QuantiFERON-TB reversion in children and adolescents with tuberculosis.

We analyzed 136 children with tuberculosis disease or infection and a positive QuantiFERON-TB (QFT) assay, followed-up for a median of 21 months (0.4-11years). QFT reversed in 16.9% of cases, with significant decreases in TB1 (-1.72 vs. -0.03 IU/ml, p=0.001) and TB2 (-1.65 vs. -0.43 IU/ml, p=0.005) levels compared to non-reverters. We found a higher QFT reversion rate among children under 5 years (25.0% vs 11.9%, p=0.042), and those with TST induration <15mm (29% vs 13.3%, p=0.055). Our data reveal that, although QFT test remained positive in the majority of children, reversion occurred in 16% of cases in a progressive and stable pattern. Younger age and reduced TST induration were associated with QFT reversion.

Multiplex PCR and Antibiotic Use in Children with Community-Acquired Pneumonia.

Antibiotics are frequently prescribed to children with pneumonia, although viruses are responsible for most cases. We aimed to evaluate the impact of multiplex polymerase chain reaction (mPCR) on antibiotic use. We conducted a prospective study of children under 14 years of age admitted for suspected viral pneumonia, from October 2019 to June 2022 (except March-November 2020). A mPCR respiratory panel (FilmArray® 2plus, bioMérieux, Marcy-l'Étoile, France) was performed within 72 h of admission. Patients with positive reverse transcription PCR for respiratory syncytial virus, influenza, or SARS-CoV-2 were excluded. We compared the patients with historical controls (2017-2018) who had suspected viral pneumonia but did not undergo an aetiological study. We included 64 patients and 50 controls, with a median age of 26 months. The respiratory panel detected viral pathogens in 55 patients (88%), including 17 (31%) with co-infections. Rhinovirus/enterovirus (n = 26) and human metapneumovirus (n = 22) were the most common pathogens, followed by adenovirus and parainfluenza (n = 10). There were no statistically significant differences in the total antibiotic consumption (83% of cases and 86% of controls) or antibiotics given for ≥72 h (58% vs. 66%). Antibiotics were prescribed in 41% of the cases and 72% of the controls at discharge (p = 0.001). Ampicillin was the most commonly prescribed antibiotic among the patients (44% vs. 18% for controls, p = 0.004), while azithromycin was the most commonly prescribed among the controls (19% vs. 48% for patients and controls, respectively; p = 0.001). Our findings underscore the need for additional interventions alongside molecular diagnosis to reduce antibiotic usage in paediatric community-acquired pneumonia.

Remdesivir for COVID-19 in Hospitalized Children: A Phase 2/3 Study.

OBJECTIVES: Remdesivir decreases the risk of SARS-CoV-2 infection progressing to severe disease in adults. This study evaluated remdesivir safety and pharmacokinetics in infants and children. METHODS: This was a phase 2/3, open-label trial in children aged 28 days to 17 years hospitalized for polymerase chain reaction-confirmed SARS-CoV-2 infection. Participants received for ≤10 days once-daily intravenous remdesivir doses defined using physiologically based pharmacokinetic modeling (for ≥40 kg, 200 mg day 1, then 100 mg/day; for age ≥28 days and ≥3 to <40 kg, 5 mg/kg day 1, then 2.5 mg/kg/day). Sparse pharmacokinetic samples were analyzed using population-pharmacokinetic approaches for remdesivir and metabolites GS-704277 and GS-441524. RESULTS: Among 53 participants, at enrollment the median (Q1, Q3) number of days of COVID-19 symptoms was 5 (3, 7) and hospitalization was 1 (1, 3). Underlying conditions included obesity in 19 (37%), asthma in 11 (21%), and cardiac disorders in 11 (21%). Median duration of remdesivir treatment was 5 days (range, 1-10). Remdesivir treatment had no new apparent safety trends. Two participants discontinued treatment because of adverse events including elevated transaminases; both had elevated transaminases at baseline. Three deaths occurred during treatment (and 1 after). When compared with phase 3 adult data, estimated mean pediatric parameters (area under the concentration-time curve over 1 dosing interval, AUCτ, Cmax, and Cτ) were largely overlapping but modestly increased (remdesivir, 33%-129%; GS-704277, 37%-124%; GS-441524, 0%-60%). Recovery occurred for 62% of participants on day 10 and 83% at last assessment. CONCLUSIONS: In infants and children with COVID-19, the doses of remdesivir evaluated provided drug exposure similar to adult dosing. In this study with a small sample size, no new safety concerns were observed.

The role of veterinarians in zoonosis prevention: Advising families of immunocompromised children with pets.

Background: Pet ownership is widespread, offering numerous benefits to individuals and families. However, the risk of zoonotic diseases must be carefully considered, especially for immunosuppressed patients. Knowledge gaps in preventive measures for zoonoses have been identified, underscoring the vital role of veterinarians in addressing this issue. Objectives: This study aimed to assess the knowledge and recommendations of veterinarians regarding pet ownership by immunocompromised individuals. Additionally, we compared these insights with responses from European healthcare professionals specializing in pediatric transplant recipients. Methods: We conducted an observational, cross-sectional study involving small animal veterinarians in Spain. An online survey was administered to gather information on veterinarians' knowledge of zoonoses and their recommendations for immunocompromised pet owners. Results: A survey of 514 individuals was collected from experienced veterinarians mainly working in primary care clinics. Surprisingly, 63% of respondents did not routinely inquire about the presence of immunocompromised individuals among pet owners, although 54% offered specific recommendations for this group. Most respondents adhered to deworming guidelines for pets owned by immunocompromised individuals and demonstrated sound practices in Leishmania and Leptospira prevention, as well as the avoidance of raw food. However, gaps were noted concerning Bordetella bronchiseptica vaccination. Notably, veterinarians outperformed medical professionals in their knowledge of zoonotic cases and identification of zoonotic microorganisms. The presence of specific recommendations in veterinary clinics was viewed positively by nearly all respondents. Conclusions: Our findings indicate that veterinarians possess a superior understanding of zoonotic pathogens and exhibit greater proficiency in diagnosing zoonoses compared with physicians. They stay well-informed about recommendations outlined in established guidelines and are more likely to provide written recommendations in their clinics than physicians. Nevertheless, knowledge gaps among veterinarians emphasize the need for enhanced communication between medical and veterinary professionals. Reinforcing the "One Health" concept is imperative, with veterinarians playing a pivotal role in this collaborative effort.

Antibiotic Utilization in Hospitalized Children with Bronchiolitis: A Prospective Study Investigating Clinical and Epidemiological Characteristics at a Secondary Hospital in Madrid (2004-2022).

Bronchiolitis is a viral respiratory infection, with respiratory syncytial virus (RSV) being the most frequent agent, requiring hospitalization in 1% of affected children. However, there continues to be a noteworthy incidence of antibiotic prescription in this setting, further exacerbating the global issue of antibiotic resistance. This study, conducted at Severo Ochoa Hospital in Madrid, Spain, focused on antibiotic usage in children under 2 years of age who were hospitalized for bronchiolitis between 2004 and 2022. In that time, 5438 children were admitted with acute respiratory infection, and 1715 infants (31.5%) with acute bronchiolitis were included. In total, 1470 (87%) had a positive viral identification (66% RSV, 32% HRV). Initially, antibiotics were prescribed to 13.4% of infants, but this percentage decreased to 7% during the COVID-19 pandemic thanks to adherence to guidelines and the implementation of rapid and precise viral diagnostic methods in the hospital. HBoV- and HAdV-infected children and those with viral coinfections were more likely to receive antibiotics in the univariate analysis. A multivariate logistic regression analysis revealed a statistically independent association between antibiotic prescription and fever > 38 °C (p < 0.001), abnormal chest-X ray (p < 0.001), ICU admission (p = 0.015), and serum CRP (p < 0.001). In conclusion, following guidelines and the availability of rapid and reliable viral diagnostic methods dramatically reduces the unnecessary use of antibiotics in infants with severe bronchiolitis.

Adenovirus Infection in Hematopoietic and Solid Organ Paediatric Transplant Recipients: Treatment, Outcomes, and Use of Cidofovir.

BACKGROUND: human adenovirus (hAdV) infection constitutes an important cause of morbidity and mortality in transplant recipients, due to their immune status. Among drugs currently available, cidofovir (CDF) is the most prescribed. METHODS: Retrospective study of hAdV infection in paediatric transplant recipients from a tertiary paediatric centre, describing characteristics, management, and outcomes, and focused on the role of CDF. RESULTS: 49 episodes of infection by hAdV were detected during a four-year period: 38 episodes in patients that received allogeneic hematopoietic stem cell transplantation (77.6%) and 11 in solid organ transplant recipients (22.4%). Twenty-five patients (52.1%) were symptomatic, presenting mainly fever and/or diarrhoea. CDF was prescribed in 24 patients (49%), with modest results. CDF use was associated with the presence of symptoms resulting in lower lymphocyte count, paediatric intensive care unit admission, and high viral load. Other therapeutic measures included administration of intravenous immunoglobulin, reducing immunosuppression, and T-lymphocyte infusion. Despite treatment, 22.9% of patients did not resolve the infection and there were three deaths related to hAdV infection. All-cause mortality was 16.7% (8 episodes) by 30 days, and 32.7% (16 episodes) by 90 days, of which, 3 episodes (3/16, 18.8%) were attributed to hAdV directly. CONCLUSIONS: hAdV infection had high morbidity and mortality in our series. CDF use is controversial, and available therapeutic options are limited. Transplant patients with low lymphocyte count are at higher risk of persistent positive viremias, and short-term survival of these patients was influenced by the resolution of hAdV infection.

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.

Usefulness of daptomycin lock therapy in children with catheter-related bacteremia after failed vancomycin lock therapy.

PURPOSE: Catheter-related bacteremia (CRB) is a significant cause of morbidity, resource expenditure and prolonged hospital stays in patients with long-term catheters, whose numbers have increased considerably in recent years. Antibiotic lock therapy reaches high concentrations in the catheter, allowing good penetration into the biofilm, being vancomycin the most commonly used one in gram-positive infections. Several authors have recently reported the superior in vitro efficacy of daptomycin compared with vancomycin, especially for eradicating biofilms. Although there is some data on the use of daptomycin for antibiotic lock in animal models and adults, there are no data on its use in children. METHODS: A descriptive study was conducted in a tertiary hospital, including patients younger than 16 years in whom daptomycin lock therapy was employed between 2018 and 2022. RESULTS: We report three pediatric patients in whom CRB was confirmed on admission by paired blood cultures positive for CoNS sensitive to vancomycin, daptomycin and linezolid. All patients started vancomycin lock therapy and systemic antibiotic therapy with proven sensitivity for the isolated bacteria, without achieving negative blood cultures. Due to the persistence of positive cultures, vancomycin lock therapy was replaced by daptomycin, and blood cultures turned negative, with no relapses or need for catheter removal. CONCLUSION: The use of daptomycin lock therapy could be considered in children with CoNS catheter infection, especially when other antibiotic lock therapy had failed.

Actualización del diagnóstico y tratamiento de la tuberculosis / Update on the diagnosis and treatment of tuberculosis

Más de un millón de pacientes menores de 15 años desarrollan tuberculosis (TB) anualmente en el mundo, según estimaciones de la OMS. La TB por cepas resistentes a los fármacos de primera línea alcanza al 25% de los nuevos casos en algunas regiones. Aunque España es considerada un país de baja incidencia, varios centenares de niños y adolescentes enferman de TB cada año. La importancia de la TB pediátrica ha sido minimizada durante años por la dificultad en confirmar el diagnóstico microbiológico y la escasa contagiosidad que asocia. Sin embargo, en los últimos 15 años, se han reportado mejoras relevantes en los informes epidemiológicos de la TB en niños y adolescentes, han surgido nuevos test inmunodiagnósticos, se dispone de estudios de biología molecular que permiten un diagnóstico microbiológico y una identificación de mutaciones asociadas a resistencia rápidos, han surgido nuevos fármacos antituberculosos de segunda línea, también en pediatría, y se han publicado ensayos clínicos que validan tratamientos acortados en algunos pacientes. Este documento, realizado por un grupo de expertos de la Sociedad Española de Infectología Pediátrica y la Sociedad Española de Neumología Pediátrica, actualiza y complementa las recomendaciones previas para el manejo diagnóstico y terapéutico del niño con TB en España, en base a las nuevas evidencias científicas disponibles. (AU)

According to WHO estimates, more than 1 million patients aged less than 15 years develop tuberculosis (TB) each year worldwide. In some regions, up to 25% of new TB cases are caused by drug-resistant strains. Although Spain is considered a low-incidence country, several hundred children and adolescents develop TB each year. The importance of paediatric TB has been minimized for years due to the lack of microbiological confirmation in many patients and because these patients are not usually contagious. Nevertheless, in the past 15 years there have been major improvements in the epidemiological reporting of TB in children and adolescents, new immunodiagnostic tests have been developed, molecular methods that allow rapid microbiological diagnosis and detection of variants associated with drug resistance have become available, novel second-line antituberculosis drugs have been discovered, including for paediatric use, and the results of clinical trials have validated shorter courses of treatment for some patients. This document, developed by a group of experts from the Sociedad Española de Infectología Pediátrica and the Sociedad Española de Neumología Pediátrica, updates and complements the previous guidelines for the diagnostic and therapeutic management of children with TB in Spain based on the newly available scientific evidence. (AU)

Update on the diagnosis and treatment of tuberculosis.

According to World Health Organization estimates, more than 1 million patients aged less than 15 years develop tuberculosis (TB) each year worldwide. In some regions, up to 25% of new TB cases are caused by drug-resistant strains. Although Spain is considered a low-incidence country, several hundred children and adolescents develop TB each year. The importance of paediatric TB has been minimized for years due to the lack of microbiological confirmation in many patients and because these patients are not usually contagious. Nevertheless, in the past 15 years there have been major improvements in the epidemiological reporting of TB in children and adolescents, new immunodiagnostic tests have been developed, molecular methods that allow rapid microbiological diagnosis and detection of variants associated with drug resistance have become available, novel second-line antituberculosis drugs have been discovered, including for paediatric use, and the results of clinical trials have validated shorter courses of treatment for some patients. This document, developed by a group of experts from the Sociedad Española de Infectología Pediátrica and the Sociedad Española de Neumología Pediátrica, updates and complements the previous guidelines for the diagnostic and therapeutic management of children with TB in Spain based on the newly available scientific evidence.

Bloodstream Infection in Children With Epidermolysis Bullosa.

BACKGROUND: Epidermolysis bullosa (EB) is frequently complicated by skin infection, which can lead to bacteremia. However, bloodstream infections (BSI) in patients with EB have not been well described. METHODS: Retrospective study of BSI in children 0-18 years with EB from a national reference unit in Spain, in 2015-2020. RESULTS: Among 126 children with EB, we identified 37 BSI episodes in 15 patients (14 recessive dystrophic EB, 1 junctional EB). The most frequent microorganisms were Pseudomonas aeruginosa (n = 12) and Staphylococcus aureus (n = 11). Five P. aeruginosa isolates were ceftazidime-resistant (42%), 4 of which were also resistant to meropenem and quinolones (33%). As for S. aureus , 4 (36%) were methicillin-resistant and 3 (27%) clindamycin-resistant. In 25 (68%) BSI episodes skin cultures had been performed in the previous 2 months. The most frequent isolates were also P. aeruginosa (n = 15) and S. aureus (n = 11). In 13 cases (52%), smear and blood cultures grew the same microorganism, with the same antimicrobial resistance pattern in 9 isolates. Twelve patients (10%) died during follow-up (9 RDEB and 3 JEB). BSI was the cause of death in 1 case. In patients with severe RDEB, a history of BSI was associated with higher mortality (OR 6.1, 95% CI: 1.33-27.83, P = 0.0197). CONCLUSIONS: BSI is an important cause of morbidity in children with severe forms of EB. The most frequent microorganisms are P. aeruginosa and S. aureus , with high rates of antimicrobial resistance. Skin cultures can help guide treatment decisions in patients with EB and sepsis.

Adequacy of the 10 mg/kg Daily Dose of Antituberculosis Drug Isoniazid in Infants under 6 Months of Age.

In 2010, the WHO recommended an increase in the daily doses of first-line anti-tuberculosis medicines in children. We aim to characterize the pharmacokinetics of the once-daily isoniazid (INH) dose at 10 mg/kg of body weight in infants <6 months of age. We performed a multicenter pharmacokinetic study in Spain. The N-acetyltransferase 2 gene was analyzed to determine the acetylation status. Samples were analyzed using a validated UPLC-UV assay. A non-compartmental pharmacokinetic analysis was performed. Twenty-three pharmacokinetic profiles were performed in 20 infants (8 females) at a median (IQR) age of 19.0 (12.6-23.3) weeks. The acetylator statuses were homozygous fast (n = 1), heterozygous intermediate (n = 12), and homozygous slow (n = 7). INH median (IQR) Cmax and AUC0-24h values were 4.8 (3.7-6.7) mg/L and 23.5 (13.4-36.7) h*mg/L and the adult targets (>3 mg/L and 11.6-26.3 h*mg/L) were not reached in three and five cases, respectively. The age at assessment or acetylator status had no impact on Cmax values, but a larger INH AUC0-24h (p = 0.025) and trends towards a longer half-life (p = 0.055) and slower clearance (p = 0.070) were observed in homozygous slow acetylators. Treatment was well tolerated; mildly elevated alanine aminotransferase levels were observed in three cases. In our series of young infants receiving isoniazid, no major safety concerns were raised, and the target adult levels were reached in most patients.

Treatments for multi-system inflammatory syndrome in children - discharge, fever, and second-line therapies.

Scarce evidence exists about the best treatment for multi-system inflammatory syndrome (MIS-C). We analyzed the effects of steroids, intravenous immunoglobulin (IVIG), and their combination on the probability of discharge over time, the probability of switching to second-line treatment over time, and the persistence of fever 2 days after treatment. We did a retrospective study to investigate the effect of different treatments on children with MIS-C from 1 March 2020 to 1 June 2021. We estimated the time-to-event probability using a Cox model weighted by propensity score to balance the baseline characteristics. Thirty of 132 (22.7%) patients were initially treated with steroids alone, 29/132 (21.9%) with IVIG alone, and 73/132 (55%) with IVIG plus steroids. The probability of early discharge was higher with IVIG than with IVIG plus steroids (hazard ratio [HR] 1.65, 95% CI 1.11-2.45, p = 0.013), but with a higher probability of needing second-line therapy compared to IVIG plus steroids (HR 3.05, 95% CI 1.12-8.25, p = 0.028). Patients on IVIG had a higher likelihood of persistent fever than patients on steroids (odds ratio [OR] 4.23, 95% CI 1.43-13.5, p = 0.011) or on IVIG plus steroids (OR 4.4, 95% CI 2.05-9.82, p < 0.001). No differences were found for this endpoint between steroids or steroids plus IVIG.    Conclusions: The benefits of each approach may vary depending on the outcome assessed. IVIG seemed to increase the probability of earlier discharge over time but also of needing second-line treatment over time. Steroids seemed to reduce persistent fever, and combination therapy reduced the need for escalating treatment. What is Known: • Steroids plus intravenous immunoglobulin, compared with intravenous immunoglobulin alone for multi-system inflammatory syndrome (MIS-C) might reduce the need for hemodynamic support and the duration of fever, but the certainty of the evidence is low. What is New: • Intravenous immunoglobulin, steroids, and their combination for MIS-C may have different outcomes. • In this study, intravenous immunoglobulin increased the probability of discharge over time, steroids reduced persistent fever, while combination therapy reduced the need for second-line treatments.

A challenging differential diagnosis in a patient with autosomal dominant STAT3 deficiency.

Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immunodeficiency caused by loss-of-function (LOF) mutations in the Signal Transducer and Activator of Transcription 3 (STAT3) gene. In these patients, performing a correct differential diagnosis of pulmonary infections is difficult and challenging, as they usually have atypical presentations. However, establishing a correct diagnostic and therapeutic approach is essential, as pulmonary complications are responsible for high morbidity and mortality rates in these patients. We report the case of a teenage girl with AD-HIES and respiratory symptoms and fever in whom performing a correct differential diagnosis was challenging.

Balancing the Risks and Benefits of Pet Ownership in Pediatric Transplant Recipients.

In recent decades, the number of pediatric transplantations and their survival rates have increased. Psychological problems and poorer quality of life are notable among children undergoing transplantation and can have long-lasting consequences and affect immunosuppressive therapy adherence. Pet ownership and animal contact have been associated with physical, mental, and social health benefits. Despite these potential benefits, however, companion animals are known to be a source of infection, which is one of the main concerns for clinicians. Because of immunosuppression, these children are particularly vulnerable to infections. Zoonoses comprise a long list of infectious diseases and represent a major public health problem. Nevertheless, many families and most healthcare providers are unaware of these potential risks, and there is a worrisome lack of recommendations to manage the risk-benefit balance, which could pose a risk for acquiring a zoonosis. Furthermore, no data are available on the number of transplanted patients with pets, and this risk-benefit balance is difficult to adequately evaluate. In this document, we review the currently available evidence regarding the epidemiology of zoonotic infections in patients undergoing transplantation, focusing on pediatric patients from a risk-benefit perspective, to help inform decision-making for clinicians. Families and healthcare professionals should be aware of the risks, and clinicians should actively screen for pets and offer comprehensive information as part of routine clinical practice. A multidisciplinary approach will ensure proper care of patients and pets and will establish preventive measures to ensure patients are safe living with their pets.

Impact of cytomegalovirus infection prior to hematopoietic stem cell transplantation in children with inborn errors of immunity.

The presence of active viral infections has an impact on the prognosis of patients undergoing hematopoietic stem cell transplantation (HSCT). Nevertheless, the number of reports of cytomegalovirus infection in patients with inborn errors of immunity (IEI) who undergo HSCT is relatively low. To analyze the effect of cytomegalovirus infection acquired prior to curative treatment on patient survival in 123 children with IEI. An observational and retrospective study was performed with patients younger than 18 years diagnosed with IEI who were candidates for HSCT, gene therapy, or thymus transplantation at five hospitals in Spain between 2008 and 2019. We included 123 children, 25 infected by cytomegalovirus prior to undergoing curative treatment (20.3%). At IEI diagnosis, 24 of the patients were already infected, 21 of whom had symptomatic cytomegalovirus disease (87%), while the other three patients developed disease before undergoing curative treatment. The patients with cytomegalovirus infection had higher mortality than those without (p = 0.006). Fourteen patients developed refractory cytomegalovirus infection (56%), all of whom died, while no patients with non-refractory infection died (p = 0.001) All deaths that occurred before curative treatment and three of the five after the treatment were attributed to cytomegalovirus. Patients with refractory cytomegalovirus disease had the highest pre-HSCT mortality rate (64.3%), compared with the non-infected children and those with non-refractory cytomegalovirus disease (10.1%) (p < 0.0001). CONCLUSION: Prevention and prompt control of cytomegalovirus infection, together with early HSCT/gene therapy, are crucial for improving the prognosis in children with IEI. WHAT IS KNOWN: • Cytomegalovirus is the most frequent viral infection in children with inborn errors of immunity who are candidates to hematopoietic stem cell transplantation (HSCT). • Active viral infections at the time of HSCT lead to worse prognosis. WHAT IS NEW: • In children with inborn errors of immunity and indication of HSCT, refractory cytomegalovirus disease is associated with a very high mortality rate, compared with non-infected children and those with non-refractory cytomegalovirus disease. • In patients with novel transplantation indications, the presence and treatment response of CMV infection should be considered to decide the best possible moment for HSCT.

Pets for pediatric transplant recipients: To have or not to have.

Pets have many health, emotional and social benefits for children, but the risk of zoonotic infections cannot be underestimated, especially for immunosuppressed patients. We report the recommendations given by health professionals working with pediatric transplant recipients to their families regarding pet ownership. An online survey addressing zoonosis knowledge and recommendations provided by health care practitioners regarding pets was distributed to clinicians treating pediatric transplant recipients. The European Society of Pediatric Infectious Disease (ESPID) and the European Reference Network ERN-TransplantChild, which works to improve the quality of life of transplanted children, allowed the online distribution of the survey. A total of 151 practitioners from 28 countries participated in the survey. Up to 29% of the respondents had treated at least one case of zoonosis. Overall, 58% of the respondents considered that the current available evidence regarding zoonotic risk for transplanted children of having a pet is too scarce. In addition, up to 23% of the surveyed professionals recognized to be unaware or outdated. Still, 27% of the respondents would advise against buying a pet. Practitioners already owning a pet less frequently advised patients against pet ownership, whereas non-pet-owners were more keen to advise against pet ownership (p = 0.058). 61% of the participants stated that there were no institutional recommendations regarding pets in their centers/units. However, 43% of them reported therapeutic initiatives that involved animals in their centers. Infectious disease specialists were more likely to identify zoonotic agents among a list of pathogens compared to other specialists (p < 0.05). We have observed a huge heterogeneity among the recommendations that health care providers offer to families in terms of risk related to pet ownership for transplant recipients. The lack of evidence regarding these recommendations results in practitioners' recommendations based on personal experience.

Humoral and cellular immune response to mRNA SARS-CoV-2 BNT162b2 vaccine in adolescents with rheumatic diseases.

BACKGROUND: Data about safety and efficacy of the mRNA SARS-CoV-2 vaccine in adolescents with rheumatic diseases (RD) is scarce and whether these patients generate a sufficient immune response to the vaccine remains an outstanding question. OBJECTIVE: To evaluate safety and humoral and cellular immunity of the BNT162b2 vaccine in adolescents 12 to 18 years with RD and immunosuppressive treatment compared with a healthy control group. METHODS: Adolescents from 12 to 18 years with RD followed at Hospital La Paz in Madrid (n = 40) receiving the BNT162b2 mRNA vaccination were assessed 3 weeks after complete vaccination. Healthy adolescents served as controls (n = 24). Humoral response was measured by IgG antiSpike antibodies, and cellular response by the quantity of IFN-γ and IL-2 present in whole blood stimulated with SARS-CoV-2 Spike and M proteins. RESULTS: There were no differences in spike-specific humoral or cellular response between groups (median IFN-γ response to S specific protein; 528.80 pg/ml in controls vs. 398.44 in RD patients, p 0.78, and median IL-2 response in controls: 635.68 pg/ml vs. 497.30 in RD patients, p 0.22. The most frequent diagnosis was juvenile idiopathic arthritis (26/40, 65%) followed by Lupus (6/40, 15%). 60% of cases (23/40) received TNF inhibitors and 35% (14/40) methotrexate. 40% of patients (26/64) had previous SARS-CoV-2 infection, 9 in the control group and 17 in the RD patients without differences. Of note, 70% of infections were asymptomatic. A higher IFN-γ production was found in COVID-19 recovered individuals than in naive subjects in both groups (controls: median 859 pg/ml in recovered patients vs. 450 in naïve p 0.017, and RD patients: 850 in recovered vs. 278 in naïve p 0.024). No serious adverse events or flares were reported following vaccination. CONCLUSIONS: We conclude that standard of care treatment for adolescents with RD including TNF inhibitors and methotrexate did not affect the humoral and the cellular immunity to BNT162b2 mRNA vaccination compared to a healthy control group. The previous contact with SARS-CoV-2 was the most relevant factor in the immune response.

Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia.

BACKGROUND: Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP. METHODS: This phase 2/3, randomized, open-label, active-control, multicenter study randomly assigned solithromycin (capsules, suspension or intravenous) or an appropriate comparator antibiotic in a 3:1 ratio (planned n = 400) to children 2 months to 17 years of age with CABP. Primary safety endpoints included treatment-emergent adverse events (AEs) and AE-related drug discontinuations. Secondary effectiveness endpoints included clinical improvement following treatment without additional antimicrobial therapy. RESULTS: Unrelated to safety, the sponsor stopped the trial prior to completion. Before discontinuation, 97 participants were randomly assigned to solithromycin (n = 73) or comparator (n = 24). There were 24 participants (34%, 95% CI, 23%-47%) with a treatment-emergent AE in the solithromycin group and 7 (29%, 95% CI, 13%-51%) in the comparator group. Infusion site pain and elevated liver enzymes were the most common related AEs with solithromycin. Study drug was discontinued due to AEs in 3 subjects (4.3%) in the solithromycin group and 1 (4.2%) in the comparator group. Forty participants (65%, 95% CI, 51%-76%) in the solithromycin group achieved clinical improvement on the last day of treatment versus 17 (81%, 95% CI, 58%-95%) in the comparator group. The proportion achieving clinical cure was 60% (95% CI, 47%-72%) and 68% (95% CI, 43%-87%) for the solithromycin and comparator groups, respectively. CONCLUSIONS: Intravenous and oral solithromycin were generally well-tolerated and associated with clinical improvement in the majority of participants treated for CABP.