Clinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak.

In December 2022, an alert was published in the UK and other European countries reporting an unusual increase in the incidence of Streptococcus pyogenes infections. Our aim was to describe the clinical, microbiological, and molecular characteristics of group A Streptococcus invasive infections (iGAS) in children prospectively recruited in Spain (September 2022-March 2023), and compare invasive strains with strains causing mild infections. One hundred thirty isolates of S. pyogenes causing infection (102 iGAS and 28 mild infections) were included in the microbiological study: emm typing, antimicrobial susceptibility testing, and sequencing for core genome multilocus sequence typing (cgMLST), resistome, and virulome analysis. Clinical data were available from 93 cases and 21 controls. Pneumonia was the most frequent clinical syndrome (41/93; 44.1%), followed by deep tissue abscesses (23/93; 24.7%), and osteoarticular infections (11/93; 11.8%). Forty-six of 93 cases (49.5%) required admission to the pediatric intensive care unit. iGAS isolates mainly belonged to emm1 and emm12; emm12 predominated in 2022 but was surpassed by emm1 in 2023. Spread of M1UK sublineage (28/64 M1 isolates) was communicated for the first time in Spain, but it did not replace the still predominant sublineage M1global (36/64). Furthermore, a difference in emm types compared with the mild cases was observed with predominance of emm1, but also important representativeness of emm12 and emm89 isolates. Pneumonia, the most frequent and severe iGAS diagnosed, was associated with the speA gene, while the ssa superantigen was associated with milder cases. iGAS isolates were mainly susceptible to antimicrobials. cgMLST showed five major clusters: ST28-ST1357/emm1, ST36-ST425/emm12, ST242/emm12.37, ST39/emm4, and ST101-ST1295/emm89 isolates. IMPORTANCE: Group A Streptococcus (GAS) is a common bacterial pathogen in the pediatric population. In the last months of 2022, an unusual increase in GAS infections was detected in various countries. Certain strains were overrepresented, although the cause of this raise is not clear. In Spain, a significant increase in mild and severe cases was also observed; this study evaluates the clinical characteristics and the strains involved in both scenarios. Our study showed that the increase in incidence did not correlate with an increase in resistance or with an emm types shift. However, there seemed to be a rise in severity, partly related to a greater rate of pneumonia cases. These findings suggest a general increase in iGAS that highlights the need for surveillance. The introduction of whole genome sequencing in the diagnosis and surveillance of iGAS may improve the understanding of antibiotic resistance, virulence, and clones, facilitating its control and personalized treatment.

Acute Suppurative Thyroiditis in Children: Clinical Decision-Making.

Acute suppurative thyroiditis are infrequent infections, although their early and proper management are needed to reduce complications and recurrences. We review the clinical presentation, etiology, clinical outcome and management of 9 cases of thyroid infections diagnosed in children, and analyze the existence of predisposing factors for these infections.

Epidemiology and clinical features of Streptococcus pyogenes bloodstream infections in children in Madrid, Spain.

Studies have shown increased invasive Group A Streptococcus (GAS) disease, including bloodstream infections (GAS-BSI). However, the epidemiological data of GAS-BSI are limited in children. We aimed to describe GAS-BSI in children in Madrid, over 13 years (2005-2017). Multicenter retrospective cohort study from 16 hospitals from Madrid, Spain. Epidemiology, symptomatology, laboratory, treatment, and outcome of GAS-BSI in children ≤ 16 years were analyzed. 109 cases of GAS-BSI were included, with incidence rate of 4.3 episodes/100,000 children attended at the emergency department/year. We compared incidence between two periods (P1: 2005-June 2011 vs P2: July 2011-2017) and observed a non-significant increase along the study period (annual percentage change: + 6.0% [95%CI: -2.7, + 15.4]; p = 0.163). Median age was 24.1 months (IQR: 14.0-53.7), peaking during the first four years of life (89/109 cases; 81.6%). Primary BSI (46.8%), skin and soft tissue (21.1%), and osteoarticular infections (18.3%) were the most common syndromes. We compared children with primary BSI with those with a known source and observed that the former had shorter hospital stay (7 vs. 13 days; p = 0.003) and received intravenous antibiotics less frequently (72.5% vs. 94.8%; p = 0.001) and for shorter duration of total antibiotic therapy (10 vs. 21 days; p = 0.001). 22% of cases required PICU admission. Factors associated with severity were respiratory distress, pneumonia, thrombocytopenia, and surgery, but in multivariate analysis, only respiratory distress remained significant (adjusted OR:9.23 [95%CI: 2.16-29.41]). Two children (1.8%) died.   Conclusion: We observed an increasing, although non-significant, trend of GAS-BSI incidence within the study. Younger children were more frequently involved, and primary BSI was the most common and less severe syndrome. PICU admission was frequent, being respiratory distress the main risk factor. What is known: • In recent decades, several reports have shown a worldwide increase in the incidence of invasive Group A streptococcal disease (GAS), including bloodstream infection (BSI). Recently, there have been a few reports showing an increase in severity as well. • There needs to be more information on the epidemiology in children since most studies predominantly include adults. What is new: • This study, carried out in children with GAS-BSI in Madrid, shows that GAS-BSI affects mostly younger children, with a broad spectrum of manifestations, needing PICU admission frequently. Respiratory distress was the leading risk factor for severity, whereas primary BSI seemed to be less severe. • We observed an increasing, although non-significant, trend of GAS-BSI incidence in recent years (2005-2017).

Comparison of pneumonia features in children caused by SARS-CoV-2 and other viral respiratory pathogens.

BACKGROUND: Pneumonia is a frequent manifestation of coronavirus disease 2019 (COVID-19) in hospitalized children. METHODS: The study involved 80 hospitals in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spanish Pediatric National Cohort. Participants were children <18 years, hospitalized with SARS-CoV-2 community-acquired pneumonia (CAP). We compared the clinical and radiological characteristics of SARS-CoV-2-associated CAP with CAP due to other viral etiologies from ValsDance (retrospective) cohort. RESULTS: In total, 151 children with SARS-CoV-2-associated CAP and 138 with other viral CAP were included. Main clinical features of SARS-CoV-2-associated CAP were cough, fever, or dyspnea. Lymphopenia was found in 43% patients and 15% required admission to the pediatric intensive care unit (PICU). Chest X-ray revealed condensation (42%) and other infiltrates (58%). Compared with CAP from other viral pathogens, COVID-19 patients were older, with lower C-reactive protein (CRP) levels, less wheezing, and greater need of mechanical ventilation (MV). There were no differences in the use of continuous positive airway pressure (CPAP) or HVF, or PICU admission between groups. CONCLUSION: SARS-CoV-2-associated CAP in children presents differently to other virus-associated CAP: children are older and rarely have wheezing or high CRP levels; they need less oxygen but more CPAP or MV. However, several features overlap and differentiating the etiology may be difficult. The overall prognosis is good.

Staphylococcus aureus Community-acquired Pneumonia in Children After 13-Valent Pneumococcal Vaccination (2008-2018): Epidemiology, Clinical Characteristics and Outcomes.

BACKGROUND: The epidemiology of community-acquired pneumonia (CAP) has changed, influenced by sociosanitary conditions and vaccination status. We aimed to analyze the recent epidemiology of bacterial CAP in hospitalized children in a setting with high pneumococcal vaccination coverage and to describe the clinical characteristics of pediatric Staphylococcus aureus CAP. METHODS: Children <17 years old hospitalized from 2008 to 2018 with bacterial CAP in 5 tertiary hospitals in Spain were included. Cases with pneumococcal CAP were randomly selected as comparative group following a case-control ratio of 2:1 with S. aureus CAP. RESULTS: A total of 313 bacterial CAP were diagnosed: Streptococcus pneumoniae CAP (n = 236, 75.4%), Streptococcus pyogenes CAP (n = 43, 13.7%) and S. aureus CAP (n = 34, 10.9%). Throughout the study period, the prevalence of S. pyogenes increased (annual percentage change: +16.1% [95% CI: 1.7-32.4], P = 0.031), S. pneumoniae decreased (annual percentage change: -4.4% [95 CI: -8.8 to 0.2], P = 0.057) and S. aureus remained stable. Nine isolates of S. aureus (26.5%) were methicillin-resistant. Seventeen cases (50%) with S. aureus CAP had some pulmonary complication and 21 (61.7%) required intensive care. S. pneumoniae CAP showed a trend toward higher prevalence of pulmonary complications compared with S. aureus CAP (69.1% vs. 50.0%, P = 0.060), including higher frequency of pulmonary necrosis (32.4% vs. 5.9%, P = 0.003). CONCLUSIONS: The incidence of S. aureus CAP in children remained stable, whereas the prevalence of pneumococcal CAP decreased and S. pyogenes CAP increased. Patients with S. aureus presented a high frequency of severe outcomes, but a lower risk of pulmonary complications than patients with S. pneumoniae.

Antibiotic Prescribing in Children Hospitalized With COVID-19 and Multisystem Inflammatory Syndrome in Spain: Prevalence, Trends, and Associated Factors.

The SARS-CoV-2 pandemic has caused an increase in antibiotic use in different settings. We describe the antibiotic prescribing prevalence, associated factors and trends, as well as concomitant bacterial infections in children hospitalized with COVID-19 or multisystemic inflammatory syndrome related to SARS-CoV-2 in Spain.

Clinical spectrum of COVID-19 and risk factors associated with severity in Spanish children.

We aimed to identify the spectrum of disease in children with COVID-19, and the risk factors for admission in paediatric intensive care units (PICUs). We conducted a multicentre, prospective study of children with SARS-CoV-2 infection in 76 Spanish hospitals. We included children with COVID-19 or multi-inflammatory syndrome (MIS-C) younger than 18 years old, attended during the first year of the pandemic. We enrolled 1200 children. A total of 666 (55.5%) were hospitalised, and 123 (18.4%) required admission to PICU. Most frequent major clinical syndromes in the cohort were mild syndrome (including upper respiratory tract infection and flu-like syndrome, skin or mucosae problems and asymptomatic), 44.8%; bronchopulmonary syndrome (including pneumonia, bronchitis and asthma flare), 18.5%; fever without a source, 16.2%; MIS-C, 10.6%; and gastrointestinal syndrome, 10%. In hospitalised children, the proportions were 28.5%, 25.7%, 16.5%, 19.1% and 10.2%, respectively. Risk factors associated with PICU admission were age in months (OR: 1.007; 95% CI 1.004 to 1.01), MIS-C (OR: 14.4, 95% CI 8.9 to 23.8), chronic cardiac disease (OR: 4.8, 95% CI 1.8 to 13), asthma or recurrent wheezing (OR: 2.5, 95% CI 1.2 to 5.2) and after excluding MIS-C patients, moderate/severe liver disease (OR: 8.6, 95% CI 1.6 to 47.6). However, asthmatic children were admitted into the PICU due to MIS-C or pneumonia, not due to asthma flare.Conclusion: Hospitalised children with COVID-19 usually present as one of five major clinical phenotypes of decreasing severity. Risk factors for PICU include MIS-C, elevation of inflammation biomarkers, asthma, moderate or severe liver disease and cardiac disease. What is Known: • All studies suggest that children are less susceptible to serious SARS-CoV-2 infection when compared to adults. Most studies describe symptoms at presentation. However, it remains unclear how these symptoms group together into clinically identifiable syndromes and the severity associated with them. What is New: • We have gathered the primary diagnoses into five major syndromes of decreasing severity: MIS-C, bronchopulmonary syndrome, gastrointestinal syndrome, fever without a source and mild syndrome. Classification of the children in one of the syndromes is unique and helps to assess the risk of critical illness and to define the spectrum of the disease instead of just describing symptoms and signs.

Dynamics of Reverse Transcription-Polymerase Chain Reaction and Serologic Test Results in Children with SARS-CoV-2 Infection.

OBJECTIVES: To determine the time to reverse transcription-polymerase chain reaction (RT-PCR) negativity after the first positive RT-PCR test, factors associated with longer time to RT-PCR negativity, proportion of children seroconverting after proven severe acute respiratory syndrome coronavirus 2 infection, and factors associated with the lack of seroconversion. STUDY DESIGN: The Epidemiological Study of Coronavirus in Children of the Spanish Society of Pediatrics is a multicenter study conducted in Spanish children to assess the characteristics of coronavirus disease 2019. In a subset of patients, 3 serial RT-PCR tests on nasopharyngeal swab specimens were performed after the first RT-PCR test, and immunoglobulin G serology for severe acute respiratory syndrome coronavirus 2 antibodies was performed in the acute and follow-up (<14 and ≥14 days after diagnosis) phase. RESULTS: In total, 324 patients were included in the study. The median time to RT-PCR negativity was 17 days (IQR, 8-29 days), and 35% of patients remained positive more than 4 weeks after the first RT-PCR test. The probability of RT-PCR negativity did not differ across groups defined by sex, disease severity, immunosuppressive drugs, or clinical phenotype. Globally, 24% of children failed to seroconvert after infection. Seroconversion was associated with hospitalization, persistence of RT-PCR positivity, and days of fever. CONCLUSIONS: Time to RT-PCR negativity was long, regardless of the severity of symptoms or other patient features. This finding should be considered when interpreting RT-PCR results in a child with symptoms, especially those with mild symptoms. Seroprevalence and postimmunization studies should consider that 11 in 4 infected children fail to seroconvert.

A Bayesian Model to Predict COVID-19 Severity in Children.

BACKGROUND: We aimed to identify risk factors causing critical disease in hospitalized children with COVID-19 and to build a predictive model to anticipate the probability of need for critical care. METHODS: We conducted a multicenter, prospective study of children with SARS-CoV-2 infection in 52 Spanish hospitals. The primary outcome was the need for critical care. We used a multivariable Bayesian model to estimate the probability of needing critical care. RESULTS: The study enrolled 350 children from March 12, 2020, to July 1, 2020: 292 (83.4%) and 214 (73.7%) were considered to have relevant COVID-19, of whom 24.2% required critical care. Four major clinical syndromes of decreasing severity were identified: multi-inflammatory syndrome (MIS-C) (17.3%), bronchopulmonary (51.4%), gastrointestinal (11.6%), and mild syndrome (19.6%). Main risk factors were high C-reactive protein and creatinine concentration, lymphopenia, low platelets, anemia, tachycardia, age, neutrophilia, leukocytosis, and low oxygen saturation. These risk factors increased the risk of critical disease depending on the syndrome: the more severe the syndrome, the more risk the factors conferred. Based on our findings, we developed an online risk prediction tool (https://rserver.h12o.es/pediatria/EPICOAPP/, username: user, password: 0000). CONCLUSIONS: Risk factors for severe COVID-19 include inflammation, cytopenia, age, comorbidities, and organ dysfunction. The more severe the syndrome, the more the risk factor increases the risk of critical illness. Risk of severe disease can be predicted with a Bayesian model.

Multi-inflammatory Syndrome in Children Related to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Spain.

Some clusters of children with a multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. We describe the epidemiological and clinical features of children with MIS-C in Spain. MIS-C is a potentially severe condition that presents in children with recent SARS-CoV-2 infection.