Search

Purpose SARS-CoV-2 infections cause COVID-19 and have a wide spectrum of morbidity. Severe disease courses among children are rare. To date, data on the variability of morbidity in relation to variant of concern (VOC) in children has been sparse and inconclusive. We compare the clinical severity of SARS-CoV-2 infection among children and adolescents in Germany during the Wildtype and Alpha combined, Delta and Omicron phases of the COVID-19 pandemic. Methods Comparing risk of COVID-19-related hospitalization, intensive care unit (ICU) admission and death due to COVID-19 in children and adolescents, we used: (1) a multi-center seroprevalence study (SARS-CoV-2-KIDS study); (2) a nationwide registry of pediatric patients hospitalized with SARS-CoV-2 infections; and (3) compulsory national reporting for RT-PCR-confirmed SARS-CoV-2 infections in Germany. Results During the Delta predominant phase, risk of COVID-19-related hospitalization among all SARS-CoV-2 seropositive children was 3.35, ICU admission 1.19 and fatality 0.09 per 10,000; hence about halved for hospitalization and ICU admission and unchanged for deaths as compared to the Wildtype- and Alpha-dominant period. The relative risk for COVID-19-related hospitalization and ICU admission compared to the alpha period decreased during Delta [0.60 (95% CI 0.54; 0.67) and 0.51 (95% CI 0.42; 0.61)] and Omicron [0.27 (95% CI 0.24; 0.30) and 0.06 (95% CI 0.05; 0.08)] period except for the Conclusion Morbidity caused by SARS-CoV-2 infections among children and adolescents in Germany decreased over the course of the COVID-19 pandemic, as different VOCs) emerged.

Background Respiratory syncytial virus (RSV) is a leading cause of hospitalizations in children (≤5 years of age); limited data compare burden by age. Methods This single-center retrospective study included children (≤5 years of age) hospitalized for >24 hours with reverse-transcription polymerase chain reaction (RT-PCR)–confirmed RSV infection (2015–2018). Hospital length of stay (LOS), intensive care unit (ICU) admissions, ICU LOS, supplemental oxygen, and medication use were assessed. Multivariate logistic regression analyses identified predictors of hospital LOS >5 days. Results Three hundred twelve patients had RSV infection (ages 0 to Conclusions RSV causes substantial burden in hospitalized children (≤5 years), particularly preterm infants and those aged

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

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.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.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.These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity.

Background Recently, emergence of a higher proportion of serotype 3 in children with parapneumonic pleural effusion/empyema (PPE/PE) were observed in Germany despite general immunization with 13-valent pneumococcal conjugate vaccine (PCV13) since 2009. The impact of PCV13 on the overall incidence of PPE/PE in children is unclear. Methods Annual incidence of PPE/PE in children were determined using secondary health care data for 2009–2018, provided by the Barmer statutory health insurer, serving about 11% of the German population. Temporal trends of the annual incidence were modelled applying generalized additive models. Results Overall incidence of PPE/PE in children ( ≤18 years) in the ten-year observation period was 18.17 per 100,000. The 0–1 year olds showed the highest incidence (43.09 per 100 000). PPE/PE incidence decreased from 2009 until 2013 (nadir 2013 was 15.36; 95% CI: 13.41–17.31). Since 2013, the data show an annual increase. The nadir of incidence for the 2–5 year olds (15.85; 95% CI: 11.27–20.43) and the 6–18 year olds (12.29; 95% CI: 10.23–14.36) was also in 2013, whereas for the 0–1 year olds it was found in 2014 (32.66; 95% CI: 23.79–41.54). The GAM across all age groups showed a nearly U-shaped curve between time and incidence of PPE/PE by calendar year (p-non-linear = 0.0017). The model confirms the nadir in the year 2013. Discussion We found a nonlinear temporal trend of PPE/PE incidence in children with a decrease from 2009 to 2013 and a subsequent increase until 2018. The former might be explained by a quasi elimination of serotype 1, the latter by an increase in the proportion of serotype 3 as demonstrated in German surveillance data of pediatric PPE/PE cases generated during the same observation period.

Respiratory viruses were detected by multiplex-polymerase chain reaction from oropharyngeal swabs in 114/168 (67.9%) children with acute respiratory infection presenting to 5 pediatric practices in Germany between November 2020 and April 2021. In contrast to rhino- (48.8%), adeno- (14.3%) and endemic coronaviruses (14.9%), SARS-CoV-2 and influenza virus were detected only once; respiratory syncytial virus was not detected. This demonstrates differing impacts of pandemic infection control measures on the spread of respiratory viruses.

Zusammenfassung Hintergrund Die zunehmende Verbreitung von Antibiotikaresistenzen und die fehlende Weiterentwicklung von neuen Antibiotika erfordern eine rationale, leitlinienkonforme Antibiotikatherapie. Das gilt v. a. für die ambulante Medizin, in deren Bereich 85 % aller Antibiotika verordnet werden. Ziele Die Arbeitsgemeinschaft Antibiotic Stewardship ambulante Pädiatrie hat praxisnahe Empfehlungen zur antibiotischen Standardtherapie häufiger Infektionskrankheiten in der pädiatrischen Praxis formuliert. Material und Methoden Die Empfehlungen berücksichtigen Leitlinien zur rationalen Antibiotikatherapie und sind nach einem Konsentierungsprozess unter Beteiligung der Fachgesellschaften Berufsverband der Kinder- und Jugendärzte (BVKJ) und Deutsche Gesellschaft für pädiatrische Infektiologie (DGPI) erstellt worden. Ergebnisse Kurz gefasste Empfehlungen zur antibiotischen Standardbehandlung der häufigsten ambulant erworbenen Infektionskrankheiten der oberen und unteren Atemwege, Harnwege, Haut, Augen und Darm sowie in der Kinderchirurgie. Schlussfolgerung Mit den Empfehlungen soll sowohl eine Reduktion als auch eine Verbesserung der Qualität der Antibiotikaverordnungen in der ambulanten Pädiatrie erreicht werden. Unnötige Antibiotikatherapien sollen vermieden bzw. rasch beendet werden. Bei unklaren Situationen ohne Risikokonstellation soll statt einer antibiotischen Therapie eine kurzfristige Kontrolle vorgenommen werden. Antibiotika sollen so kurz und so schmal wie möglich verschrieben werden. Topische Antibiotika sollen vermieden werden, ebenso kritische Antibiotika wie Cephalosporine und Azithromycin (Risikofaktoren für eine Resistenzentwicklung). Es wird angeregt, die Empfehlungen in einem lokalen intersektoralen Konsensprozess anzupassen, um breite Akzeptanz und Verbindlichkeit zu steigern sowie Konflikte zu reduzieren, die sich aus der hohen Variabilität der Verordnungspraxis ergeben.

ZusammenfassungDie vorliegende Fassung der deutschsprachigen AWMF-Leitlinie soll unter Berücksichtigung der vorliegenden Evidenz die medizinische Versorgung von Kindern und Jugendlichen mit ambulant erworbener Pneumonie (pediatric community acquired pneumonia, pCAP) verbessern. In Mitteleuropa steht einer Prävalenz von ca. 300 Fällen pro 100 000 Kinder/Jahr eine sehr geringe Mortalität gegenüber, die Prävention umfasst Hygiene-Maßnahmen und Impfung z. B. gegen Pneumokokken, Hämophilus, Masern und Influenza. Hauptsymptome der pCAP sind Fieber und Tachypnoe, die Diagnosestellung erfolgt primär klinisch durch Anamnese, körperliche Untersuchung und Pulsoxymetrie. Das zusätzliche Vorliegen von Warnsymptomen wie stark reduzierter Allgemeinzustand, Nahrungsverweigerung, Dehydratation, Bewusstseinsstörung oder Krampfanfälle definiert die schwere pCAP in Abgrenzung zur nicht-schweren pCAP. Das Erregerspektrum ist altersabhängig, zur Differenzierung zwischen viraler, bakterieller oder gemischt viral-bakterieller Infektion stehen jedoch keine zuverlässigen Biomarker zur Verfügung. Die meisten Kinder und Jugendlichen mit nicht-schwerer pCAP und O2-Sättigung > 92 % können ohne weitere Röntgen-, Labor- und Erreger-Diagnostik ambulant betreut werden. Der Einsatz von Antiinfektiva ist nicht grundsätzlich indiziert, vor allem bei jungen Kindern, bronchialer Obstruktion und anderen Hinweisen auf virale Genese kann darauf i. d. R. verzichtet werden. Zur kalkulierten Antibiotika-Therapie sind Aminopenicilline Mittel der Wahl, bei gewährleisteter Einnahme und Resorption sind die orale (Amoxicillin) und intravenöse Verabreichung (Ampicillin) von vergleichbarer Wirksamkeit. Nach 48 – 72 Stunden ist eine Verlaufsbeurteilung notwendig, um den Behandlungserfolg und mögliche Komplikationen wie z. B. parapneumonische Ergüsse oder Pleuraempyeme, die eine Erweiterung bzw. Änderung der Therapie erforderlich machen, rechtzeitig zu erfassen.

Das klinische Wissen zu Verlauf, Komplikationen und Therapie von COVID-19 bei Kindern und Jugendlichen ist bisher begrenzt. Der vorliegende systematische Review fasst die aktuelle wissenschaftliche Evidenz zum klinischen Verlauf von COVID-19 bei hospitalisierten Kindern zusammen. Zusatzlich werden die ersten Daten aus Deutschland aus einem Kinderklinik-Survey der Deutschen Gesellschaft fur Padiatrische Infektiologie e. V. (DGPI) vorgestellt. Ausgewertet wurden insgesamt 12 Fallserien aus China mit 6 bis 2143 SARS-CoV-2-infizierten Kindern, die uber eine PubMed-Literatursuche bis zum 31.03.2020 identifiziert wurden. Die Datenbank des deutschlandweiten COVID-19 Kinderklinik-Survey der DGPI wurde am 06.04.2020 abgefragt. In den Fallserien lag das mediane Alter zwischen 2 und 7 Jahren, mit einem Anteil von Sauglingen von 18 bis 45 %. Am haufigsten berichtete Symptome waren Fieber und Husten; bei 40–100 % lag eine radiologisch (zumeist CT) bestatigte Lungenbeteiligung vor. Schwere/kritische Verlaufe – inklusive 2 Todesfalle – wurden bei bis zu 8 % der Kinder berichtet. Die Hospitalisierungsdauer lag bei 5 bis 20 Tagen. Der COVID-19-Survey der DGPI erfasste bis zum 06.04.2020 33 Kinder aus 21 Kliniken, mit uberwiegenden Infektionen der oberen Atemwege. 45 % waren Sauglinge, 32 % hatten eine Vorerkrankung. Bislang benotigten 3 Kinder (9 %) eine intensivstationare Behandlung. COVID-19 bei hospitalisierten Kindern und Jugendlichen verlauft uberwiegend als unkomplizierte febrile Erkrankung der oberen oder der unteren Atemwege. Nur sehr selten kommt es bei Kindern zu schweren Komplikationen oder Todesfallen. Weitere Informationen zum Verlauf von COVID-19 bei Neugeborenen, Sauglingen und Patienten mit Vorerkrankungen sowie zu therapeutischen und praventiven Masnahmen werden dringend benotigt.

ZUSAMMENFASSUNGPertussis, die häufigste Form des Keuchhustens, ist eine meldepflichtige Infektionskrankheit des Respirationstraktes, die durch Bordetella pertussis verursacht wird. In ungeimpften Populationen tritt Pertussis überwiegend im Alter zwischen 2 und 6 Jahren auf. Trotz hoher Pertussis-Durchimpfungsraten im Säuglings- und Kleinkindesalter werden in den letzten 20 Jahren eine Zunahme der Inzidenz und eine Verschiebung von Pertussiserkrankungen in das Adoleszenten- und Erwachsenenalter beobachtet. Dies liegt an 3 Ursachen: erstens an der erhöhten Aufmerksamkeit bei Patienten und Ärzten gegenüber Pertussis, zweitens der einfacheren Diagnosestellung durch sensitive Methoden wie der PCR oder Serologie und drittens an der zeitlich begrenzten Wirksamkeit von Pertussisimpfstoffen. Regelmäßige Auffrischimpfungen auch über das Kindesalter hinaus sind von hoher Bedeutung, um Ausbreitung, Ausbrüche und Komplikationen der Pertussis zu begrenzen. Die bestehenden Empfehlungen zur Pertussisimpfung im Erwachsenenalter werden jedoch nur unzureichend umgesetzt. Die fehlende Empfehlung der STIKO analog zu Diphtherie und Tetanus gegen Pertussis alle 10 Jahre zu impfen, trägt ebenfalls dazu bei, dass die Impfung bei Erwachsenen kaum durchgeführt wird. Dadurch entstehen Übertragungswege auf ungeimpfte Neugeborene und Säuglinge, die das höchste Komplikations- und Mortalitätsrisiko tragen. Hohe Durchimpfungsraten und regelmäßige mindestens 10-jährige Auffrischimpfungen auch im Erwachsenenalter sind die beste Präventionsstrategie und dringend erforderlich, um die weitere Ausbreitung von Pertussis zu begrenzen. Eine maternale (Auffrisch-) Impfung im letzten Trimenon der Schwangerschaft kann zusätzlich Pertussis bei Neugeborenen wirksam verhindern. Die Entwicklung neuer wirksamerer Pertussisimpfstoffe ist notwendig, um den Keuchhusten in seinen unterschiedlichen klinischen Ausprägungen zu kontrollieren.

Nontuberculous mycobacteria (NTM) are an emerging cause of infections, including chronic lymphadenitis in children. To identify risk factors for NTM lymphadenitis, particularly complicated disease, we collected epidemiologic, clinical, and microbiological data on 138 cases of NTM lymphadenitis in children across 13 centers in Germany and Austria. We assessed lifestyle factors but did not identify specific risk behaviors. We noted that more cases of NTM lymphadenitis occurred during cold months than during warm months. Moreover, we noted female sex and age

Vaccine 38(3), 570-577 (2020). doi:10.1016/j.vaccine.2019.10.056, Published by Elsevier, Amsterdam

Outpatient antibiotic use is closely related to antimicrobial resistance and in Germany, almost 70% of antibiotic prescriptions in human health are issued by primary care physicians (PCPs). The aim of this study was to explore PCPs, namely General Practitioners’ (GPs) and outpatient pediatricians’ (PDs) knowledge of guideline recommendations on rational antimicrobial treatment, the determinants of confidence in treatment decisions and the perceived need for training in this topic in a large sample of PCPs from southern Germany. Out of 3753 reachable PCPs, 1311 completed the survey (overall response rate = 34.9%). Knowledge of guideline recommendations and perceived confidence in making treatment decisions were high in both GPs and PDs. The two highest rated influencing factors on prescribing decisions were reported to be guideline recommendations and own clinical experiences, hence patients’ demands and expectations were judged as not influencing treatment decisions. The majority of physicians declared to have attended at least one specific training course on antibiotic use, yet almost all the participating PCPs declared to need more training on this topic. More studies are needed to explore how consultation-related and context-specific factors could influence antibiotic prescriptions in general and pediatric primary care in Germany beyond knowledge. Moreover, efforts should be undertaken to explore the training needs of PCPs in Germany, as this would serve the development of evidence-based educational interventions targeted to the improvement of antibiotic prescribing decisions rather than being focused solely on knowledge of guidelines.

Objectives Identifying infection aetiology is essential for appropriate antibiotic use. Previous studies showed a host-protein signature consisting of TNF-related apoptosis-induced ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) can accurately differentiate bacterial from viral infections. Methods This prospective, multicentre cohort study titled “AutoPilot-Dx”, aimed to validate signature performance and 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 (2/2017–12/2018), of which 1008 met 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 sensitivity of 93.7% (95% CI, 88.7–98.7), specificity of 94.2% (92.2–96.1), positive predictive value of 73.0% (65.0–81.0), negative predictive value of 98.9% (98.0–99.8), and 9.8% equivocal test results. The signature performed consistently across different patient subgroups and detected bacterial immune response in viral PCR positive patients. Conclusions The findings validate 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. Trial registration Clinicaltrials.gov identifier: NCT03052088.

BackgroundAntigen rapid diagnostic tests (RDT) for SARS-CoV-2 are fast, broadly available, and inexpensive. Despite this, reliable clinical performance data is sparse.MethodsIn a prospective performance evaluation study, RDT from three manufacturers (NADAL®, Panbio™, MEDsan®) were compared to quantitative reverse transcription polymerase chain reaction (RT-qPCR) in 5 068 oropharyngeal swabs for detection of SARS-CoV-2 in a hospital setting. Viral load was derived from standardized RT-qPCR Cycle threshold (Ct) values. The data collection period ranged from November 12, 2020 to February 28, 2021.FindingsOverall, sensitivity of RDT compared to RT-qPCR was 42·57% (95% CI 33·38%–52·31%), and specificity 99·68% (95% CI 99·48%–99·80%). Sensitivity declined with decreasing viral load from 100% in samples with a deduced viral load of ≥108SARS-CoV-2 RNA copies per ml to 8·82% in samples with a viral load lower than 104SARS-CoV-2 RNA copies per ml. No significant differences in sensitivity or specificity could be observed between the three manufacturers, or between samples with and without spike protein variant B.1.1.7. The NPV in the study cohort was 98·84%; the PPV in persons with typical COVID-19 symptoms was 97·37%, and 28·57% in persons without or with atypical symptoms.InterpretationRDT are a reliable method to diagnose SARS-CoV-2 infection in persons with high viral load. RDT are a valuable addition to RT-qPCR testing, as they reliably detect infectious persons with high viral loads before RT-qPCR results are available.FundingGerman Federal Ministry for Education and Science (BMBF), Free State of BavariaResearch in contextEvidence before this studyWe searched PubMED an MedRxiv for articles including “COVID-19”, “COVID”, “SARS-CoV-2”, “coronavirus” as well as “antigen detection”, “rapid antigen test”, “Point-of-Care test” in title or abstract, published between January 1, 2020 and February 28, 2021. The more than 150 RDT on the market at the end of February 2021 represent a huge expansion of diagnostic possibilities.1Performance of currently available RDT is evaluated in several international studies, with heterogeneous results. Sensitivity values of RDT range from 0·0%2to 98·3%3, specificity from 19·4%4to 100·0%.2,5–14. Some of this data differs greatly from manufacturers’ data. However, these previously published performance evaluation studies were conducted under laboratory conditions using frozen swabs, or in small cohorts with middle-aged participants. Comparable RDT performance data from large-scale clinical usage is missing.5–19Added value of this studyBased on previous examinations the real life opportunities and limitations of SARS-CoV-2 RDT as an instrument of hospital infection detection and control are still unclear as well as further study results are limited in transferability to general public. Our findings show that RDT performance in daily clinical routine is reliable in persons with high viral for punctual detection and isolation of infectious persons before RT-qPCR become available. In persons with lower viral load, or in case of asymptomatic patients SARS-CoV2 detection by RDT was unsuccessful. The general sensitivity of 42·57% is too low to accept the RDT in clinical use as an alternative to RT-qPCR in diagnosis of COVID-19. Calculated specificity was 99.68%. The results are based on a huge study cohort with more than 5 000 participants including a representative ages structure with pediatric patients up to geriatric individuals, which portrays approximately the demographic structure of the local society.Implications of all the available evidenceDue to the low general sensitivity RDT in clinical use cannot be accepted as an alternative but as an addition to RT-qPCR in SARS-CoV-2 diagnosis. The benefit of early detection of highly infectious persons has to be seen in context of the effort of testing and isolation of false positive tested persons.

Akute Bauchschmerzen im Kindes- und Jugendalter sind ein häufiger Grund ärztlicher Konsultation. Die Ätiologien der Beschwerden sind vielfältig und oft eine diagnostische Herausforderung für den Kliniker. Komplizierend führen auch extraabdominelle Erkrankungen zum Leitsymptom „Bauchschmerzen“. Wichtig ist die Unterscheidung zwischen akuten Krankheitsbildern, die einer sofortigen diagnostischen oder therapeutischen, ggf. auch chirurgischen Intervention bedürfen und denen, die zunächst beobachtet werden können. Auch müssen lebensbedrohliche Zustände erkannt und rasch behandelt werden. Die Schmerzursachen unterscheiden sich je nach Alter und Vorgeschichte der Patienten erheblich, so kann bspw. ein mechanischer Ileus auf dem Boden unterschiedlichster Erkrankungen entstehen (Yang WC, Chen CY, Wu HP. Etiology of non-traumatic acute abdomen in pediatric emergency departments. World J Clin Cases 2013; 1(9): 276–284). Im vorgestellten Fall soll die Schwierigkeit der ätiologischen Zuordnung eines mechanischen Ileus aufgezeigt werden.

Die weltweite Zunahme von Antibiotikaresistenzen hat dazu gefuhrt, dass in allen Bereichen der Medizin uber einen rationalen und kritischen Einsatz von Antibiotika nachgedacht wird. Eine Fulle von strukturellen Masnahmen ist v. a. fur den Bereich der stationaren Behandlung entwickelt worden, die unter dem Begriff „Antibiotic Stewardship“ zusammengefasst werden. In der im Folgenden zusammengefassten interdisziplinaren Leitlinie hat ein Team von Autoren die veroffentlichte Literatur zum Bereich der Padiatrie gesichtet, aufgrund dieser Publikationen Empfehlungen erarbeitet und mit den beteiligten Fachgesellschaften konsentiert. Diese Leitlinie wurde von der Arbeitsgruppe Antibiotic Stewardship im Auftrag der Deutschen Gesellschaft fur Padiatrische Infektiologie (DGP) von einem Redaktionskomitee, bestehend aus J. Hubner, A. Simon, T. Tenenbaum, J. Liese, M. Hufnagel, S. Weichert, U. von Both, A. Pecar und V. Strenger, ausgearbeitet und durch mandatierte Vertreter weiterer Fachgesellschaften (ADKA, DAKJ, DGHM, DGKJ, DGI, GNPI, GPOH, GPGE, GPP, OGKJ, PIGS, PEG, BVKJ, DGKH, DGKCH) in einem internetbasierten Delphi-Verfahren abgestimmt. Interessenkonflikte wurden nach den Regularien der AWMF offengelegt. Insgesamt wurden 70 Empfehlungen zu den Bereichen strukturelle Voraussetzungen, antimikrobielle Therapie, diagnostische Aspekte (Mikrobiologie, Resistenztestung), Fortbildung und Schulung, Qualitatsindikatoren und klinisch-infektiologische Audits, Rolle der Informationstechnologie, nosokomiale Infektionen, Bedeutung von Clostridium difficile bei padiatrischen Patienten, Management von multiresistenten Erregern sowie den padiatrischen Spezialbereichen Neonatologie und Kinderonkologie erarbeitet. Die vorgestellte Leitlinie stellt die erste derartige Leitlinie fur den Bereich der Padiatrie im deutschsprachigen Raum dar und wird bei der Etablierung und Evaluierung von ABS-Programmen in der Kinder- und Jungendmedizin hilfreich sein.

Varicella is a common vaccine-preventable disease that usually presents as a mild disorder but can lead to severe complications. Before the implementation of universal varicella vaccination (UVV) in some European countries, the burden of varicella disease was broadly similar across the region. Despite this, countries adopted heterogeneous varicella vaccination strategies. UVV is currently recommended in 12 European countries. Known barriers to UVV implementation in Europe include (1) a perceived low disease burden and low public health priority; (2) cost-effectiveness and funding availability; (3) concerns related to a shift in varicella disease and incidence of herpes zoster and (4) safety concerns related to measles, mumps, rubella and varicella-associated febrile seizures after the first dose. Countries that implemented UVV experienced decreases in varicella incidence, hospitalizations and complications, showing overall beneficial impact. Alternative strategies targeting susceptible individuals at higher risk of complications have been less effective. This article discusses ways to overcome the barriers to move varicella forward as a truly vaccine preventable disease.

Background Vaccination during pregnancy can protect both the expecting mother and the unborn and newborn child from infectious diseases. Methods This review is based on publications retrieved by a selective literature search on the immunological particularities of infectious diseases affecting pregnant women, unborn children, and neonates, with particular attention to the guidelines of the German Standing Committee on Vaccinations (Standige Impfkommission, STIKO) and the pertinent guidelines. Results Vaccination during pregnancy protects the expecting mother from a severe course of a number of different infectious diseases. Vaccination with inactivated vaccines against influenza, tetanus, and pertussis is effective, safe, and well tolerated. Women who are pregnant or of child-bearing age should be immunized against tetanus according to the STIKO recommendations. All pregnant women from the second trimester onward should receive an inactivated quadrivalent influenza vaccine. The immunity acquired after vaccination with an acellular pertussis vaccine is present only for a limited time. In a cohort study involving 72,781 pregnant women, pertussis vaccination during pregnancy was found to yield 91% protection against pertussis for their subsequently born children in the first three months of life. Further types of vaccine can also be given during pregnancy if indicated. Additional reasonable measures to protect the health of mother and child include the vaccination of other persons in close contact as well as the closure of relevant vaccination gaps among young adults, particularly women of child-bearing age. Treating physicians play a crucial role in encouraging vaccine acceptance by their patients. Conclusion Maternal immunization is a safe and effective strategy for giving neo - nates passive immune protection against life-threatening infections by the vertical transmission of maternal antibodies until they are able to build up their own adaptive immunity.

Parapneumonic pleural effusion and pleural empyema (PPE/PE) are complications of community-acquired pneumonia. The objective of this study was to analyze prehospital antibiotic therapy (PH-ABT) of children with PPE/PE and investigate its effects on clinical outcome and pathogen detection.Prospective nationwide active surveillance in Germany between October 2010 and June 2018. Children and adolescents18 years of age with pneumonia-associated PE or PPE requiring drainage or with persistence of PPE/PE7 days were included.A total of 1724 children with PPE/PE were reported, of whom 556 children (32.3% of 1719 with available data) received PH-ABT. Children with PH-ABT had a shorter median hospital length of stay (15 vs. 18 days, P0.001), a longer time from onset of symptoms until hospital discharge (25 vs. 23 days, P = 0.002), a lower rate of intensive care unit admission (58.3% vs. 64.4%, P = 0.015) and fewer infectious complications (5.9% vs. 10.0%; P = 0.005). Bacterial pathogens in blood or pleural fluid culture were detected in 597 (34.5%) of 1513 children. Positive culture results were less frequent in children with than without PH-ABT (81/466 [17.4%] vs. 299/1005 [29.8%]; P0.001), whereas detection rates in pleural fluid samples by polymerase chain reaction were similar (91/181 [50.3%] vs. 220/398 [55.3%]; P = 0.263).In children with PPE/PE, PH-ABT significantly reduced the overall rate of bacterial pathogen detection by culture, but not by polymerase chain reaction. PH-ABT was associated with a lower rate of infectious complications but did not affect the overall duration of disease. We therefore speculate that the duration of PPE/PE is mainly a consequence of an infection-induced inflammatory process, which can only partially be influenced by antibiotic treatment.

Background: Investigating the role of children in the COVID-19 pandemic is pivotal to prevent the virus spreading. In most cases, children infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) develop non-specific symptoms or are asymptomatic. Therefore, the infection rate among this age group remains unclear. Seroprevalence studies, including clinical questionnaires, may contribute to our understanding of the time course and clinical manifestations of SARS-CoV-2 infections. Methods: SARS-CoV-2-KIDS is a longitudinal, hospital-based, multicentre study in Germany on the seroprevalence of anti-SARS-CoV-2 immunoglobulin G, as determined by an Enzyme-Linked Immunosorbent Assay in children (aged ≤17 years). A study-specific questionnaire provided additional information on clinical aspects. Findings: This analysis included 10,358 participants recruited from June 2020 to May 2021. The estimated anti-SARS-CoV-2 seroprevalence increased from 2·0% (95% confidence interval (95% CI) 1·6, 2·5) to 10·8% (95% CI 8·7, 12·9) in March 2021, without major change afterwards and was higher in children with migrant background (on average 6·6% vs. 2·8%). In the pandemic early stages, children under three years were 3·5 (95% CI 2·2, 5·6) times more likely to be seropositive than older children, with the levels equalising in later observations. History of self-reported respiratory tract infections or pneumonia was associated with seropositivity (OR 1·8 (95% CI 1·4, 2·3);2·7 (95% CI 1·7, 4·1)). Interpretation: The majority of children in Germany do not have detectable SARS-CoV-2 IgG. To some extent, this may reflect the effect of differing containment measures implemented in the federal states. Detection levels might have been greater in certain age groups or migrant background. Lifting containment measurements is likely to cause a general increase in respiratory tract infections, which already pose a challenge to paediatric medical care during regular winter seasons. This challenge might become critical with additional infections caused by SARS-CoV-2.

This evidence‐based clinical guideline provides consensus‐recommendations for the treatment and care of patients with primary antibody deficiencies (PADs). The guideline group comprised 20 clinical and scientific expert associations of the German, Swiss, and Austrian healthcare system and representatives of patients. Recommendations were based on results of a systematic literature search, data extraction, and evaluation of methodology and study quality in combination with the clinical expertise of the respective representatives. Consensus‐based recommendations were determined via nominal group technique. PADs are the largest clinically relevant group of primary immunodeficiencies. Most patients with PADs present with increased susceptibility to infections, however immune dysregulation, autoimmunity, and cancer affect a significant number of patients and may precede infections. This guideline therefore covers interdisciplinary clinical and therapeutic aspects of infectious (e.g., antibiotic prophylaxis, management of bronchiectasis) and non‐infectious manifestations (e.g., management of granulomatous disease, immune cytopenia). PADs are grouped into disease entities with definitive, probable, possible, or unlikely benefit of IgG‐replacement therapy. Summary and consensus‐recommendations are provided for treatment indication, dosing, routes of administration, and adverse events of IgG‐replacement therapy. Special aspects of concomitant impaired T‐cell function are highlighted as well as clinical data on selected monogenetic inborn errors of immunity formerly classified into PADs (APDS, CTLA‐4‐, and LRBA‐deficiency).

Atemwegsinfektionen (AWI) sind die haufigste Indikation fur eine Antibiotikatherapie bei Kindern und Jugendlichen, v. a. im ambulanten Bereich und im kinderarztlichen Notdienst der Kliniken. Die hier vorliegende Konsensusempfehlung verschiedener padiatrischer Fachgesellschaften und des Berufsverbandes der niedergelassenen Kinder‐ und Jugendarzte beschreibt in Kurze die klinischen Symptome und die Diagnostik sowie die Indikationen fur eine leitlinienkonforme antibiotische Therapie von AWI (exklusive Pneumonie). Sie soll Kinder- und Jugendmediziner bei einem restriktiven Antibiotikaeinsatz, bei der Auswahl des bestmoglichen Antibiotikums und im Hinblick auf eine moglichst kurze Therapiedauer unterstutzen. Des Weiteren werden AWI beschrieben, bei denen keine Antibiotikatherapie erfolgen sollte oder bei denen nur sehr selten eine Antibiotikatherapie erforderlich ist.

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition with impairment of cytotoxic T-cells and natural killer cells. Causes in infants are mostly hereditary immune defects as well as various infectious triggering factors, amongst these cytomegalovirus (CMV). Vertical CMV transmission may occur in utero, during birth, and by breast feeding. Usually, a CMV infection transmitted via breast milk is symptomatic only in very immature preterm infants. We report on a late preterm infant born after 35 + 5 weeks of gestation with a birth weight of 1840 g, being admitted to our intensive care unit at the age of 9 weeks with acute enteritis and severe dehydration. After a prolonged recovery, the infant developed a sepsis-like condition with hyperpyrexia, hepatosplenomegaly, and pancytopenia. Combination with high ferritin levels (2809 μg/l), hypertriglyceridaemia (481 mg/dl), elevated soluble IL-2 receptor (sCD25, 9120 U/ml), and reduced perforin expression allowed diagnosis of HLH, caused by an acute CMV infection. Since connatal CMV infection had been ruled out earlier, we report the rare case of secondary HLH triggered by a postnatally acquired symptomatic CMV infection in an immunocompetent infant, most likely transmitted via breast milk. The infant was successfully treated with ganciclovir without need for immunosuppressive therapy.

Universal varicella vaccination for 1-year-old children was introduced in Germany in 2004. We investigated changes in the incidence and type of varicella-associated neurologic complications in children during the first 7 years after universal vaccination recommendation.A surveillance study was conducted based on patients17 years of age with an International Classification of Diseases (10th Revision) discharge diagnosis of varicella, annually reported by 22-29 pediatric hospitals in Bavaria, Germany, 2005 to 2011. Annual incidences were estimated and linear trend across years was assessed by Poisson regression models.Of a total of 1263 varicella-associated pediatric hospitalizations, 228 children (18.1%) had neurologic complications (median age 4 years, interquartile range 2-7; 56% male). The most frequent neurologic complications were febrile convulsion (32.0% of 228 children, median age 3.0 years), varicella encephalitis or meningitis (28.9%; median age 4.5 years), syncope (13.2%; median age 7.0 years) and cerebral convulsion (11.0%; median age 4.0 years). Other complications included ataxia (3.1%), facial nerve palsy (2.6%) and cerebral vasculitis/infarction (1.8%). Neurologic complications showed a continuous decrease between 2005 and 2011, from an incidence of 2.8 (95% confidence interval: 2.1-3.6) per 100,000 children17 years of age to 1.2 (95% confidence interval: 0.7-2.1; P0.001). In particular, a marked decline was observed among children up to 7 years of age, mainly because of a decrease in the number of febrile convulsions and encephalitis or meningitis.The incidence of varicella-associated neurologic complications in children decreased approximately by 60% during the first 7 years following the recommendation for universal vaccination.

Context Long-term data on enzyme replacement treatment of hypophosphatasia (HPP) are limited. Objective To evaluate efficacy and safety of asfotase alfa in patients aged ≤5 years with HPP followed for up to 6 years. Design Phase 2 open-label study (July 2010 to September 2016). Setting Twenty-two sites; 12 countries. Participants Sixty-nine patients [median (range) age: 16.0 (0.02 to 72) months] with severe HPP and sign/symptom onset before age 6 months. Intervention Asfotase alfa 2 mg/kg three times/week or 1 mg/kg six times/week subcutaneously. Main Outcome Measures Primary efficacy measure: Radiographic Global Impression of Change (RGI-C) score [−3 (severe worsening) to +3 (complete/near-complete healing)]. Additional outcome measures: respiratory status, growth, and safety. Post hoc analysis: characteristics of radiographic responders vs nonresponders at Year 1 (RGI-C: ≥+2 vs, Most infants and young children with hypophosphatasia, treated with asfotase alfa, showed improved skeletal manifestations, respiratory function, and growth within 1 year, maintained up to 6 years.

Objective: To report clinical characteristics and medical history data obtained retrospectively for a large cohort of pediatric patients with perinatal and infantile hypophosphatasia. Study design: Medical records from academic medical centers known to diagnose and/or treat hypophosphatasia were reviewed. Patients born between 1970 and 2011 with hypophosphatasia and any of the following signs/symptoms at age 70% of patients between birth and age 5 years. Vitamin B6–dependent seizures and respiratory distress and failure were associated significantly (P

Pediatric pulmonology 52(4), 540-547 (2017). doi:10.1002/ppul.23562, Published by Wiley-Liss, New York, NY [u.a.]

Parapneumonic pleural effusions/empyema (PPE/PE) are severe complications of community-acquired pneumonia. We investigated the bacterial aetiology and incidence of paediatric PPE/PE in Germany after the introduction of universal pneumococcal conjugate vaccine (PCV) immunization for infants.Children18 years of age hospitalized with pneumonia-associated PPE/PE necessitating pleural drainage or persisting7 days were reported to the German Surveillance Unit for Rare Diseases in Childhood between October 2010 and June 2017. All bacteria detected in blood or pleural fluid (by culture/PCR) were included, with serotyping for Streptococcus pneumoniae.The median age of all 1447 PPE/PE patients was 5 years (interquartile range 3-10). In 488 of the 1447 children with PPE/PE (34%), 541 bacteria (40 species) were detected. Aerobic gram-positive cocci accounted for 469 of 541 bacteria detected (87%); these were most frequently Streptococcus pneumoniae (41%), Streptococcus pyogenes (19%) and Staphylococcus aureus (6%). Serotype 3 accounted for 45% of 78 serotyped S. pneumoniae strains. Annual PPE/PE incidence varied between 14 (95%CI 12-16) and 18 (95%CI 16-21) PPE/PE per million children. Incidence of S. pneumoniae PPE/PE decreased from 3.5 (95%CI 2.5-4.6) per million children in 2010/11 to 1.5 (95%CI 0.9-2.4) in 2013/14 (p 0.002), followed by a re-increase to 2.2 (95%CI 1.5-3.2) by 2016/17 (p 0.205).In the era of widespread PCV immunization, cases of paediatric PPE/PE were still caused mainly by S. pneumoniae and, increasingly, by S. pyogenes. The re-increase in the incidence of PPE/PE overall and in S. pneumoniae-associated PPE/PE indicates ongoing changes in the bacterial aetiology and requires further surveillance.

BACKGROUND Limited data on the influenza burden in pediatric outpatients are available, especially regarding direct comparison of the cocirculating (sub)types A(H1N1)pdm09, A(H3N2) and B. METHODS Children 1-5 years of age, unvaccinated against influenza and presenting with febrile acute respiratory infections (ARIs), were enrolled in 33 pediatric practices in Germany from 2013 to 2015 (January-May). Influenza was confirmed by multiplex polymerase chain reaction from pharyngeal swabs and (sub)typed. RESULTS In 805 children with ARI, influenza was the most frequently detected respiratory virus (n = 305; 37.9%). Of 217 influenza patients included, 122 (56.2%) were infected with A(H3N2), 56 (25.8%) with A(H1N1)pdm09 and 39 (18.0%) with B. Median age was 3.7 years [interquartile range (IQR), 2.1-4.8]; 11% had underlying conditions. Median fever duration was 4 days (IQR, 3-5), and the disease duration was 9 days (IQR, 7-12). Most frequent diagnoses were pharyngitis (26%), bronchitis (18%) and acute otitis media (10%). Children received mainly antipyretics (86%) and adrenergic nasal drops/spray (53%); 9% received antibiotics and 3% oseltamivir. Thirty-six percent required at least 1 additional practice visit; 1% was hospitalized. Median absences from childcare were 5 days (IQR, 3-7); parents lost 4 workdays (IQR, 2-6). Symptoms, severity and impact on the family were largely unrelated to (sub)type. However, patients with A(H1N1)pdm09 had fewer underlying conditions (P = 0.017), whereas patients with B more often had pharyngitis (P = 0.022), acute otitis media (P = 0.012) and stenosing laryngotracheitis (P = 0.007). CONCLUSIONS Influenza was the most frequently detected viral pathogen in outpatient children with febrile, mostly uncomplicated ARI. In this setting, clinical manifestations and severity were similar across the (sub)types prevalent during the postpandemic seasons.

A 4-year-old Turkish girl of consanguineous parents was hospitalized for the evaluation of headaches and recurrent febrile episodes of unknown origin. Her medical history was unremarkable except for a few episodes of uncomplicated oral thrush. Meningitis was diagnosed, and Candida albicans was the only pathogen identified by polymerase chain reaction and culture. Despite systemic antifungal multidrug therapy, a prolonged course of 16 months of therapy was necessary to clear C. albicans from the cerebrospinal fluid. Molecular genetic analysis revealed a homozygous caspase recruitment domain 9 (CARD9) mutation (Q295X), which was reported to predispose to chronic mucocutaneous candidiasis. Immunologic workup excluded predisposing B-cell and T-cell defects. In addition, T cells producing interleukin-17 were repeatedly measured within the normal range. Analyses of neutrophils demonstrated normal nicotinamide adenine dinucleotide phosphate oxidase activity in response to various stimuli including Staphylococcus aureus and C. albicans. Additional neutrophilic functional testing, however, showed a decreased cytotoxicity to nonopsonized C. albicans, indicating an impaired killing mechanism against Candida spp. independent from the production of reactive oxygen species by the nicotinamide adenine dinucleotide phosphate oxidase system. Because this defect was only demonstrated in the absence of opsonins, it might especially predispose to chronic C. albicans infections in the central nervous system where opsonin concentrations are usually low. We, therefore, suggest that due to an additional neutrophil dependent defect CARD9 deficiency predisposes not only to chronic mucocutaneous candidiasis, but also to invasive chronic Candida infections, especially of the central nervous system.

Infants with history of prematurity (37 weeks gestation) and low birth weight (LBW,2500 g) are at high risk of infection due to functional immaturity of normal physical and immunological defense mechanisms. Despite current recommendations that infants with history of prematurity/LBW should receive routine immunization according to the same schedule and chronological age as full-term infants, immunization is often delayed.Here we summarize 10 clinical studies and 15 years of post-marketing safety surveillance of GSK's hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular-pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib) conjugate vaccine, when administered alone, or co-administered with pneumococcal conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus IgG to infants with history of prematurity/LBW in clinical trials.At least 92.5% of infants with history of prematurity/LBW as young as 24 weeks gestation in clinical studies were seropositive to all vaccine antigens after 3-dose primary vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine, with robust immune responses to booster vaccination. Seropositivity rates and antibody concentrations to hepatitis B and Hib appeared lower in infants with history of prematurity/LBW than term infants. Between 13-30% of medically stable infants with history of prematurity developed apnea after vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine; usually after dose 1. The occurrence of post-immunization cardiorespiratory events appears to be influenced by the severity of any underlying neonatal condition. Most cardiorespiratory events resolve spontaneously or require minimal intervention. GSK's hexavalent DTPa-HBV-IPV/Hib vaccine was well tolerated in co-administration regimens.GSK's hexavalent DTPa-HBV-IPV/Hib vaccine alone or co-administered with other pediatric vaccines has a clinically acceptable safety and immunogenicity profile when used in infants with history of prematurity/LBW for primary and booster vaccination. Additional studies are needed in very premature and very LBW infants. However, currently available data support using GSK's hexavalent DTPa-HBV-IPV/Hib vaccine to immunize infants with history of prematurity/LBW according to chronological age.