Die rationale Antibiotikaverordnung ist angesichts des inadäquaten und übermäßigen Einsatzes von Antibiotika sowie der kritischen Resistenzentwicklung zu einer zentralen Priorität in der Humanmedizin geworden. In Deutschland ist bereits eine Reihe von Maßnahmen zur Optimierung des Antibiotikagebrauchs ergriffen worden. Hierzu zählen curriculare Antibiotic-Stewardship(ABS)-Fortbildungen zur Ausbildung zertifizierter ABS-Experten, die Erstellung einer S3-Leitlinie für ABS-Programme in Kliniken, der Aufbau regionaler ABS-Netzwerke mit Spezialisten aus Praxis, Pharmazie und Labor sowie geförderte Interventionsstudien in der ambulanten Versorgung. Signifikantes Verbesserungspotenzial liegt in der Etablierung und Finanzierung von ABS-Teams, infektiologischen Konsiliardiensten und Infektionsboards im Krankenhausbereich sowie in der Förderung innovativer mikrobiologischer Diagnostik und der Entwicklung nachhaltiger Konzepte für die ambulante Versorgung. Die systematische Integration mikrobiologischer und pharmazeutischer Expertise sowie die fortlaufende Implementierung und Weiterentwicklung moderner elektronischer Verordnungssysteme sind wichtige Bausteine. Sie können die Verordnungsqualität verbessern und unterstützen Schlüsselstrategien zur zielgerichteten Therapie und zur Verkürzung der Therapiedauer. Zur dauerhaften Etablierung dieser neuen Strukturen und ihrer Weiterentwicklung an intersektoralen Schnittstellen sind politische Unterstützung und umfassende Investitionen erforderlich.

Given the inadequate and excessive use of antibiotics and the critical development of resistance, the rational prescription of antibiotics has become a key priority in human medicine. A broad range of initiatives to optimize antibiotic use has already been implemented in Germany. These include comprehensive antibiotic stewardship (ABS) training leading to the certification of ABS specialists; the development of a guideline for ABS programs in hospitals; the establishment of regional ABS networks integrating expertise from clinical practice, pharmacy, and microbiology; and the execution of funded interventional studies within the outpatient sector. There is significant potential for improvement in the establishment and financing of ABS teams, infectious disease consultation services, and infection boards in hospitals as well as in the promotion of innovative microbiological diagnostics and the development of sustainable concepts for outpatient care. The systematic integration of microbiological and pharmaceutical expertise into ABS programs is essential, as is the ongoing implementation and further development of modern electronic prescription systems. All these measures substantially improve prescription quality and support key strategies for targeted therapy and shorter treatment durations. To ensure the long-term establishment of these new structures and their further development at intersectoral interfaces, political support and substantial investment are indispensable.

BACKGROUND To enhance antibiotic stewardship and effectively address antimicrobial resistance (AMR), better understanding of subnational antibiotic consumption patterns is essential. AIM We aimed to assess antibiotic consumption in Germany using data from 2022 and integrated from two surveillance systems, focusing on regional differences by examining non-university acute care hospitals. METHODS We used pharmacy dispensing data from 525 regional or local hospitals and 35 university hospitals, covering 46.5 million patient days (PD), nearly half of all occupied bed days nationwide, to calculate antibiotic use densities (AUD) for systemic antibiotics, expressed as World Health Organization (WHO) ATC/DDD (Anatomical Therapeutic Chemical/Defined Daily Dose) per 100 patient days (DDD/100 PD). The analysis primarily focused on consumption patterns in non-university hospitals, assessing key antibiotic groups through mixed-effects regression. For sensitivity analyses, we employed hospital-adapted daily dose definitions. RESULTS Pooled AUD for participating non-university hospitals was 51.8 DDD/100 PD, with aminopenicillins/beta-lactamase inhibitors being the most prescribed group. Regression analyses, adjusted for hospital size and ward type/admitting specialty, indicated notable regional variation. We identified statistically significant differences in antibiotic consumption, particularly for beta-lactam antibiotics, fluoroquinolones and tetracyclines. For example, several regions exhibited up to 1.4-fold higher use of first- and second-generation cephalosporins compared with the western reference region. CONCLUSION This study highlights substantial regional variation in antibiotic use in German acute care hospitals, underlining the importance of further investigation into influencing factors such as regional guidelines and resistance rates. The methodological approach applied here may serve as a model for other countries interested in analysing regional differences in antibiotic consumption.

Persistent symptoms following SARS-CoV-2 infection, known as post-COVID syndrome (PCS), severely affect patients’ quality of life. Despite its prevalence, the underlying mechanisms and reliable biomarkers remain elusive. We investigated the antibody response and epitope recognition patterns in PCS to uncover potential biomarkers and pathophysiological links to immune dysregulation. Humoral immune responses were analyzed in PCS patients (n = 64) and convalescent controls (n = 64), matched for sex, age, and time since acute infection, further corroborated in three independent PCS validation cohorts (n = 420). PCS was associated with significantly elevated levels of neutralizing IgG, IgA and IgM antibodies targeting the SARS-CoV-2 receptor-binding domain and spike subdomains, but not against nucleocapsid or seasonal coronaviruses. Next, we identified three discriminatory PCS-specific spike epitopes, primarily located in the membrane-proximal region, as demonstrated by customized peptide microarray, ELISA and luminex methods. Binary logistic regression analysis revealed 82.8% specificity and 60.0% sensitivity for PCS diagnosis in seropositive patients. PCS-specific antibody levels correlated directly (D-Dimers) or inversely (6 min-walk distance, diffusion capacity) with clinical markers. These findings highlight enhanced spike-specific humoral responses in PCS and propose novel epitope-based biomarkers for PCS diagnosis and mechanistic insights. This project was supported by the German Ministry of Education and Research (BMBF; grant no. 01EP2105A). Viral Immunology (VIR)

OBJECTIVES:This study aimed to identify and develop a standard set of competencies needed for members of an antimicrobial stewardship (AMS) team. METHODS:A panel of experts in AMS utilized a survey based on a modified Delphi technique to establish consensus on AMS competencies. RESULTS:The authors identified 88 competencies covering 15 domains with strong agreement by 58 international experts. The identified domains were: the objectives of AMS; management of infection; microbiology diagnostics; pharmacology of antimicrobial agents; general principles of antibiotic use; the structure and the position of AMS; antimicrobial stewardship interventions; AMS in special settings; surveillance and monitoring; behaviour change and communication; infection prevention and control; quality management and patient safety; information technology (IT) support; communication with patients and general public and governance/policy framework. The consensus-based list of competencies was ratified by the European Study Group for Antimicrobial Stewardship Executive Committee. CONCLUSIONS:The identified competencies can be used as a tool in planning of AMS training and to develop and optimize AMS programmes worldwide.

For almost a century, antibiotics have played an important role in the treatment of infectious diseases. However, the efficacy of these very drugs is now threatened by the development of resistances, which pose major challenges to medical professionals and decision-makers. Thereby, the consumption of antibiotics in hospitals is an important driver that can be targeted directly. To illuminate the relation between consumption and resistance depicts a very important step in this procedure. With the help of comprehensive ecological and clinical data, we applied a variety of different computational approaches ranging from classical linear regression to artificial neural networks to analyze antibiotic resistance in Germany. These mathematical and statistical models demonstrate that the amount and particularly the structure of currently available data sets lead to contradictory results and do, therefore, not allow for profound conclusions. More effort and attention on both data collection and distribution is necessary to overcome this problem. In particular, our results suggest that at least monthly or quarterly antibiotic use and resistance data at the department and ward level for each hospital (including application route and type of specimen) are needed to reliably determine the extent to which antibiotic consumption influences resistance development.

Die Antibiotikaverordnung bei stationären Patienten unterscheidet sich je nach Fachrichtung sowohl hinsichtlich der Intensität als auch bezüglich des Wirkstoffspektrums. Es wird eine Analyse und Bewertung der aktuellen Daten zur Antibiotikaverbrauchsdichte (AD) in deutschen urologischen Fachabteilungen durchgeführt. Die Antibiotikaverordnungsdaten von 107 urologischen Fachabteilungen wurden für den Zeitraum 2022/23 ausgewertet. Die Berechnung der AD erfolgte als Tagesdosen (festgelegt nach Empfehlungen für erwachsene stationäre Patienten, sog. „recommended daily doses“, RDD) pro 100 Pflegetage (RDD/100). Die AD betrug im Median 71 RDD/100 mit einer großen Spannweite von minimal 15,9 bis maximal 138,7 RDD/100. Es gab keine signifikanten Unterschiede nach Krankenhausgröße. Fluorchinolone waren mit einer medianen AD von 6,0 RDD/100 nach Cephalosporinen der dritten bzw. vierten Generation (Median 16,2 RDD/100), Aminopenicillin/Betalaktamaseinhibitor-Kombinationen (Median 10,8 RDD/100) und Piperacillin-Tazobactam bzw. Piperacillin (Median 8,9 RDD/100) die viertstärkste Substanzgruppe. Das Verhältnis Penicilline zu Cephalosporinen schwankte zwischen 6:94 und 98:2 (insgesamt 52:48). Aminoglykoside (< 1

Background: The patterns and intensity of inpatient antibiotic prescribing vary according to medical specialty. Objectives: Analysis of recent data on antibiotic use density in hospital departments of urology in Germany. Methods: Annual surveillance data of 107 departments for the period 2022/2023 were evaluated. We used a daily dose definition adapted for adult hospitalized patients (recommended daily doses, RDD), and 100 patient days as the denominator (RDD/100). Results: The overall median antibiotic use density was 71 RDD/100 with a wide range between 15.9 and 138.7 RDD/100 but no significant differences according to hospital size. Fluoroquinolones (median 6.0 RDD/100) were prescribed as the fourth most frequent antibiotic class after broad-spectrum cephalosporins (median 16.2 RDD/100), aminopenicillin/beta-lactamase inhibitor combinations (median 10.8 RDD/100), and broad-spectrum penicillins (piperacillin-tazobactam and piperacillin) (median 8.9 RDD/100). The ratio between penicillin and cephalosporin RDD per hospital ranged from 6:94 to 98:2 (overall 52:48). The proportion of aminoglycosides (< 1%) and parenteral fosfomycin (< 0.1%) was very small. Cotrimoxazole (median 4.0 RDD/100) was less frequently prescribed than fluoroquinolones. The proportion of oral agents was 44.7% overall, with only small differences according to hospital size. Oral fosfomycin, pivmecillinam, nitrofurantoin, and nitroxoline were much less frequently prescribed than oral beta-lactams, fluoroquinolones, and cotrimoxazole. Conclusion: The overall antibiotic use density in urological hospital departments varied substantially in 2022/2023. Beta-lactam antibiotics were the most frequently used antibiotics, while fluoroquinolones (often as oral agents) continued to be prescribed with a large range similar to overall antibiotic use and independent of hospital size. Inpatient prescribing of the agents recommended and typically used for uncomplicated cystitis was rare. Penicillins and cotrimoxazole should more often be considered as the treatment option. Aminoglycosides and parenteral fosfomycin should be discussed in cases of otherwise drug-resistant pathogens.

ZusammenfassungEine wichtige Voraussetzung für die Sicherung einer rationalen Antibiotika-Verordnung ist die Verfügbarkeit und Prüfung von Verbrauchsdaten. Wir haben erstmals vor 10 Jahren solche Daten für Akutkrankenhäuser in Deutschland vorgestellt und möchten die Entwicklungen seither beschreiben.Die jährlichen Antibiotika-Verordnungsmengen aus Akutkrankenhäusern wurden für den Zeitraum 2012/13 bis 2021/22 analysiert, dargestellt als Tagesdosen pro 100 Pflegetage, wobei die Tagesdosis-Definition speziell für den Krankenhausbereich adaptiert wurde („recommended daily dose“, RDD). Zusätzlich wurde eine Hochrechnung auf die Gesamtbevölkerung unter Verwendung der seitens der WHO definierten Tagesdosen („defined daily doses“, DDD) vorgenommen.Die Antibiotika-Verbrauchsdichte in deutschen Akutkrankenhäusern ist im betrachteten 10-Jahres-Zeitraum nicht angestiegen. Sie betrug im Median im Jahre 2012/13 insgesamt 41,9 RDD/100 Pflegetage (n=169, Interquartilbereich 35–48 RDD/100) im Vergleich zu 42,1 RDD/100 im Jahre 2021/22 (n=329, Interquartilbereich 35–48 RDD/100). Auf die Bevölkerung bezogen lag der Verbrauch 2021/22 bei 1,85 DDD pro 1000 Bewohner und Tag. Die Verbrauchsdichte war in Universitätskliniken (54,0 RDD/100) signifikant höher als in den nicht universitären Krankenhäusern unterschiedlicher Größe, deren Verbrauchswerte sich nur wenig unterschieden (Mediane 39,8–44,0 RDD/100). Penicilline wurden zunehmend häufiger (Anstieg des Anteils an allen Wirkstoffen +63%), Fluorchinolone (– 54%) und Cephalosporine der ersten und zweiten Generation (– 41%) seltener eingesetzt. Auf Intensivstationen war die Verordnungsdichte rund doppelt so hoch wie auf den Normalstationen. Hohe Verordnungsdichten wurden auch in universitären hämatologisch-onkologischen Abteilungen (Median 96,8 RDD/100) und in Fachabteilungen für Urologie (Mediane 65,1–70,5 RDD/100) und HNO-Heilkunde (Mediane 49,1–60,9 RDD/100) beobachtet.Bei gleichbleibender Antibiotika-Verordnungsdichte im Krankenhaus insgesamt gab es Verschiebungen im Spektrum der Wirkstoffgruppen, mit einer zunehmenden Bevorzugung von Penicillin-Derivaten. Auf die Bevölkerung hochgerechnet lag der Verbrauch leicht oberhalb des europäischen Durchschnitts.

Background: Previous studies found that the coronavirus disease 2019 (COVID-19) pandemic had a variable impact on the consumption of antimicrobial drugs in human medicine, with trends in several European countries differing between community and inpatient prescribing. Aim: This study analysed changes in the volumes and use density of antibacterial and antifungal drugs dispensed in acute care hospitals in Germany between 2019 and 2022. Methods: Surveillance data for the four years available from 279 hospitals were expressed as the total volumes of daily doses or as use density (daily doses per 100 patient/occupied bed days) per year and analysed descriptively, using recommended hospital-adapted daily dose definitions (RDDs) and (as sensitivity analysis) WHO/ATC-defined daily dose definitions (DDD). Hospitals were stratified according to size (number of beds), university affiliation, and location (East, West, South). Results: There were significant decreases in both the total number of patient days and antibacterial drug volumes in 2020 through 2022 compared with 2019. The relative changes between 2019 and 2020, 2021, and 2022 were −12.8%, −13.5%, and −13.3% for patient days, and −9.7%, −11.0%, and −10.1% for antibacterial RDDs, respectively. Broad-spectrum betalactams, notably piperacillin–tazobactam and carbapenems, increased in volume, unlike most other drug classes. The resulting antibacterial drug use density was slightly but significantly increased, with pooled means (and medians) of 43.3 (40.0) RDD/100 in 2019 compared to 44.8 (41.7), 44.5 (40.80), and 44.9 (41.7) RDD/100 in the years 2020 through 2022, respectively. Antifungal drug volumes and use density increased after 2019 and peaked in 2021 (the difference between 2019 and 2021 for total volumes was +6.4%, and that for pooled mean use density values was +22.9%, respectively). These trends were similar in the different hospital strata and comparable when DDDs instead of RDDs were used. Conclusions: Similar to what has been observed in a majority of European countries, the total volume of antibacterial drug use in German acute care hospitals decreased with the pandemic, without a rebound phenomenon in 2022. In association with restricted hospital capacities and presumably more immunocompromised general medicine patients, however, inpatient prescribing of (primarily broad-spectrum) antibacterials and of antifungal drugs increased.

An important prerequisite for ascertaining rational antibiotic prescribing is the availability and evaluation of antibiotic use data. In this study we report evolving trends of antibiotic use in German hospitals during the last decade.Using drug dispensing data from acute care hospital pharmacies, we calculated yearly antibiotic use density values for the period from 2012/13 through to 2021/22. Use density was expressed as daily doses per 100 patient days, using both hospital adapted doses of antibiotics ("recommended daily dose", RDD) as well as WHO-"defined daily doses" (DDD). The 2021/22 data were extrapolated to estimate the hospital consumption in DDD per 1000 population and day.The overall antibiotic use density remained stable during the observation period. It was 41.9 RDD/100 patient days (median, n=169 hospitals, interquartile range 35-48 RDD/100) in the year 2012/13 and 42.1 RDD/100 (median, n=329, interquartile range 35-48 RDD/100) in the year 2021/22, respectively. The estimated national use per population in 2021/22 was 1.85 DDD per 1000 inhabitants and day. The antibiotic use levels in university hospitals (54.0 RDD/100) were higher than in non-university hospitals that showed a similar use density across different hospital size categories (medians between 39.8 and 44.0 RDD/100). Overall, penicillin use increased over time (change in proportion +63%), while fluoroquinolones (- 54%) and first and second generation cephalosporins (- 41%) were prescribed less frequently. Antibiotic use density in intensive care units was approximately twice as high as in normal wards. High levels of antibiotic use were also observed in haematology-oncology divisions at teaching hospitals (median 96.8 RDD/100), in urology (medians between 65.1 and 70.5 RDD/100) and oto-rhino-laryngology (medians between 49.1 and 60.9 RDD/100) and urology divisions.During the last decade, there was no increasing use of antibiotics in German acute care hospitals. We observed shifts in selected drug classes, in particular an increasing use of penicillins. The estimated hospital antibiotic consumption per population was slightly above the European average.

This study investigates the care provision and the role of infectious disease (ID) specialists during the coronavirus disease-2019 (COVID-19) pandemic. A survey was conducted at German study sites participating in the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS). Hospitals certified by the German Society of Infectious diseases (DGI) were identified as ID centers. We compared care provision and the involvement of ID specialists between ID and non-ID hospitals. Then we applied a multivariable regression model to analyse how clinical ID care influenced the mortality of COVID-19 patients in the LEOSS cohort. Of the 40 participating hospitals in the study, 35

Genetic defects in the interferon (IFN) system or neutralizing autoantibodies against type I IFNs contribute to severe COVID-19. Such autoantibodies were proposed to affect post-COVID-19 syndrome (PCS), possibly causing persistent fatigue for >12 weeks after confirmed SARS-CoV-2 infection. In the current study, we investigated 128 patients with PCS, 21 survivors of severe COVID-19, and 38 individuals who were asymptomatic. We checked for autoantibodies against IFN-alpha, IFN-beta, and IFN-omega. Few patients with PCS had autoantibodies against IFNs but with no neutralizing activity, indicating a limited role of type I IFNs in PCS pathogenesis. In a subset consisting of 28 patients with PCS, we evaluated IFN-stimulated gene activity and showed that it did not correlate with fatigue. In conclusion, impairment of the type I IFN system is unlikely responsible for adult PCS.

Antimicrobial stewardship (AMS) programs are effective tools for improving antibiotic prescription quality. Their implementation requires the regular surveillance of antibiotic consumption at the patient and institutional level. Our study captured and analyzed antibiotic consumption density (ACD) for hospitalized pediatric patients. We collected antibacterial drug consumption data for 2020 from hospital pharmacies at 113 pediatric departments of acute care hospitals in Germany. ACD was calculated as defined daily dose (DDD, WHO/ATC Index 2019) per 100 patient days (pd). In addition, we analyzed the trends in antibiotic use during 2013–2020. In 2020, median ACD across all participating hospitals was 26.7 DDD/100 pd, (range: 10.1–79.2 DDD/100 pd). It was higher at university vs. non-university hospitals (38.6 vs. 25.2 DDD/100 pd, p < 0.0001). The highest use densities were seen on oncology wards and intensive care units at university hospitals (67.3 vs. 38.4 DDD/100 pd). During 2013–2020, overall ACD declined (− 10

Recently, unexpectedly high virus-specific IgG4 levels were reported after more than two mRNA vaccinations. Class switch towards IgG4 occurs after long-term antigen exposure, downregulates immune responses and is associated with several autoimmune diseases. Here, we examined differences in antigen-specific IgG subtypes in serum samples from 64 Post-COVID patients and an equally sized cohort of convalescent controls. In both cohorts, the relative amounts of spike protein-specific IgG subtypes were comparable. IgG1 was the most frequent, followed by IgG3, IgG2, and IgG4. A difference between cohorts was observed only for IgG2, which was significantly lower in the Post-COVID cohort. Further analysis of the reactive IgG4 revealed a small but significant difference for the spike protein receptor-binding domain but not for the spike ectodomain. Since the total IgG4 levels are very low, we do not expect a biologically relevant role in Post-COVID syndrome. However, reduced virus-specific IgG2 levels could contribute to the persistence of SARS-CoV-2, causing chronic inflammation in the setting of Post-COVID syndrome.

Introduction: This study describes the development and validation of structure indicators for clinical infectious disease (ID) care in German hospitals, which is important to adequately face the future challenges in ID medicine.Methods: A team of experts developed the structure indicators in a three-stage, multicriteria decision-making process: (1) identification of potential structure indicators based on a literature review, (2) written assessment process, and (3) face-to-face discussion to reach consensus and final selection of appropriate structure indicators. A field study was conducted to assess the developed structure indicators. A score based on the structure indicators was determined for each hospital and validated via receiver operator characteristic (ROC) curves using externally validated ID expertise (German Society of ID (DGI) Centre).Results: Based on a list of 45 potential structure indicators, 18 suitable indicators were developed for clinical ID care structures in German hospitals. Out of these, ten key indicators were defined for the general and coronavirus disease 2019-(COVID-19-) specific clinical ID care structures. In the field survey of clinical ID care provision for COVID-19 patients in 40 German hospitals, the participating facilities achieved 0 to 9 points (median 4) in the determined score. The area under the ROC curve was 0.893 (95% CI: 0.797, 0.988; p < 0.001).Discussion/Conclusion: The structure indicators developed within the framework of a transparent and established development process can be used in the future to both capture the current state and future developments of ID care quality in Germany and enable comparisons.