AST using the Accelerate Pheno™ System (RAPID). Methods Patients with positive blood cultures with Gram stains showing GNB were randomized to SOC testing with antimicrobial stewardship review (AS) or RAPID with AS, at two medical centers between 10/2017-10/2018. The primary outcome was time to first antibiotic modification within 72 hours of randomization. Results Of 500 randomized subjects, 448 were included (226 SOC, 222 RAPID). Mean (S.D.) hours to results was faster for RAPID than SOC for organism ID [2.7 (1.2) vs 11.7 (10.5), p < 0.001] and AST [13.5 (56) vs. 44.9 (12.1), p<0.001]. Median (IQR) hours to first antibiotic modification was faster in the RAPID vs. SOC arm for overall antibiotics [8.6 (2.6, 27.6) vs. 14.9 (3.3, 41.1), difference 6.3, p=0.02] and Gram-negative antibiotics [17.3 (4.9, 72) vs. 42.1 (10.1, 72), difference 24.8, p<0.001]. Median (IQR) hours to antibiotic escalation was faster in the RAPID vs. SOC arm for antimicrobial-resistant BSIs [18.4 (5.8, 72) vs. 61.7 (30.4, 72), difference 43.3, p=0.01]. There were no statistically significant differences between the arms in patient outcomes including mortality and length of stay. Conclusion Rapid organism ID and phenotypic AST led to faster changes in antibiotic therapy for Gram-negative BSIs. (Funded by the U.S. NIH UM1AI104681; ClinicalTrials.gov number, NCT03218397.)

Background 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. Methods 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. Results 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. Conclusions 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.

Proper assessment of antimicrobial use in pediatric populations is challenging due to the common metric unit, the defined daily dose. In this study, the authors quantified pediatric antimicrobial use using days of therapy per 100 patient days, a value that is numerically comparable with adult antibiotic use. An overview of systemic antibacterial and antifungal use according to ward at the Alberta Children’s Hospital (Calgary, Alberta) is also provided. The authors suggest that their data act as a benchmark for future reference in other antimicrobial studies and pediatric institutions.