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BACKGROUND: Estimates of rotavirus vaccine effectiveness (VE) in the United States appear higher in years with more rotavirus activity. We hypothesized rotavirus VE is constant over time but appears to vary as a function of temporal variation in local rotavirus cases and/or misclassified diagnoses. METHODS: We analyzed 6 years of data from eight US surveillance sites on 8- to 59-month olds with acute gastroenteritis symptoms. Children’s stool samples were tested via enzyme immunoassay (EIA); rotavirus-positive results were confirmed with molecular testing at the US Centers for Disease Control and Prevention. We defined rotavirus gastroenteritis cases by either positive on-site EIA results alone or positive EIA with Centers for Disease Control and Prevention confirmation. For each case definition, we estimated VE against any rotavirus gastroenteritis, moderate-to-severe disease, and hospitalization using two mixed-effect regression models: the first including year plus a year–vaccination interaction, and the second including the annual percent of rotavirus-positive tests plus a percent positive–vaccination interaction. We used multiple overimputation to bias-adjust for misclassification of cases defined by positive EIA alone. RESULTS: Estimates of annual rotavirus VE against all outcomes fluctuated temporally, particularly when we defined cases by on-site EIA alone and used a year–vaccination interaction. Use of confirmatory testing to define cases reduced, but did not eliminate, fluctuations. Temporal fluctuations in VE estimates further attenuated when we used a percent positive–vaccination interaction. Fluctuations persisted until bias-adjustment for diagnostic misclassification. CONCLUSIONS: Both controlling for time-varying rotavirus activity and bias-adjusting for diagnostic misclassification are critical for estimating the most valid annual rotavirus VE.

Background As of 2017 (WHO, 2017), diarrheal disease ranked second as a cause of worldwide mortality for children under five years of age. Approximately 50-70% of acute gastroenteritis (AGE) is viral in etiology, with commonly detected viruses including norovirus, rotavirus, and adenovirus. However, the epidemiology of less commonly detected viruses, specifically enterovirus (EV) and parechovirus A (PeV-A), associated AGE in the United States is not well described. The purpose of our study was to determine the prevalence of EV and PeV-A in children with AGE vs. healthy controls (HC) over a 7-year period. Methods From December 2011 – November 2018, we screened stool samples from children less than 18 years of age prospectively enrolled in Children’s Mercy-Kansas City’s (CM-KC) site for the CDC’s New Vaccine Surveillance Network; 3005 samples from subjects presenting with AGE and 1097 from HC. Samples from 2011 – 2016 (AGE: 2453; HC:752) and 2017 – 2018 (AGE:552; HC:344) were tested at CDC and CM-KC respectively by a real-time-PCR assay using specific EV and PeV-A primers targeting the highly conserved 5’ untranslated region. Demographic data were collected from EMR. Results Among 3005 AGE samples, EV was detected in 12.5% (n=386/3004), and PeV-A in 10.3% (n=252/3005). Among 1097 HC samples, EV was detected in 9.0% (99/1096), and PeV-A in 11.9% (130/1097). In 2014-2015 EV detection in AGE was highest (17.9%) among all years and significantly higher (p=0.004) than in HC samples (9.1%), whereas PeV-A detection in AGE was 9.5% vs. 15.6% in HC samples, p=0.008 (Table 1). Co-infections with EV and PeV-A were seen in 55 AGE and 21 HC. Most EV detections (45.1%) were in 1- to 2-year-olds, whereas PeV-A detections (47.3%) were in children < 1 year old (Table 2). Both EV (58.3%) and PeV-A (48.4%) detections were significantly more frequent in male children (p=0.006). The highest frequency of EV detections was in summer to fall months, and for PeV-A in late summer through early winter. Conclusion We report a higher prevalence of EV infections in AGE, and PeV-A infections in HC during 2011 to 2018, plus their seasonal and age distributions. Although our data do not currently demonstrate an association between detection of EV or PeV-A types and AGE, additional data could provide more clarity into a potential association. Disclosures Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Mary E. Moffatt, M.D., Becton and Dickinson and Company: Stocks/Bonds|Biogen: Stocks/Bonds|Coloplast B: Stocks/Bonds|Express Scripts: Stocks/Bonds|Novo Nordisk A/S Spons ADR: Stocks/Bonds|Novo Nordisk A/S-B: Stocks/Bonds|Steris PLC: Stocks/Bonds|Stryker Corp: Stocks/Bonds|Thermo Fisher Scientific: Stocks/Bonds Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.

Background Non-polio Enteroviruses (EV) are important neonatal CNS pathogens. Multiple EV genotypes have been detected in pediatric CSF, e.g. Echovirus (E) 6 and E30. CSF innate immune responses to EV genotypes remain poorly defined. Most data are from EV-A71 or E30 CNS infections and do not compare responses between these or other EV types. We sought to better define innate immune responses to EV genotypes in CSF. Methods Salvaged standard of care CSF samples from ≤6 month olds (real time EV PCR(+) or EV PCR(-) controls) from Jan 2010 - Dec 2020 were tested in duplicate on a 21- cytokine bead panel (MilliporeSigma). EV positive samples were previously genotyped by sequencing the viral capsid gene. Cytokine levels calculated from the standard curve were compared by Kruskal-Wallis and post-hoc analysis (GraphPad Prism 8.4.3). Natural partitioning of participants was explored using principal component analysis and cluster analysis (IBM SPSS v27). The utility of cytokine signatures in predicting EV status was explored using discriminant analysis and ROC analysis (IBM SPSS v27). Results Data from 72 CSF with E6 (N=16), E9 (N= 9), E18 (N=9), and E30 (N=21) showed significant differences among EV genotypes vs. controls for 20 cytokines (IL-17 was excluded). Significant differences in cytokine levels in EV CSF vs controls were seen: E6 for all 20 cytokines; E9 for Fractalkine, IP10, and MCP1; E18 for Fractalkine and MCP1; E30 19 cytokines (not GM-CSF). PCA revealed only minor overlap of controls and EV positives; EV types overlapped, except E30, differing most from E9 and E18 but overlapping E6. The most important type-differentiating cytokines by PCA were MCP1, Fractalkine, IL-8, and IL-10. Patterns in DA resembled PCA; controls clearly separated from EV CSF, E30 being the most distinct. Overall, the discriminant model correctly classified EV type or controls at a 63% rate - highest for controls (94.1%) and E30 (74.1%). In the DA model, the most important cytokines were IP-10, IL-2, IL-1Ra, and Fractalkine. Discriminant scores had the largest area under the curve (AUC), 0.990. Among cytokines, IFNa2 had the largest AUC, 0.987. Conclusion Preliminary data show significant EV-genotype differences in innate immune response to CNS infections. Cytokine patterns may serve as a key predictor for discerning EV genotypes. Disclosures Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.

Background Mycoplasma pneumoniae (MP), a common pediatric pneumonia pathogen, has 2 subtypes based on P1 adhesin gene variation. Macrolide-resistant MP (MRMP), seen since 2000 in many countries, has been subtype associated. Limited U.S. pediatric data exist on MP subtype or MRMP frequency and their clinical importance. Methods During 2015–2020, mid-turbinate nasal swab (MTNS) specimens and/or throat swabs were collected from children with acute respiratory illness (ARI) enrolled in emergency department (ED) or outpatient and inpatient settings at 4 CDC-funded New Vaccine Surveillance Network sites (Cincinnati, Seattle, Houston, and Kansas City). Specimens were tested for MP and common respiratory viruses by singleplex or multiplex polymerase chain reaction assay (PCR). P1-subtyping for MP positive specimens used multiplex TaqMan real-time PCR while MR was assessed by real time PCR with melt curve analysis (Lightmix®, TIBMolbiol). Select demographic/clinical data were analyzed by P1 subtype (P1–1 vs. P1–2). Results Of 208 MTNS specimens from 208 children (median age 5.5 years), 110 (53%) were P1–1, 89 (43%) P1–2, and 9 (4%) untypeable. Of 199 typeable specimens, 111 (56%) came from inpatients while 88 (44%) came from ED/outpatients.Overall MRMP prevalence during 2015–2020 was low (3/208,1.4%); all MRMP (Houston: 1 each in 2016–2017 and 2019–2020, Seattle: 1 in 2018–2019) were P1–1. Differences in P1–2 vs. P1–1 proportions were significant in 2 years: P1–2 dominated in 2015–2016; P1-1 in 2019–2020 (Figure 1). Common clinical symptoms for 199 MP-positive patients were fever (84%, mean 102.5±1.5oF), shortness of breath (82%), wheezing (67%), and cough (60%). Clinical manifestations, hospitalization, and antibiotic use did not differ in P1-1 vs. P1-2 patients. Antibiotics were used in 59/199 (30%) patients overall; amoxicillin was most frequent (48/199, 24%), followed by cefdinir (9/199, 5%) and azithromycin (5/199, 3%). Conclusion MP subtypes co-circulated during 2015–2020; P1-2 dominated in 2015–2016, P1-1 in 2018–2019. Signs/symptoms were similar for P1-1 and P1-2. MRMP detection was uncommon among our pediatric subjects. Ongoing surveillance is important to assess potential changes in MR prevalence and temporal subtype variation. Disclosures Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Mary E. Moffatt, M.D., Becton and Dickinson and Company: Stocks/Bonds|Biogen: Stocks/Bonds|Coloplast B: Stocks/Bonds|Express Scripts: Stocks/Bonds|Novo Nordisk A/S Spons ADR: Stocks/Bonds|Novo Nordisk A/S-B: Stocks/Bonds|Steris PLC: Stocks/Bonds|Stryker Corp: Stocks/Bonds|Thermo Fisher Scientific: Stocks/Bonds Janet A. Englund, MD, Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccine: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|SanofiPasteur: Advisor/Consultant.

Background An optimal specimen collection method is important for pathogen detection in respiratory surveillance studies. Mid-turbinate swab (MTS) in combination with throat swab (TS) were used for collecting samples from children enrolled in Kansas City site of the New Vaccine Surveillance Network (NVSN), a prospective surveillance network for acute respiratory infections. A standalone MTS is used for standard of care (SOC) testing. We compared detections from NVSN MTS+TS vs. SOC MTS samples collected ±1 day of each other to evaluate the sensitivity of the single MTS collection in children. Methods Nucleic acid extracts from NVSN MTS+TS samples were tested by Luminex NxTag Respiratory Pathogen Panel (NxTag RPP). SOC MTS samples were tested by BioFire® Respiratory Panel 1.7. (FilmArray). All children, aged < 18 years enrolled in the inpatient and Emergency Department for NVSN (November 2015 to May 2019) with available historical MTS SOC testing results ±1 day of enrollment were included in the study. Concordance between results of NVSN MTS+TS and SOC MTS testing was measured. Results Paired NVSN and SOC samples were available from 315 subjects with median age of 16.8 months (IQR 5.0 months – 61.7 months); 59.3% (189/315) were from male subjects. An overall positivity of 93.6% was noted with 295 detections by one sample or the other. Of the 295 detections, 231 (78%) detections were in both samples; 35 (12%) detections by MTS+TS; and 29 (10%) detections by MTS only. High concordance ( >90%) and very good Kappa values (Table 1) between the 2 specimen collection methods was noted for most pathogens. 72% of discrepant samples were from children with median age 13.2 months (IQR 8.0 months – 38.6 months). Conclusion We observed high concordance between MTS and MTS+TS for all targets. Most discrepant samples were from young children in whom adequate sampling can be challenging, perhaps reducing sensitivity. Differences in time of collection and testing, and platform differences (NxTag RPP vs. FilmArray) may have impacted our data, e.g. due to variable assay sensitivities for specific targets. Regardless of these differences, our data show comparable performance between MTS alone and MTS+TS suggesting that MTS alone may be sufficient for respiratory pathogen surveillance in children. Disclosures Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.

Background Adenovirus (AdV) is a common cause of acute respiratory illness (ARI). Multiple respiratory AdV types have been identified in humans, but it remains unclear which are the most common in U.S. children with ARI. Methods We conducted a multicenter, prospective viral surveillance study at seven U.S. children’s hospitals, the New Vaccine Surveillance Network, during 12/1/16–11/30/19, prior to the COVID-19 pandemic. Children < 18 years of age seen in the emergency department or hospitalized with fever and/or respiratory symptoms were enrolled, and mid-turbinate nasal +/- throat swabs were tested using multiplex respiratory pathogen assays or real time polymerase chain reaction (PCR) test for AdV, respiratory syncytial virus (RSV), human metapneumovirus, rhinovirus/enterovirus (RV), influenza, parainfluenza viruses, and endemic coronaviruses. AdV-positive specimens were subsequently typed using single-plex qPCR assays targeting sequences in the hexon gene specific for types 1-7, 11, 14, 16 and 21. Demographics, clinical characteristics, and outcomes were compared between AdV types. Results Of 29,381 enrolled children, 2,106 (7.2%) tested positive for AdV. The distribution of types among the 1,330 (63.2%) successfully typed specimens were as follows: 31.7% AdV-2, 28.9% AdV-1, 15.3% AdV-3, 7.9% AdV-5, 5.9% AdV-7, 1.4% AdV-4, 1.2% AdV-6, 0.5% AdV-14, 0.2% AdV-21, 0.1% AdV-11, and 7.0% ≥1 AdV type. Most children with AdV-1 or AdV-2 detection were < 5 years of age (Figure 1a). Demographic and clinical characteristics varied by AdV types, including age, race/ethnicity, smoke exposure, daycare/school attendance, and hospitalization (Table 1). Co-detection with other viruses was common among all AdV types, with RV and RSV being the most frequently co-detected (Figure 1b). Fever and cough were the most common symptoms for all AdV types (Figure 2). Children with AdV-7 detected as single pathogen had higher odds of hospitalization (adjusted odds ratio 6.34 [95% CI: 3.10, 12.95], p= 0.027). Conclusion AdV-2 and AdV-1 were the most frequently detected AdV types among children over the 3-year study period. Notable clinical heterogeneity of the AdV types warrants further surveillance studies to identify AdV types that could be targeted for pediatric vaccine development. Disclosures Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support John Williams, MD, GlaxoSmithKline: Advisor/Consultant|Quidel: Advisor/Consultant Mary A. Staat, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Cepheid: Grant/Research Support|National Institute of Health: Grant/Research Support|Uptodate: Royalties Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Mary E. Moffatt, M.D., Becton and Dickinson and Company: Stocks/Bonds|Biogen: Stocks/Bonds|Coloplast B: Stocks/Bonds|Express Scripts: Stocks/Bonds|Novo Nordisk A/S Spons ADR: Stocks/Bonds|Novo Nordisk A/S-B: Stocks/Bonds|Steris PLC: Stocks/Bonds|Stryker Corp: Stocks/Bonds|Thermo Fisher Scientific: Stocks/Bonds Geoffrey A. Weinberg, MD, Merck & Co.: Honoraria|Merck & Co.: Honoraria for composing and reviewing textbook chapters, Merck Manual of Therapeutics Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Natasha B. Halasa, MD, Quidel: Grant/Research Support|Quidel: equipment donation|Sanofi: Grant/Research Support|Sanofi: HAI testing and vaccine donation.

Background Children ≤5 years of age have the highest rates of pneumococcal colonization and play an important role in the spread of pneumococcus. Our objective was to determine whether the public health measures (physical distancing, masking, and shelter-in-place orders) implemented to slow the spread of SARS-CoV-2 pandemic had an impact on pneumococcal colonization rates among children aged ≤5 years with and without respiratory symptoms during the first year of SARS-CoV-2 pandemic (4/1/20 to 3/31/21). Methods This is a single center retrospective cohort study. The study period was divided in 3 four-month periods to represent the initial period of strict adherence to public health measures (period 1: Apr-Jul), relaxation of some of these measures (period 2: Aug-Nov) and Northern hemisphere winter season (period 3: Dec-Mar). We used salvaged mid-turbinate samples obtained as part of routine care from patients without respiratory symptoms but screened for SARS-CoV-2 prior to surgery or aerosol generating procedures (asymptomatic) or from patients with respiratory symptoms tested for SARS-CoV-2 and/or other respiratory viruses (symptomatic). Samples were evaluated for pneumococcal colonization by real-time PCR using CDC lytA primers. Sample size was calculated based on the assumption of lower colonization rates in period 1 and gradual increase (10-15%) in the following study periods. Results A total of 311 patients were included (185 asymptomatic and 126 symptomatic). Demographics, SARS-CoV-2 PCR and pneumococcal colonization results are shown in Table 1. Pneumococcal colonization rates for asymptomatic and symptomatic children were 14% and 22% (p=0.06), respectively. The odds of colonization of asymptomatic children were similar during period 2 (OR 0.96 [95%CI 0.34-2.67]) and period 3 (OR 0.53 [95%CI 0.17-1.62]), using period 1 as reference and after adjusting for age, sex, and SARS-COV-2 results. The odds of colonization of symptomatic children were also similar across the 3 study periods (period 2 OR 1.28 [95%CI 0.41-4.01] and period 3 OR 0.73 [95% CI 0.24-2.18]). Table 1.Characteristics of asymptomatic and symptomatic groups Conclusion Pneumococcal colonization rates were not significantly impacted by public health measures implemented during the first year of the SARS-CoV-2 pandemic and did not correlate with SARS-CoV-2 positivity. Disclosures Liset Olarte, MD, MSc, GSK: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support Douglas S. Swanson, MD, Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J. Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric News: Honoraria|Pfizer: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.

Background According to the 2018 Infectious Diseases Society of America (IDSA) clinical practice guidelines and Centers for Disease Control and Prevention (CDC) guidance, clinicians should start antiviral treatment as soon as possible for children who are hospitalized with suspected or confirmed influenza. We assessed the use of influenza-specific antiviral therapy in children hospitalized with symptoms of acute respiratory illness and laboratory-confirmed influenza. Methods We conducted active, population-based surveillance of children hospitalized with fever and/or respiratory symptoms (12/01/2016–02/28/2020) at the seven U.S. medical centers that comprise the CDC New Vaccine Surveillance Network. We excluded children who did not undergo clinical testing (by rapid antigen testing or nucleic acid amplification test [NAAT]) or research testing (by NAAT) for influenza, those who presented out of influenza season (site- and season-specific), and those whose date of antiviral therapy or whether antiviral therapy was given was unknown. We assessed the use of influenza-specific antiviral therapy in this cohort and defined timely antiviral therapy as administration within 2 days of hospitalization. Results Of 11,275 eligible children, 1,149 (10.2%) tested positive for influenza by clinical and/or research assays (Table 1). Overall, 154 influenza cases (13.4%) were detected by clinical testing only, 428 (37.2%) by research testing only, and 567 (49.3%) by both. During their influenza-associated hospitalization, 620 children (54.0%) received influenza-specific antivirals, and therapy was timely in 572 cases (92.3%). Of those who tested positive clinically, 445/721 (61.7%) received timely antiviral therapy, 38 (5.3%) received delayed antiviral therapy, and 238 (33.0%) received no antiviral therapy. Oseltamivir was the antiviral used in all treated cases. The distribution of antiviral-treated cases varied by race and Hispanic origin and study site, but not by age at presentation or influenza season (Figure 1). Table 1 Demographic characteristics of 1,149 children with influenza enrolled in the New Vaccine Surveillance Network over four influenza seasons between December 1, 2016, and February 28, 2020. Figure 1Proportions of children with influenza enrolled in the New Vaccine Surveillance Network who received timely, delayed, or no antiviral therapy by age at presentation, race and Hispanic origin, study site, and influenza season (N=1,149). Conclusion Although antiviral therapy is recommended for all influenza-associated hospitalizations in children, antiviral prescribing remains suboptimal. Further studies would help identify and address barriers to antiviral therapy in children with influenza. Disclosures John Williams, MD, GlaxoSmithKline: Advisor/Consultant|Quidel: Advisor/Consultant Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support Mary A. Staat, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Cepheid: Grant/Research Support|National Institute of Health: Grant/Research Support|Uptodate: Royalties Geoffrey A. Weinberg, MD, Merck & Co.: Honoraria|Merck & Co.: Honoraria for composing and reviewing textbook chapters, Merck Manual of Therapeutics Flor M. Munoz, MD, MSc, Gilead: Grant/Research Support|Moderna: DSMB|Pfizer: DSMB Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Natasha B. Halasa, MD, Quidel: Grant/Research Support|Quidel: equipment donation|Sanofi: Grant/Research Support|Sanofi: HAI testing and vaccine donation.

Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data.Using NONMEM v7.3, Monte Carlo simulations (N=10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 hours (standard-dose), AMOX 45 mg/kg/dose PO every 12 hours (high-dose), and PENG 62,500 units/kg/day IV every 6 hours using six virtual subjects with ages spanning 3 months to 15 years old. The probability of target attainment (PTA) was determined for both serum and epithelial lining fluid (ELF) to achieve free drug concentrations above the minimum inhibitory concentration (%fTMIC) across the population of pneumococci for 30-50% of the dosing interval.In 2018, all 21 (100%) pneumococcal isolates were susceptible to both PENG and AMOX based on Clinical and Laboratory Standards Institute (CLSI; MIC at 2 mg/L) breakpoints, and 15 of 21 (71%) were susceptible based on EUCAST (MIC at 0.5 mg/L) breakpoints. As compared with CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% fTMIC in the serum at the susceptible MICs, standard-dose AMOX achieved4% PTA (CLSI) and86% PTA (EUCAST); high-dose AMOX achieved73% PTA (CLSI) and99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard-dose AMOX, high-dose AMOX, and PENG achieved71%,93%, and 100% PTA, respectively, in the serum at 30-50%fTMIC when each patient was stochastically linked to an MIC based on the frequency distribution of national susceptibility data. The PTA was consistently lower in ELF as compared with serum for all regimens.Based on the recent rates of resistance, antibiotic doses evaluated provide appropriate exposure for pediatric CAP based on the serum and ELF data associated with predicted clinical and microbiologic success for pneumococcus. High-dose AMOX may still be required to treat pediatric CAP, especially if using CLSI breakpoints. Ongoing surveillance for resistance is essential.

The fusion (F) protein of respiratory syncytial virus (RSV) is the major target of immunoprophylactic monoclonal antibodies (mAbs) and vaccines. Recently reported mutations in F gene antigenic sites can vary among RSV types A and B. To further understand mutations in RSV F proteins, we performed subtyping and F gene sequencing on 400 RSV-positive respiratory samples collected at four pediatric hospitals within the United States from children under 2 years old between 2018 and 2020. RSV B was predominant in 2018-2019 and RSV A in 2019-2020 (55.5% and 85.5% respectively). Compared to the reference sequence, all RSV B samples had at least one antigenic polymorphism with the most changes at sites AM14/V (100%) and Ø (93.3%) followed by II (5.8%), IV (3.9%), and p27 (2.9%). The most frequent mutations among RSV B for AM14/V site were in L172Q (100%), S173L (100%), and K191R (95.2%) while for Ø site they were in I206M (93.3%) and Q209R (93.3%). Conversely, polymorphisms were observed in only 15.3% of RSV A samples overall, specifically at antigenic sites p27 (5.9%), IV (3.0%), II (2.5%), AM14/V (2.0%), I (2.0%), and Ø (0.5%). Among RSV A cases, T122A at p27 (n = 10) and S276N at II (n = 3) were the most common substitution sites. S276N at site II was found in both RSV types. Although polymorphisms in F proteins of RSV B were more common than those in RSV A samples, changes in both subtypes were observed in key F antigenic sites which could potentially impact the efficacy of mAb therapies and vaccines.

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.

To offer: (1) Insight into the antivaccine movement's use of social media negatively impacting vaccine hesitancy and disease outbreaks, (2) Examples via case observations, and (3) Selected resources to combat vaccine hesitancy.For the past 25 years, daily social media usage has risen continually, allowing information to spread widely to a reading/listening/viewing audience via mostly unvetted social media sites. During a pandemic/epidemic (e.g., coronavirus disease 2019 pandemic), an overabundance of information from many sources, including social media, has led to what is now termed as an 'infodemic'. Infodemics arise from overwhelming amounts of both correct and incorrect information from experts and nonexperts alike. Differentiating correct from incorrect information is difficult for social media users who can be swayed by nonscientific 'influencers' or fear-mongering more than by vetted expert scientific information. Consequently, vaccine misinformation is steadily increasing via social media, the use of which is often believed to be associated with vaccine hesitancy. Stopping the spread of misinformation has been a difficult task.Vaccine misinformation on social media has been detrimental to public health. Vaccine advocates must increase the use of social media to the advantage of public health in the persistent struggle against vaccine hesitancy/refusal.

Background Human adenovirus (HAdV) is commonly associated with acute respiratory illnesses (ARI) in children and is also frequently co-detected with other viral pathogens. We compared clinical presentation and outcomes in young children with HAdV detected alone vs co-detected with other respiratory viruses. Methods We used data from a multicenter, prospective, viral surveillance study of children seen in the emergency department and inpatient pediatric settings at seven US sites. Children less than 18 years old with fever and/or respiratory symptoms were enrolled between 12/1/16 and 10/31/18 and tested by molecular methods for HAdV, human rhinovirus/enterovirus (HRV/EV), respiratory syncytial virus (RSV), parainfluenza (PIV, types 1–4), influenza (flu, types A-C), and human metapneumovirus (HMPV). Our primary measure of illness severity was hospitalization; among hospitalized children, secondary severity outcomes included oxygen support and length of stay (LOS). Results Of the 18,603 children enrolled, HAdV was detected in 1,136 (6.1%), among whom 646 (56.9%) had co-detection with at least one other respiratory virus. HRV/EV (n = 293, 45.3%) and RSV (n = 123, 19.0%) were the most frequent co-detections. Children with HRV/EV (aOR = 1.61; 95% CI = [1.11–2.34]), RSV (aOR = 4.48; 95% CI = [2.81–7.14]), HMPV (aOR = 3.39; 95% CI = [1.69–6.77]), or ≥ 2 co-detections (aOR = 1.95; 95% CI = [1.14–3.36]) had higher odds of hospitalization compared to children with HAdV alone. Among hospitalized children, HAdV co-detection with RSV or HMPV was each associated with higher odds of oxygen support, while co-detection with PIV or influenza viruses was each associated with higher mean LOS. Conclusions HAdV co-detection with other respiratory viruses was associated with greater disease severity among children with ARI compared to HAdV detection alone.

Acute viral respiratory infections are a major health burden in children worldwide. In recent years, rapid and sensitive multiplex nucleic acid amplification tests (NAATs) have replaced conventional methods for routine virus detection in the clinical laboratory.We compared BioFire® FilmArray® Respiratory Panel (FilmArray V1.7), Luminex NxTag® Respiratory Pathogen Panel (NxTag RPP) and Applied Biosystems TaqMan Array Card (TAC) for the detection of eight viruses in pediatric respiratory specimens. Results from the three platforms were analyzed with a single-plex real-time RT-PCR (rRT-PCR) assay for each virus.Of the 170/210 single-plex virus-positive samples, FilmArray detected a virus in 166 (97.6%), TAC in 163 (95.8%) and NxTag RPP in 160 (94.1%) samples. The Positive Percent Agreement (PPA) of FilmArray, NxTag RPP and TAC was highest for influenza B (100%, 100% and 95.2% respectively) and lowest for seasonal coronaviruses on both FilmArray (90.2%) and NxTag RPP (81.8%), and for parainfluenza viruses 1- 4 on TAC (84%). The Negative Percent Agreement (NPA) was lowest for rhinovirus/enterovirus (92.9%, 96.7% and 97.3%) on FilmArray, NxTag RPP and TAC respectively. NPA for all three platforms was highest (100%) for both parainfluenza viruses 1- 4 and influenza A and B, and 100% for human metapneumovirus with TAC as well.All three multiplex platforms displayed high overall agreement (gt;90%) and high NPA (gt;90%), while PPA was pathogen dependent and varied among platforms; high PPA (gt;90%) was observed for FilmArray for all eight viruses, TAC for six viruses and NxTag RPP for 4 viruses.