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Antibiotic resistance is a major threat to global health. Optimizing the use of antibiotics is a key measure to prevent and control this problem. Antimicrobial Stewardship Programs (ASPs) are designed to improve clinical outcomes, minimize adverse effects and protect patients, and to ensure the administration of cost-effective treatments. Inappropriate use of antibiotics also occurs in pediatric clinical practice. For this reason, ASPs should include specific objectives and strategies aimed at pediatricians and families. Implementing these programs requires the involvement of institutions and policy makers, healthcare providers as well as individuals, adapting them to the characteristics of each healthcare setting. Pediatric primary care (PPC) faces specific issues such as high demand and immediacy, scarce specialized professional resources, difficulties to access regular training and to obtain feedback. This requires the design of specific policies and strategies to achieve the objectives, including structural and organizational measures, improvement of the information flow and accessibility to frequent trainings. These programs should reach all health professionals, promoting regular trainings, prescription support tools and supplying diagnostic tests, with adequate coordination between health care levels. Periodic evaluations and surveillance tools are useful to assess the impact of the actions taken and to provide feedback to health providers in order to adapt and improve their clinical practice to meet ASPs objectives., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Invasive group A streptococcal disease (iGASD) is a serious infection in children. Several studies have shown an increased incidence in the past years., Objective: To evaluate the characteristics and outcome of iGASD in children, and to determine changes in incidence or severity., Material and Methods: A retrospective study was conducted on children≤16 years evaluated in a tertiary paediatric hospital in Madrid, and diagnosed with iGASD (June 2005-July 2013). An analysis was made of the demographics, symptomatology, microbiology, and treatment. The changes throughout the period studied were evaluated, as well as parameters associated with disease severity., Results: The study included a total of 55 children with iGASD, with 33 (60%) females, and a median age of 48.5 (20.5-88.9) months. The most frequent clinical syndromes were cellulitis/subcutaneous abscess (21.8%), ENT abscess (20%), pneumonia (16.4%), osteoarticular infection (16.4%), and mastoiditis (12.7%). The incidence of iGASD (cases/10 5 emergencies/year) increased from 5.6 (4.2-7.2) between June 2005-May 2009 to 18.9 (15.1-26) between June 2009-May 2013; P=.057. Surgery and admission to PICU was required by 35 (63.6%) and 10 (18.2%) patients, respectively. Children in PICU were younger (26.5 vs 52.6 months, P=.116), had a higher C-reactive protein (24.5 vs 10.7mg/dl, P<.001) and higher frequency of pneumonia (60 vs 7%, P<.001). In the multivariate analysis, only C-reactive protein was a risk factor for admission to PICU (OR: 1.14 [1.004-1.286], P=.04). There were no sequelae., Conclusions: An increased incidence of iGASD was observed in the children in this study. Lower age, pneumonia, and higher C-reactive protein were associated with disease severity in this series., (Copyright © 2019 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem., Objectives: To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection., Methods: We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response, and clinical disease severity., Measurements and Main Results: We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae- and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling., Conclusions: Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.

Objectives: Animal studies suggest that RSV increases nasopharyngeal (NP) bacterial colonization facilitating bacterial infections. We investigated the influence of antibiotic treatment and colonization with potentially pathogenic bacteria on inflammatory markers and disease severity in RSV-infected in infants., Methods: Healthy young infants hospitalized with RSV bronchiolitis (n = 136) and age-matched healthy controls (n = 23) were enrolled and NP samples cultured for potentially pathogenic bacteria including: Gram-positive bacteria (GPB): Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic Streptococcus; and Gram-negative bacteria (GNB): Moraxella catarrhalis and Haemophilus influenzae. Clinical parameters and plasma IL-8, IL-6 and TNF-α concentrations were compared according to the bacterial class and antibiotic treatment., Results: Antibiotic treatment decreased by 10-fold NP bacterial recovery. Eighty-one percent of RSV infants who did not receive antibiotics before sample collection were colonized with pathogenic bacteria. Overall, GNB were identified in 21% of patients versus 4% of controls who were mostly colonized with GPB. Additionally, in RSV patients NP white blood cell counts (p = 0.026), and blood neutrophils (p = 0.02) were higher in those colonized with potentially pathogenic bacteria versus respiratory flora. RSV patients colonized with GNB had higher plasma IL-8 (p = 0.01) and IL-6 (p < 0.01) concentrations than controls, and required longer duration of oxygen (p = 0.049)., Conclusions: Infants with RSV bronchiolitis colonized with potentially pathogenic bacteria had increased numbers of mucosal and systemic inflammatory cells. Specifically, colonization with GNB was associated with higher concentrations of proinflammatory cytokines and a trend towards increased disease severity., (Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract infection (LRTI) and hospitalization in infants. Mostly because of the incomplete understanding of the disease pathogenesis, there is no licensed vaccine, and treatment remains symptomatic. We analyzed whole blood transcriptional profiles to characterize the global host immune response to acute RSV LRTI in infants, to characterize its specificity compared with influenza and human rhinovirus (HRV) LRTI, and to identify biomarkers that can objectively assess RSV disease severity., Methods and Findings: This was a prospective observational study over six respiratory seasons including a cohort of infants hospitalized with RSV (n = 135), HRV (n = 30), and influenza (n = 16) LRTI, and healthy age- and sex-matched controls (n = 39). A specific RSV transcriptional profile was identified in whole blood (training cohort, n = 45 infants; Dallas, Texas, US) and validated in three different cohorts (test cohort, n = 46, Dallas, Texas, US; validation cohort A, n = 16, Turku, Finland; validation cohort B, n = 28, Columbus, Ohio, US) with high sensitivity (94% [95% CI 87%-98%]) and specificity (98% [95% CI 88%-99%]). It classified infants with RSV LRTI versus HRV or influenza LRTI with 95% accuracy. The immune dysregulation induced by RSV (overexpression of neutrophil, inflammation, and interferon genes, and suppression of T and B cell genes) persisted beyond the acute disease, and immune dysregulation was greatly impaired in younger infants (<6 mo). We identified a genomic score that significantly correlated with outcomes of care including a clinical disease severity score and, more importantly, length of hospitalization and duration of supplemental O2., Conclusions: Blood RNA profiles of infants with RSV LRTI allow specific diagnosis, better understanding of disease pathogenesis, and assessment of disease severity. This study opens new avenues for biomarker discovery and identification of potential therapeutic or preventive targets, and demonstrates that large microarray datasets can be translated into a biologically meaningful context and applied to the clinical setting. Please see later in the article for the Editors' Summary.

Background: Most patients with respiratory syncytial virus (RSV) bronchiolitis requiring admission to the pediatric intensive care unit (PICU) have no risk factors for severe disease. We sought to investigate the relationship between serum cytokine concentrations, innate immune responsiveness, and RSV disease severity., Methods: Previously healthy infants (median age, 2.6 months) with RSV bronchiolitis (PICU, n = 20; floor, n = 46) and healthy matched controls (n = 14) were enrolled, and blood samples were obtained within 24 hours of admission to measure plasma tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) concentrations and, whole blood lipopolysaccharide-stimulated cytokine production capacity., Results: Plasma IL-6, IL-8, and IL-10 concentrations were comparable between PICU and floor patients, but higher than in healthy controls (P < .05). In contrast, TNF-α, IL-6, and IL-8 production capacity was significantly decreased in PICU compared with both floor patients and healthy controls. In adjusted analyses, only impaired TNF-α and IL-8 production capacity were associated with longer length of stay (P = .035) and greater disease severity scores (P = .001)., Conclusions: Infants with severe RSV bronchiolitis had increased plasma cytokine concentrations and yet impaired innate immunity cytokine production capacity, which predicted worse disease outcomes. Immune monitoring of otherwise healthy infants with RSV lower respiratory tract infection could help identify patients at risk for severe disease at the time of hospitalization.

Two Spanish siblings, a boy and girl, with transcobalamin II (TCII) deficiency are described. Both have grown and developed mentally normally after 10 years of vitamin B12 therapy. Two other siblings died soon after birth and it is almost certain that they also suffered from TCII deficiency.