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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.

Purpose To quantify the number of SARS-CoV-2 infections in students and teachers in 14 Secondary schools in eastern Saxony, Germany. Seroprevalence of SARS-CoV-2 antibodies in study population. Number of undetected cases. Methods Serial seroprevalence study. Results The role of educational settings in the SARS-CoV-2 Pandemic is still controversial. Seroprevalence increases from 0.8 to 5.9% from October to December when schools remained open and to 12.2% in March/April during a strict lockdown with closed schools. The ratio of undetected to detected cases decreased from 0.76 to 0.44 during the study period. Conclusion During the second and third wave of the pandemic in Germany, students and teachers are not overrepresented in SARS-CoV-2 infections. The percentage of undetected cases is moderate and decreases over time. The risk of contracting SARS-CoV-2 within the household is higher than contracting it in educational settings making school closures rather ineffective in terms of pandemic control measures or individual risk reduction in children and adolescents. Trial registration DRKS00022455 (July 23rd, 2020).

The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 in Wuhan challenges pediatric oncologists in an unexpected way. We provide a comprehensive overview, which systematically summarizes and grades evidence (QoE) on SARS-CoV-2 infections in pediatric cancer patients at 1.5 years of pandemic. A systematic literature search in PubMed combined with an additional exploratory literature review in other international databases was conducted to identify studies on children (aged Conclusion: Despite a favorable COVID-19 outcome in most pediatric cancer patients, the morbidity is reported higher than in children without comorbidities. However, no severe COVID-19 complications were associated to the continuation of chemotherapy in some cohort studies and reports on two patients. Therefore, the risk of cancer progress or relapse due to interruption of chemotherapy has carefully to be weighed against the risk of severe COVID-19 disease with potentially fatal outcome. What is Known:• Most of pediatric patients with malignant diseases show an asymptomatic, mild or moderate clinical course of SARS-CoV-2 infection. • Current need for a basis for decision-making, whether to stop or interrupt cancer treatment in a patient infected with SARS-CoV-2, and when to continue chemotherapy. What is New:• Review results comprising over 1000 pediatric COVID-19 cancer patients confirm mild courses of SARS-CoV-2 infection in most patients but also show the attributable mortality is at least 10 times higher compared to reports on hospitalized children without comorbidities.• Review identifies that chemotherapy was continued despite SARS-CoV-2 positivity in 18% of patients with individual chemotherapy modification according to the clinical course of SARS-CoV-2 infection and existing comorbidities. On this basis, no severe COVID-19 complications were associated to the continuation of chemotherapy in several cohort studies and two case reports.

Zusammenfassung Hintergrund Seltene Erkrankungen (SE) manifestieren sich ganz überwiegend im Kindes- und Jugendalter, sind heterogen, multisystemisch, haben meist einen chronischen Verlauf und stellen eine große Herausforderung für alle Beteiligten dar. Finanziert durch den Innovationsfonds des G‑BA hatte das Versorgungsprojekt TRANSLATE-NAMSE das Ziel, Vorschläge zur besseren Versorgung von Menschen mit SE zu entwickeln und zu erproben. Fragestellung Für Patienten aller Altersgruppen mit einer Verdachtsdiagnose aus einer von 5 Gruppen definierter Indikatorerkrankungen (seltene Anämien, Endokrinopathien, Autoinflammationserkrankungen, primäre Immundefekte und Stoffwechselerkrankungen) sollte ein generischer Versorgungspfad entwickelt werden, der den Weg von der Konfirmationsdiagnostik bis hin zur Langzeitbetreuung dieser Patienten abbildet. Methodik Der Versorgungspfad wurde als allgemeines Ablaufschema dargelegt; die Prozessschritte wurden in eine Checkliste übertragen, inhaltlich ausformuliert und an 6 universitären Standorten an 587 Personen mit der Verdachtsdiagnose einer Indikatorerkrankungen erprobt. Ergebnisse Für 369 (62,9 %) Fälle mit der Verdachtsdiagnose einer Indikatorerkrankung konnte eine Diagnose gestellt werden, davon in 25,2 % mit innovativer genetischer Diagnostik; 104 (17,7 %) Verdachtsdiagnosen erwiesen sich als falsch-positiv; 114 (19,4 %) Fälle blieben ungeklärt. An Fallkonferenzen zur multiprofessionellen Versorgung nahmen im Median 4 Spezialisten teil. Die Versorgung (Diagnoseeröffnung, Schulung, Beratung, Information) begann im Median am Tag des Diagnostikergebnisses. In einer externen Evaluation erwies sich die Zufriedenheit der Sorgeberechtigten mit dem Versorgungspfad als hoch. Schlussfolgerungen Im bisher in Deutschland einzigartigen TRANSLATE-NAMSE-Projekt wurde ein Versorgungspfad für SE in der Pädiatrie entwickelt und erfolgreich erprobt. Zur Verstetigung dieser Versorgungsform ist eine auskömmliche Finanzierung in der Regelversorgung anzustreben.

Background In preterm infants with premature rupture of membranes, antibiotic treatment is frequently started but rates of early onset sepsis are lower. In line with national guidelines, a stratified approach in the decision to start antibiotic treatment using maternal history, clinical impression and biomarkers has been implemented in our level III neonatal center and its results are evaluated. Methods Retrospective cohort study of all preterm newborns with rupture of membranes at least 1 h prior to delivery admitted to our tertiary neonatal intensive care unit. Data on antibiotic exposure, mortality and major neonatal complications were extracted from the electronic patient charts to evaluate the effects and safety of our stratified approach. Results Four hundred fifty-six infants met the inclusion criteria. 120 (26%) received primary antibiotics whereas 336 (74%) did not. Of those receiving primary antibiotics, 13 (11%) had a blood culture positive sepsis, 46 (38%) met the criteria of clinical sepsis and in 61 (51%) sepsis was ruled out and antibiotics were stopped after 48-96 h. All infants with blood culture positive sepsis were identified and treated within the first 24 h of life using this approach. None of the 336 infants who were not started on antibiotics primarily needed antibiotic therapy within the first 5 days of life. There were no deaths or major neonatal complications in the group that did not receive empiric antibiotics. Conclusions Our stratified approach for preterm infants with premature rupture of membranes allows a safe reduction of antibiotic exposure even in this high risk population. As a result, only 25% of high risk preterm newborns are treated with antibiotics of which more than half receive less than 5 days of treatment. To treat one infant with blood culture positive sepsis, only 9 infants receive empiric antibiotics.

Das Tragen von Masken (Alltagsmaske oder chirurgische Maske) ist neben der Abstandswahrung und Hygienemasnahmen zu einem wesentlichen Mittel zur Eindammung der SARS-CoV-2-Pandemie geworden. Sie stellen eine wesentliche Barriere fur infektiose Tropfchen im Nahfeld dar und konnen neben dem Fremdschutz moglicherweise auch den Trager schutzen. Nach Darstellung moglicher korperlicher oder seelischer Nebenwirkungen bei Erwachsenen werden die wenigen Daten zu unerwunschten Wirkungen bei Kindern referiert. Bei bestimmungsgemaser Anwendung sind bislang keine wesentlichen Nebenwirkungen bekannt geworden. Allerdings konnen Masken sehr lastig sein. Die Schlussfolgerung besagt, dass bei gesunden wachen Kindern, die jederzeit in der Lage sind, die Maske selbststandig abzunehmen, unerwunschte Wirkungen nicht zu befurchten sind. Wahrend Kinder etwa ab 10 Jahren mit einer Maske nach altersgemaser Aufklarung und Demonstration sinnvoll und effektiv umgehen konnen, sodass das Tragen auch vorgeschrieben werden kann, sollten Grundschuler nicht dazu verpflichtet und Vorschulkinder davon befreit werden. Die Tragedauer sollte begrenzt werden, und Schulkinder, die an ihrem Platz unter Einhaltung des Abstandsgebotes sitzen, sollen die Maske abnehmen durfen.

Due to the shortage of pediatric hospital beds in general and due to the large annual burden of hospital admissions for common respiratory tract infections, such as influenza or RSV [respiratory syncytial virus] in particular, it can be expected that hospitalization of children with suspected or confirmed SARS-CoV‑2 infections will face hospitals with an even more tense situation than usual in the winter 2020/2021. This tenuous shortage may touch various aspects but in the first place it will affect isolation and cohorting. In addition, this shortage will not only apply to acutely ill children with viral respiratory tract infections but all children with need for hospital care, either chronically ill or e.g. being premature babies or newborns. Therefore, approaches are required which on the one hand are based on pragmatic grounds but on the other hand fulfill the basics of hygiene and infection control. The recommendations proposed in this statement are intended to give assistance to hospitals for the management of testing, isolation and cohorting of pediatric patients with suspected or confirmed SARS-CoV‑2 infections. The most important factor navigating the essential measures is the cumulative incidence of newly diagnosed infections per 100,000 over the last 7 days, which is given by the RKI or the local public health authorities. In the situation of low ( 50/100,000) incidence the respective diagnostic measures and the admission have to be performed under SARS-CoV‑2 precautions as specified by the RKI, and the children have to be isolated until the results of SARS-CoV‑2 test are available. The assessment of the incidence figures and the respective measures may be adapted by the local public health authorities on an individual basis. In case of shortfalls in admission capacities, the requirement of acute emergency care may necessitate that isolation and cohorting in the hospital will have to be performed temporarily in a less restrictive way than recommended here for standard.

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.

The last nationwide surveillance study on neonatal and young infant sepsis due to Group B Streptococci (GBS) and Escherichia coli in Germany was conducted between 2009 and 2010. The aim of this study is to provide longitudinal epidemiological data on neonatal and young infant sepsis caused by GBS and E. coli to reevaluate existing data and to inform clinical decision-making. Every positive blood culture for GBS and E. coli within the first 90 days of life that occurred at our center from 2008 until 2018 was identified. The epidemiological, clinical, laboratory, and microbiological data of all affected patients were analyzed through retrospective chart review, along with the pathogen’s antimicrobial susceptibility results. In total, 106 episodes of neonatal sepsis were described; 31% (n = 33) being caused by GBS and 69% (n = 73) by E. coli; 87% of GBS early-onset disease (EOD) cases did not receive intrapartum antibiotic prophylaxis (IAP). Contrary to general trends, the proportion of resistant E. coli isolates decreased for all tested antibiotics over time. Coincidentally, antenatal antibiotic use beyond IAP during that period decreased significantly in our center.Conclusions: (1) Data at our center suggests at least a regional implementation gap in GBS screening and IAP. (2) The decline in the resistance rate of E. coli for all antimicrobial substances might indicate that the reduction of prenatal antibiotics use is beneficial and that neonatal antibiotic stewardship programs should include pregnant women as well. What is Known:• GBS screening and intrapartum antibiotic prophylaxis led to a 32%-reduction in GBS disease in Germany with a 0.75 (92:122) ratio of early-onset disease to late-onset disease in 2009–2010.• Prenatal antibiotic use might increase the risk of E. coli early-onset disease and antibiotic resistances. What is New:• The GBS early-onset disease rates were twice as high as those of late-onset disease, the ratio was 1.75 (21:12) in 2008–2018 at our institution. This suggests that there are at least regional implementation gaps in the antenatal GBS screening in Germany.• We found a decline in E. coli resistance rates over time for all antimicrobial substances. Reduction in use of prenatal antibiotics might be an explanation.

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.

Streptococcus pyogenes or Group A Streptococcus (GAS) infections are the leading cause of bacterial tonsillopharyngitis. The bacterium can survive and persist within the human host for a long time as it is observed in up to 40% of the population who are considered as carriers. Recurrent tonsillopharyngitis is a particular problem in children which is caused either by relapses due to failed bacterial clearance or by reinfection. A prolonged survival in tonsillar crypts or on inanimate surfaces might be sources for reinfection. We therefore examined 64 clinical GAS isolates from children with tonsillopharyngitis for their long-term survival under either liquid or desiccated culture conditions. After 6 weeks, the overall GAS survival rate was 400-fold increased under desiccated culture conditions compared to liquid culture conditions, but varied depending on the emm-type between 20-fold (emm4) and 14000-fold (emm3). The survival rates of isolates from emm75 were significantly lower which is probably due to their production of hydrogen peroxide up to fatal doses. No hydrogen peroxide production could be detected for other emm-types. Furthermore, 11 isolates from patients with recurrent tonsillopharyngitis were compared to isolates of the same emm-type from patients with single episodes of tonsillopharyngitis. A significant elevated pH value and an increased survival rate for isolates from patients with recurrent infections were observed. In conclusion, significant differences in long-term survival of different GAS isolates as well as survival under desiccated culture conditions might contribute to both failed bacterial clearance and reinfection in patients with recurrent tonsillopharyngitis.

Fieber ist im Kindesalter in bis zu 20 % der Falle der Grund fur eine Arztkonsultation. Die Hauptsteuerung der Korpertemperatur erfolgt im Zentralnervensystem. Fieber ist meist eine Abwehrreaktion auf Infektionserreger. Bei jungen Sauglingen (Alter ≤ 3 Monate) wird Fieber als eine Rektaltemperatur >38,0 °C definiert. Die klinische Entitat Fieber ohne Fokus (FOF) wird einzig bei Sauglingen und Kleinkindern beobachtet. Sie stellt eine bedeutende Herausforderung dar: Die klinische Beurteilung fuhrt zur Entscheidung, ob die Wahrscheinlichkeit fur eine schwere bakterielle Infektion, sprich fur einen gefahrlichen Verlauf, als hoch oder gering anzunehmen ist, und bestimmt somit das therapeutische Vorgehen. Standardisierte klinische Voraussagemodelle fur FOF sind ohne zusatzliche Diagnostik fur die klinische Praxis von begrenztem Wert. Erganzend zur klinischen Einschatzung verbessert die durchdachte Bestimmung von Laborparametern die Wahrscheinlichkeitsabschatzung und das therapeutische Vorgehen entscheidend.

Group A streptococcus (GAS) is an important human pathogen whose clinical isolates differ in their ability to produce hydrogen peroxide (H2O2). H2O2 is primarily produced by the enzyme lactate oxidase (LctO), an in depth in silico research revealed that all genome-sequenced GAS possess the required gene lctO. The importance of lctO for GAS is underlined by its highly conserved catabolite control element (cre box) as well as its perfect promotor sequence in comparison to the known consensus sequences of the Gram-positive model organism Bacillus subtilis. In this study, we provide further insight in the function and regulation of lactate oxidase by analyzing a large group of clinical GAS isolates. We found that H2O2 production increased over time in the late stationary phase; after 4 days of incubation, 5.4% of the isolates showed a positive result at 37 °C, while the rate increased to 16.4% at 20 °C. This correlation between H2O2 production and low temperatures suggests additional regulatory mechanisms for lctO besides catabolite control protein A (CcpA) and indicates that lctO might play a role for GAS energy metabolism at sub-body temperatures. Furthermore, we could identify that H2O2 production was different among clinical isolates; we could correlate H2O2 production to emm-types, indicating that emm-types 6 and 75 had the highest rate of H2O2 production. The emm-type- and temperature-dependent H2O2 production of clinical GAS isolates might contribute to their different survival strategies.

Prevalence of invasive ß-haemolytic streptococci (BHS) at a tertiary care hospital and molecular diversity of S. pyogenes and S. dysgalactiae was studied. Between 2012 and 2016, all blood culture sets (n = 55,839), CSF (n = 8413) and soft tissue (n = 20,926) samples were analysed for BHS positivity using HYBASE software. Molecular profiles of 99 S. pyogenes and S. dysgalactiae were identified by sequencing of M protein genes (emm types) and multiplex PCR typing of 20 other virulence determinants. Streptococci contributed to 6.2% of blood, 10.7% of CSF and 14.5% of soft tissue isolates, being among the most common invasive isolates. The overall rates of invasive S. pyogenes, S. agalactiae, S. dysgalactiae and S. pneumoniae were 2.4, 4.4, 2.1, and 5.3%. Whereas S. pneumoniae was 1.5% more common in CSF samples, BHS isolates were 2-fold and 11-fold higher in bacteraemia and invasive soft tissue infections. Genetic BHS typing revealed wide molecular diversity of invasive and noninvasive group A and group G BHS, whereas one emm-type (stG62647.0) and no other virulence determinants except scpA were detected in invasive group C BHS. BHS were important invasive pathogens, outpacing S. pneumoniae in bacteraemia and invasive soft tissue infections. The incidence of S. dysgalactiae infections was comparable to that of S. pyogenes even with less diversity of molecular virulence. The results of this study emphasise the need for awareness of BHS invasiveness in humans and the need to develop BHS prevention strategies.

Haut- und Weichgewebeinfektionen zahlen zu den haufigsten bakteriellen Infektionen im Kindes- und Jugendalter. Neben der initial meist klinisch-deskriptiven Diagnose ist die differenzierte Betrachtung der Erreger notwendig, um eine empirische antibiotische Therapie kalkuliert einsetzen und diese – nach entsprechender Diagnostik und Verlaufsbeurteilung – gezielt anpassen zu konnen. Uberwiegend verursachen im Kindesalter Staphylococcus aureus und β‑hamolysierende Streptokokken der Lancefield-Gruppen A (S. pyogenes), C und G Haut- und Weichgewebeinfektionen. (Misch‑)Infektionen durch gramnegative Bakterien und Anaerobier sind v. a. unter Immunsuppression, bei verschmutzten Wunden, bei Abszedierungen aus dem Intestinal- oder Genitaltrakt sowie nach Bissverletzungen zu berucksichtigen. Die differenzialdiagnostische Abgrenzung zu autoinflammatorisch- und autoimmunvermittelten Systemerkrankungen kann im Einzelfall schwierig sein. Das fruhzeitige Erkennen insbesondere von nekrotisierender Fasziitis, Toxinschocksyndrom und Gasbrand/-gangran ist von entscheidender prognostischer Bedeutung. Aufgrund potenziell hoher Letalitat erfordern diese Infektionen neben kalkulierter antibiotischer und adjuvanter Therapie umgehende intensivmedizinische und ggf. chirurgische Masnahmen.

The article “Survival of Group A Streptococcus (GAS) is Enhanced Under Desiccated Culture Conditions”, written by Leonhard Menschner, Uta Falke, Peter Konrad, Nicole Toepfner, Reinhard Berner, was originally published electronically on the publisher's internet portal on 2 April 2020 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on 4 June 2021 to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0.

Das phanotypische und genetische Spektrum autoinflammatorischer Erkrankungen hat in den letzten Jahren stetig zugenommen. So sind mittlerweile mehrere monogen bedingte autoinflammatorische Erkrankungen bekannt, bei denen Fieberschube nicht im Vordergrund stehen und die neben Zeichen systemischer Entzundung auch Autoimmunphanomene oder eine pathologische Infektanfalligkeit aufweisen. Fur autoinflammatorische Erkrankungen, die mit einer unkontrollierten Aktivitat der Zytokine, IL-1β, TNF-α oder Typ-1-IFN einhergehen, stehen kausale Therapien zur Verfugung. Daher kommt der Sicherung der genetischen Diagnose eine grose Rolle zu. Die molekulargenetische Abklarung eines Patienten mit Autoinflammation sollte in Abhangigkeit von der Symptomkonstellation stufenweise erfolgen. Bei eindeutigen Symptomen kann als Erstes die Einzelgensequenzierung erfolgen. NGS-basierte Methoden wie die Panelsequenzierung und die Exomsequenzierung sowie die Array-CGH sind bei unklarer Symptomatik sinnvoll.

"Choosing Wisely" is a growing international campaign aiming at practice changes to improve patient health and safety by both, conduct of essential and avoidance of unnecessary diagnostic, preventive and therapeutic procedures. The goal is to create an easily recognizable and distributable list ("Choosing Wisely items") that addresses common over- and underuse in the management of infectious diseases.The German Society of Infectious Diseases (DGI) participates in the campaign "Klug Entscheiden" by the German Society of Internal Medicine. Committee members of the (DGI) listed potential 'Choosing Wisely items'. Topics were subjected to systematic evidence review and top ten items were selected for appropriateness. Five positive and negative recommendations were approved via individual member vote.The final recommendations are: (1) Imperatively start antimicrobial treatment and remove the focus in Staphylococcus aureus bloodstream infection. (2) Critically ill patients with signs of infection need early appropriate antibiotic therapy. (3) Annual influenza vaccination should be given to individuals with age60 years, patients with specific co-morbidities and to contact persons who may spread influenza to others. (4) All children should receive measles vaccine. (5) Prefer oral formulations of highly bioavailable antimicrobials whenever possible. (6) Avoid prescribing antibiotics for uncomplicated upper respiratory tract infections. (7) Do not treat asymptomatic bacteriuria with antibiotics. (8) Do not treat Candida detected in respiratory or gastrointestinal tract specimens. (9) Do not prolong prophylactic administration of antibiotics in patients after they have left the operating room. (10) Do not treat an elevated C-reactive protein (CRP) or procalcitonin with antibiotics for patients without signs of infection.Physicians will reduce potential harm to patients and increase the value of health care when implementing these recommendations.

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.

Der vom Nationalen Aktionsbundnis fur Menschen mit Seltenen Erkrankungen (NAMSE) ausgearbeitete nationale Aktionsplan sieht als eine zentrale Masnahme die Einrichtung von Zentren fur seltene Erkrankungen vor. Mithilfe einer Forderung des Innovationsfonds werden von April 2017 bis Marz 2020 neun universitare padiatrische Zentren fur seltene Erkrankungen diese Masnahme umsetzen und ihre Wirksamkeit evaluieren. In Kompetenzbereichen, krankheitsubergreifend (NAMSE-Typ-A-Zentren) und krankheitsspezifisch (NAMSE-Typ B-Zentren), werden sektorenubergreifende, IT-gestutzte Patientenpfade implementiert. Die Zentren fur seltene Erkrankungen bilden ein Netzwerk, das durch spezifische Expertenpanels die Qualitat der interdisziplinaren Diagnostik und Behandlung bei seltenen Erkrankungen uberregional verbessern soll. Die Beteiligung von Experten in standortubergreifenden Fallkonferenzen wird – fur den Patienten erkennbar – sicherstellen, dass die derzeit verfugbare Expertise fur das unklare oder seltene Krankheitsbild eingeholt wird. Die innovative genetische Diagnostik wird durch die Indikationsstellung im Expertenpanel und die Validierung mit Einbeziehung der behandelnden Arzte qualitatsgesichert durchgefuhrt. In der Versorgung von Patienten mit ausgewahlten Indikatordiagnosen, z. B. Krankheiten, die im Neugeborenenscreening detektiert werden, werden interdisziplinares Fallmanagement, Fallkonferenzen, Zugang zu einer prazisen Diagnostik und Therapie eine bessere Behandlungsqualitat erzielen. Die strukturierte Transition von der Padiatrie in die Erwachsenenmedizin wird die Nachhaltigkeit steigern. Eine verbesserte Kommunikation mit den Primarversorgern wird durch die IT-gestutzte Zugriffsmoglichkeit auf die aktualisierten Krankenhausdaten der Patienten erreicht, sodass Verzogerungen von notwendigen Masnahmen, z. B. von Therapieanpassungen, verhindert werden.

Erratum zu: Monatsschr Kinderheilkd 2019 https://doi.org/10.1007/s00112-019-00767-0 In Tabelle 5 (Diagnostisches Vorgehen bei jungen Sauglingen imAlter ≤90 Tage mit Fieber ohne Fokus (FOF), S. 937) hat sich ein Fehler eingeschlichen. Dort ist unter „Korperliche Untersuchung“ bei „Vitalzeichen“ der …

Historically, osteomyelitis was considered an infectious disorder. More recently, inflammatory mechanisms were recognized causing a significant proportion of pediatric osteomyelitis. This study was to compare characteristics of children with chronic non-bacterial (CNO) and bacterial osteomyelitis (BOM). A chart review of osteomyelitis patients from the departments of pediatrics, pediatric surgery, orthopedic surgery, and oral and maxillofacial surgery was conducted in a tertiary referral center, covering the years 2004–2014. Institutional incidences of CNO (n = 49) and BOM (n = 56) were comparable. Differentiation between CNO and BOM based on clinical or laboratory findings was mostly impossible. However, children with BOM more frequently presented with local inflammatory signs (47 vs. 68 %, p = 0.040), fever (12 vs. 38 %, p = 0.003), and abscesses (0 vs. 39 %, p < 0.001). Peripheral arthritis (14 vs. 0 %, p < 0.001), inflammatory bowel disease (10 vs. 2 %, p = ns), and hyperostosis (29 vs. 4 %, p = 0.001) were more common in CNO. Whole-body MRI was performed in 76 % of CNO patients, unveiling multifocal lesions in 80 % (CRMO). Though considered a rare disorder, institutional incidences of CNO were comparable to BOM, and the discrimination between CNO and BOM solely based on clinical aspects was mostly impossible. This is of special interest, since a correct and timely diagnosis is of utmost importance for long-term outcomes in both disorders. Whole-body MRIs should be considered in chronic osteomyelitis to (1) detect clinically inapparent lesions in CNO and (2) indirectly exclude (usually unifocal) chronic bacterial infections. Prospective studies are warranted to establish evidence-based diagnostic and therapeutic approaches to CNO.

Entzundungen der knochernen Strukturen konnen im Kindes- und Jugendalter zur erheblichen Einschrankung der Lebensqualitat sowie zu psychischen und korperlichen Schaden fuhren. Entgegen der Annahme ausschlieslich infektioser Ursachen der Osteomyelitiden (OM) gewinnen zunehmend die nichtinfektiosen, (auto-)inflammatorischen Ursachen an Bedeutung. Die haufigste autoinflammatorische Knochenerkrankung ist die chronische nichtbakterielle Osteomyelitis (CNO), die vorwiegend das knocherne Skelett betrifft, aber auch inflammatorische Veranderungen an Haut, Darm und Gelenken verursachen kann. Das breite klinische Spektrum reicht von zeitlich limitierten Knochenentzundungen an einzelnen Knochen bis zu chronisch aktiven oder rekurrierenden Verlaufen mit symmetrischem Befall mehrerer Knochen. Der Beitrag fasst Daten bezuglich der Differenzialdiagnose infektioser und nichtinfektioser OM zusammen und gibt evidenzbasierte Empfehlungen zu Differenzialdiagnostik und Therapie der CNO.

Bei einer bundesweiten Erhebung regionaler Tonsillektomiehaufigkeiten wurden 2007–2012 deutliche Differenzen festgestellt, die auf eine unterschiedliche Gesundheitsversorgung innerhalb Deutschlands hinweisen. Als konsentierte Entscheidungsgrundlage wurde die S2k-Leitlinie der AWMF – Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF-Register Nr. 017/024) „Therapie entzundlicher Erkrankungen der Gaumenmandeln – Tonsillitis“ durch mehrere Fachgesellschaften entwickelt. Aufgrund der erhohten Morbiditat nach Tonsillektomie wird eine strenge, leitlinienkonforme Indikationsstellung empfohlen. Zur Entscheidung fur oder gegen eine operative Therapie der Gaumenmandeln muss bei jeder Episode des Krankheitsbildes „Halsschmerzen“ zwischen viraler und bakterieller Infektion unterschieden werden. Auserdem ist die Festlegung auf eine der folgenden Diagnosen zentral: „akute Tonsillitis“, „akute Tonsillopharyngitis“ oder „akute Pharyngitis“. Das therapeutische Vorgehen richtet sich entsprechend den Leitlinienempfehlungen nach der Zahl bakterieller Tonsillitiden und bakterieller Tonsillopharyngitiden uber einen arztlich evaluierten Beobachtungszeitraum von mindestens 12 Monaten.

Die Typ-1-Interferonopathien stellen eine Gruppe genetisch bedingter seltener Erkrankungen dar, die durch eine Fehlfunktion des angeborenen Immunsystems hervorgerufen werden. Gemeinsames Kennzeichen ist eine Dysregulation der antiviralen Typ-1-Interferon(IFN)-Achse, die zu einer konstitutiven Typ-1-IFN-Aktivierung fuhrt. Als systemisch-entzundliche Erkrankungen ist das klinische Spektrum der Typ-1-Interferonopathien sehr breit und sowohl durch Autoinflammation als auch durch Autoimmunitat gekennzeichnet. Hierbei stehen neurologische und kutane Manifestationen im Vordergrund. Pathogenetisch liegen den Typ-1-Interferonopathien Storungen im Metabolismus und in der immunologischen Erkennung von intrazellularen Nukleinsauren zugrunde. Unser derzeitiges Verstandnis der molekularen Pathogenese der Typ-1-Interferonopathien weist darauf hin, dass eine immunmodulatorische Intervention, die der inadaquaten Typ-1-IFN-Aktvierung entgegenwirkt, therapeutisch wirksam sein konnte.

To review recent scientific advances and therapeutic approaches in the expanding field of type I interferonopathies. Type I interferonopathies represent a genetically and phenotypically heterogenous group of disorders of the innate immune system caused by constitutive activation of antiviral type I interferon (IFN). Clinically, type I interferonopathies are characterized by autoinflammation and varying degrees of autoimmunity or immunodeficiency. The elucidation of the underlying genetic causes has revealed novel cell-intrinsic mechanisms that protect the organism against inappropriate immune recognition of self nucleic acids by cytosolic nucleic acid sensors. The type I IFN system is subject to a tight and complex regulation. Disturbances of its checks and balances can spark an unwanted immune response causing uncontrolled type I IFN signaling. Novel mechanistic insight into pathways that control the type I IFN system is providing opportunities for targeted therapeutic approaches by repurposing drugs such as Janus kinase inhibitors or reverse transcriptase inhibitors.

Der Einsatz von Aminoglykosiden, wie Genatamicin und Amikacin, in der Therapie bakterieller Infektionen ist heute umstritten. Doch angesichts zunehmender Antibiotikaresistenzen stellt sich die Frage: Kommt die Padiatrie tatsachlich ohne Aminoglykoside aus oder haben diese Antibiotika nach wie vor ihren Stellenwert?

Group A streptococcus (GAS) and possibly other β-hemolytic streptococci (BHS) account for a considerable morbidity and mortality burden in African populations; however, disproportionately little is known about the epidemiology of BHS in sub-Saharan Africa. This study assessed the prevalence of GAS, group G streptococcus (GGS) and group C streptococcus (GCS) carriage and tonsillopharyngitis in a Central African population.A prospective cross-sectional study was performed to assess the prevalence of and risk factors for BHS carrier status and tonsillopharyngitis in children and adults in Gabon.The overall BHS carrier prevalence was 135/1,005 (13.4%); carrier prevalence of GAS, GGS, and GCS was 58/1,005 (5.8%), 50/1,005 (5.0%), and 32/1,005 (3.2%), respectively. Streptococcal carriage was associated with school and pre-school age (adjusted OR 2.65, 95% CI 1.62-4.36, p = 0.0001 and 1.90, 95% CI 1.14-3.17, p = 0.0141, respectively). Participants residing in urban areas were less likely carriers (OR 0.52, p = 0.0001). The point-prevalence of BHS-positive tonsillopharyngitis was 1.0% (9/1,014) and 15.0% (6/40) in school children with sore throat.Non-GAS exceeded GAS throat carriage and tonsillopharyngitis suggesting a yet underestimated role of non-GAS streptococci in BHS diseases.

Author(s): Fotis, Lampros; Shaikh, Nur; Baszis, Kevin; French, Anthony; Tarr, Phillip; Grevich, Sriharsha; Lee, Peggy; Ringold, Sarah; Leroux, Brian; Leahey, Hannah; Yuasa, Megan; Foster, Jessica; Sokolove, Jeremy; Lahey, Lauren; Robinson, William; Newsom, Joshua; Stevens, Anne; Karasawa, Rie; Tamaki, Mayumi; Tanaka, Megumi; Sato, Toshiko; Yudoh, Kazuo; Jarvis, James N; Moncrieffe, Halima; Bennett, Mark F; Tsoras, Monica; Luyrink, Lorie; Xu, Huan; Prahalad, Sampath; Morris, Paula; Dare, Jason; Nigrovic, Peter A; Rosenkranz, Margalit; Becker, Mara; O’Neil, Kathleen M; Griffin, Thomas; Lovell, Daniel J; Grom, Alexei A; Medvedovic, Mario; Thompson, Susan D; Zhu, Lisha; Jiang, Kaiyu; Wong, Laiping; Buck, Michael J; Chen, Yanmin; Moncrieffe, Halima; Brungs, Laura; Liu, Tao; Wang, Ting; Jarvis, James N; Alsaeid, Khaled; Alfailakawi, Jasim; Alenezi, Hamid; Alsaeed, Hazim; Beukelman, Tim; Natter, Marc; Ilowite, Norm; Mieszkalski, Kelly; Burrell, Grendel; Best, Brian; Bristow, Helen; Carr, Shannon; Dennos, Anne; Kaufmann, Rachel; Kimura, Yukiko; Schanberg, Laura; Blier, Peter R; Boneparth, Alexis; Wenderfer, Scott E; Moorthy, L Nandini; Radhakrishna, Suhas M; Sagcal-Gironella, Anna Carmela P; von Scheven, Emily; Gedik, Kader Cetin; Siddique, Salma; Aguiar, Cassyanne L; Erkan, Doruk; Cohen, Ezra; Lee, Yvonne; Dossett, Michelle; Mehta, Darshan; Davis, Roger; Gilbert, Mileka; Goilav, Beatrice; Meidan, Esra

Symptoms of acute febrile respiratory tract infection are often unspecific, but the rapid identification of pathogens allows optimised patient management. The objective of this study was to evaluate a novel multiplex polymerase chain reaction (PCR) suspension microarray which detects 19 viral and four atypical bacterial targets. A comprehensive set of sensitive monoplex real-time PCR assays was used for each pathogen as the gold standard. A panel of archived as well as 300 prospectively collected clinical samples was analysed by both methods. At least one target was detected in 165/300 (55 %) samples by monoplex PCR and in 140/300 (46 %) samples by multiplex PCR, respectively. The positivity rate was significantly higher in paediatric patients compared to adults [126/154 (82 %) vs. 39/146 (27 %) by monoplex and 114/154 (74 %) vs. 26/146 (18 %) by multiplex PCR, respectively]. Among all samples, 17/300 (5.6 %) were positive for atypical bacteria by monoplex and 8/300 (2.6 %) by multiplex PCR, respectively. Multiple detections were recorded in 35/300 (11.6 %) samples by monoplex and 26/300 (8.7 %) by multiplex PCR. For the most common pathogens, the sensitivity ranged from 57 to 93 % and the specificity ranged from 95 to 100 %. The overall concordance between both methods was 77 % [95 % confidence interval (CI) 72-81 %]. False-negative results by multiplex PCR were mainly due to the low target concentration. Compared to monoplex PCR, the novel microarray assay proved its principle but displayed overall lower sensitivities, potentially restricting its use to paediatric patients. For some targets, only small numbers of positive samples were available, requiring larger studies to firmly assess the sensitivity and specificity.

Group A streptococcus (GAS) is considered to be a major pathogen of bacterial tonsillopharyngitis in children. Although GAS is generally susceptible to penicillin, macrolides are often used as the second-line treatment. Over the last several decades, the rising macrolide resistance of GAS has been detected in several countries. With the current study, we aimed to determine the development of macrolide resistance at our paediatric centre. From March 2006 to May 2009, 350 GAS isolates were tested for susceptibility to erythromycin, azithromycin, clindamycin, penicillin and cefotaxime. Macrolide-resistant isolates were screened for the presence of genes related to macrolide resistance (mefA, ermB, ermTR, prtF1). In comparison to a prior study at our hospital, the erythromycin resistance rate decreased significantly from 13.6 to 2.6%. This effect may be attributable to a more restrictive use of macrolides in children in our region.

Akute Halsschmerzen sind eine der haufigsten Ursachen fur kinder- und hausarztliche Konsultationen. In den meisten Fallen liegt eine virale Ursache zugrunde, aber auch bei einer GAS-Tonsillopharyngitis (GAS: Gruppe-A-Streptokokken) ist der Spontanverlauf gunstig. Um die bislang sehr haufige antibiotische Therapie bei Halsschmerzen zu begrenzen, wurde 2009 von der Deutschen Gesellschaft fur Allgemeinmedizin und Familienmedizin (DEGAM), der Deutschen Gesellschaft fur Kinder- und Jugendmedizin (DGKJ) und der Deutschen Gesellschaft fur Padiatrische Infektiologie (DGPI) eine Leitlinie Beratungsanlass: Halsschmerzen veroffentlicht. Nur bei ausgepragten Symptomen und dem hochgradigen klinischen Verdacht und – bei Kindern und Jugendlichen – dem Nachweis von GAS oder aber komplizierten Verlaufen wird heute eine antibiotische Therapie empfohlen. Die Indikation zur antibiotischen Therapie des klassischen Scharlachs, invasiver Infektionen oder Haut- und Weichteilinfektionen durch GAS andert sich durch die neue Leitlinie nicht.

Although tularemia is a long-known disease, its significance had diminished over the last decades in Middle Europe. However, over the past years, there is new evidence suggesting that tularemia has re-emerged in Germany. In 2007, the highest number of human cases for almost 50 years has been notified. Beside typical vectors, new ways of transmission seem to gain significance. So far, mosquito bite-transmitted tularemia has only been known from Scandinavia but not from Middle Europe.We report the first case of a 1-year-old toddler from Southwestern Germany with mosquito bite-associated ulceroglandular tularaemia. The new and interesting features of this case are the young age of the patient and the unusual transmission route. The available data suggesting changes in the epidemiology for tularemia in Germany are reviewed. This is an interesting case of infantile tularemia with a very unusual transmission route, highlighting ongoing changes in the epidemiology of tularemia in Germany.

Over the last 20 years, a number of medical innovations with impact on the incidence of bacterial and fungal bloodstream infections (BSIs) in children have been developed and implemented. Although appropriate empirical antimicrobial therapy is a prerequisite to the successful treatment of BSIs, to date, epidemiological data on long-term microbiological trends in BSIs of hospitalized children have not been available. Two cohorts of pediatric patients who were hospitalized in a single-center tertiary care hospital in Germany over a 20-year time span (period A from 1985 to 1995 vs. period B from 1997 to 2006) were retrospectively analyzed and compared with respect to the epidemiology and microbiology of BSIs. A total of 1,646 cases of monomicrobial BSIs were detected. The rate of positive blood culture results dropped from 4.5% in period A to 2.0% in period B. The proportion of gram-positive vs. gram-negative pathogens recovered from blood cultures remained stable. Among gram-positive pathogens, an increase in enterococci (3.3% vs. 8.2%) and in coagulase-negative staphylococci (CoNS) (22.9 vs. 28.2%) was observed. In contrast, BSIs caused by Staphylococcus aureus (16.4% vs. 11.7%), Streptococcus agalactiae (4.9% vs. 2.1%), Haemophilus influenzae (7.3% vs. 0.7%), and Neisseria meningitidis (1.9% vs. 0.5%) diminished. In analyzing subgroups, an increase of enterococcal and CoNS infections was noted among patients with immunosuppression and neonatal early-onset sepsis (EOS), while a decrease was found among late-onset sepsis (LOS) cases with S. viridans. Notably, aminopenicillin-resistant enterococci and aminopenicillin- and fluoroquinolone-resistant Enterobacteriaceae all increased over time, while the overall resistance pattern was still favorable. The overall mortality rate of BSIs decreased (5.2% vs. 2.6%). Over the 20-year study period, the spectrum of specific microorganisms among BSIs shifted, with opportunistic pathogens becoming predominant. Despite an increase in the proportion of antibiotic-resistant organisms, however, the mortality rate decreased.

Introduction Surveillance systems for acute respiratory infections (ARI) in children currently are often limited in terms of the panel of pathogens and the age range investigated or are only syndromic and at times only active in the winter season. Methods Within PID-ARI.net, a research network for ARI in children in Germany, an active, year-round surveillance system was formed in three regions from north to south for population-based analysis. Children from birth to 16 years of age were included and up to 19 noncolonizing airway pathogens were tested for with multiplex RT-PCR. Results In the 10-year period from July 1996 to June 2006, a total of 18,899 samples were tested. The positive rate increased with the size of the test panel to up to 72.9%. Picornaviruses (35–39%), paramyxoviruses (23–28%) and orthomyxoviruses (5.8–12.5%) comprised the highest fraction. Reoviruses and Legionella pneumophila were not found at all and Chlamydia pneumoniae and Bordetella parapertussis only rarely. Respiratory syncytial virus and parainfluenza virus (PIV) type 3 were anticyclical in rhythmicity with metapneumovirus and PIV1 and PIV2. The age medians per pathogen depended predominantly upon the attack rate and interepidemic intervals. Conclusion Active surveillance systems for ARI are superior to passive systems. They should be pathogen-specific and comprehensive for viruses and bacteria and age ranges. They should be population-based and multilevel to avoid bias. The impact of atypical bacteria in children was highly overestimated in earlier studies.