The Association of the MeMed BV Test With Radiographic Pneumonia in Children.

BACKGROUND: The MeMed BV Test produces a score that increases with increasing likelihood of bacterial infection. We evaluated its association with radiographic pneumonia in children. METHODS: We performed a secondary analysis of a multicenter prospective study of febrile children 90 days to 18 years presenting to an emergency department. We evaluated the association of the MeMed BV test with radiographic pneumonia in adjusted logistic regression models. RESULTS: Of 182 children, 74 (41%) had radiographic pneumonia. Among children with a high likelihood of having viral illness per the BV test, 26% had radiographic pneumonia; this increased to 64% among those with a BV test which indicated a high likelihood of bacterial infection. The sensitivity and specificity for radiographic pneumonia when using a BV test classification of moderate or high likelihood of bacterial infection were 60.8% and 62.0%, respectively. A BV test indicating the highest likelihood of bacterial infection had 23.61 higher adjusted odds (95% confidence interval 6.30-88.6) of radiographic pneumonia. The most common radiographic finding among children classified as having a high likelihood of viral infection by the BV test was interstitial opacities. The most common finding among children classified as having a high likelihood of bacterial infection were infiltrates. Except for antibiotic use, clinical outcomes occurred in similar proportions by BV category. CONCLUSIONS: Children with moderate to high likelihoods of bacterial infection on the BV test had higher odds of radiographic pneumonia. Apart from antibiotic use, the test was not significantly associated with clinical outcomes in this study.

The severity of respiratory syncytial virus infection in children during the SARS-CoV-2/COVID-19 pandemic: A nationwide study of 11,915 cases in Germany.

PURPOSE: Respiratory syncytial virus (RSV) infection is a major cause of childhood hospitalization. The COVID-19 pandemic has disrupted the usual seasonal pattern of RSV, resulting in high activity during the off-season. This study aims to evaluate the effects of the pandemic on the severity of RSV infections. METHODS: Data from 11,915 children hospitalized due to RSV infection between 2016 and 2022 were analyzed. The hospitalized patients were categorized into two groups, from January 2016 to February 2020 (PreCoV19 group) and from March 2020 to December 2022 (CoV19 group). The hospitalization duration, intensive care unit (ICU) admissions, length of stay at ICU, mechanical ventilation requirement and duration, Elixhauser comorbidity index scores, and in-hospital mortality were analyzed. RESULTS: Children in the PreCoV19 group had a mean age of 0.4 ± 0.7, whereas those in the CoV19 group had a mean age of 0.6 ± 1.0 years. Children during the pandemic had significantly shorter hospital stays (4.3 ± 2.6 days) compared to children of the pre-pandemic period (4.9 ± 3.3 days). Although ICU admission rates did not change, the duration of ICU stays decreased in the CoV19 group. Moreover, the in-hospital mortality did not differ between the groups. A multivariable analysis showed that younger age, regardless of the pandemic period, was associated with prolonged hospital stays, higher ICU admission rates, and an increased requirement for mechanical ventilation. CONCLUSION: Our findings highlight significant changes of the clinical characteristics of RSV infections during the pandemic, with implications for clinical management and public health strategies.

Clinical and economic inpatient burden of respiratory syncytial virus (RSV) infections in children < 2 years of age in Germany, 2014-2019: a retrospective health claims analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause for severe lower respiratory tract infections (LRTI) in children < 2 years of age in Germany - though little is known about the clinical and economic burden of RSV in children with and without risk factors per month of life. METHODS: In a retrospective health claims analysis, we identified RSV inpatient cases between 2014 and 2019. We assessed incidence rates, mortality rate, healthcare resource utilization, associated direct costs per case and excess costs for 30, 90 and 365 days after hospital admission matched to a control group. The outcomes are reported separately for the first and second year of life (i.e., for infants and toddlers) and were stratified by month of life, preterm and risk status (i.e., presence of underlying disease: chronic respiratory or cardiac disease, immunosuppression, neurological diseases, diabetes, conditions originating in the perinatal period). RESULTS: RSV-attributable hospital incidence rate was higher in infants (30.25/1,000) than toddlers (14.52/1,000), highest in the first three months of life (44.21/1,000), in infants born preterm (64.76/1,000) or with any underlying disease (54.85/1,000). Mortality rate was also higher for infants (0.08/1,000) than toddlers (0.04/1,000). Mean 30-day excess costs ranged from 2,953 € for infants born full-term at no risk, hospitalized for 5 days, to 6,694 € for infants born extremely premature, hospitalized for 7 days. CONCLUSION: In Germany, the clinical and economic burden of RSV is substantial, especially in the most vulnerable population, that is, very young infants, those born premature and/or those with an underlying disease.

Are Invasive Group A Streptococcal Infections Preventable by Antibiotic Therapy?: A Collaborative Retrospective Study.

BACKGROUND: In winter 2022/2023, a resurgence of invasive group A streptococcal (iGAS) infections in children was observed in Europe, including Germany and Switzerland. While a simultaneous increase in consultations for scarlet fever and pharyngitis was reported in England, leading to the recommendation to treat any suspected GAS disease with antibiotics, guidelines in Germany and Switzerland remained unchanged. We aimed to investigate whether this policy was appropriate. METHODS: We conducted a retrospective multicenter study of children hospitalized for invasive GAS disease between September 2022 and March 2023 in pediatric departments in Dresden and Berlin (Germany) and Basel (Switzerland). We reviewed medical records and conducted structured telephone interviews to analyze whether suspected GAS infections with or without antibiotic treatment were reported prehospitalization. RESULTS: In total, 63 patients met the inclusion criteria (median age 4.2 years, 57% males); however, clinical information was not complete for all analyzed characteristics; 32/54 (59%) had ≥1 physician visit ≤4 weeks prehospitalization. In 4/32 (13%) patients, GAS disease, that is, tonsillitis or scarlet fever, was suspected; 2/4 of them received antibiotics, and a positive rapid antigen test for GAS was documented in 1 of them. CONCLUSIONS: A small minority of patients had suspected GAS infection within 4 weeks before iGAS disease. These data suggest that there is little opportunity to prevent iGAS disease by antibiotic therapy, because in most patients-even if seen by a physician-there was either no evidence of GAS disease or when GAS disease was suspected and treated with antibiotics, consecutive invasive GAS disease was not prevented.

Respiratory Syncytial Virus-Associated Respiratory Diseases in Children and Adults.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections (LRTI), particularly in neonates, infants and young children, with approximately 33 million infections worldwide each year. 1-2% of episodes lead to hospitalization. There are hardly any reliable epidemiological figures on hospital - ization in adults, whose burden of disease from RSV is probably markedly underestimated. METHODS: This review is based on publications retrieved by a selective search in PubMed, with particular attention to recommendations for the prevention of RSV infection. RESULTS: There is no approved antiviral therapy for clinical practice, but preventive strategies are increasingly becoming available. Passive immunization in infants is well tolerated and highly effective, as is the active vaccination of pregnant women to prevent severe RSV infection in young infants. The former was found to lower the frequency of severe LRTI (5/4037 in the vaccination group vs. 19/4031 individuals in the placebo group), yielding an efficacy of 75.7%; for the latter, the corresponding findings were a reduction to 19/3682 in the vaccination group vs. 62/3676 in the placebo group, or 69.4% efficacy. For the active vaccination of older adults, both a recombinant vaccine with adjuvant and a bivalent vaccine have recently been approved. These, too, are well tolerated and highly effective: the former lowered the frequency of severe LRTI to 1/12466 in the vaccination group vs. 17/12494 in the placebo group (94.1% efficacy), while the latter lowered the frequency of LRTI with 3 or more manifestations to 2/17215 in the vaccination group vs. 14/17069 in the placebo group (85.7% efficacy). CONCLUSION: The approval of new RSV-specific monoclonal antibodies and active vaccinations enables targeted prevention of RSV infection in the main population groups at risk.

The Increase in Invasive Bacterial Infections With Respiratory Transmission in Germany, 2022/2023.

BACKGROUND: In late 2022, health care institutions in Germany reported an unusual number of severe, invasive bacterial infections in association with a high incidence of viral respiratory infections. METHODS: We analyzed routine data on invasive infections due to Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes (2017-2023) from a voluntary, laboratory-based surveillance system involving continuously participating facilities providing diagnostic routine data that cover approximately one-third of the German population. RESULTS: In the first quarter (Q1) of 2023, the number of invasive S. pyogenes isolates rose by 142% (n = 837 vs. mean Q1/2017-2019 = 346, 95% CI [258; 434]), while the number of H. influenzae isolates rose by 90% (n = 209 in Q1/2023 vs. mean Q1/2017-2019 = 110, 95% CI [79; 142]), compared to pre-pandemic seasonal peak values. The number of invasive S. pneumoniae isolates was high in two quarters (n = 1732 in Q4/2022 und Q1/2023). Adults aged 55 and older and children younger than 5 years were most affected by invasive H. influenzae, S. pneumoniae, and S. pyogenes infections. N. meningitidis was most commonly found in children under age 5. CONCLUSION: The reason for the marked rise in invasive bacterial infections may be an increased circulation of respiratory pathogens and elevated susceptibility in the population after relaxation of the measures taken to prevent COVID-19 infection. Coinfections with respiratory viruses may have reinforced this effect. We recommend continuous surveillance, preventive measures such as raising awareness about invasive bacterial diseases, and vaccination as recommended by the German Standing Committee on Vaccinations (STIKO).

Clinical recommendations for the inpatient management of lower respiratory tract infections in children and adolescents with severe neurological impairment in Germany.

Children and adolescents with severe neurological impairment (SNI) require specialized care due to their complex medical needs. In particular, these patients are often affected by severe and recurrent lower respiratory tract infections (LRTIs). These infections, including viral and bacterial etiology, pose a significant risk to these patients, often resulting in respiratory insufficiency and long-term impairments. Using expert consensus, we developed clinical recommendations on the management of LRTIs in children and adolescents with SNI. These recommendations emphasize comprehensive multidisciplinary care and antibiotic stewardship. Initial treatment should involve symptomatic care, including hydration, antipyretics, oxygen therapy, and respiratory support. In bacterial LRTIs, antibiotic therapy is initiated based on the severity of the infection, with aminopenicillin plus a beta-lactamase inhibitor recommended for community-acquired LRTIs and piperacillin-tazobactam for patients with chronic lung disease or tracheostomy. Ongoing management includes regular evaluations, adjustments to antibiotic therapy based on pathogen identification, and optimization of supportive care. Implementation of these recommendations aims to improve the diagnosis and treatment of LRTIs in children and adolescents with SNI. What is Known: • Children and adolescents with severe neurological impairment are particularly affected by severe and recurrent lower respiratory tract infections (LRTIs). • The indication and choice of antibiotic therapy for bacterial LRTI is often difficult because there are no evidence-based treatment recommendations for this heterogeneous but vulnerable patient population; the frequent overuse of broad-spectrum or reserve antibiotics in this patient population increases selection pressure for multidrug-resistant pathogens. What is New: • The proposed recommendations provide a crucial framework for focused diagnostics and treatment of LRTIs in children and adolescents with severe neurological impairment. • Along with recommendations for comprehensive and multidisciplinary therapy and antibiotic stewardship, ethical and palliative care aspects are taken into account.

Epidemiology of 7375 children and adolescents hospitalized with COVID-19 in Germany, reported via a prospective, nationwide surveillance study in 2020-2022.

By means of a nationwide, prospective, multicenter, observational cohort registry collecting data on 7375 patients with laboratory-confirmed SARS-CoV-2 admitted to children's hospitals in Germany, March 2020-November 2022, our study assessed the clinical features of children and adolescents hospitalized due to SARS-CoV-2, evaluated which of these patients might be at highest risk for severe COVID-19, and identified underlying risk factors. Outcomes tracked included: symptomatic infection, case fatality, sequelae at discharge and severe disease. Among reported cases, median age was one year, with 42% being infants. Half were admitted for reasons other than SARS-CoV-2. In 27%, preexisting comorbidities were present, most frequently obesity, neurological/neuromuscular disorders, premature birth, and respiratory, cardiovascular or gastrointestinal diseases. 3.0% of cases were admitted to ICU, but ICU admission rates varied as different SARS-CoV-2 variants gained prevalence. Main risk factors linked to ICU admission due to COVID-19 were: patient age (> 12 and 1-4 years old), obesity, neurological/neuromuscular diseases, Trisomy 21 or other genetic syndromes, and coinfections at time of hospitalization. With Omicron, the group at highest risk shifted to 1-4-year-olds. For both health care providers and the general public, understanding risk factors for severe disease is critical to informing decisions about risk-reduction measures, including vaccination and masking guidelines.

High burden of acute respiratory tract infections leading to hospitalization at German pediatric hospitals: fall/winter 2022-2023.

PURPOSE: Given reduced immunity levels for seasonally occurring respiratory infections and the experience of an unusually early, severe wave of RSV infections during 2021, a preexisting clinician-led reporting system (CLRS) was updated to prospectively monitor the anticipated high burden of respiratory infections (ARI) in German pediatric hospitals during fall/winter 2022-2023. METHODS: From September 13, 2022 through March 31, 2023, children hospitalized with ARI as a primary diagnosis were monitored via a national CLRS established by the German Society for Pediatric Infectious Diseases (DGPI). Once a week, the CLRS collected overall number of new hospital admissions, ARI-related admissions according to pathogen (SARS-CoV-2, RSV, influenza, and other), plus number of patients admitted to ICU with ARI as a primary diagnosis. RESULTS: With a high participation among children's hospitals across Germany (22.8%), 76 centers submitted 1,053 survey reports. ARI-related hospital admissions showed a steep rise starting in late September 2022 and reached their highpoint in early December 2022 (50.1% of all admissions). In parallel, the average number of newly admitted patients (aNA) with RSV (3.6) peaked, as did those with influenza (2.1) one week later. The average highpoint of ARI patients on ICU (aICU) (2.9) was reached shortly thereafter. Again, RSV (1.6) und influenza (1.2) were predominant pathogens. CONCLUSION: In fall/winter 2022-2023, German hospitals reported a sharp increase in patients with ARIs. While RSV and influenza represented the greatest proportion of ARI, SARS-CoV-2 played a less significant role. Systematic, dynamic collection of ARI data is critical for assessing real burdens on the health care system.

The choroid plexus acts as an immune cell reservoir and brain entry site in experimental autoimmune encephalomyelitis.

The choroid plexus (ChP) has been suggested as an alternative central nervous system (CNS) entry site for CCR6+ Th17 cells during the initiation of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). To advance our understanding of the importance of the ChP in orchestrating CNS immune cell entry during neuroinflammation, we here directly compared the accumulation of CD45+ immune cell subsets in the ChP, the brain and spinal cord at different stages of EAE by flow cytometry. We found that the ChP harbors high numbers of CD45int resident innate but also of CD45hi adaptive immune cell subsets including CCR6+ Th17 cells. With the exception to tissue-resident myeloid cells and B cells, numbers of CD45+ immune cells and specifically of CD4+ T cells increased in the ChP prior to EAE onset and remained elevated while declining in brain and spinal cord during chronic disease. Increased numbers of ChP immune cells preceded their increase in the cerebrospinal fluid (CSF). Th17 but also other CD4+ effector T-cell subsets could migrate from the basolateral to the apical side of the blood-cerebrospinal fluid barrier (BCSFB) in vitro, however, diapedesis of effector Th cells including that of Th17 cells did not require interaction of CCR6 with BCSFB derived CCL20. Our data underscore the important role of the ChP as CNS immune cell entry site in the context of autoimmune neuroinflammation.

Immunization technologies: Time to consider new preventative solutions for respiratory syncytial virus infections.

New technologies for the prevention of infectious diseases are emerging to address unmet medical needs, in particular, the use of long-acting monoclonal antibodies (mAb) to prevent Respiratory Syncytial Virus (RSV) lower respiratory tract disease in infants during their first RSV season. The lack of precedent for mAbs for broad population protection creates challenges in the assessment of upcoming prophylactic long-acting mAbs for RSV, with associated consequences in legislative and registration categorization, as well as in recommendation, funding, and implementation pathways. We suggest that the legislative and regulatory categorization of preventative solutions should be decided by the effect of the product in terms of its impact on the population and health-care systems rather than by the technology used or its mechanism of action. Immunization can be passive and active, both having the same objective of prevention of infectious diseases. Long-acting prophylactic mAbs work as passive immunization, as such, their recommendations for use should fall under the remit of National Immunization Technical Advisory Groups or other relevant recommending bodies for inclusion into National Immunization Programs. Current regulations, policy, and legislative frameworks need to evolve to embrace such innovative preventative technologies and acknowledge them as one of key immunization and public health tools.

Antimicrobial use in pediatric oncology and hematology in Germany and Austria, 2020/2021: a cross-sectional, multi-center point-prevalence study with a multi-step qualitative adjudication process.

Background: Due to the high risk of severe infection among pediatric hematology and oncology patients, antimicrobial use is particularly high. With our study, we quantitatively and qualitatively evaluated, based on institutional standards and national guidelines, antimicrobial usage by employing a point-prevalence survey with a multi-step, expert panel approach. We analyzed reasons for inappropriate antimicrobial usage. Methods: This cross-sectional study was conducted at 30 pediatric hematology and oncology centers in 2020 and 2021. Centers affiliated to the German Society for Pediatric Oncology and Hematology were invited to join, and an existing institutional standard was a prerequisite to participate. We included hematologic/oncologic inpatients under 19 years old, who had a systemic antimicrobial treatment on the day of the point prevalence survey. In addition to a one-day, point-prevalence survey, external experts individually assessed the appropriateness of each therapy. This step was followed by an expert panel adjudication based upon the participating centers' institutional standards, as well as upon national guidelines. We analyzed antimicrobial prevalence rate, along with the rate of appropriate, inappropriate, and indeterminate antimicrobial therapies with regard to institutional and national guidelines. We compared the results of academic and non-academic centers, and performed a multinomial logistic regression using center- and patient-related data to identify variables that predict inappropriate therapy. Findings: At the time of the study, a total of 342 patients were hospitalized at 30 hospitals, of whom 320 were included for the calculation of the antimicrobial prevalence rate. The overall antimicrobial prevalence rate was 44.4% (142/320; range 11.1-78.6%) with a median antimicrobial prevalence rate per center of 44.5% (95% confidence interval [CI] 35.9-49.9). Antimicrobial prevalence rate was significantly higher (p < 0.001) at academic centers (median 50.0%; 95% CI 41.2-55.2) compared to non-academic centers (median 20.0%; 95% CI 11.0-32.4). After expert panel adjudication, 33.8% (48/142) of all therapies were labelled inappropriate based upon institutional standards, with a higher rate (47.9% [68/142]) when national guidelines were taken into consideration. The most frequent reasons for inappropriate therapy were incorrect dosage (26.2% [37/141]) and (de-)escalation/spectrum-related errors (20.6% [29/141]). Multinomial, logistic regression yielded the number of antimicrobial drugs (odds ratio, OR, 3.13, 95% CI 1.76-5.54, p < 0.001), the diagnosis febrile neutropenia (OR 0.18, 95% CI 0.06-0.51, p = 0.0015), and an existing pediatric antimicrobial stewardship program (OR 0.35, 95% CI 0.15-0.84, p = 0.019) as predictors of inappropriate therapy. Our analysis revealed no evidence of a difference between academic and non-academic centers regarding appropriate usage. Interpretation: Our study revealed there to be high levels of antimicrobial usage at German and Austrian pediatric oncology and hematology centers with a significant higher number at academic centers. Incorrect dosing was shown to be the most frequent reason for inappropriate usage. Diagnosis of febrile neutropenia and antimicrobial stewardship programs were associated with a lower likelihood of inappropriate therapy. These findings suggest the importance of febrile neutropenia guidelines and guidelines compliance, as well as the need for regular antibiotic stewardship counselling at pediatric oncology and hematology centers. Funding: European Society of Clinical Microbiology and Infectious Diseases, Deutsche Gesellschaft für Pädiatrische Infektiologie, Deutsche Gesellschaft für Krankenhaushygiene, Stiftung Kreissparkasse Saarbrücken.

Association of viral load with TRAIL, IP-10, CRP biomarker signature and disease severity in children with respiratory tract infection or fever without source: A prospective, multicentre cohort study.

BACKGROUND: To investigate the association of viral load (VL) with (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10, C-reactive protein, and a combinatorial score (BV score), and (ii) clinical severity. STUDY DESIGN: In this prospective, multicentre cohort substudy, children with respiratory tract infection or fever without source were enrolled. VL for influenza virus, rhinovirus, respiratory syncytial virus, and adenovirus was measured from nasopharyngeal swabs. The reference standard diagnosis was established based on expert panel adjudication. RESULTS: Of 1140 recruited patients, 333 had a virus monodetection. VL for the aggregated data set correlated with TRAIL and IP-10 levels, with the length of oxygen therapy, and inversely with the BV score. At a single viral level, only the influenza VL yielded a correlation with TRAIL, IP-10 levels, and the BV score. Children with a viral reference standard diagnosis had significantly higher VL than those with bacterial infection (p = 0.0005). Low TRAIL (incidence rate ratio [IRR] 0.6, 95% confidence interval [CI] 0.39-0.91) and young age (IRR 0.62, 95% CI 0.49-0.79) were associated with a longer hospital stay, while young age (IRR 0.33, 95% CI 0.18-0.61), low TRAIL (IRR 0.25, 95% CI 0.08-0.76), and high VL (IRR 1.16, 95% CI 1.00-1.33) were predictive of longer oxygen therapy. CONCLUSION: These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity.

Burden of Pediatric SARS-CoV-2 Hospitalizations during the Omicron Wave in Germany.

(1) Background: When the Omicron variant of SARS-CoV-2 first emerged in Germany in January 2022, data on related disease severity among children and adolescents were not yet available. Given Omicron's high transmissibility, the ability to assess its impact on admission and hospitalization rates in children's hospitals is critical for the purpose of understanding the scope of its burden on the German healthcare system. (2) Methods: From 24 January 2022 to 31 July 2022, SARS-CoV-2 cases admitted to German pediatric hospitals were monitored via a national, clinician-led reporting system (CLRS) established by the German Society for Pediatric Infectious Diseases (DGPI). Cases treated on general wards and intensive care units, as well as patient age and the need for respiratory support, were recorded. (3) Results: From January to July 2022, a median of 1.7 cases (range 0.4-3) per reporting pediatric hospital per day was hospitalized in general wards, whereas a median of 0.1 cases (range 0-0.4 cases) was admitted to intensive care units. Of all hospitalized patients, 4.2% received respiratory support. (4) Conclusions: Despite the high incidence rates documented in connection with the Omicron variant in early 2022, the number of pediatric hospital admissions, and especially the number of cases with the need for intensive care treatment and respiratory support due to symptomatic SARS-CoV-2 infection, remained relatively low. Higher Omicron incidence rates had only a modest impact on SARS-CoV-2-related admissions and hospitalization in German children's hospitals.

[Severe courses of meningitis and encephalitis in children and adolescents]. / Schwer verlaufende Meningitis und Enzephalitis bei Kindern und Jugendlichen.

Bacterial meningitis and viral encephalitis are infectious diseases of the central nervous system (CNS), mostly with severe sequelae up to a fatal outcome. Despite progress in prevention by vaccination, the global impact of bacterial meningitis is enormous. Before the coronavirus disease 2019 (COVID-19) pandemic, the incidence of viral encephalitis in childhood was increasing also due to the growing incidence of emerging pathogens, such as enterovirus (EV)-A71 and West Nile virus in temperate climates as well as the wider use of immunosuppressive treatment and stem cell transplantation in childhood. The following article summarizes the data on the frequency and clinical signs of infectious CNS diseases and presents the current treatment recommendations.

High burden of RSV hospitalizations in Germany 2021-2022.

BACKGROUND: Public health measures implemented to mitigate the effects of the COVID-19 pandemic disrupted the worldwide transmission of endemic respiratory viruses such as RSV, as well as other typical, seasonal, and viral respiratory pathogens. METHODS: From October 18, 2021 to March 31, 2022, RSV cases admitted to German pediatric hospitals were monitored via a newly established, national, Clinician-Led Reporting System (CLRS) that recorded patient age and type of respiratory support. A subanalysis of the first 4 months of the monitoring period was additionally performed. RESULTS: In October 2021, a total of 471 hospitalized pediatric RSV cases per day were documented by 67 reporting hospitals. By January 2022, this number dropped to three cases at 11 hospitals (median of reporting hospitals: 37 (11%)). During these months, the median of hospitalized children on general wards and intensive care units was 133 and 15, respectively. In the subanalysis conducted to examine the period October to January, an average of 3.6 ± 2.2 patients per hospital per day were hospitalized on general wards (median 4 cases; range 0.3-8 cases), whereas 0.4 ± 2.2 patients were on intensive care units (median 0.3 cases; range 0-0.9 cases), with 11.5% receiving respiratory support. The majority of patients were under 2 years old. CONCLUSION: The overall burden of out-of-season RSV cases was extraordinarily high in Germany in 2021-2022. The newly established CLRS may help evaluate and, therefore, better allocate local and national pediatric care resources.

Antimicrobial Use in Pediatric Oncology and Hematology: Protocol for a Multicenter Point-Prevalence Study With Qualitative Expert Panel Assessment.

BACKGROUND: Because infections are a major driver of morbidity and mortality in children with hematologic or oncologic diseases, antimicrobials are frequently prescribed in pediatric oncology practice. However, excess or inappropriate use of antimicrobials is directly linked to the emergence of antimicrobial resistance. Although point-prevalence studies have examined the extent of antimicrobial use, a comprehensive qualitative evaluation of individual antimicrobial prescriptions remains lacking. OBJECTIVE: The aim of this study is to identify appropriate versus inappropriate antimicrobial use among pediatric cancer patients in a point-prevalence study, followed by an expert panel adjudication process and a subsequent report of these findings to participating centers. This study also aims to improve the quality of patient care by informing centers about discrepancies between internal standards of care and national guidelines. METHODS: Our point-prevalence study is performed at pediatric cancer centers in Germany and Austria. All patients under 18 years old who are hospitalized at the time of the study are included. As a supplement to the point-prevalence study, an expert panel is qualitatively assessing each of the antimicrobial prescriptions at the participating centers to review local guidelines and compare them with national guidelines. RESULTS: As of December 2021, the point-prevalence survey has been conducted at 30 sites and expert panel adjudication for qualitative assessment of each antimicrobial use is ongoing. Results of the study are expected in 2022. CONCLUSIONS: This is the first point-prevalence study conducted among pediatric cancer centers with an integrated, multistep, qualitative approach that assesses each antimicrobial prescription. The results of this study will inform possible interventions for internal guidelines and antimicrobial stewardship programs implemented at pediatric cancer centers. In addition, local guidelines will be compared with national guidelines. Furthermore, this study will contribute to the overall integration of antimicrobial stewardship principles and initiatives in pediatric oncology and hematology, thereby improving safety and quality of care for children and adolescents with cancer and blood disorders. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35774.

[Recommendation for standardized medical care for children and adolescents with long COVID]. / Einheitliche Basisversorgung von Kindern und Jugendlichen mit Long COVID: Stellungnahme einer multidisziplinären Arbeitsgruppe der DGKJ-Konvent-Gesellschaften (Stand: Februar 2022).

This current consensus paper for long COVID complements the existing AWMF S1 guidelines for long COVID with a detailed overview on the various clinical aspects of long COVID in children and adolescents. Members of 19 different pediatric societies of the DGKJ convent and collaborating societies together provide expert-based recommendations for the clinical management of long COVID based on the currently available but limited academic evidence for long COVID in children and adolescents. It contains screening questions for long COVID and suggestions for a structured, standardized pediatric medical history and diagnostic evaluation for patients with suspected long COVID. A time and resource-saving questionnaire, which takes the clinical complexity of long COVID into account, is offered via the DGKJ and DGPI websites as well as additional questionnaires suggested for an advanced screening of specific neurocognitive and/or psychiatric symptoms including post-exertional malaise (PEM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). According to the individual medical history as well as clinical signs and symptoms a step by step diagnostic procedure and a multidisciplinary therapeutic approach are recommended.

A host signature based on TRAIL, IP-10, and CRP for reducing antibiotic overuse in children by differentiating bacterial from viral infections: a prospective, multicentre cohort study.

OBJECTIVES: Identifying infection aetiology is essential for appropriate antibiotic use. Previous studies have shown that a host-protein signature consisting of TNF-related apoptosis-induced ligand (TRAIL), interferon-γ-induced protein-10 (IP-10), and C-reactive protein (CRP) can accurately differentiate bacterial from viral infections. METHODS: This prospective, multicentre cohort study, entitled AutoPilot-Dx, aimed to validate signature performance and to estimate its potential impact on antibiotic use across a broad paediatric population (>90 days to 18 years) with respiratory tract infections, or fever without source, at emergency departments and wards in Italy and Germany. Infection aetiology was adjudicated by experts based on clinical and laboratory investigations, including multiplex PCR and follow-up data. RESULTS: In total, 1140 patients were recruited (February 2017-December 2018), of which 1008 met the eligibility criteria (mean age 3.5 years, 41.9% female). Viral and bacterial infections were adjudicated for 628 (85.8%) and 104 (14.2%) children, respectively; 276 patients were assigned an indeterminate reference standard outcome. For the 732 children with reference standard aetiology, the signature discriminated bacterial from viral infections with a sensitivity of 93.7% (95%CI 88.7-98.7), a specificity of 94.2% (92.2-96.1), positive predictive value of 73.0% (65.0-81.0), and negative predictive value of 98.9% (98.0-99.8); in 9.8% the test results were equivocal. The signature performed consistently across different patient subgroups and detected bacterial immune responses in viral PCR-positive patients. CONCLUSIONS: The findings validate the high diagnostic performance of the TRAIL/IP-10/CRP signature in a broad paediatric cohort, and support its potential to reduce antibiotic overuse in children with viral infections.