Direct oral challenge for immediate and non-immediate beta-lactam allergy in children: A real-world multicenter study.

BACKGROUND: Allergy to beta-lactam antibiotics (BLA) is frequently suspected in children, but a drug provocation test (DPT) rules it out in over 90% of cases. Direct oral DPT (DODPT), without skin or other previous tests, is increasingly been used to delabel non-immediate BLA reactions. This real-world study aimed to assess the safety and effectiveness of DODPT in children with immediate and non-immediate reactions to BLAs. METHODS: Ambispective registry study in children (<15 years), attended between 2016 and 2023 for suspected BLA allergy in 15 hospitals in Spain that routinely perform DODPT. RESULTS: The study included 2133 patients with generally mild reactions (anaphylaxis 0.7%). Drug provocation test with the implicated BLA was performed in 2014 patients (94.4%): 1854 underwent DODPT (86.9%, including 172 patients with immediate reactions). One hundred forty-five (7.2%) had symptoms associated with DPT, although only four reactions were severe: two episodes of anaphylaxis and two of drug-induced enterocolitis syndrome, which resolved rapidly with treatment. Of the 141 patients with mild reactions in the first DPT, a second DPT was considered in 87 and performed in 57, with 52 tolerating it without symptoms. Finally, BLA allergy was ruled out in 90.9% of the sample, confirmed in 3.4%, and remained unverified, usually due to loss to follow-up, in 5.8%. CONCLUSIONS: Direct oral DPT is a safe, effective procedure even in immediate mild reactions to BLA. Many reactions observed in DPT are doubtful and require confirmation. Severe reactions are exceptional and amenable to treatment. Direct oral DPT can be considered for BLA allergy delabeling in pediatric primary care.

SARS-CoV-2 infection in children with cystic fibrosis: A cross-sectional multicenter study in Spain. New waves, new knowledge.

INTRODUCTION: The association between viral infections and pulmonary exacerbations in children with cystic fibrosis (cwCF) is well established. However, the question of whether cwCF are at a higher risk of COVID-19 or its adverse consequences remains controversial. METHODS: We conducted an observational, multicenter, cross-sectional study of cwCF infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) between March 2020 and June 2022, (first to sixth COVID-19 pandemic waves) in Spain. The study aimed to describe patients' basal characteristics, SARS-CoV-2 clinical manifestations and outcomes, and whether there were differences across the pandemic waves. RESULTS: During study time, 351 SARS-CoV2 infections were reported among 341 cwCF. Median age was 8.5 years (range 0-17) and 51% were female. Cases were unevenly distributed across the pandemic, with most cases (82%) clustered between November 2021 and June 2022 (sixth wave, also known as Omicron Wave due to the higher prevalence of this strain in that period in Spain). Most cwCF were asymptomatic (24.8%) or presented with mild Covid-19 symptoms (72.9%). Among symptomatic, most prevalent symptoms were fever (62%) and increased cough (53%). Infection occurring along the sixth wave was the only independent risk factor for being symptomatic. Just eight cwCF needed hospital admission. No multisystem inflammatory syndrome, persisting symptoms, long-term sequelae, or deaths were reported. CONCLUSIONS: Spanish current data indicate that cwCF do not experience higher risks of SARS-CoV-2 infection nor worse health outcomes or sequelae. Changes in patients' basal characteristics, clinical courses, and outcomes were detected across waves. While the pandemic continues, a worldwide monitoring of COVID-19 in pediatric CF patients is needed.

Epidemiology of pediatric parapneumonic pleural effusion during 13-valent pneumococcal conjugate vaccine implementation.

INTRODUCTION: The reported incidence of parapneumonic pleural effusion, including empyema, has shown fluctuations in the last decades. It has been related to the implementation of different types of conjugate pneumococcal vaccines. METHODS: We have retrospectively reviewed data from all 10 public hospitals in Alicante Province (Spain) covering a population of 279,000 children under 15 years of age, between 2010 and 2018. Effusions less than 10 mm (PE-) and those of 10 mm or more (PE+) were separated. RESULTS: A total of 366 episodes of parapneumonic pleural effusion have been analyzed, 178 PE- (48.6%) and 188 PE+ (51.4%), with a median age of 4 years (interquartile range: 2-7 years) and marked seasonality with the maximum in winter and the minimum in summer. A culture proven bacterial agent was identified in 34 patients (9.3%), mainly Streptococcus pneumoniae (24 patients) followed by Streptococcus pyogenes (7 patients). The most frequent S. pneumoniae serotype was 19A (6 patients) and 3 vaccine failures were observed. The mean annual incidence rate was 14.3 cases per 100,000 children under 15 years of age (7.0 for PE- and 7.3 for PE+). No significant changes were observed in incidence over time, but noticeable differences in incidence were observed in different health departments. CONCLUSIONS: We have not found temporal variations in incidence of parapneumonic effusion despite the implementation of the 13-valent pneumococcal conjugate vaccine. The unexplained disparity in incidence between close departments is noteworthy.

Positive drug provocation with beta-lactam antibiotics in children: A single test may not be enough.

BACKGROUND: Drug provocation tests (DPTs) are considered the gold standard for diagnosing beta-lactam allergy. However, positive results tend to be mild and difficult to interpret. This study aimed to describe pediatric patients with a presumedly positive or inconclusive DPT, assess the decision to repeat the DPT, and describe its outcome. METHODS: Retrospective review of all presumedly positive or inconclusive DPTs performed in six pediatric allergy clinics from 2017 to 2019. We describe the interpretation of results, focusing on the decision to repeat the DPT and its outcome. RESULTS: Of 439 children challenged with a beta-lactam, 26 (5.9%) with a presumedly positive or inconclusive result were included in this study. Most were girls (n = 16, 61.5%), and the median age was 5 years (range 1-13). The initial DPT used amoxicillin (n = 13, 50.0%), amoxicillin-clavulanic acid (n = 12, 46.2%), or cefadroxil (n = 1, 3.8%). Reactions were early (n = 11, 42.3 %), delayed (n = 14, 53.8 %), or not registered (n = 1, 3.8 %), but mild in all cases. A second confirmatory DPT was proposed in 19 patients (73.1%) and performed in 17 patients (65.4%). Nine DPTs were performed from 1 day to 4 months after the first DPT, and the remaining eight took place 6 months to 2 years later. Fifteen children tolerated the drug in the second DPT: 88.2% of those reevaluated and 57.5% of the whole study group. CONCLUSION: The positive predictive value of DPT may be lower than expected. Given the mildness of observed reactions, a second confirmatory DPT is warranted within a few weeks or months.

Positive drug provocation with beta-lactam antibiotics in children: A single test may not be enough

Background: Drug provocation tests (DPTs) are considered the gold standard for diagnosing beta-lactam allergy. However, positive results tend to be mild and difficult to interpret. This study aimed to describe pediatric patients with a presumedly positive or inconclusive DPT, assess the decision to repeat the DPT, and describe its outcome.Methods: Retrospective review of all presumedly positive or inconclusive DPTs performed in six pediatric allergy clinics from 2017 to 2019. We describe the interpretation of results, focusing on the decision to repeat the DPT and its outcome.Results: Of 439 children challenged with a beta-lactam, 26 (5.9%) with a presumedly positive or inconclusive result were included in this study. Most were girls (n = 16, 61.5%), and the median age was 5 years (range 1–13). The initial DPT used amoxicillin (n = 13, 50.0%), amoxicillin-clavulanic acid (n = 12, 46.2%), or cefadroxil (n = 1, 3.8%). Reactions were early (n = 11, 42.3 %), delayed (n = 14, 53.8 %), or not registered (n = 1, 3.8 %), but mild in all cases. A second confirmatory DPT was proposed in 19 patients (73.1%) and performed in 17 patients (65.4%). Nine DPTs were performed from 1 day to 4 months after the first DPT, and the remaining eight took place 6 months to 2 years later. Fifteen children tolerated the drug in the second DPT: 88.2% of those reevaluated and 57.5% of the whole study group.Conclusion: The positive predictive value of DPT may be lower than expected. Given the mildness of observed reactions, a second confirmatory DPT is warranted within a few weeks or months (AU)

Population-Based Cohort of Children With Parapneumonic Effusion and Empyema Managed With Low Rates of Pleural Drainage.

Introduction: The most appropriate treatment for parapneumonic effusion (PPE), including empyema, is controversial. We analyzed the experience of our center and the hospitals in its reference area after adopting a more conservative approach that reduced the use of chest tube pleural drainage (CTPD). Methods: Review of the clinical documentation of all PPE patients in nine hospitals from 2010 to 2018. Results: A total of 318 episodes of PPE were reviewed; 157 had a thickness of <10 mm. The remaining 161 were 10 mm or thicker and were subdivided into three increasing sizes: PE+1, PE+2, and PE+3. There was a strong relationship between the size of the effusion and complicated effusion/empyema, defined by its appearance on imaging studies or by the physical or bacteriological characteristics of the pleural fluid. The size of effusion was also strongly related to the duration of fever and intravenous treatment and was the best independent predictor of the length of hospital stay (LHS) (p < 0.001). CTPD was placed in 2.9% of PE+1 patients, 19.3% of PE+2, and 63.9% of PE+3 (p < 0.001). The referral of patients with PE+1 decreased over time (p = 0.033), as did the use of CTPD in the combined PE+1/PE+2 group (p = 0.018), without affecting LHS (p = 0.814). There were no changes in the use of CTPD in the PE+3 group (p = 0.721). Conclusions: The size of the PPE is strongly correlated with its severity and with LHS. Most patients can be treated with antibiotics alone.

Could imbalances in the composition of gut microbiota be implicated in the origin of atopic dermatitis?

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