Differences in pediatric SARS-CoV-2 symptomology and Co-infection rates among COVID-19 Pandemic waves.

An estimated 12.8 million pediatric SARS-CoV-2 infections have occurred within the United States as of March 1 2022, with multiple epidemic waves due to emergence of several SARS-CoV-2 variants. The aim of this study was to compare demographics, clinical presentation, and detected respiratory co-infections during COVID-19 waves to better understand changes in pediatric SARS-CoV-2 epidemiology over time.

Adapted from: Prevention of Viridans Group Streptococcal Infective Endocarditis: A Scientific Statement From the American Heart Association.

BACKGROUND: In 2007, the American Heart Association published updated evidence-based guidelines on the recommended use of antibiotic prophylaxis to prevent viridans group streptococcal (VGS) infective endocarditis (IE) in cardiac patients undergoing invasive procedures. The 2007 guidelines significantly scaled back the underlying conditions for which antibiotic prophylaxis was recommended, leaving only 4 categories thought to confer the highest risk of adverse outcome. The purpose of this update is to examine interval evidence of the acceptance and impact of the 2007 recommendations on VGS IE and, if needed, to make revisions based on this evidence. METHODS AND RESULTS: A writing group was formed consisting of experts in prevention and treatment of infective endocarditis including members of the American Dental Association, the Infectious Diseases Society of America, and the American Academy of Pediatrics, in addition to the American Heart Association. MEDLINE database searches were done for English language articles on compliance with the recommendations in the 2007 guidelines and the frequency of and morbidity or mortality from VGS IE after publication of the 2007 guidelines. Overall, there was good general awareness of the 2007 guidelines but variable compliance with recommendations. There was no convincing evidence that VGS IE frequency, morbidity, or mortality has increased since 2007. CONCLUSIONS: On the basis of a review of the available evidence, there are no recommended changes to the 2007 VGS IE prevention guidelines. We continue to recommend VGS IE prophylaxis only for categories of patients at highest risk for adverse outcome while emphasizing the critical role of good oral health and regular access to dental care for all. Randomized controlled studies to determine whether antibiotic prophylaxis is effective against VGS IE are needed to further refine recommendations.

Maternal parechovirus A (PeV-A) shedding, serostatus, and the risk of central nervous system PeV-A infections in infants.

BACKGROUND: Parechovirus A (PeV-A) has emerged as a leading cause of infant central nervous system (CNS) infections. Risk factors associated with infant acquisition of PeV-A are not well understood. METHODS: We conducted prospective PeV-A/enterovirus (EV) CNS infection surveillance, enrolling 461 hospitalized infants <90 days old who underwent sepsis evaluations and lumbar puncture during 2011-2012. Infants were grouped by RT-PCR detection of PeV-A, EV, or neither virus (Neg) in CSF. We collected demographic/clinical data and tested specimens from all infants. For 427 mothers, we collected demographic/clinical data and evaluated PeV-A3 and EV shedding, and PeV-A3 neutralizing antibody for 147 mothers. RESULTS: PeV-A was detected in 40 infants (8.7%), 4 in 2011 and 36 in 2012. EV was detected in 35 infants (7.6%), 16 in 2011, and 19 in 2012. PeV-A infected infants presented with irritability, abdominal discomfort, fever, and tachycardia, plus both lymphopenia and absence of CSF pleocytosis which help differentiate PeV-A from EV CNS infection. PeV-A was detected in 9/427 maternal throat swabs; eight of their infants also had PeV-A CNS infection. Infants whose mothers had PeV-A3-positive throat swabs were more likely to be PeV-A3-positive than infants whose mothers had negative throat swabs (relative risk [RR], 13.4 [95% CI, 8.6 - 20.7]). Maternal PeV-A3 seropositivity decreased with increasing maternal age. Mothers of PeV-A-positive infants had lower median PeV-A3 neutralizing titers and were more likely seronegative. CONCLUSIONS: Maternal viral shedding, serostatus and neutralization titers appear to be important factors in infant PeV-A3 CNS infections.

Prevention of Viridans Group Streptococcal Infective Endocarditis: A Scientific Statement From the American Heart Association.

BACKGROUND: In 2007, the American Heart Association published updated evidence-based guidelines on the recommended use of antibiotic prophylaxis to prevent viridans group streptococcal (VGS) infective endocarditis (IE) in cardiac patients undergoing invasive procedures. The 2007 guidelines significantly scaled back the underlying conditions for which antibiotic prophylaxis was recommended, leaving only 4 categories thought to confer the highest risk of adverse outcome. The purpose of this update is to examine interval evidence of the acceptance and impact of the 2007 recommendations on VGS IE and, if needed, to make revisions based on this evidence. METHODS AND RESULTS: A writing group was formed consisting of experts in prevention and treatment of infective endocarditis including members of the American Dental Association, the Infectious Diseases Society of America, and the American Academy of Pediatrics, in addition to the American Heart Association. MEDLINE database searches were done for English language articles on compliance with the recommendations in the 2007 guidelines and the frequency of and morbidity or mortality from VGS IE after publication of the 2007 guidelines. Overall, there was good general awareness of the 2007 guidelines but variable compliance with recommendations. There was no convincing evidence that VGS IE frequency, morbidity, or mortality has increased since 2007. CONCLUSIONS: On the basis of a review of the available evidence, there are no recommended changes to the 2007 VGS IE prevention guidelines. We continue to recommend VGS IE prophylaxis only for categories of patients at highest risk for adverse outcome while emphasizing the critical role of good oral health and regular access to dental care for all. Randomized controlled studies to determine whether antibiotic prophylaxis is effective against VGS IE are needed to further refine recommendations.

Childhood Outcomes Following Parechovirus Infections in a US Young Infant Cohort.

BACKGROUND: Parechovirus A type 3 (PeV-A3) is associated with central nervous system infection in young infants. There are limited data regarding long-term outcomes, mostly reported from Australia and European populations. The objective of this study was to assess frequency of neurodevelopmental impairment (NDI) following PeV-A3 infection in our US cohort. METHODS: Infants hospitalized during the 2014 outbreak with laboratory-confirmed PeV-A3 infection were evaluated with medical history, neurologic examination, parental completion of Ages and Stages Questionnaire and developmental assessment using Bayley Scales of Infant and Toddler Development, Third Edition cognitive, motor and language quotients. Determination of NDI was based on published criteria. Relationship of severity of PeV disease to outcome measures was determined using Fisher exact, χ2 and Mann-Whitney U test as appropriate. RESULTS: Nineteen children, term gestation, were evaluated at ~3 years of age; PeV-A3 illness was uncomplicated for 6 (32%), complex, non-neurologic for 9 (47%) and encephalitis/seizures for 4 (21%). No differences were noted in mean Bayley Scales of Infant and Toddler Development, Third Edition quotients between infants by clinical presentation. Quotients for all were within 1 SD of population norms. Two (11%) children had mild NDI; 1 with mild cerebral palsy. Ages and Stages Questionnaire results included 11% at referral level and 37% suspect concern. Parents of 6 (32%) noted behavior concerns. These findings were unrelated to severity of the PeV-A3 illness. CONCLUSIONS: Parent concerns were identified frequently following infant PeV-A3 disease. Eleven percent had neurodevelopmental impairment at 3 years of age. Severity at presentation did not correlate with adverse childhood outcomes. Longitudinal developmental monitoring following infantile PeV-A3 disease is warranted.

Policy Statement: Antibiotic Stewardship in Pediatrics.

Antibiotic overuse contributes to antibiotic resistance, which is a threat to public health. Antibiotic stewardship is a practice dedicated to prescribing antibiotics only when necessary and, when antibiotics are considered necessary, promoting the use of the appropriate agent(s), dose, duration, and route of therapy to optimize clinical outcomes while minimizing the unintended consequences of antibiotic use. Because there are differences in common infectious conditions, drug-specific considerations, and the evidence surrounding treatment recommendations (eg, first-line therapy and duration of therapy) between children and adults, this statement provides specific guidance for the pediatric population. This policy statement discusses the rationale for inpatient and outpatient antibiotic stewardship programs (ASPs); essential personnel, infrastructure, and activities required; approaches to evaluating their effectiveness; and gaps in knowledge that require further investigation. Key guidance for both inpatient and outpatient ASPs are provided.

Antibiotic Stewardship in Pediatrics.

Antibiotic overuse contributes to antibiotic resistance, which is a threat to public health. Antibiotic stewardship is a practice dedicated to prescribing antibiotics only when necessary and, when antibiotics are considered necessary, promoting use of the appropriate agent(s), dose, duration, and route of therapy to optimize clinical outcomes while minimizing the unintended consequences of antibiotic use. Because there are differences in common infectious conditions, drug-specific considerations, and the evidence surrounding treatment recommendations (eg, first-line therapy, duration of therapy) between children and adults, this statement provides specific guidance for the pediatric population. This policy statement discusses the rationale for inpatient and outpatient antibiotic stewardship programs; essential personnel, infrastructure, and activities required; approaches to evaluating their effectiveness; and gaps in knowledge that require further investigation. Key guidance for both inpatient and outpatient antibiotic stewardship programs are provided.

The Kawasaki Disease Comparative Effectiveness (KIDCARE) trial: A phase III, randomized trial of second intravenous immunoglobulin versus infliximab for resistant Kawasaki disease.

BACKGROUND: Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease (KD), the most common cause of acquired heart disease in children, 10-20% of patients are IVIG-resistant and require additional therapy. This group has an increased risk of coronary artery aneurysms (CAA) and there has been no adequately powered, randomized clinical trial in a multi-ethnic population to determine the optimal therapy for IVIG-resistant patients. OBJECTIVES: The primary outcome is duration of fever in IVIG-resistant patients randomized to treatment with either infliximab or a second IVIG infusion. Secondary outcomes include comparison of inflammatory markers, duration of hospitalization, and coronary artery outcome. An exploratory aim records parent-reported outcomes including signs, symptoms and treatment experience. METHODS: The KIDCARE trial is a 30-site randomized Phase III comparative effectiveness trial in KD patients with fever ≥36 h after the completion of their first IVIG treatment. Eligible patients will be randomized to receive either a second dose of IVIG (2 g/kg) or infliximab (10 mg/kg). Subjects with persistent or recrudescent fever at 24 h following completion of the first study treatment will cross-over to the other treatment arm. Subjects will exit the study after their first outpatient visit (5-18 days following last study treatment). The parent-reported outcomes, collected daily during hospitalization and at home, will be compared by study arm. CONCLUSION: This trial will contribute to the management of IVIG-resistant patients by establishing the relative efficacy of a second dose of IVIG compared to infliximab and will provide data regarding the patient/parent experience of these treatments.

Neutralizing Antibody against Enterovirus D68 in Children and Adults before 2014 Outbreak, Kansas City, Missouri, USA1.

We evaluated enterovirus D68 seroprevalence in Kansas City, Missouri, USA, from samples obtained during 2012-2013. Neutralizing antibodies against Fermon and the dominant 2014 Missouri isolate were universally detected. Titers increased with age. Widespread circulation of enterovirus D68 occurred before the 2014 outbreak. Research is needed to determine a surrogate of protection.

Impact of multiplex molecular assay turn-around-time on antibiotic utilization and clinical management of hospitalized children with acute respiratory tract infections.

BACKGROUND: Empiric antibiotic treatment is common among children with acute respiratory tract infections (ARTI), despite infections being predominately viral. The use of molecular respiratory panel assays has become increasingly common for medical care of patients with ARTIs. STUDY DESIGN: This was a 6-year retrospective, single-centered study of pediatric inpatients who tested positive for an ARTI respiratory pathogen. We examined the relationship between clinical outcomes and whether the patient was tested using the Luminex Respiratory Viral Panel ([RVP]; in-use: Dec. 2009 - Jul. 2012) or Biofire Respiratory Pathogen Panel ([RP]; in-use Aug. 2012 - Jun. 2016). The prevalence and duration of pre-test empiric antibiotics, post-test oseltamivir administration to influenza patients, chest x-rays and length of stay between the two assays was compared. RESULTS: A total of 5142 patients (1264 RVP; 3878 RP) were included. The median laboratory turn-around-time for RP was significantly shorter than RVP (1.4 vs. 27.1 h, respectively; p < .001). Patients tested with RP were less likely to receive empiric antibiotics (OR: 0.45; p < .001; 95% CI: 0.39, 0.52) and had a shorter duration of empiric broad-spectrum antibiotics (6.4 h vs. 32.9 h; p < .001) compared to RVP patients. RP influenza patients had increased oseltamivir use post- test compared to RVP influenza patients (OR: 13.56; p < .001; 95% CI: 7.29, 25.20). CONCLUSIONS: Rapid molecular testing positively impacts patient management of ARTIs. Adopting assays with a shorter turn-around-time improves decision making by decreasing empirical antibiotic use and duration, decreasing chest x-rays, increasing timely oseltamivir administration, and reducing length of stay.