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

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

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Impact environnemental de la prescription en médecine de famille. Exemple de l’infection urinaire simple

L’industrie pharmaceutique ne cesse de croître, tandis que la présence et l’impact des résidus médicamenteux dans les eaux sont de mieux en mieux documentés. Ces derniers se retrouvent dans les eaux usées après leur consommation par l’homme, puis dans celles de surface en l’absence d’une élimination suffisante dans les stations d’épuration, nuisant aux organismes aquatiques, même en quantités infimes. Les antibiotiques et les AINS sont les plus préoccupants pour l’environnement. Nous proposons ici une stratégie de réduction de leur prescription dans l’infection urinaire, en tenant compte d’une guérison spontanée dans la moitié des cas. Nous indiquons des alternatives plus naturelles avec un niveau de sécurité raisonnable malgré un niveau de preuve faible.As the pharmaceutical industry keeps growing, the presence and impact of drug residues in water is becoming increasingly well documented. These end up in wastewater after human consumption, and then in surface water if they are not sufficiently removed in wastewater treatment plants, harming aquatic organisms even in minute quantities. Antibiotics and NSAIDs are the most worrying for the environment. We would recommend here a reduction in their prescription in urinary tract infections, considering that spontaneous healing occurs in half of the cases. We indicate more natural alternatives, with a reasonable level of safety despite a low level of evidence

Immunohistochemically Characterized Intratumoral Heterogeneity Is a Prognostic Marker in Human Glioblastoma

Tumor heterogeneity is considered to be a hallmark of glioblastoma (GBM). Only more recently, it has become apparent that GBM is not only heterogeneous between patients (intertumoral heterogeneity) but more importantly, also within individual patients (intratumoral heterogeneity). In this study, we focused on assessing intratumoral heterogeneity. For this purpose, the heterogeneity of 38 treatment-na&iuml;ve GBM was characterized by immunohistochemistry. Perceptible areas were rated for ALDH1A3, EGFR, GFAP, Iba1, Olig2, p53, and Mib1. By clustering methods, two distinct groups similar to subtypes described in literature were detected. The classical subtype featured a strong EGFR and Olig2 positivity, whereas the mesenchymal subtype displayed a strong ALDH1A3 expression and a high fraction of Iba1-positive microglia. 18 tumors exhibited both subtypes and were classified as &ldquo;subtype-heterogeneous&rdquo;, whereas the areas of the other tumors were all assigned to the same cluster and named &ldquo;subtype-dominant&rdquo;. Results of epigenomic analyses corroborated these findings. Strikingly, the subtype-heterogeneous tumors showed a clearly shorter overall survival compared to subtype-dominant tumors. Furthermore, 21 corresponding pairs of primary and recurrent GBM were compared, showing a dominance of the mesenchymal subtype in the recurrent tumors. Our study confirms the prognostic impact of intratumoral heterogeneity in GBM, and more importantly, makes this hallmark assessable by routine diagnostics

Impact of Vegetation Fires on the Composition and Circulation of the Atmosphere

Vegetation fires are a significant source for atmospheric trace gases and aerosol particles (APs) on both local and global scale. The biomass burning APs affect cloud formation as well as microphysical and chemical processes in clouds. They influence the radiation budget directly and via altered cloud properties. Finally, this results in changes of the atmospheric energy budgets and circulation. The joint research project EFEU addressed these topics with a combined experimental and numerical approach of eight different research groups. Three series of experiments were carried out at the laboratory oven facility at MPI Mainz. Characteristic vegetation from different burning regions was investigated, e.g., Musasa (Africa), aleppo pine (Mediterranian), spruce (boreal) and peat (Indonesia). Trace gases and a wide range of AP parameters were measured, including size distributions as well as morphological, chemical, hygroscopic and radiative properties. Experimental results indicate that hygroscopic properties and drop nucleating abilities are rather similar for APs from burns of different types of hard wood but different to APs from other burning material such as maize or peat. Generally, the soluble fraction of the APs is quite small and their EC content fairly high. Radiative properties (single scattering albedo) are well correlated with the burn conditions (flaming/smoldering). For the numerical studies of the complex impact of biomass burning emissions on the atmosphere a suite of independent models was employed. Ranging from the microscale to the regional scale they complement each other in terms of spatial and temporal resolution as well as complexity of the processes described. Modelling efforts covered a detailed description of the microphysics including the ice phase, the evolution of individual biomass burning plumes, effects of radiative transport on chemistry and dynamics as well as regional atmospheric budgets of trace constituents, water and energy. Main results are: Precipitation is initiated only via the ice phase in the clouds explored. The dilution of an individual plume was predicted successfully and realistic heating and photolysis rates were simulated. Total particulate matter was correctly calculated for the Indonesian case study using emission factors and sizes of the burning areas