Guidance for prevention and management of COVID-19 in children and adolescents: A consensus statement from the Pediatric Infectious Diseases Society Pediatric COVID-19 Therapies Taskforce.

BACKGROUND: Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. RESULTS: There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available.

Disseminated Nocardia nova in a child with relapsed acute lymphoblastic leukemia: a case report.

BACKGROUND: Nocardiosis is a rare infection that typically results from inhalation of or inoculation with Nocardia organisms. It may cause invasive disease in immunocompromised patients. This case describes nocardiosis with bacteremia and pulmonary involvement in a child with a hematologic malignancy. CASE PRESENTATION: A boy with testicular relapsed acute lymphoblastic leukemia with marrow involvement presented with sudden onset of fever, body aches, headaches, chills, and moderate respiratory distress during continuation 2 chemotherapy. Radiographic imaging demonstrated consolidation and ground glass opacities in bilateral lower lungs. Central line blood cultures grew Nocardia nova complex, prompting removal of the central line and initiation of triple therapy with imipenem-cilastatin, linezolid, and trimethoprim-sulfamethoxazole with rapid improvement of symptoms. Antibiotic susceptibilities showed a multidrug-susceptible isolate. The patient is anticipated to remain on trimethoprim-sulfamethoxazole for at least 12 months. CONCLUSIONS: In an immunocompromised child, blood cultures, chest imaging, and head imaging can aid in the diagnosis of disseminated nocardiosis. Long-term antibiotic therapy is necessary, guided by the organism and simplified with the results of antimicrobial susceptibility testing.

Risk Factors for Pediatric Critical COVID-19: A Systematic Review and Meta-Analysis.

Background: Risk stratification is a cornerstone of the Pediatric Infectious Diseases Society COVID-19 treatment guidance. This systematic review and meta-analysis aimed to define the clinical characteristics and comorbidities associated with critical COVID-19 in children and adolescents. Methods: Two independent reviewers screened the literature (Medline and EMBASE) for studies published through August 2023 that reported outcome data on patients aged ≤21 years with COVID-19. Critical disease was defined as an invasive mechanical ventilation requirement, intensive care unit admission, or death. Random effects models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (CI), and heterogeneity was explored through subgroup analyses. Results: Among 10,178 articles, 136 studies met the inclusion criteria for review. Data from 70 studies, which collectively examined 172,165 children and adolescents with COVID-19, were pooled for meta-analysis. In previously healthy children, the absolute risk of critical disease from COVID-19 was 4% (95% CI, 1%-10%). Compared with no comorbidities, the pooled OR for critical disease was 3.95 (95% CI, 2.78-5.63) for presence of one comorbidity and 9.51 (95% CI, 5.62-16.06) for ≥2 comorbidities. Key risk factors included cardiovascular and neurological disorders, chronic pulmonary conditions (excluding asthma), diabetes, obesity, and immunocompromise, all with statistically significant ORs >2.00. Conclusions: While the absolute risk for critical COVID-19 in children and adolescents without underlying health conditions is relatively low, the presence of one or more comorbidities was associated with markedly increased risk. These findings support the importance of risk stratification in tailoring pediatric COVID-19 management.

Severe multiple organ failure as a consequence of diabetic ketoacidosis in an adolescent with new-onset type 1 diabetes: A case report.

The initial presentation of pediatric diabetes is variable, making prompt diagnosis and treatment challenging. The overlap between type 1 and type 2 diabetes and presence of developmental delays can complicate diagnosis, resulting in delays and severe illness at presentation. Here we describe a case of a 13-year-old male with autism and attention deficit hyperactivity disorder who presented with severe diabetic ketoacidosis, multiple organ failure, and shock. Within 2 weeks of this initial presentation, he had further clinical decompensation due to an intestinal perforation. Cultures from resected gastrointestinal tissue grew mucormycosis, protracting his hospital stay and recovery. He was able to go home several months later with remarkable improvement. This case highlights the necessity of careful history taking and early testing, and how investigation for rare complications of diabetes is vital when patients do not improve as expected.

Early antibiotic exposure in very-low birth weight infants and infection risk at 3-7 days after birth.

OBJECTIVE: To determine rates of late-onset infection (LOI) during postnatal days 3-7 among preterm infants, based on antibiotic exposure during days 0-2. STUDY DESIGN: Retrospective cohort study of infants born <1500 grams and ≤30 weeks gestation, 2005-2018. We analyzed the incidence and microbiology of LOI at days 3-7 based on antibiotic exposure during postnatal days 0-2. RESULTS: The cohort included 88,574 infants, of whom 85% were antibiotic-exposed. Fewer antibiotic-exposed compared to unexposed infants developed LOI (1.5% vs. 2.1%; adjusted hazard ratio, 0.28, 95% CI 0.24-0.33). Among antibiotic-exposed compared to unexposed infants, Gram-negative (38% vs. 28%, p = 0.002) and fungal (11% vs. 1%, p < 0.001) species were more commonly isolated, and gram-positive organisms (49% vs. 70%, p < 0.001) were less commonly isolated. CONCLUSIONS: We observed low overall rates of LOI at days 3-7 after birth, but antibiotic exposure from birth was associated with lower rates, and with differing microbiology, compared to no exposure.

Benchmarking of Outpatient Pediatric Antibiotic Prescribing: Results of a Multicenter Collaborative.

BACKGROUND: Most antibiotic use occurs in ambulatory settings. No benchmarks exist for pediatric institutions to assess their outpatient antibiotic use and compare prescribing rates to peers. We aimed to share pediatric outpatient antibiotic use reports and benchmarking metrics nationally. METHODS: We invited institutions from the Sharing Antimicrobial Reports for Pediatric Stewardship OutPatient (SHARPS-OP) Collaborative to contribute quarterly aggregate reports on antibiotic use from January 2019 to June 2022. Outpatient settings included emergency departments (ED), urgent care centers (UCC), primary care clinics (PCC) and telehealth encounters. Benchmarking metrics included the percentage of: (1) all acute encounters resulting in antibiotic prescriptions; (2) acute respiratory infection (ARI) encounters resulting in antibiotic prescriptions; and among ARI encounters receiving antibiotics, (3) the percentage receiving amoxicillin ("Amoxicillin index"); and (4) the percentage receiving azithromycin ("Azithromycin index"). We collected rates of antibiotic prescriptions with durations ≤7 days and >10 days from institutions able to provide validated duration data. RESULTS: Twenty-one institutions submitted aggregate reports. Percent ARI encounters receiving antibiotics were highest in the UCC (40.2%), and lowest in telehealth (19.1%). Amoxicillin index was highest for the ED (76.2%), and lowest for telehealth (55.8%), while the azithromycin index was similar for ED, UCC, and PCC (3.8%, 3.7%, and 5.0% respectively). Antibiotic duration of ≤7 days varied substantially (46.4% for ED, 27.8% UCC, 23.7% telehealth, and 16.4% PCC). CONCLUSIONS: We developed a benchmarking platform for key pediatric outpatient antibiotic use metrics drawing data from multiple pediatric institutions nationally. These data may serve as a baseline measurement for future improvement work.

Monoclonal Antibodies for COVID-19 in Children: Case Series Should be Just the Start.

Two new articles describe the use and implementation of monoclonal antibodies to treat COVID-19 in children. While these studies provide valuable guidance for pediatric clinicians, more studies of monoclonal antibodies and other COVID-19 therapies in children are needed.

Multi-institutional experience with COVID-19 convalescent plasma in children.

BACKGROUND AND OBJECTIVES: Convalescent COVID-19 plasma (CCP) was developed and used worldwide as a treatment option by supplying passive immunity. Adult studies suggest administering high-titer CCP early in the disease course of patients who are expected to be antibody-negative; however, pediatric experience is limited. We created a multi-institutional registry to characterize pediatric patients (<18 years) who received CCP and to assess the safety of this intervention. METHODS: A REDCap survey was distributed. The registry collected de-identified data including demographic information (age, gender, and underlying conditions), COVID-19 disease features and concurrent treatments, CCP transfusion and safety events, and therapy response. RESULTS: Ninety-five children received CCP: 90 inpatients and 5 outpatients, with a median age of 10.2 years (range 0-17.9). They were predominantly Latino/Hispanic and White. The most frequent underlying medical conditions were chronic respiratory disease, immunosuppression, obesity, and genetic syndromes. CCP was primarily given as a treatment (95%) rather than prophylaxis (5%). Median total plasma dose administered and transfusion rates were 5.0 ml/kg and 2.6 ml/kg/h, respectively. The transfusions were well-tolerated, with 3 in 115 transfusions reporting mild reactions. No serious adverse events were reported. Severity scores decreased significantly 7 days after CCP transfusion or at discharge. Eighty-five patients (94.4%) survived to hospital discharge. All five outpatients survived to 60 days. CONCLUSIONS: CCP was found to be safe and well-tolerated in children. CCP was frequently given concurrently with other COVID-19-directed treatments with improvement in clinical severity scores ≥7 days after CCP, but efficacy could not be evaluated in this study.

Standardizing Strep Throat Documentation in a Pediatric Outpatient Setting During COVID-19: A Quality Improvement Pilot Project.

Clinicians' nonadherence to the 2012 Infectious Diseases Society of America's group A streptococcal (GAS) pharyngitis guidelines leads to unnecessary in-person clinic visits, unnecessary use of bacterial testing, and inappropriate antibiotic prescriptions. Quality improvement methodology was used during nurse telephone triage at an outpatient pediatric clinic to standardize nurse documentation to align with the GAS guidelines. This pilot project's standardization resulted in improved communication among clinicians and decreased unnecessary resource and antibiotic use despite encountering barriers related to COVID-19.

Encouraging healthier grocery purchases online: A randomised controlled trial and lessons learned.

Online supermarket platforms present an opportunity for encouraging healthier consumer purchases. A parallel, double-blind randomised controlled trial tested whether promoting healthier products (e.g. lower fat and lower calorie) on the Sainsbury's online supermarket platform would increase purchases of those products. Participants were Nectar loyalty membership scheme cardholders who shopped online with Sainsbury's between 20th September and 10th October 2017. Intervention arm customers saw advertisement banners and recipe ingredient lists containing healthier versions of the products presented in control arm banners and ingredient lists. The primary outcome measure was purchases of healthier products. Additional outcome measures were banner clicks, purchases of standard products, overall purchases and energy (kcal) purchased. Sample sizes were small due to customers navigating the website differently than expected. The intervention encouraged purchases of some promoted healthier products (spaghetti [B = 2.10, p < 0.001], spaghetti sauce [B = 2.06, p < 0.001], spaghetti cheese [B = 2.45, p = 0.001], sour cream [B = 2.52, p < 0.001], fajita wraps [B = 2.10, p < 0.001], fajita cheese [B = 1.19, p < 0.001], bakery aisle products (B = 3.05, p = 0.003) and cola aisle products [B = 0.97, p < 0.002]) but not others (spaghetti mince, or products in the yogurt and ice cream aisles). There was little evidence of effects on banner clicks and energy purchased. Small sample sizes may affect the robustness of these findings. We discuss the benefits of collaborating to share expertise and implement a trial in a live commercial environment, alongside key learnings for future collaborative research in similar contexts.

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

BACKGROUND: Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion. RESULTS: The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults. CONCLUSIONS: Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities.

Antibiotics prior to age 2 years have limited association with preschool growth trajectory.

BACKGROUND: Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2-5 years. METHODS: We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0-12 months of age, ≥1 at 12-30 months, and ≥2 between 25 and 72 months. Prescriptions were grouped into episodes by time and by antimicrobial spectrum. Longitudinal rate regression was used to assess differences in growth rate from 25 to 72 months of age. Models were adjusted for sex, race/ethnicity, steroid use, diagnosed asthma, complex chronic conditions, and infections. RESULTS: 430,376 children from 29 health U.S. systems were included, with 58% receiving antibiotics before 24 months. Exposure to any antibiotic was associated with an average 0.7% (95% CI 0.5, 0.9, p < 0.0001) greater rate of weight gain, corresponding to 0.05 kg additional weight. The estimated effect was slightly greater for narrow-spectrum (0.8% [0.6, 1.1]) than broad-spectrum (0.6% [0.3, 0.8], p < 0.0001) drugs. There was a small dose response relationship between the number of antibiotic episodes and weight gain. CONCLUSION: Oral antibiotic use prior to 24 months of age was associated with very small changes in average growth rate at ages 2-5 years. The small effect size is unlikely to affect individual prescribing decisions, though it may reflect a biologic effect that can combine with others.

Evaluation of the Infectious Diseases Society of America's Core Antimicrobial Stewardship Curriculum for Infectious Diseases Fellows.

BACKGROUND: Antimicrobial stewardship (AS) programs are required by Centers for Medicare and Medicaid Services and should ideally have infectious diseases (ID) physician involvement; however, only 50% of ID fellowship programs have formal AS curricula. The Infectious Diseases Society of America (IDSA) formed a workgroup to develop a core AS curriculum for ID fellows. Here we study its impact. METHODS: ID program directors and fellows in 56 fellowship programs were surveyed regarding the content and effectiveness of their AS training before and after implementation of the IDSA curriculum. Fellows' knowledge was assessed using multiple-choice questions. Fellows completing their first year of fellowship were surveyed before curriculum implementation ("pre-curriculum") and compared to first-year fellows who complete the curriculum the following year ("post-curriculum"). RESULTS: Forty-nine (88%) program directors and 105 (67%) fellows completed the pre-curriculum surveys; 35 (64%) program directors and 79 (50%) fellows completed the post-curriculum surveys. Prior to IDSA curriculum implementation, only 51% of programs had a "formal" curriculum. After implementation, satisfaction with AS training increased among program directors (16% to 68%) and fellows (51% to 68%). Fellows' confidence increased in 7/10 AS content areas. Knowledge scores improved from a mean of 4.6 to 5.1 correct answers of 9 questions (P = .028). The major hurdle to curriculum implementation was time, both for formal teaching and for e-learning. CONCLUSIONS: Effective AS training is a critical component of ID fellowship training. The IDSA Core AS Curriculum can enhance AS training, increase fellow confidence, and improve overall satisfaction of fellows and program directors.

Pediatric antimicrobial stewardship practices at discharge: A national survey.

We surveyed pediatric antimicrobial stewardship program (ASP) site leaders within the Sharing Antimicrobial Reports for Pediatric Stewardship collaborative regarding discharge stewardship practices. Among 67 sites, 13 (19%) reported ASP review of discharge antimicrobial prescriptions. These findings highlight discharge stewardship as a potential opportunity for improvement during the hospital-to-home transition.

Implementation of Electronic Clinical Decision Support Tools for Antibiotic Stewardship in Pediatric Appendicitis.

BACKGROUND: The efficacy of clinical decision support (CDS) tools to promote antibiotic stewardship in pediatric appendicitis remains poorly understood. Here, we developed an electronic order panel (OP) to assist with decreased utilization of extended spectrum antibiotics. METHODS: Retrospective review of patients (≤18 years) at a single institution from May 2018 to October 2019 treated with ≥1 dose of preferred (narrow) or nonpreferred (broad-spectrum) antibiotics was performed, and they were categorized as pre- (PIC) or postimplementation cohorts (PISC). RESULTS: Of 234 encounters, 170 (73%) and 107 (46%) received preferred and nonpreferred antibiotics, respectively. Postimplementation cohort encounters had a sustained 50% increase in preferred antibiotic use compared to PIC (92% vs 42%, P = .014). Order panel utilization accounted for 31% of overall encounters and 44% of PISC encounters. CONCLUSION: Despite sustained improvement in antibiotic stewardship, OP utilization remains low. The use of CDS tools may not be a good process measure for quality improvement.

A National Survey of Outpatient Parenteral Antibiotic Therapy Practices.

We conducted a national survey of pediatric infectious diseases (ID) clinicians on outpatient parenteral antibiotic therapy (OPAT) practices and post-discharge ID follow-up. Only 15% of sites required ID consultation for all OPAT. ID division resources for post-discharge care varied. Opportunities exist to increase ID involvement in post-discharge management of serious infections.