Altered amino acid profile in patients with SARS-CoV-2 infection.

Low plasma arginine bioavailability has been implicated in endothelial dysfunction and immune dysregulation. The role of arginine in COVID-19 is unknown, but could contribute to cellular damage if low. Our objective was to determine arginine bioavailability in adults and children with COVID-19 vs. healthy controls. We hypothesized that arginine bioavailability would be low in patients with COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We conducted a prospective observational study of three patient cohorts; arginine bioavailability was determined in asymptomatic healthy controls, adults hospitalized with COVID-19, and hospitalized children/adolescents <21 y old with COVID-19, MIS-C, or asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection identified on admission screen. Mean patient plasma amino acids were compared to controls using the Student's t test. Arginine-to-ornithine ratio, a biomarker of arginase activity, and global arginine bioavailability ratio (GABR, arginine/[ornithine+citrulline]) were assessed in all three groups. A total of 80 patients were included (28 controls, 32 adults with COVID-19, and 20 pediatric patients with COVID-19/MIS-C). Mean plasma arginine and arginine bioavailability ratios were lower among adult and pediatric patients with COVID-19/MIS-C compared to controls. There was no difference between arginine bioavailability in children with COVID-19 vs. MIS-C. Adults and children with COVID-19 and MIS-C in our cohort had low arginine bioavailability compared to healthy adult controls. This may contribute to immune dysregulation and endothelial dysfunction in COVID-19. Low arginine-to-ornithine ratio in patients with COVID-19 or MIS-C suggests an elevation of arginase activity. Further study is merited to explore the role of arginine dysregulation in COVID-19.

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents.

BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).

Cardiac complications in children with acute COVID-19 vs multisystem inflammatory syndrome in children (MIS-C).

BACKGROUND: Cardiac involvement can lead to significant morbidity in children with acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C). However, the presentation and outcomes of cardiac involvement may differ among these 2 conditions. We aimed to compare the frequency and extent of cardiac involvement among children admitted with acute COVID-19 vs those with MIS-C. METHODS: We conducted a cross sectional study of patients admitted to our hospital from March 2020 to August 2021 with symptomatic acute COVID-19 or MIS-C. Cardiac involvement was defined by presence of 1 or more of the following: elevated troponin, elevated brain natriuretic peptide, reduced left ventricular ejection fraction on echocardiogram, coronary dilation on echocardiogram, or abnormal electrocardiogram reading. RESULTS: Among 346 acute COVID-19 patients with median age of 8.9 years and 304 MIS-C patients with median age of 9.1 years, cardiac involvement was present in 33 acute COVID-19 patients (9.5%) and 253 MIS-C patients (83.2%). The most common cardiac abnormality was abnormal electrocardiogram in acute COVID-19 patients (7.5%) and elevated troponin in MIS-C patients (67.8%). Among acute COVID-19 patients, obesity was significantly associated with cardiac involvement. Among MIS-C patients, non-Hispanic Black race/ethnicity was significantly associated with cardiac involvement. CONCLUSIONS: Cardiac involvement is much more common in children with MIS-C than in those with acute COVID-19. These results reinforce our standardized practice of performing full cardiac evaluations and follow-up in all patients with MIS-C but only in acute COVID-19 patients with signs or symptoms of cardiac involvement.

Six-month cardiac outcomes in children with multisystem inflammatory syndrome in children.

BACKGROUND: Multisystem inflammatory syndrome in children is a rare, post-infectious complication of SARS-CoV-2 infection in children. We aimed to assess the long-term sequelae, particularly cardiac, in a large, diverse population. METHODS: We performed a retrospective cohort study of all children (aged 0-20 years, n = 304) admitted to a tertiary care centre with a diagnosis of multisystem inflammatory syndrome in children from March 1, 2020 to August 31, 2021 and had at least one follow-up visit through December 31, 2021. Data were collected at hospitalisation, 2 weeks, 6 weeks, 3 months, and 1 year after diagnosis, where applicable. Cardiovascular outcomes included left ventricular ejection fraction, presence or absence of pericardial effusion, coronary artery abnormalities, and abnormal electrocardiogram findings. RESULTS: Population was median age 9 years (IQR 5-12), 62.2% male, 61.8% African American (AA), and 15.8% Hispanic. Hospitalisation findings included abnormal echocardiogram 57.2%, mean worst recorded left ventricular ejection fraction 52.4% ± 12.4%, non-trivial pericardial effusion 13.4%, coronary artery abnormalities 10.6%, and abnormal ECG 19.6%. During follow-up, abnormal echocardiogram significantly decreased to 6.0% at 2 weeks and 4.7% at 6 weeks. Mean left ventricular ejection fraction significantly increased to 65.4% ± 5.6% at 2 weeks and stabilised. Pericardial effusion significantly decreased to 3.2% at 2 weeks and stabilised. Coronary artery abnormalities significantly decreased to 2.0% and abnormal electrocardiograms significantly decreased to 6.4% at 2 weeks and stabilised. CONCLUSION: Children with multisystem inflammatory syndrome in children have significant echocardiographic abnormalities during the acute presentation, but these findings typically improve within weeks. However, a small subset of patients may have persistent coronary abnormalities.

Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH).

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening sequela of severe acute respiratory syndrome coronavirus 2 infection characterized by hyperinflammation and multiorgan dysfunction. Although hyperinflammation is a prominent manifestation of MIS-C, there is limited understanding of how the inflammatory state of MIS-C differs from that of well-characterized hyperinflammatory syndromes such as hemophagocytic lymphohistiocytosis (HLH). OBJECTIVES: We sought to compare the qualitative and quantitative inflammatory profile differences between patients with MIS-C, coronavirus disease 2019, and HLH. METHODS: Clinical data abstraction from patient charts, T-cell immunophenotyping, and multiplex cytokine and chemokine profiling were performed for patients with MIS-C, patients with coronavirus disease 2019, and patients with HLH. RESULTS: We found that both patients with MIS-C and patients with HLH showed robust T-cell activation, markers of senescence, and exhaustion along with elevated TH1 and proinflammatory cytokines such as IFN-γ, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10. In comparison, the amplitude of T-cell activation and the levels of cytokines/chemokines were higher in patients with HLH when compared with patients with MIS-C. Distinguishing inflammatory features of MIS-C included elevation in TH2 inflammatory cytokines such as IL-4 and IL-13 and cytokine mediators of angiogenesis, vascular injury, and tissue repair such as vascular endothelial growth factor A and platelet-derived growth factor. Immune activation and hypercytokinemia in MIS-C resolved at follow-up. In addition, when these immune parameters were correlated with clinical parameters, CD8+ T-cell activation correlated with cardiac dysfunction parameters such as B-type natriuretic peptide and troponin and inversely correlated with platelet count. CONCLUSIONS: Overall, this study characterizes unique and overlapping immunologic features that help to define the hyperinflammation associated with MIS-C versus HLH.

Infectious events in pediatric patients with acute lymphoblastic leukemia/lymphoma undergoing evaluation for fever without severe neutropenia.

BACKGROUND: Infections cause significant treatment-related morbidity during pediatric acute lymphoblastic leukemia/lymphoma (ALL/LLy) therapy. Fevers during periods without severe neutropenia are common, but etiologies are not well-described. This study sought to describe the bloodstream infection (BSI) and non-BSI risk in children undergoing therapy for ALL/LLy. METHODS: Demographic and clinical data were abstracted for febrile episodes without severe neutropenia at two children's hospitals. Treatment courses were stratified by intensity. Multivariate logistic regression evaluated characteristics associated with infection. RESULTS: There were 1591 febrile episodes experienced by 524 patients. Of these, 536 (34%) episodes had ≥1 infection; BSI occurred in 30 (1.9%) episodes. No BSIs occurred in episodes with a recent procedural sedation or cytarabine exposure. Presence of hypotension, chills/rigors, higher temperature, and infant phenotype were independently associated with BSI (p < .05). Of the 572 non-BSIs, the most common was upper respiratory infection (URI) (n = 381, 67%). Compared to episodes without infection, URI symptoms, higher temperature, absolute neutrophil count 500-999/µl, and evaluation during a low-intensity treatment course were more likely to be associated with a non-BSI (p < .05) and inpatient status was less likely to be associated with a non-BSI (p < .05). CONCLUSIONS: The BSI rate in pediatric patients with ALL/LLy and fever without severe neutropenia is low, but one-third of the time, patients have a non-BSI. Future research should test if the need for empiric antibiotics can be tailored based on the associations identified in this study.

Multisystem Inflammatory Syndrome in Children: Survey of Protocols for Early Hospital Evaluation and Management.

OBJECTIVE: To describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US. STUDY DESIGN: We conducted a cross-sectional survey from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which >5 patients had been treated vs those in which ≤5 patients had been treated. RESULTS: In all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which >5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided. CONCLUSIONS: There are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C.

Chest radiograph features of multisystem inflammatory syndrome in children (MIS-C) compared to pediatric COVID-19.

BACKGROUND: Although the radiographic features of coronavirus disease 2019 (COVID-19) in children have been described, the distinguishing features of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 are not well characterized. OBJECTIVE: We compared the chest radiographic findings of MIS-C with those of COVID-19 and described other distinguishing imaging features of MIS-C. MATERIALS AND METHODS: We performed a retrospective case series review of children ages 0 to 18 years who were hospitalized at Children's Healthcare of Atlanta from March to May 2020 and who either met the Centers for Disease Control and Prevention (CDC) case definition for MIS-C (n=11) or who had symptomatic, laboratory-confirmed COVID-19 (n=16). Two radiologists reviewed the most severe chest radiographs for each patient. The type and distribution of pulmonary opacities and presence or absence of pleural effusions were recorded. The chest radiographs were categorized based on potential COVID-19 imaging findings as typical, indeterminate, atypical or negative. An imaging severity score was also assigned using a simplified version of the Radiographic Assessment of Lung Edema Score. Findings were statistically compared between patients with MIS-C and those with COVID-19. Additional imaging findings of MIS-C were also described. RESULTS: Radiographic features of MIS-C included pleural effusions (82% [9/11]), pulmonary consolidations (73% [8/11]) and ground glass opacities (91% [10/11]). All of the lung opacities (100% [10/10]) were bilateral, and the majority of the pleural effusions (67% [6/9]) were bilateral. Compared to children with COVID-19, children with MIS-C were significantly more likely to develop pleural effusions on chest radiograph (82% [9/11] vs. 0% [0/0], P-value <0.01) and a lower zone predominance of pulmonary opacifications (100% [10/10] vs. 38% [5/13], P-value <0.01). Children with MIS-C who also had abdominal imaging had intra-abdominal inflammatory changes. CONCLUSION: Key chest radiographic features of MIS-C versus those of COVID-19 were pleural effusions and lower zone pulmonary opacifications as well as intra-abdominal inflammation. Elucidating the distinguishing radiographic features of MIS-C may help refine the case definition and expedite diagnosis and treatment.

The Challenge of Patient Notification and the Work of Follow-Up Generated by a 2-Step Testing Protocol for Group A Streptococcal Pharyngitis in the Pediatric Emergency Department.

OBJECTIVE: Current guidelines recommend confirmatory testing for negative rapid antigen detection tests (RADTs) for group A streptococcal pharyngitis in children. We sought to describe the work of follow-up generated by this process and frequency of our inability to notify patients of positive results. METHODS: We retrospectively reviewed laboratory and outreach nurse records of patients who had group A streptococcal pharyngitis testing performed in an academic pediatric emergency department during 2014. For patients with a negative RADT and subsequent positive backup direct nucleic acid probe test, we recorded whether the patient was successfully notified of the positive result, the number of contact attempts, and the time to antibiotic prescription. RESULTS: There were 6504 patients who had an RADT performed, of which 5474 (84.2%) were negative with a confirmatory test performed. There were 234 patients with positive confirmatory testing and not prescribed antibiotics at the time of the initial visit. Of these, 90.1% were ultimately contacted and prescribed appropriate antibiotics, whereas 7.3% were lost to follow-up and 2.6% had potentially unnecessary repeat visits. Of those contacted, 43.1% were reached only after multiple telephone calls or a letter. The median time from the negative RADT to the submission of an electronic prescription was 19.6 hours (interquartile range, 7.5-24.9 hours; range, 6-144 hours). CONCLUSIONS: Although confirmatory testing after a negative RADT in children is currently the standard of care, this practice requires a substantial amount of work. Furthermore, a significant fraction of patients are lost to follow-up or have unnecessary repeat visits.

Healthcare Claims Data: An Underutilized Tool for Pediatric Outpatient Antimicrobial Stewardship.

BACKGROUND.: Healthcare claims are underutilized to identify factors associated with high outpatient antibiotic use. METHODS.: We evaluated ambulatory encounter claims of Medicaid-insured children in 34 Ohio counties in 2014. Rates of total antibiotic and azithromycin prescriptions dispensed were determined by county of patient residence. Standardized treatment rates by county were estimated for uncomplicated upper respiratory tract encounters (acute otitis media, pharyngitis, sinusitis, presumed viral infection) after adjusting for patient age and encounter provider type. Uncomplicated encounters included healthy children at initial presentation of illness. Adjusted odds of treatment were calculated for patient age, provider type, and county characteristics (rural vs metropolitan; poverty rate). RESULTS.: Retail pharmacies dispensed 255291 antibiotics to this cohort in 2014. More than 25% were to children <3 years. County rates of total antibiotic and azithromycin prescriptions dispensed were 530.4-1548.3 and 57.3-378.7 per 1000 person-years, respectively. Of 246866 uncomplicated upper respiratory tract encounters, antibiotics were dispensed (within 3 days) in 46.1%. Presumed viral infection accounted for 18.5% of antibiotics. Standardized treatment rates by county ranged widely from 35.9% (95% confidence interval [CI], 33.3%-38.5%) to 63.2% (95% CI, 61.5%-64.9%). Compared to encounters with pediatricians, adjusted odds ratio of treatment was 2.02 (95% CI, 1.96-2.07) for family physicians and 1.74 (95% CI, 1.68-1.79) for nurse practitioners. Residence in rural or high-poverty counties increased odds of treatment. CONCLUSIONS.: Healthcare claims were useful to identify populations and providers with high antibiotic use. Claims data could be considered to track and report antibiotic prescribing frequency, especially where electronic medical records are not available.

Performance Characteristics of FilmArray Respiratory Panel v1.7 for Detection of Adenovirus in a Large Cohort of Pediatric Nasopharyngeal Samples: One Test May Not Fit All.

The FilmArray Respiratory Panel (RP) v1.7 assay has improved sensitivity for detection of human adenovirus (HAdV), compared to an earlier version (RP v1.6). RP v1.7 was designed for detection of species B, C, and E but may show variable detection of species A, D, and F. We sought to evaluate the clinical and analytical performance of RP v1.7 for detection of HAdV in a large pediatric cohort. Respiratory specimens obtained from a tertiary care children's hospital between February 2014 and February 2015 were tested for HAdV by RP v1.7. If the RP v1.7 results were negative for HAdV, then the specimens were reflexed to a HAdV-specific laboratory-developed PCR (LD-PCR) assay for confirmation. A subset of specimens underwent secondary confirmatory testing using another commercially available HAdV PCR assay and a molecular typing assay for species identification. Among 4,750 specimens, a total of 146 specimens (3.1%) were HAdV positive by RP v1.7. HAdV was detected by LD-PCR in an additional 220 specimens that were negative by RP v1.7. Overall, a nearly 5% increase in HAdV detection was observed when RP v1.7-negative specimens were reflexed to LD-PCR testing. RP v1.7 did not detect HAdV with either low viral burden (threshold cycle values of >30) or nonrespiratory species (species A, D, and F), as shown in both clinical and analytic data. While the level of sensitivity of RP v1.7 may be adequate for testing among otherwise healthy children, the decreased sensitivity may be problematic for immunocompromised patients, in whom low levels of HAdV in the respiratory tract may precede systemic infection and require early intervention.

Clinical and Virologic Characteristics May Aid Distinction of Acute Adenovirus Disease from Kawasaki Disease with Incidental Adenovirus Detection.

Incidental adenovirus detection in Kawasaki disease (KD) is important to differentiate from acute adenovirus disease. Twenty-four of 25 children with adenovirus disease and mimicking features of KD had <4 KD-like features, predominance of species B or E, and higher viral burden compared with those with KD and incidental adenovirus detection.

Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial.

BACKGROUND: Kawasaki disease, the most common cause of acquired heart disease in developed countries, is a self-limited vasculitis that is treated with high doses of intravenous immunoglobulin. Resistance to intravenous immunoglobulin in Kawasaki disease increases the risk of coronary artery aneurysms. We assessed whether the addition of infliximab to standard therapy (intravenous immunoglobulin and aspirin) in acute Kawasaki disease reduces the rate of treatment resistance. METHODS: We undertook a phase 3, randomised, double-blind, placebo-controlled trial in two children's hospitals in the USA to assess the addition of infliximab (5 mg per kg) to standard therapy. Eligible participants were children aged 4 weeks-17 years who had a fever (temperature ≥38·0°C) for 3-10 days and met American Heart Association criteria for Kawasaki disease. Participants were randomly allocated in 1:1 ratio to two treatment groups: infliximab 5 mg/kg at 1 mg/mL intravenously over 2 h or placebo (normal saline 5 mL/kg, administered intravenously). Randomisation was based on a randomly permuted block design (block sizes 2 and 4), stratified by age, sex, and centre. Patients, treating physicians and staff, study team members, and echocardiographers were all masked to treament assignment. The primary outcome was the difference between the groups in treatment resistance defined as a temperature of 38·0°C or higher at 36 h to 7 days after completion of the infusion of intravenous immunoglobulin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00760435. FINDINGS: 196 patients were enrolled and randomised: 98 to the infliximab group and 98 to placebo. One patient in the placebo group was withdrawn from the study because of hypotension before receiving treatment. Treatment resistance rate did not differ significantly (11 [11·2%] for infliximab and 11 [11·3%] for placebo; p=0·81). Compared with the placebo group, participants given infliximab had fewer days of fever (median 1 day for infliximab vs 2 days for placebo; p<0·0001). At week 2, infliximab-treated patients had greater mean reductions in erythrocyte sedimentation rate (p=0·009) and a two-fold greater decrease in Z score of the left anterior descending artery (p=0·045) than did those in the placebo group, but this difference was not significant at week 5. Participants in the infliximab group had a greater mean reduction in C-reactive protein concentration (p=0·0003) and in absolute neutrophil count (p=0·024) at 24 h after treatment than did those given placebo, but by week 2 this difference was not significant. At week 5, none of the laboratory values differed significantly compared with baseline. No significant differences were recorded between the two groups at any timepoint in proximal right coronary artery Z scores, age-adjusted haemoglobin values, duration of hospital stay, or any other laboratory markers of inflammation measured. No reactions to intravenous immunoglobulin infusion occurred in patients treated with infliximab compared with 13 (13·4%) patients given placebo (p<0·0001). No serious adverse events were directly attributable to infliximab infusion. INTERPRETATION: The addition of infliximab to primary treatment in acute Kawasaki disease did not reduce treatment resistance. However, it was safe and well tolerated and reduced fever duration, some markers of inflammation, left anterior descending coronary artery Z score, and intravenous immunoglobulin reaction rates. FUNDING: US Food and Drug Administration, Robert Wood Johnson Foundation, and Janssen Biotech.

Multicenter Clinical Evaluation of the Novel Alere i Strep A Isothermal Nucleic Acid Amplification Test.

Rapid detection of group A beta-hemolytic streptococcus (GAS) is used routinely to help diagnose and treat pharyngitis. However, available rapid antigen detection tests for GAS have relatively low sensitivity, and backup testing is recommended in children. Newer assays are more sensitive yet require excessive time for practical point-of-care use as well as laboratory personnel. The Alere i strep A test is an isothermal nucleic acid amplification test designed to offer highly sensitive results at the point of care within 8 min when performed by nonlaboratory personnel. The performance of the Alere i strep A test was evaluated in a multicenter prospective trial in a Clinical Laboratory Improvement Amendments (CLIA)-waived setting in comparison to bacterial culture in 481 children and adults. Compared to culture, the Aleri i strep A test had 96.0% sensitivity and 94.6% specificity. Discrepant results were adjudicated by PCR and found the Alere i strep A test to have 98.7% sensitivity and 98.5% specificity. Overall, the Alere i strep A test could provide a one-step, rapid, point-of-care testing method for GAS pharyngitis and obviate backup testing on negative results.

Diagnosis of systemic-onset juvenile idiopathic arthritis after treatment for presumed Kawasaki disease.

OBJECTIVES: To estimate the incidence of systemic-onset juvenile idiopathic arthritis (SoJIA) within 6 months after treatment for presumed Kawasaki disease (KD) (presumed patients with KD with subsequent diagnosis of SoJIA [pKD/SoJIA]) and describe presentation differences from sole KD. STUDY DESIGN: We identified patients treated for KD at Nationwide Children's Hospital and from the Pediatric Health Information System from 2009-2013. We then identified the subset of children, pKD/SoJIA, who received an International Classification of Diseases, Ninth Revision code for SoJIA and had it listed at least once 3 months after and within 6 months after KD diagnosis. Demographic characteristics, readmission rates, treatments, and complications were noted. A literature review was also performed to identify clinical, laboratory, and echocardiographic data of previously documented patients with KD later diagnosed with SoJIA. RESULTS: There were 6745 total treated patients with KD in the Pediatric Health Information System database during the study period; 10 patients were identified to have pKD/SoJIA (0.2% of cohort). Those with pKD/SoJIA were predominantly Caucasian compared with patients with KD (90% and 46.8%, respectively; P=.003). Macrophage activation syndrome was more common in patients with pKD/SoJIA than in sole patients with KD (30% and 0.30%, respectively; P<.001). Fifteen cases of pKD/SoJIA were identified by literature and chart review, 12 of whom were initially diagnosed with incomplete KD. CONCLUSIONS: We reported a 0.2% incidence of pKD/SoJIA, which was associated with Caucasian race, macrophage activation syndrome, and an incomplete KD phenotype.

Healthcare Sustainability to Address Climate Change: Call for Action to the Infectious Diseases Community.

The US healthcare system's contribution to greenhouse gas emissions and climate change is disproportionately high and harms the public. Several medical specialties are now reassessing how they can mitigate healthcare's harmful environmental impact. Healthcare sustainability is broadly defined as measures to decrease greenhouse gas emissions, waste, and other pollutants generated during the healthcare delivery process. Prior efforts and programs by infectious diseases (ID) professionals, such as antimicrobial stewardship and infection prevention and control can form a framework for ID professionals to help apply this expertise to healthcare environmental sustainability more broadly. This call to action proposes strategies for ID societies and professionals to incorporate climate change education for trainees, increase research and funding opportunities in healthcare sustainability, and calls for action by ID societies to champion system changes to decrease greenhouse gas emissions.

Antibiotic waste in a pediatric healthcare system: Wasting drugs that are in limited supply.

In a pediatric hospital system over 2 years, 58,607 doses of antibiotic were wasted, an average of 80 doses per day, including drugs in shortage nationwide. Approximately 50% of waste occurred within the first 2 days of admission or the day of discharge, with ampicillin being the most wasted drug (N = 7,789 doses).

"Give Me Five": The Case for 5 Days of Antibiotics as the Default Duration for Acute Respiratory Tract Infections.

Acute respiratory tract infections (ARTIs) account for most antibiotic prescriptions in pediatrics. Although US guidelines continue to recommend ≥10 days antibiotics for common ARTIs, evidence suggests that 5-day courses can be safe and effective. Academic imprinting seems to play a major role in the continued use of prolonged antibiotic durations. In this report, we discuss the evidence supporting short antibiotic courses for group A streptococcal pharyngitis, acute otitis media, and acute bacterial rhinosinusitis. We discuss the basis for prolonged antibiotic course recommendations and recent literature investigating shorter courses. Prescribers in the United States should overcome academic imprinting and follow international trends to reduce antibiotic durations for common ARTIs, where 5 days is a safe and efficacious course when antibiotics are prescribed.

Antimicrobial Stewardship and Improved Antibiotic Utilization in the Pediatric Cardiac Intensive Care Unit.

Background: We developed a multidisciplinary antimicrobial stewardship team to optimize antimicrobial use within the Pediatric Cardiac Intensive Care Unit. A quality improvement initiative was conducted to decrease unnecessary broad-spectrum antibiotic use by 20%, with sustained change over 12 months. Methods: We conducted this quality improvement initiative within a quaternary care center. PDSA cycles focused on antibiotic overuse, provider education, and practice standardization. The primary outcome measure was days of therapy (DOT)/1000 patient days. Process measures included electronic medical record order-set use. Balancing measures focused on alternative antibiotic use, overall mortality, and sepsis-related mortality. Data were analyzed using statistical process control charts. Results: A significant and sustained decrease in DOT was observed for vancomycin and meropenem. Vancomycin use decreased from a baseline of 198 DOT to 137 DOT, a 31% reduction. Meropenem use decreased from 103 DOT to 34 DOT, a 67% reduction. These changes were sustained over 24 months. The collective use of gram-negative antibiotics, including meropenem, cefepime, and piperacillin-tazobactam, decreased from a baseline of 323 DOT to 239 DOT, a reduction of 26%. There was no reciprocal increase in cefepime or piperacillin-tazobactam use. Key interventions involved electronic medical record changes, including automatic stop times and empiric antibiotic standardization. All-cause mortality remained unchanged. Conclusions: The initiation of a dedicated antimicrobial stewardship initiative resulted in a sustained reduction in meropenem and vancomycin usage. Interventions did not lead to increased utilization of alternative broad-spectrum antimicrobials or increased mortality. Future interventions will target additional broad-spectrum antimicrobials.