Publications by authors named "Markus Hufnagel"

51 Publications

Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis.

Rheumatology (Oxford) 2021 Jan 28. Epub 2021 Jan 28.

Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.

Objectives: To determine subcutaneous-tocilizumab (SC-TCZ) dosing regimens for systemic juvenile idiopathic arthritis (sJIA) and polyarticular JIA (pJIA).

Methods: In two 52-week phase 1 b trials, SC-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or < 30 kg, respectively. Primary endpoints were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with intravenous-tocilizumab (IV-TCZ) in sJIA and pJIA.

Results: Study participants were 51 sJIA patients and 52 pJIA patients aged 1-17 years who received SC-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with IV-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis Disease Activity Score-71 were comparable between SC-TCZ and IV-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of IV-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered related to TCZ.

Conclusion: SC-TCZ provides exposure and risk/benefit profiles similar to those of IV-TCZ. Subcutaneous administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use.

Trial Registration: ClinicalTrials.gov, NCT01904292 and NCT01904279.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keab047DOI Listing
January 2021

Prevalence of Capsular Serotype, Pilus Island Distribution, and Antibiotic Resistance in Pediatric and Adult Invasive Group B Streptococcus Isolates: Data From a Nationwide Prospective Surveillance Study in Germany.

Pediatr Infect Dis J 2021 Jan;40(1):76-82

Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

For neonates, group B Streptococcus is life threatening. Current prevention strategies remain insufficient, especially for cases of late-onset sepsis, where intrapartum antibiotic prophylaxis has demonstrated no benefit. One promising approach is the vaccination of pregnant women, which offers protective immunity via transplacental transmission of neutralizing antibodies. Our nationwide, prospective surveillance study aimed to characterize the prevalence of pilus antigen, capsular polysaccharide serotypes, and antibiotic resistance from invasive GBS infections in neonates and compare these results with those from children and adults in Germany. Our study includes 173 neonatal isolates of a total of 450 reported cases during the study period (incidence: 0.34/1000 live births), in addition to 2 pediatric and 803 adult isolates. The comparison between neonatal and adult isolates reveals age-dependent differences in capsular serotype and pilus type distribution and differences in antibiotic resistance patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000002943DOI Listing
January 2021

SARS-CoV-2 testing and infection control strategies in European paediatric emergency departments during the first wave of the pandemic.

Eur J Pediatr 2020 Oct 13. Epub 2020 Oct 13.

Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St. George's, University of London, London, UK.

Between February and May 2020, during the first wave of the COVID-19 pandemic, paediatric emergency departments in 12 European countries were prospectively surveyed on their implementation of SARS-CoV-2 disease (COVID-19) testing and infection control strategies. All participating departments (23) implemented standardised case definitions, testing guidelines, early triage and infection control strategies early in the outbreak. Patient testing criteria initially focused on suspect cases and later began to include screening, mainly for hospital admissions. Long turnaround times for test results likely put additional strain on healthcare resources.Conclusion: Shortening turnaround times for SARS-CoV-2 tests should be a priority. Specific paediatric testing criteria are needed. What is Known: • WHO and public health authorities issued case definitions, testing and infection control recommendations for COVID-19 in January. • SARS-CoV-2 testing was made available across Europe in February. What is New: • Paediatric emergency departments implemented COVID-19-specific procedures rapidly, including case definitions, testing guidelines and early triage. • A third of surveyed departments waited more than 24 h for SARS-CoV-2 test to be reported, resulting in additional strain on resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-020-03843-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553380PMC
October 2020

Anakinra And Etanercept Combination Treatment in a Child With Severe, Nonresponsive Kawasaki Disease.

Pediatr Infect Dis J 2020 10;39(10):e310-e313

From the Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377 Munich, Germany.

Kawasaki disease (KD) patients' resistance to treatment with intravenous immunoglobulins (IVIG) places them at high risk for an unfavorable progression of the disease. In these patients, there has been little evidence that alternative treatments are effective. Nevertheless, biologicals such as an interleukin-1-receptor blocker and tumor-necrosis-factor-α inhibitors increasingly have been used. If the patient does not respond to one of these therapeutics, a combination of 2 biologicals might be an alternative, but this is not yet generally accepted due to the potentially increased risk of infection. Here we report on a 3-month-old boy suffering from severe refractory KD. KD diagnosis was delayed due to the misinterpretation of a urinary tract infection and to the short and nonsimultaneous presence of classical KD symptoms. After complete KD later was able to be diagnosed, treatment with intravenous immunoglobulins was administered. However, the disease proved resistant to 2 courses of IVIG, as well as to corticosteroids. The patient developed giant coronary artery aneurysms early during the course of disease. Anakinra was initiated, but even with stepwise higher anakinra dosages, he remained febrile and coronary artery dimensions increased. Therefore, etanercept was added as a second biological. Only under combination treatment with anakinra and etanercept were his inflammation and fever able to be completely resolved. Coronary artery dimensions improved over time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000002810DOI Listing
October 2020

Hospital Admission in Children and Adolescents With COVID-19.

Dtsch Arztebl Int 2020 05;117(21):373-374

Klinik und Poliklinik für Kinderund Jugendmedizin, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden; Gesundheitsverbund Landkreis Konstanz, Klinikum Singen, Zentrum für Kinderund Jugendgesundheit; Klinik für Pädiatrische Onkologie und Hämatologie, Universitätsklinikum des Saarlandes, Homburg/Saar; Pädiatrische Infektiologie und Rheumatologie, Zentrum für Kinder und Jugendmedizin, Universitätsklinikum Freiburg; Klinik für Kinderund Jugendmedizin, Klinikum Dortmund gGmbH; Abteilung Pädiatrische Infektiologie, Dr. von Haunersches Kinderspital, Klinikum der Ludwig-Maximilian-Universität München; Deutsche Gesellschaft für Pädiatrische Infektiologie e.V., Berlin.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3238/arztebl.2020.0373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271745PMC
May 2020

Management of Care for Neonates Born to SARS-CoV-2 Positive Women with or without Clinical Symptoms (COVID-19).

Klin Padiatr 2020 07 5;232(4):173-177. Epub 2020 Jun 5.

Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1168-2845DOI Listing
July 2020

Comprehensive infectious disease screening in a cohort of unaccompanied refugee minors in Germany from 2016 to 2017: A cross-sectional study.

PLoS Med 2020 03 31;17(3):e1003076. Epub 2020 Mar 31.

Department of Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Freiburg, Germany.

Background: Information regarding the prevalence of infectious diseases (IDs) in child and adolescent refugees in Europe is scarce. Here, we evaluate a standardized ID screening protocol in a cohort of unaccompanied refugee minors (URMs) in a municipal region of southwest Germany.

Methods And Findings: From January 2016 to December 2017, we employed a structured questionnaire to screen a cohort of 890 URMs. Collecting sociodemographic information and medical history, we also performed a standardized diagnostics panel, including complete blood count, urine status, microbial stool testing, tuberculosis (TB) screening, and serologies for hepatitis B virus (HBV) and human immunodeficiency virus (HIV). The mean age was 16.2 years; 94.0% were male, and 93.6% originated from an African country. The most common health complaints were dental problems (66.0%). The single most frequent ID was scabies (14.2%). Of the 776 URMs originating from high-prevalence countries, 7.7% and 0.4% tested positive for HBV and HIV, respectively. Nineteen pathogens were detected in a total of 119 stool samples (16.0% positivity), with intestinal schistosomiasis being the most frequent pathogen (6.7%). Blood eosinophilia proved to be a nonspecific criterion for the detection of parasitic infections. Active pulmonary TB was identified in 1.7% of URMs screened. Of note, clinical warning symptoms (fever, cough >2 weeks, and weight loss) were insensitive parameters for the identification of patients with active TB. Study limitations include the possibility of an incomplete eosinophilia workup (as no parasite serologies or malaria diagnostics were performed), as well as the inherent selection bias in our cohort because refugee populations differ across Europe.

Conclusions: Our study found that standardized ID screening in a URM cohort was practicable and helped collection of relevant patient data in a thorough and time-effective manner. However, screening practices need to be ameliorated, especially in relation to testing for parasitic infections. Most importantly, we found that only a minority of infections were able to be detected clinically. This underscores the importance of active surveillance of IDs among refugees.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pmed.1003076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108686PMC
March 2020

Microarray Analysis of Group B Streptococci Causing Invasive Neonatal Early- and Late-onset Infection.

Pediatr Infect Dis J 2020 05;39(5):449-453

From the Department of Pediatrics, University Hospital Carl Gustav Carus, Dresden, Germany.

Background: Group B Streptococcus is the leading cause of meningitis and sepsis in newborns. Until now, there is no data of fast and simple typing of group B Streptococcus virulence factors using a genetic microarray and comparing these data to clinical manifestations.

Methods: A prospective active surveillance study was conducted via 2 independent and nationwide reporting systems, the German Pediatric Surveillance Unit (ESPED) and the Laboratory Sentinel Group at Robert Koch-Institute. Surveillance was performed between 2001 and 2003 and between 2008 and 2010. Typing of virulence factors, serotypes, pilus islands and alpha-like proteins was done by means of a newly developed microarray method.

Results: We evaluated 475 isolates of invasive neonatal infections. Predominant virulence factors were serotype III (63%), pilus island 2b and pilus island 1 (50%) and alp rib (64%) (alp - alpha-like protein, rib -resistance to proteases, immunity, group B). There was no significant change over time or geographically within Germany. Serotype III, pilus island 2b + 1 and alp rib showed significant associations with late-onset disease and meningitis, whereas alp 5 had a significant association with early-onset disease. Based on serotypes, pilus islands and alpha-like proteins, it was possible to cluster 86% of all isolates into 5 genetic groups.

Conclusions: The molecular epidemiology of a large collection of invasive neonatal infections showed similar distributions, as shown in smaller cohorts before. The microarray used proved to be a fast and reliable technique. Using this new tool, we were able to cluster the isolates according to their virulence factors. The clusters showed a better association with clinical data than single virulence factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000002627DOI Listing
May 2020

Risk Factors for Complicated Lymphadenitis Caused by Nontuberculous Mycobacteria in Children.

Emerg Infect Dis 2020 03;26(3):579-586

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 <5.5 years as potential risk factors. Complete extirpation of the affected lymph node appeared to be the best therapeutic measure. We integrated the study data to develop a simple risk score to predict unfavorable clinical outcomes for NTM lymphadenitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2603.191388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045849PMC
March 2020

Long-term surveillance of biologic therapies in systemic-onset juvenile idiopathic arthritis: data from the German BIKER registry.

Rheumatology (Oxford) 2020 09;59(9):2287-2298

Centre for Paediatric Rheumatology, Department of Paediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin.

Objective: Using data from the German Biologics JIA Registry (BIKER), long-term safety of biologics for systemic-onset JIA with regard to adverse events of special interest was assessed.

Methods: Safety assessments were based on adverse event reports after first dose through 90 days after last dose. Rates of adverse event, serious adverse event and 25 predefined adverse events of special interest were analysed. Incidence rates were compared for each biologic against all other biologics combined applying a mixed-effect Poisson model.

Results: Of 260 systemic-onset JIA patients in this analysis, 151 patients received etanercept, 109 tocilizumab, 71 anakinra and 51 canakinumab. Patients with etanercept had higher clinical Juvenile Arthritis Disease Activity Score 10 scores, active joint counts and steroid use at therapy start. Serious adverse events were reported with higher frequency in patients receiving canakinumab [20/100 patient years (PY)] and tocilizumab (21/100 PY). Cytopenia and hepatic events occurred with a higher frequency with tocilizumab and canakinumab. Medically important infections were seen more often in patients with IL-6 or IL-1 inhibition. Macrophage activation syndrome occurred in all cohorts with a higher frequency in patients with canakinumab (3.2/100 PY) and tocilizumab (2.5/100 PY) vs anakinra (0.83/100 PY) and etanercept (0.5/100 PY). After adjustment only an elevated risk for infections in anakinra-treated patients remained significant. Three definite malignancies were reported in patients ever exposed to biologics. Two deaths occurred in patients treated with etanercept.

Conclusion: Surveillance of pharmacotherapy as provided by BIKER is an import approach especially for patients on long-term treatment. Overall, tolerance was acceptable. Differences between several biologics were noted and should be considered in daily patient care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/kez577DOI Listing
September 2020

Long-term, single-center surveillance of non-invasive group A streptococcal (GAS) infections, emm types and emm clusters.

Eur J Clin Microbiol Infect Dis 2020 Feb 22;39(2):273-280. Epub 2019 Nov 22.

Department of Pediatrics, Carl Gustav Carus University Hospital, Technical University Dresden, Dresden, Germany.

Group A streptococci (GAS) are among the most frequent pathogens in children. Many epidemiological studies focus on specific GAS infections (such as tonsillopharyngitis or invasive disease), on GAS carriers or on post-streptococcal sequelae. By comparison, reports on regional GAS characteristics, particularly circulating non-invasive GAS in Europe, are rare. In a monocentric study, all GAS isolated from pediatric patients at a tertiary care hospital over a 6-year period (2006-2012) were characterized. GAS emm types and clusters were determined. Associated patient data were analyzed. Five hundred sixty-six GAS strains were collected. GAS tonsillopharyngitis was most common (71.6%), followed by pyoderma (6.0%), otitis media (3.7%), perineal dermatitis (3.4%), and invasive infections (1.4%). Colonizing strains represented 13.6% of GAS. GAS emm12 was most prevalent among invasive and non-invasive isolates. Emm1, emm4, emm28, and emm89 were the most frequent non-invasive GAS strains. The emm E4 cluster was most common, followed by the A-C4, A-C3, and E1. Among the GAS infections, different emm types and clusters were identified, e.g., emm4 was more common among patients with scarlet fever. Three new emm subtypes were characterized: emm29.13, emm36.7, and emm75.5. This comprehensive review of a large, local GAS cohort points to the differences between and similarities among GAS genotypes and disease manifestations, while minimizing regional variations. Considerable deviation from previous epidemiological findings is described, especially regarding the frequent detection of emm1 and emm89 in non-invasive GAS infections. Periodic updates on molecular and epidemiological GAS characteristics are needed to track the multifaceted pathogenic potential of GAS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10096-019-03719-4DOI Listing
February 2020

Intravenous Artesunate for Imported Severe Malaria in Children Treated in Four Tertiary Care Centers in Germany: A Retrospective Study.

Pediatr Infect Dis J 2019 11;38(11):e295-e300

Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Background: Intravenous artesunate (ivA) is the standard treatment for severe malaria. Data systematically evaluating the use of ivA in pediatric patients outside malaria-endemic regions are limited. The aim of this case series was to summarize efficacy and safety of ivA for imported severe malaria in children in Germany.

Methods: Our retrospective case series included pediatric patients with imported severe malaria treated with at least 1 dose of ivA (Artesun, Guilin Pharmaceutical; Shanghai, China) at 4 German tertiary care centers. Severe malaria was defined according to World Health Organization criteria.

Results: Between 2010 and 2018, 14 children with a median [interquartile range (IQR)] age of 6 (1;9.5) years were included. All children were of African descent. All but 2 patients had Plasmodium falciparum malaria; 1 child had P. vivax malaria and 1 child had P. falciparum and P. vivax co-infection. Median (IQR) parasitemia at admission in patients with P. falciparum was 9.5% (3;16.5). Patients were treated with 1-10 [median (IQR) 3 (3;4)] doses ivA. All but one patient received a full course of oral antimalarial treatment. Parasite clearance was achieved within 2-4 days, with the exception of 1 patient with prolonged clearance of peripheral parasitemia. Three patients experienced posttreatment hemolysis but none needed blood transfusion. Otherwise ivA was safe and well tolerated.

Conclusions: ivA was highly efficacious in this pediatric cohort. We observed episodes of mild to moderate posttreatment hemolysis in approximately one-third of patients. The legal status and usage of potentially lifesaving ivA should be evaluated in Europe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000002417DOI Listing
November 2019

Epidemiology of Human Parechovirus Type 3 Upsurge in 2 Hospitals, Freiburg, Germany, 2018.

Emerg Infect Dis 2019 07;25(7):1384-1388

In 2018, a cluster of pediatric human parechovirus (HPeV) infections in 2 neighboring German hospitals was detected. Viral protein 1 sequence analysis demonstrated co-circulation of different HPeV-3 sublineages and of HPeV-1 and -5 strains, thereby excluding a nosocomial outbreak. Our findings underline the need for HPeV diagnostics and sequence analysis for outbreak investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2507.190257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590756PMC
July 2019

Group B Streptococci: Declining Incidence in Infants in Germany.

Pediatr Infect Dis J 2019 05;38(5):516-519

Epidemiology Department, Helmholtz Centre for Infection Research, Braunschweig, Germany.

Group B streptococcus (GBS) is a leading cause of morbidity and mortality in newborns worldwide. From 2000 to 2008, national guidelines in Germany recommended intrapartum antibiotic prophylaxis for pregnant women displaying risk factors (eg, perinatal anogenital GBS colonization, rupture of the membranes ≥18 hours before birth) for the vertical transmission of GBS to their children. In 2008, these guidelines were revised to advocate universal, culture-based screening for GBS colonization among all pregnant women between 35 and 37 weeks of gestation. For the period 2009-2010, our prospective active surveillance study assessed the incidence of invasive GBS infections in infants 0-90 days of age in Germany. We did this by means of a capture-recapture analysis of 2 separate, independent systems (pediatric reporting versus laboratory reporting). We compared our results with those from a previous study by employing an equivalent design (2001-2003). We detected a 32% reduction in GBS incidence, from 0.47 per 1000 live births (n = 679) in 2001-2003 to 0.34 per 1000 live births (n = 450) in 2009-2010. This decline primarily is tied to a reduced number of GBS cases in children under 1 week of age. In 2009-2010, the ratio of early-onset disease to late-onset disease reversed from 1.52 (206:136), as determined in 2001-2003, to 0.75 (92:122). This study is the first to assess changes in the incidence of invasive GBS in Germany after the implementation of the guidelines for intrapartum prophylaxis for pregnant women colonized with GBS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000002115DOI Listing
May 2019

[Recommendations for Diagnostics and Therapy of Children with Cancer Presenting with Fever and Neutropenia - Comparison of Two Current Guidelines].

Klin Padiatr 2018 Apr 27;230(3):115-121. Epub 2018 Mar 27.

Pädiatrische Hämatologie und Onkologie, Universitätskinderklinik, Homburg.

Immunocompromised children and adolescents receiving treatment for cancer have a considerably increased risk for infection. Neutropenia is the most important single risk factor for infectious complications, and fever in neutropenia is considered as an emergency. Whereas guidelines for the management of fever in neutropenic adults have been established for decades, specific pediatric guidelines have not been developed until recently. As children differ in many aspects from adults such as in the underlying malignancy or in the availability and dosing of antimicrobial compounds, guidelines for pediatric patients are important. This article reviews similarities and differences between the recently published German interdisciplinary guideline of the German Societies of Pediatric Infectious Diseases and Pediatric Oncology and Hematology and a guideline developed by a panel of international experts for the management of fever in neutropenia in children and adolescents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0044-101953DOI Listing
April 2018

High Rates of Prescribing Antimicrobials for Prophylaxis in Children and Neonates: Results From the Antibiotic Resistance and Prescribing in European Children Point Prevalence Survey.

J Pediatric Infect Dis Soc 2019 May;8(2):143-151

Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium.

Background: This study was conducted to assess the variation in prescription practices for systemic antimicrobial agents used for prophylaxis among pediatric patients hospitalized in 41 countries worldwide.

Methods: Using the standardized Antibiotic Resistance and Prescribing in European Children Point Prevalence Survey protocol, a cross-sectional point-prevalence survey was conducted at 226 pediatric hospitals in 41 countries from October 1 to November 30, 2012.

Results: Overall, 17693 pediatric patients were surveyed and 36.7% of them received antibiotics (n = 6499). Of 6818 inpatient children, 2242 (32.9%) received at least 1 antimicrobial for prophylactic use. Of 11899 prescriptions for antimicrobials, 3400 (28.6%) were provided for prophylactic use. Prophylaxis for medical diseases was the indication in 73.4% of cases (2495 of 3400), whereas 26.6% of prescriptions were for surgical diseases (905 of 3400). In approximately half the cases (48.7% [1656 of 3400]), a combination of 2 or more antimicrobials was prescribed. The use of broad-spectrum antibiotics (BSAs), which included tetracyclines, macrolides, lincosamides, and sulfonamides/trimethoprim, was high (51.8% [1761 of 3400]). Broad-spectrum antibiotic use for medical prophylaxis was more common in Asia (risk ratio [RR], 1.322; 95% confidence interval [CI], 1.202-1.653) and more restricted in Australia (RR, 0.619; 95% CI, 0.521-0.736). Prescription of BSA for surgical prophylaxis also varied according to United Nations region. Finally, a high percentage of surgical patients (79.7% [721 of 905]) received their prophylaxis for longer than 1 day.

Conclusions: A high proportion of hospitalized children received prophylactic BSAs. This represents a clear target for quality improvement. Collectively speaking, it is critical to reduce total prophylactic prescribing, BSA use, and prolonged prescription.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpids/piy019DOI Listing
May 2019

Cystic Encephalomalacia following Vasculopathy and Vasospasm of Proximal Intracranial Arteries Due to Pneumococcal Meningitis in a Infant.

Neuropediatrics 2018 06 9;49(3):213-216. Epub 2018 Mar 9.

Department of Neuropediatrics and Muscle Disorders, University of Freiburg, Freiburg, Germany.

Despite the availability of modern antibiotics, pneumococcal meningitis in both children and adults remains a severe disease-one known to frequently cause grave complications and residual disability. Although the appearance of arterial vasospasms in bacterial meningitis systematically has been investigated and reported on for adult patients, such research is lacking when it comes to infants. We report on a 4-week-old infant who, 6 days after onset of pneumococcal meningitis, suffered severe neurological deterioration with treatment-resistant seizures and coma. Generalized cortical and subcortical edema developed in conjunction with diminished cerebral blood flow, as depicted in magnetic resonance angiography and serial Doppler-sonographic examinations. The ischemia resulted in extensive cystic encephalomalacia. We propose that the degree of variation in cerebral blood flow in the acute phase was the result of an extensive arterial vasculopathy involving vasospasms. Awareness of this complication and prospective serial Doppler-sonographic examinations may improve our understanding of the connection between brain edema and vasculopathy. At present, however, no effective treatment appears available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0038-1635075DOI Listing
June 2018

Failure to Predict High-risk Kawasaki Disease Patients in a Population-based Study Cohort in Germany.

Pediatr Infect Dis J 2018 09;37(9):850-855

Department of Epidemiology, Institute of Social Pediatrics and Adolescent Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.

Background: Diverse scores on high-risk Kawasaki disease (KD) patients have proven a good prognostic validity in the Japanese population. However, data on non-Japanese have been inconclusive. Do the Kobayashi, Egami and Sano scores or application of up-to-date statistical methods (Random Forest) predict response to standard intravenous immunoglobulin (IVIG) therapy and the risk of persistent coronary artery aneurysm (CAA) in patients with KD in a mainly Caucasian population in Germany?

Methods: Data on 442 children (German population-based survey, 2013 and 2014) were used to assess the prognostic validity of the Kobayashi, Egami and Sano scores for being refractory to IVIG treatment and for predicting the risk of persistent CAA. Additionally, an up-to-date statistical approach (Random Forest) was applied to identify a potentially more valid score.

Results: A total of 301 children were eligible for assessment of their response to IVIG treatment. Among those, 177 children were followed-up for 1 year to identify persistent CAA. Although all scores were significantly associated with being refractory to IVIG (relative risk range between 2.32 and 3.73), the prognostic properties were low (likelihood ratio positive: 1.83-4.57; sensitivity in the range of 0.28-0.53). None of the scores was a significant predictor of CAA 1 year after acute illness. Application of statistical analysis such as Random Forest did not yield a more valid score.

Conclusions: None of the available scores appears to be appropriate for identifying high-risk Caucasian children with KD who might need intensified therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000001923DOI Listing
September 2018

Practice and consensus-based strategies in diagnosing and managing systemic juvenile idiopathic arthritis in Germany.

Pediatr Rheumatol Online J 2018 Jan 22;16(1). Epub 2018 Jan 22.

Department of Pediatric Rheumatology and Immunology, University Hospital Münster, Münster, Albert-Schweitzer-Campus 1, Building W30, 48149, Münster, Germany.

Background: Systemic juvenile idiopathic arthritis (SJIA) is an autoinflammatory disease associated with chronic arthritis. Early diagnosis and effective therapy of SJIA is desirable, so that complications are avoided. The PRO-KIND initiative of the German Society for Pediatric Rheumatology (GKJR) aims to define consensus-based strategies to harmonize diagnostic and therapeutic approaches in Germany.

Methods: We analyzed data on patients diagnosed with SJIA from 3 national registries in Germany. Subsequently, via online surveys and teleconferences among pediatric rheumatologists with a special expertise in the treatment of SJIA, we identified current diagnostic and treatment approaches in Germany. Those were harmonized via the formulation of statements and, supported by findings from a literature search. Finally, an in-person consensus conference using nominal group technique was held to further modify and consent the statements.

Results: Up to 50% of patients diagnosed with SJIA in Germany do not fulfill the International League of Associations for Rheumatology (ILAR) classification criteria, mostly due to the absence of chronic arthritis. Our findings suggest that chronic arthritis is not obligatory for the diagnosis and treatment of SJIA, allowing a diagnosis of probable SJIA. Malignant, infectious and hereditary autoinflammatory diseases should be considered before rendering a diagnosis of probable SJIA. There is substantial variability in the initial treatment of SJIA. Based on registry data, most patients initially receive systemic glucocorticoids, however, increasingly substituted or accompanied by biological agents, i.e. interleukin (IL)-1 and IL-6 blockade (up to 27.2% of patients). We identified preferred initial therapies for probable and definitive SJIA, including step-up patterns and treatment targets for the short-term (resolution of fever, decrease in C-reactive protein by 50% within 7 days), the mid-term (improvement in physician global and active joint count by at least 50% or a JADAS-10 score of maximally 5.4 within 4 weeks) and the long-term (glucocorticoid-free clinically inactive disease within 6 to 12 months), and an explicit treat-to-target strategy.

Conclusions: We developed consensus-based strategies regarding the diagnosis and treatment of probable or definitive SJIA in Germany.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12969-018-0224-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778670PMC
January 2018

Rational Diagnostics and Therapies in Child Refugees.

Pediatr Infect Dis J 2018 03;37(3):272-274

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000001823DOI Listing
March 2018

Diffuse Unilateral Subacute Neuroretinitis Caused by Ancylostoma Hookworm.

Emerg Infect Dis 2017 02;23(2):343-344

Diffuse unilateral subacute neuroretinitis is an ocular infectious disease caused by several distinct nematodes. Definite identification of the involved nematodes is rarely achieved. We report on the molecular-based genetic identification of an Ancylostoma ceylanicum hookworm implicated in a case of diffuse unilateral subacute neuroretinitis in a child.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2302.142064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324813PMC
February 2017

Outcome and Trends in Treatment of Systemic Juvenile Idiopathic Arthritis in the German National Pediatric Rheumatologic Database, 2000-2013.

Arthritis Rheumatol 2016 12;68(12):3023-3034

German Rheumatism Research Centre Berlin and Charité University Hospital Berlin, Berlin, Germany.

Objective: To investigate the clinical presentation and medical treatment of patients with systemic juvenile idiopathic arthritis (JIA) during the first year of illness. Our study focused on 3-year outcomes in a subsample of patients who were followed up longitudinally.

Methods: From 2000 to 2013, 597 patients with systemic JIA and a disease duration of ≤12 months were recorded in the National Pediatric Rheumatologic Database. Among those patients, 3-year outcome data were available for 133. These data included the clinical Juvenile Arthritis Disease Activity Score in 10 joints (JADAS-10) and the physician's global assessment score (on a numerical rating scale), as well as assessment of joint involvement, growth retardation, and patient-reported outcomes.

Results: The median clinical JADAS-10 declined significantly, from 7 in 2000 to 2 in 2013, while the proportion of patients with inactive disease increased from 19% in 2000 to 41% in 2013. The rate of treatment with systemic glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) remained stable from 2000 to 2013. By 2013, the proportion of patients with systemic JIA who were treated with biologic DMARDs had increased to 20%. At 3-year follow-up, 72% of patients with systemic JIA had inactive disease, and 77% had no functional limitations. Growth retardation was associated with persistently high disease activity and continuing treatment with systemic glucocorticoids. At the 3-year follow-up, one-third of patients were still being treated with systemic glucocorticoids.

Conclusion: The proportion of patients with inactive disease has increased over the past decade. Possible explanations may include improved access to specialized care, additional treatment options, and earlier or faster step-up treatment. However, challenges in the management of systemic JIA remain, as ∼30% of patients continue to present with ongoing active disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.39796DOI Listing
December 2016

Importance of Local Epidemiology in Prevalence and Resistance of Cystic Fibrosis-related Pathogens.

Pediatr Infect Dis J 2016 Feb;35(2):229

Center for Pediatrics and Adolescent Medicine University Medical Center Freiburg Freiburg im Breisgau, Germany Division of Infectious Diseases and Hospital Epidemiology University Hospital Basel Basel, Switzerland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000000982DOI Listing
February 2016

Kawasaki Disease in Germany: A Prospective, Population-based Study Adjusted for Underreporting.

Pediatr Infect Dis J 2016 Feb;35(2):129-34

From the *Department of Congenital Heart Defects, Heart Center University of Freiburg, Freiburg, Germany; †Novartis Pharma BV, Amsterdam, The Netherlands; ‡Clinic and Polyclinic for Pediatrics and Adolescent Medicine, University Children's Hospital, Technische Universität Dresden, Dresden, Germany; §Department of Pediatric Cardiology, University Hospital Heidelberg, Heidelberg, Germany; ¶Division of Epidemiology, Institute of Social Pediatrics and Adolescent Medicine, Ludwig-Maximilian's University Munich, München, Germany; and ‖Section of Pediatric Infectious Diseases and Rheumatology, Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany.

Background: National estimates of Kawasaki disease (KD) incidence often do not include incomplete cases (diagnosed based on only laboratory or echocardiographic criteria), and/or they rely on retrospective case reports and data registries where underreporting is known to be a problem.

Methods: We conducted a prospective nationwide KD surveillance study in children younger than 5 years through the hospital-based German Pediatric Surveillance Unit (ESPED). We accounted for underreporting through applying capture-recapture methodology in 2 federal states using hospital discharge records with KD International Statistical Classification of Diseases and Related Health Problems 10th revision code (ie, M30.3). KD diagnosis (complete and incomplete) was established according to the American Heart Association criteria, 2004.

Results: Incidence of KD, corrected for underreporting, was 7.2 of 100,000 in children younger than 5 years in Germany. Underreporting to ESPED was estimated at 37%-44%. Overall, 315 validated KD cases were reported. Of the 64 (20%) incomplete cases, 58% (37/64) were detected through echocardiographic findings and 42% (27/64) through laboratory criteria alone. Incomplete cases were younger than complete cases (1.2 vs. 2.0 years, P = 0.0001) and had more coronary aneurysms (43% vs. 11%, P = 0.0001).

Conclusions: A substantial number of incomplete KD cases were diagnosed based on the laboratory and echocardiographic criteria only. This was particularly the case in relation to infants younger than 1 year-an age group known to have an increased risk of developing coronary aneurysms. In addition, we found a high rate of underreporting to national Pediatric Surveillance Units. We suggest that improved surveillance and development of better diagnostic tests remain a high priority.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000000953DOI Listing
February 2016

Chikungunya in Children.

Pediatr Infect Dis J 2015 Jul;34(7):789-91

From the *Pediatric Infectious Diseases Unit, University Children's Hospital Basel, The University of Basel, Switzerland; †Department of Pediatrics, The Royal Children's Hospital Melbourne, The University of Melbourne, Parkville, Australia; ‡Section of Pediatric Infectious Diseases and Rheumatology, Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Germany; §Neonatal Intensive Care Unit/Pediatric Intensive Care Unit, CHU Réunion, Groupe Hospitalier Sud Réunion, Saint Pierre cedex, La Réunion, France; and ¶UMR PIMIT 'Processus Infectieux en Milieu Insulaire Tropical '(Université de La Réunion, Inserm U 1187, CNRS 9192, IRD 249), CYROI, Sainte Clotilde, La Réunion, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000000716DOI Listing
July 2015

Comparison of pre- and intrapartum screening of group B streptococci and adherence to screening guidelines: a cohort study.

Eur J Pediatr 2015 Jun 30;174(6):827-35. Epub 2015 Apr 30.

Department of Gynecology and Obstetrics, University Medical Center Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany,

Unlabelled: Implementation of guidelines for group B streptococcal (GBS) prepartum screening (PS) rarely has been prospectively evaluated. To assess PS at 35-37 weeks of gestation and compare its predictive value to that of an intrapartum screening (IS) within 7 days of delivery, a surveillance cohort study was conducted at a tertiary care center in Freiburg, Germany, during 2011-2012. Study participants included 937 pregnant women who had intrapartum cultures taken for vaginal and rectal GBS colonization. Colonization status was compared to PS, and intrapartum antibiotic prophylaxis (IAP) rates calculated. The neonates were tested for GBS transmission via cultures from their throats and external ear canals. While 67.5% (633/937) of study participants had a PS, only 22.7% (144/633) underwent a fully guideline-compatible PS. However, maternal GBS colonization rates were similar when comparing PS (18.5% [117/633]) versus IS (17.0% [133/784]). The positive predictive value of a positive PS result for GBS positivity at delivery was 77.2 %. Women with a positive PS received IAP in 89.3% of cases (75/84). The capsular serotype distribution pattern of colonizing GBS strains has not changed in comparison to our 2003-2004 study--one with a similar study design.

Conclusions: Improved strategies for adoption of prepartum GBS screening are needed.

What Is Known: • The prediction of prepartum GBS screening for intrapartum colonization status has not been well studied. • Longitudinal studies of GBS screening are needed for screening program evaluations and vaccine development. What is New: • The rate of GBS screening has improved over 10 years, and intrapartum GBS colonization prediction was accurate. • Serotype distribution was stable and suggests the potential long-term efficacy of GBS vaccines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-015-2548-yDOI Listing
June 2015

A young girl with familial Mediterranean fever and abdominal pain.

Clin Pediatr (Phila) 2014 Oct 7;53(11):1106-8. Epub 2014 May 7.

Albert-Ludwigs-University Freiburg, Freiburg, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0009922814533593DOI Listing
October 2014

Synchronous recurrence of group B streptococcal late-onset sepsis in twins.

Pediatrics 2014 May 7;133(5):e1388-91. Epub 2014 Apr 7.

Centers for Pediatrics and Adolescent Medicine and Chronic Immunodeficiency, University Medical Center, Freiburg, Freiburg, Germany;

Group B Streptococcus (GBS) remains the leading cause of neonatal sepsis and meningitis in industrialized countries. Whereas the use of intrapartum antibiotic prophylaxis has led to a significant decline in early-onset sepsis, the incidence of late-onset sepsis has remained unchanged. Whether late-onset sepsis usually originates from established mucocutaneous GBS colonization of the infant or whether it results from an acute exogenous GBS infection remains controversial. Here we report on twins who both twice developed GBS sepsis in a strikingly parallel fashion, with both instances originating from a single hypervirulent GBS clone. Factored together, the presentation as cervical soft tissue infection in both cases, the synchronicity of the episodes, and the detection of GBS DNA in breast milk all strongly suggest an enteral mode of transmission with a short incubation period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2013-0426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006428PMC
May 2014

Dengue fever in children: where are we now?

Pediatr Infect Dis J 2013 Sep;32(9):1020-2

From the *Center of Pediatrics and Adolescent Medicine; †Centre of Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany; and ‡Swiss Tropical and Public Health Institute, Basel, Switzerland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0b013e31829fd0e9DOI Listing
September 2013

Lemierre syndrome associated with 12th cranial nerve palsy--a case report and review.

Int J Pediatr Otorhinolaryngol 2013 Sep 8;77(9):1585-8. Epub 2013 Jul 8.

Centre for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Germany.

Since the widespread availability and use of antibiotics the prevalence of Lemierre syndrome (L.S.) has decreased. It is a well-described entity, consisting of postanginal septicaemia with thrombophlebitis of the internal jugular vein with metastatic infection, most commonly in the lungs. The most common causative agent is a gram-negative, non-spore-forming obligate anaerobic bacterium, Fusobacterium necrophorum (F.n.). We describe the unusual clinical features of a 12-year-old boy with Lemierre syndrome with isolated hypoglossal nerve palsy - the latter symptom is an extremely rare manifestation of this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijporl.2013.05.030DOI Listing
September 2013