Serotypes and Clonal Composition of Streptococcus pneumoniae Isolates Causing IPD in Children and Adults in Catalonia before 2013 to 2015 and after 2017 to 2019 Systematic Introduction of PCV13.

The goal of this study was to investigate the distribution of serotypes and clonal composition of Streptococcus pneumoniae isolates causing invasive pneumococcal disease (IPD) in Catalonia, before and after systematic introduction of PCV13. Pneumococcal strains isolated from normally sterile sites obtained from patients of all ages with IPD received between 2013 and 2019 from 25 health centers of Catalonia were included. Two study periods were defined: presystematic vaccination period (2013 and 2015) and systematic vaccination period (SVP) (2017 to 2019). A total of 2,303 isolates were analyzed. In the SVP, there was a significant decrease in the incidence of IPD cases in children 5 to 17 years old (relative risk [RR] 0.61; 95% confidence interval [CI] 0.38 to 0.99), while there was a significant increase in the incidence of IPD cases in 18- to 64-year-old adults (RR 1.33; 95% CI 1.16 to 1.52) and adults over 65 years old (RR 1.23; 95% CI 1.09 to 1.38). Serotype 8 was the major emerging serotype in all age groups except in 5- to 17-year-old children. In children younger than 5 years old, the main serotypes in SVP were 24F, 15A, and 3, while in adults older than 65 years they were serotypes 3, 8, and 12F. A significant decrease in the proportions of clonal complexes CC156, CC191, and ST306 and an increase in those of CC180, CC53, and CC404 were observed. A steady decrease in the incidence of IPD caused by PCV13 serotypes indicates the importance and impact of systematic vaccination. The increase of non-PCV13 serotypes highlights the need to expand serotype coverage in future vaccines and rethink vaccination programs for older adults. IMPORTANCE We found that with the incorporation of the PCV13 vaccine, the numbers of IPD cases caused by serotypes included in this vaccine decreased in all of the age groups. Still, there was an unforeseen increase of the serotypes not included in this vaccine causing IPD, especially in the >65-year-old group. Moreover, a significant increase of serotype 3 included in the vaccine has been observed; this event has been reported by other researchers. These facts call for the incorporation of more serotypes in future vaccines and a more thorough surveillance of the dynamics of this microorganism.

Pneumococcal serotypes in children, clinical presentation and antimicrobial susceptibility in the PCV13 era.

The aim was to analyse invasive pneumococcal disease (IPD) serotypes in children aged ⩽17 years according to clinical presentation and antimicrobial susceptibility. We conducted a prospective study (January 2012-June 2016). IPD cases were diagnosed by culture and/or real-time polymerase chain reaction (PCR). Demographic, microbiological and clinical data were analysed. Associations were assessed using the odds ratio (OR) and 95% confidence intervals (CI). Of the 253 cases, 34.4% were aged <2 years, 38.7% 2-4 years and 26.9% 5-17 years. Over 64% were 13-valent pneumococcal conjugate vaccine (PCV13) serotypes. 48% of the cases were diagnosed only by real-time PCR. Serotypes 3 and 1 were associated with complicated pneumonia (P < 0.05) and non-PCV13 serotypes with meningitis (OR 7.32, 95% CI 2.33-22.99) and occult bacteraemia (OR 3.6, 95% CI 1.56-8.76). Serotype 19A was more frequent in children aged <2 years and serotypes 3 and 1 in children aged 2-4 years and 5-17 years, respectively. 36.1% of cases were not susceptible to penicillin and 16.4% were also non-susceptible to cefotaxime. Serotypes 14, 24F and 23B were associated with non-susceptibility to penicillin (P < 0.05) and serotypes 11, 14 and 19A to cefotaxime (P < 0.05). Serotype 19A showed resistance to penicillin (P = 0.002). In conclusion, PCV13 serotypes were most frequent in children aged ⩽17 years, mainly serotypes 3, 1 and 19A. Non-PCV13 serotypes were associated with meningitis and occult bacteraemia and PCV13 serotypes with pneumonia. Non-susceptibility to antibiotics of non-PCV13 serotypes should be monitored.

Outbreak of brainstem encephalitis associated with enterovirus-A71 in Catalonia, Spain (2016): a clinical observational study in a children's reference centre in Catalonia.

OBJECTIVES: To describe the characteristics of an outbreak of brainstem encephalitis and encephalomyelitis related to enterovirus (EV) infection in Catalonia (Spain), a setting in which these manifestations were uncommon. METHODS: Clinical and microbiological data were analysed from patients with neurological symptoms associated with EV detection admitted to a reference paediatric hospital between April and June 2016. RESULTS: Fifty-seven patients were included. Median age was 27.7 months (p25-p75 17.1-37.6). Forty-one (72%) were diagnosed with brainstem encephalitis, seven (12%) with aseptic meningitis, six (11%) with encephalitis, and three (5%) with encephalomyelitis (two out of three with cardiopulmonary failure). Fever, lethargy, and myoclonic jerks were the most common symptoms. Age younger than 12 months, higher white-blood-cell count, and higher procalcitonin levels were associated with cardiopulmonary failure. Using a PAN-EV real-time PCR, EV was detected in faeces and/or nasopharyngeal aspirate in all the patients, but it was found in cerebrospinal fluid only in patients with aseptic meningitis. EV was genotyped in 47 out of 57 and EV-A71 was identified in 40 out of 47, being the only EV type found in patients with brainstem symptoms. Most of the detected EV-A71 strains were subgenogroup C1. Intravenous immunoglobulins were used in 34 patients. Eight cases (14%) were admitted to the intensive care unit. All the patients but three, those with encephalomyelitis, showed a good clinical course and had no significant sequelae. No deaths occurred. CONCLUSIONS: The 2016 outbreak of brainstem encephalitis in Catalonia was associated with EV-A71 subgenogroup C1. Despite the clinical manifestations of serious disease, a favourable outcome was observed in the majority of patients.

[Blood cultures in the paediatric emergency department. Guidelines and recommendations on their indications, collection, processing and interpretation]. / Hemocultivos en urgencias pediátricas. Guía práctica de recomendaciones: indicaciones, técnica de extracción, procesamiento e interpretación.

Blood culture (BC) is the gold standard when a bacteraemia is suspected, and is one of the most requested microbiological tests in paediatrics. Some changes have occurred in recent years: the introduction of new vaccines, the increasing number of patients with central vascular catheters, as well as the introduction of continuous monitoring BC systems. These changes have led to the review and update of different factors related to this technique in order to optimise its use. A practice guideline is presented with recommendations on BC, established by the Spanish Society of Paediatric Emergency Care and the Spanish Society for Paediatric Infectious Diseases. After reviewing the available scientific evidence, several recommendations for each of the following aspects are presented: BC indications in the Emergency Department, how to obtain, transport and process cultures, special situations (indications and interpretation of results in immunosuppressed patients and/or central vascular catheter carriers, indications for anaerobic BC), differentiation between bacteraemia and contamination when a BC shows bacterial growth and actions to take with a positive BC in patients with fever of unknown origin.

[The role of complementary examinations and home monitoring in patient at risk from apparent life threatening event, apneas and sudden infant death syndrome]. / Papel de las exploraciones complementarias y de la monitorización domiciliaria en los pacientes de riesgo de episodio aparentemente letal, apneas y síndrome de muerte súbita del lactante.

INTRODUCTION: Home apnea monitors detect abnormalities in cardiac and respiratory frequency, but their use in the diagnosis of respiratory -related sleep disturbances in children has not been demonstrated, as was originally thought. OBJECTIVE: To describe the type of patients being monitored, for how long and their outcome. MATERIAL AND METHODS: A retrospective descriptive study was conducted on patients with controlled home cardiorespiratory monitoring from October 2008 to September 2012 in the Outpatient department of a Maternity tertiary hospital. RESULTS: During the study period 88 patients were included, 58% of them were male, with a median age of 15.5 days, and followed up for a period of 4.7 months. The reason for monitoring was in a 20.5% due to a history of sudden death without finding underlying pathology in 20.5%, 25% due to apnea of prematurity, 20.5% due to apparent life-threatening event, and 14.8% due to choking. Other causes accounted for 19.3% (apnea/hypopnea, desaturation and periodic breathing). Of these last three groups, pathological events were observed in 50% of them: reflux disease (9), apnea of prematurity (2), neurological causes (3), and apnea of unknown cause (10). CONCLUSIONS: Suspected infant apnea is a cause for consultation that creates a great deal of concern to the family and the pediatrician. Home monitoring is useful in detecting changes in cardiac and respiratory frequency, but is necessary to limit its indications and ensure proper monitoring of these patients, avoiding the abuse of other tests or treatments.

[Community acquired pneumonia in children: Treatment of complicated cases and risk patients. Consensus statement by the Spanish Society of Paediatric Infectious Diseases (SEIP) and the Spanish Society of Paediatric Chest Diseases (SENP)]. / Neumonía adquirida en la comunidad: tratamiento de los casos complicados y en situaciones especiales. Documento de consenso de la Sociedad Española de Infectología Pediátrica (SEIP) y Sociedad Española de Neumología Pediátrica (SENP).

The incidence of community-acquired pneumonia complications has increased during the last decade. According to the records from several countries, empyema and necrotizing pneumonia became more frequent during the last few years. The optimal therapeutic approach for such conditions is still controversial. Both pharmacological management (antimicrobials and fibrinolysis), and surgical management (pleural drainage and video-assisted thoracoscopic surgery), are the subject of continuous assessment. In this paper, the Spanish Society of Paediatric Infectious Diseases and the Spanish Society of Paediatric Chest Diseases have reviewed the available evidence. Consensus treatment guidelines are proposed for complications of community-acquired pneumonia in children, focusing on parapneumonic pleural effusion. Recommendations are also provided for the increasing population of patients with underlying diseases and immunosuppression.

Bacteremia in previously healthy children in emergency departments: clinical and microbiological characteristics and outcome.

A blood culture (BC) is frequently requested in both patients with a suspected occult bacteremia/invasive infection as well as those with certain focal infections. Few data are available on the characteristics of patients in whom a bacteremia is identified in the Pediatric Emergency Department (PED). A prospective multicenter registry was established by the Spanish Pediatric Emergency Society. Epidemiological data, complementary test results, clinical management, and final outcome were recorded. Data from the first three years of the registry were analyzed. A true bacterial pathogen grew in 932 of 65,169 BCs collected [1.43 %; 95 % confidence interval (CI) 1.34-1.51 %], with 711 of them collected in patients without previously known bacteremia risk factors. Among them, 335 (47.1 %) were younger than 1 year old and 467 (65.7 %) had a normal Pediatric Assessment Triangle (PAT) on admission. Overall, the most frequently isolated bacterial species was Streptococcus pneumoniae (27.3 %; 47.6 % among patients with an altered PAT). The main pathogens were Escherichia coli (40.3 %) and S. agalactiae (35.7 %) among patients younger than 3 months, S. pneumoniae among patients 3-60 months old (40.0 %), and S. aureus (31.9 %) among patients over 60 months of age. Neisseria meningitidis was the leading cause of sepsis in patients older than 3 months. Eight patients died; none of them had a pneumococcal bacteremia and all had abnormal PAT findings on admission. S. pneumoniae is the main cause of bacteremia in patients without bacteremia risk factors who attended Spanish PEDs. Age and general appearance influence the frequency of each bacterial species. General appearance also influences the associated mortality.

[Community acquired pneumonia in children: Outpatient treatment and prevention]. / Neumonía adquirida en la comunidad: tratamiento ambulatorio y prevención.

There have been significant changes in community acquired pneumonia (CAP) in children in the last decade. These changes relate to epidemiology and clinical presentation. Resistance to antibiotics is also a changing issue. These all have to be considered when treating CAP. In this document, two of the main Spanish pediatric societies involved in the treatment of CAP in children, propose a consensus concerning therapeutic approach. These societies are the Spanish Society of Paediatric Infectious Diseases and the Spanish Society of Paediatric Chest Diseases. The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) has also been involved in the prevention of CAP. An attempt is made to provide up-to-date guidelines to all paediatricians. The first part of the statement presents the approach to ambulatory, previously healthy children. We also review the prevention with currently available vaccines. In a next second part, special situations and complicated forms will be addressed.

Estimation of the invasive disease potential of Streptococcus pneumoniae in children by the use of direct capsular typing in clinical specimens.

Traditionally, invasiveness indexes have been based on culture methods. We aimed to establish a new classification of the invasive disease potential of pneumococcal serotypes causing invasive pediatric disease in the era of conjugate vaccines in Catalonia, Spain, by adding capsular typing of Streptococcus pneumoniae in direct sample. Two samples of children attended at the University Hospital Sant Joan de Déu (Barcelona, Spain) between 2007 and 2011 were compared: a first sample of 358 children with invasive pneumococcal disease and a second sample of 402 pneumococcal nasopharyngeal carriers selected from 714 healthy children admitted for minor surgical procedures. The most common invasive serotypes were 1 (20.1 %, n = 72), 19A (13.9 %, n = 50), 3 (12.3 %, n = 44), and 7FA (7.5 %, n = 27), whereas the most common serotypes in carriage were 19A (8.7 %, n = 38), 10FC33C (7.8 %, n = 34), 6C (6.9 %, n = 30), and 19FBC (5.5 %, n = 24). We detected a rate of cocolonization of 26.4 % (n = 89) among the 336 samples serotyped in the carriers population. Serotypes 1, 3, and 7FA were significantly associated with high invasiveness. Serotypes 6C, 10FC33C, 23A, 35B, 19FBC, 21, 11AD, 15BC, 23B, 34, and 6A were significantly associated with low invasiveness. Our results proved that the use of molecular techniques in direct sample for both the detection and the capsular identification of Streptococcus pneumoniae is very useful to obtain a more accurate calculation of the invasiveness of the different pneumococcal serotypes.

Respiratory viruses, such as 2009 H1N1 influenza virus, could trigger temporal trends in serotypes causing pneumococcal disease.

In order to determine if the novel influenza A(H1N1)pdm09 was associated with temporal trends of main serotypes causing invasive pneumococcal disease (IPD), we studied 384 episodes of IPD in <18-year-old patients from 2007 to 2012. The number of IPD episodes diagnosed during the 2009 pandemic period meant almost one-third of all the episodes diagnosed in the five included influenza periods (51/156). The number of IPD episodes diagnosed during the 2009 pandemic period meant almost one-third of all the episodes diagnosed in the five included influenza periods. Most of them occurred in <5-year-old children. Serotype 1 was the main serotype detected over the period, except for the 2009 pandemic, when it practically disappeared. Seasonality and viral infections could trigger temporal trends of serotypes causing IPD.

[Status of pediatric hospital medicine in Spain: a report by the Spanish Pediatric Hospital Medicine Society (SEPHO)]. / Situación de la pediatría hospitalaria en España: informe de la Sociedad Española de Pediatría Hospitalaria (SEPHO).

Few reports are available on the status of pediatric hospital medicine in Spain. This has prompted the Spanish Society of Hospital Pediatrics (SEPHO) to conduct a study to determine the status of pediatric hospital care received. Data released by the Ministry of Health, the National Institute of Statistics have been used in the study, and an analysis was made of the results of a computerized survey designed and developed by SEPHO and available on the Internet for completion from November 2011 to December 2012 among Spanish hospitals. The results of this survey are part of the beginning of our journey as an association, and the current status of child and family welfare during hospitalization needs to be determined in order to consider and, where appropriate, make recommendations for improvement and standardization of care. The study, still unpublished, is to determine the state of pediatric hospital care as seen and analyzed from the perspective of the professionals directly involved in pediatric general hospital care. We included hospitals of different size and complexity of care. The aim of this report is to present the results of the survey and relate it to demographic and health care data from official sources.

Prescripción antibiótica en los pacientes hospitalizados desde Urgencias. Estudio multicéntrico / Prescribing of antibiotics in patients admitted from Emergency Departments: a multicenter study

Introducción: La patología infecciosa constituye el principal motivo de consulta en Urgencias y es causa frecuente de ingreso hospitalario con antibióticos. Nuestros objetivos son: 1) conocer la prevalencia y las patologías atendidas en Urgencias que son motivo de ingreso con antibiótico; 2) conocer los métodos microbiológicos empleados, y 3) analizar las características del tratamiento antibiótico indicado. Material y métodos: Estudio prospectivo multicéntrico realizado en 22 hospitales españoles. Se incluyeron los pacientes menores de 18 años atendidos en Urgencias el día 14 de cada mes entre junio de 2009 y mayo de 2010 a los que se indicó ingreso hospitalario con antibiótico sistémico. Se excluyeron los pacientes que ingresaron en la Unidad de Cuidados Intensivos. Resultados: Consultaron en Urgencias 30.632 pacientes, 1.446 (4,7%) ingresaron, 395 (27,3%) de ellos con antibiótico. Habían recibido antibiótico previo al ingreso 95 (24,1%) pacientes. A 320 (81%) niños se les realizó algún examen microbiológico, siendo el hemocultivo (69,9%) y el urocultivo (30,9%) los más solicitados. Los principales diagnósticos fueron neumonía (29,4%), infección de orina (15,4%) y síndrome febril sin foco (12,1%). Se pautaron 25 antibióticos distintos, siendo los más prescritos cefotaxima (27,8%) y amoxicilina-ácido clavulánico (23,4%). El 80,8% de los niños recibieron un único antimicrobiano y la vía parenteral fue la más empleada (93,7%). Conclusiones: Se prescribió antibiótico a uno de cada 4 pacientes que precisó ingreso hospitalario. La neumonía fue la etiología más frecuente. El hemocultivo fue el examen microbiológico más solicitado. La mayoría de las prescripciones correspondieron a un número reducido de antibióticos betalactámicos (AU)

Introduction: The infectious disease is the main source of care demand in Pediatric Emergency Departments (PED) and is a frequent cause of hospital admission with antibiotics. Our objectives are: 1) to determine the diseases that are seen in PED that required admission with antibiotics; 2) to determine the microbiological methods used and, 3) to analyze the characteristics of the indicated treatment. Material and methods: A prospective multicenter study was conducted in 22 Spanish hospitals. We included patients younger than 18 years seen in PED on day 14 of each month between June 2009 and May 2010 who required hospitalization with systemic antibiotics. Patients admitted to Intensive Care Unit were excluded. Results: There were 30,632 consultations in the PED during the study period. A total of 1,446 (4.7%) patients were hospitalized, 395 (27.3%) of them with antibiotics. Ninety-five patients (24.1%) had received antibiotics before admission. Three hundred twenty (81%) children underwent at least one microbiological test, with blood culture (69.9%) and urine culture (30.9%) being the most requested ones. The main diagnoses at admission were pneumonia (29.4%), urinary tract infection (15.4%), and fever without source (12.1%). Twenty five different antibiotics were prescribed, with cefotaxime (27.8%) and amoxicillin-clavulanate (23.4%) being the most prescribed ones. A single antibiotic was prescribed to 80.8% of patients, and parenteral administration was the most indicated (93.7%). Conclusions: Antibiotic therapy was prescribed in one in every 4 patients who required admission to hospital. Pneumonia was the most common source. Blood culture was the most frequent microbiological test requested in the PED. A limited number of beta-lactam antibiotics represented the majority of antibiotic prescriptions (AU)

Clinical features of influenza disease in admitted children during the first postpandemic season and risk factors for hospitalization: a multicentre Spanish experience.

The main objectives of this study were to describe the characteristics of children with influenza infection during the postpandemic outbreak, and to compare sociodemographic and clinical data between patients who required hospitalization and those managed on an outpatient basis with a matched case-control study design. This is a multicentre paediatric study in Spain that included patients aged 6 month to 18 years in whom influenza infection was confirmed by real-time reverse transcription-polymerase chain reaction between December 2010 and March 2011. Among the 143 admitted patients, the main reason for admission was respiratory failure (123/143). In 55 there was some previously known disease. The median age was lower in patients without comorbidity (1.8 years: interquartile range 1.0-3.0 versus 5.3 years: interquartile range 1.3-10.7); p <0.01). The lag time from onset of symptoms to starting antiviral treatment was correlated with the length of hospital stay (Rho Spearman = + 0.32; p 0.01). Twenty patients required admission to the paediatric intensive care units, all due to respiratory failure. Children with chest X-ray opacities in more than one quadrant more frequently required admission to intensive care. Having a neurological disease conferred the highest risk of requiring hospitalization (OR 17.18) in a multivariate analysis. This study concludes that influenza in the paediatric population requiring hospitalization during the postpandemic season affected mainly children with neurological or pulmonary comorbidities and children of parents with a lower educational level. Most of the influenza infections caused respiratory symptoms, although neurological manifestations were also observed. Early initiation of oseltamivir was associated with a shorter length of hospital stay.

[Prescribing of antibiotics in patients admitted from Emergency Departments: a multicenter study]. / Prescripción antibiótica en los pacientes hospitalizados desde Urgencias. Estudio multicéntrico.

INTRODUCTION: The infectious disease is the main source of care demand in Pediatric Emergency Departments (PED) and is a frequent cause of hospital admission with antibiotics. Our objectives are: 1) to determine the diseases that are seen in PED that required admission with antibiotics; 2) to determine the microbiological methods used and, 3) to analyze the characteristics of the indicated treatment. MATERIAL AND METHODS: A prospective multicenter study was conducted in 22 Spanish hospitals. We included patients younger than 18 years seen in PED on day 14 of each month between June 2009 and May 2010 who required hospitalization with systemic antibiotics. Patients admitted to Intensive Care Unit were excluded. RESULTS: There were 30,632 consultations in the PED during the study period. A total of 1,446 (4.7%) patients were hospitalized, 395 (27.3%) of them with antibiotics. Ninety-five patients (24.1%) had received antibiotics before admission. Three hundred twenty (81%) children underwent at least one microbiological test, with blood culture (69.9%) and urine culture (30.9%) being the most requested ones. The main diagnoses at admission were pneumonia (29.4%), urinary tract infection (15.4%), and fever without source (12.1%). Twenty five different antibiotics were prescribed, with cefotaxime (27.8%) and amoxicillin-clavulanate (23.4%) being the most prescribed ones. A single antibiotic was prescribed to 80.8% of patients, and parenteral administration was the most indicated (93.7%). CONCLUSIONS: Antibiotic therapy was prescribed in one in every 4 patients who required admission to hospital. Pneumonia was the most common source. Blood culture was the most frequent microbiological test requested in the PED. A limited number of beta-lactam antibiotics represented the majority of antibiotic prescriptions.

Sociedad Española de Pediatría Hospitalaria / Spanish Society of Hospital Paediatrics

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Serotype 3 is a common serotype causing invasive pneumococcal disease in children less than 5 years old, as identified by real-time PCR.

Serotype 3 is one of the most often detected pneumococcal serotypes in adults and it is associated with serious disease. In contrast, the isolation of serotype 3 by bacterial culture is unusual in children with invasive pneumococcal disease (IPD). The purpose of this study was to learn the serotype distribution of IPD, including culture-negative episodes, by using molecular methods in normal sterile samples. We studied all children<5 years of age with IPD admitted to two paediatric hospitals in Catalonia, Spain, from 2007 to 2009. A sequential real-time polymerase chain reaction (PCR) approach was added to routine methods for the detection and serotyping of pneumococcal infection. Among 257 episodes (219 pneumonia, 27 meningitis, six bacteraemia and five others), 33.5% were identified by culture and the rest, 66.5%, were detected exclusively by real-time PCR. The most common serotypes detected by culture were serotypes 1 (26.7%) and 19A (25.6%), and by real-time PCR, serotypes 1 (19.8%) and 3 (18.1%). Theoretical coverage rates by the PCV7, PCV10 and PCV13 vaccines were 10.5, 52.3 and 87.2%, respectively, for those episodes identified by culture, compared to 5.3, 31.6 and 60.2% for those identified only by real-time PCR. Multiplex real-time PCR has been shown to be useful for surveillance studies of IPD. Serotype 3 is underdiagnosed by culture and is important in paediatric IPD.