Epidemiological trends and susceptibility patterns of bloodstream infections caused by Enterococcus spp. in six German university hospitals: a prospectively evaluated multicentre cohort study from 2016 to 2020 of the R-Net study group.

PURPOSE: To analyse recent epidemiological trends of bloodstream infections (BSI) caused by Enterococcus spp. In adult patients admitted to tertiary care centres in Germany. METHODS: Epidemiological data from the multicentre R-NET study was analysed. Patients presenting with E. faecium or E. faecalis in blood cultures in six German tertiary care university hospitals between October 2016 and June 2020 were prospectively evaluated. In vancomycin-resistant enterococci (VRE), the presence of vanA/vanB was confirmed via molecular methods. RESULTS: In the 4-year study period, 3001 patients with BSI due to Enterococcus spp. were identified. E. faecium was detected in 1830 patients (61%) and E. faecalis in 1229 patients (41%). Most BSI occurred in (sub-) specialties of internal medicine. The pooled incidence density of enterococcal BSI increased significantly (4.0-4.5 cases per 10,000 patient days), which was primarily driven by VRE BSI (0.5 to 1.0 cases per 10,000 patient days). In 2020, the proportion of VRE BSI was > 12% in all study sites (range, 12.8-32.2%). Molecular detection of resistance in 363 VRE isolates showed a predominance of the vanB gene (77.1%). CONCLUSION: This large multicentre study highlights an increase of BSI due to E. faecium, which was primarily driven by VRE. The high rates of hospital- and ICU-acquired VRE BSI point towards an important role of prior antibiotic exposure and invasive procedures as risk factors. Due to limited treatment options and high mortality rates of VRE BSI, the increasing incidence of VRE BSI is of major concern.

Role and benefits of infectious diseases specialists in the COVID-19 pandemic: Multilevel analysis of care provision in German hospitals using data from the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) cohort.

PURPOSE: This study investigates the care provision and the role of infectious disease (ID) specialists during the coronavirus disease-2019 (COVID-19) pandemic. METHODS: 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. RESULTS: Of the 40 participating hospitals in the study, 35% (14/40) were identified as ID centers. Among those, clinical ID care structures were more commonly established, and ID specialists were always involved in pandemic management and the care of COVID-19 patients. Overall, 68% (27/40) of the hospitals involved ID specialists in the crisis management team, 78% (31/40) in normal inpatient care, and 80% (28/35) in intensive care. Multivariable analysis revealed that COVID-19 patients in ID centers had a lower mortality risk compared to those in non-ID centers (odds ratio: 0.61 (95% CI 0.40-0.93), p = 0.021). CONCLUSION: ID specialists played a crucial role in pandemic management and inpatient care.

Antimicrobial resistance is not increasing in subsequent cases of ischaemic foot infections, a single-centre cohort from 2012 to 2021.

Patients with chronic limb-threatening ischaemia (CLTI) are at risk of foot infections, which is associated with an increase in amputation rates. The use of antibiotics may lead to a higher incidence of antimicrobial resistance (AMR) in subsequent episodes of ischaemic foot infections (IFI). This retrospective single-centre cohort study included 130 patients with IFI undergoing endovascular revascularisation. Staphylococcus aureus and Pseudomonas aeruginosa were the two most common pathogens, accounting for 20.5% and 10.8% of cases, respectively. The prevalence of antimicrobial resistance (AMR) and multi-drug resistance did not significantly increase between episodes (10.2% vs. 13.4%, p = 0.42). In 59% of subsequent episodes, the identified pathogens were unrelated to the previous episode. However, the partial concordance of identified pathogens significantly increased to 66.7% when S. aureus was identified (p = 0.027). Subsequent episodes of IFI in the same patient are likely to differ in causative pathogens. However, in the case of S. aureus, the risk of reinfection, particularly with S. aureus, is increased. Multi-drug resistance does not appear to change between IFI episodes. Therefore, recommendations for empirical antimicrobial therapy should be based on local pathogen and resistance statistics without the need to broaden the spectrum of antibiotics in subsequent episodes.

Health care utilisation of asylum seekers and refugees in the South-West of Germany.

BACKGROUND: Limited evidence on utilisation of health care by recently arrived asylum seekers and refugees in high-income countries is available. This study aims to describe the implementation of an integrated care facility (ICF) in an initial reception centre and measure the utilisation of care and the influence of operational parameters. METHODS: In a retrospective cohort study design, using medical records, we followed inhabitants of a reception centre in Germany between 11.10.2015 and 30.05.2018. We assessed frequency of visits and revisits to a newly established integrated care facility (ICF), and the effects of the ICF on visits to the local emergency department (LED) in the regional tertiary hospital using survival analysis and time series regression. We also explore the influence of operational parameters on the different implementation phases; phase 1: provisional clinic with 1-2 hours of physician presence daily, phase 2: implementation of ICF with 2-4 hours of care by a team of doctors and nurses daily, phase 3: routine running of ICF with daily operational hours of 10am-2pm with care provided by an interdisciplinary team of doctors and nurses. RESULTS: 14,419 total medical visits were recorded from 1,883 persons seeking health care in the ICF. The absolute number of visits per day remained similar over the study period (19·9/day), yet the relative number of visits changed from 2·2 to 15 per 100 inhabitants from phase 2 to 3, respectively. Most visits were due to respiratory infections (612/3080, 20%), and trauma and musculoskeletal conditions (441/3080, 14%). The rate of revisits to ICF was 2·9 per person per month (95%CI 2·9-3), more for those older, female, from North Africa and those with a translator present. The ratio of visits to the LED changed from 0·3/100 inhabitants per day to 0·14/100 inhabitants after implementation of the ICF and back to 0·3/100 inhabitants during the routine running. CONCLUSIONS: Though seasonal variation and referral practices must be considered, a high rate of revisits to the ICF were recorded. While visits to the LED decreased after the implementation of the ICF, visits returned to the pre-ICF levels during the routine running of the ICF. The results show that AS&R require reliable access to health care, yet the needs of specific groups of migrants may be different, especially those with language barriers, minority groups or those from certain regions. As such, care should be migrant sensitive and adapt to the changing needs of the population. Though more research is required to better understand the differing needs of migrants, this study may help to inform guidelines surrounding migrant sensitive standards of care in Germany.

[Infectious Diseases - a new specialty for postgraduate training in Germany]. / Infektiologie ­ eine neue Facharztdisziplin in Deutschland.

Medicine in Germany is currently facing major structural and economic challenges. Infectious Diseases, with the recent introduction of a new specialty in "Internal Medicine and Infectious Diseases" and with the existing additional training for almost all specializations, will make an important contribution to overcoming these challenges. Expertise in infectious diseases has to be very broad and requires high interdisciplinarity, which makes infectious diseases an attractive and demanding specialty. The complex fundamentals of infectious diseases must now be quickly conveyed to as many physicians as possible in a short period of time, as part of their specialization or as additional training. Until this is achieved, transitional solutions will be necessary for some time. The adaptation of the current billing and reimbursement system for infectious diseases services and improved intersectoral cooperation are of the utmost importance for the further development of the specialty.

Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue.

After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition, marked by neurologic symptoms such as cognitive deficits, olfactory dysfunction, and fatigue. Despite this, biomarkers and pathophysiological understandings of this condition remain limited. Employing magnetic resonance imaging, we conduct a comparative analysis of cerebral microstructure among patients with Post-COVID-Condition, healthy controls, and individuals that contracted COVID-19 without long-term symptoms. We reveal widespread alterations in cerebral microstructure, attributed to a shift in volume from neuronal compartments to free fluid, associated with the severity of the initial infection. Correlating these alterations with cognition, olfaction, and fatigue unveils distinct affected networks, which are in close anatomical-functional relationship with the respective symptoms.

Cardioprotective effects of vaccination in hospitalized patients with COVID-19.

COVID-19 vaccination has been shown to prevent and reduce the severity of COVID-19 disease. The aim of this study was to explore the cardioprotective effect of COVID-19 vaccination in hospitalized COVID-19 patients. In this retrospective, single-center cohort study, we included hospitalized COVID-19 patients with confirmed vaccination status from July 2021 to February 2022. We assessed outcomes such as acute cardiac events and cardiac biomarker levels through clinical and laboratory data. Our analysis covered 167 patients (69% male, mean age 58 years, 42% being fully vaccinated). After adjustment for confounders, vaccinated hospitalized COVID-19 patients displayed a reduced relative risk for acute cardiac events (RR: 0.33, 95% CI [0.07; 0.75]) and showed diminished troponin T levels (Cohen's d: - 0.52, 95% CI [- 1.01; - 0.14]), compared to their non-vaccinated peers. Type 2 diabetes (OR: 2.99, 95% CI [1.22; 7.35]) and existing cardiac diseases (OR: 4.31, 95% CI [1.83; 10.74]) were identified as significant risk factors for the emergence of acute cardiac events. Our findings suggest that COVID-19 vaccination may confer both direct and indirect cardioprotective effects in hospitalized COVID-19 patients.

Vaccination protects against acute respiratory distress syndrome (ARDS) in hospitalized patients with COVID-19.

This study aimed to analyze the effect of COVID-19 vaccination on the occurrence of ARDS in hospitalized COVID-19 patients. The study population of this retrospective, single-center cohort study consisted of hospitalized COVID-19 patients with known vaccination status and chest computed tomography imaging between July 2021 and February 2022. The impact of vaccination on ARDS in COVID-19 patients was assessed through logistic regression adjusting for demographic differences and confounding factors with statistical differences determined using confidence intervals and effect sizes. A total of 167 patients (69% male, average age 58 years, 95% CI [55; 60], 42% fully vaccinated) were included in the data analysis. Vaccinated COVID-19 patients had a reduced relative risk (RR) of developing ARDS (RR: 0.40, 95% CI [0.21; 0.62]). Consequently, non-vaccinated hospitalized patients had a 2.5-fold higher probability of developing ARDS. This risk reduction persisted after adjusting for several confounding variables (RR: 0.64, 95% CI [0.29; 0.94]) in multivariate analysis. The protective effect of COVID-19 vaccination increased with ARDS severity (RR: 0.61, 95% CI [0.37; 0.92]). Particularly, patients under 60 years old were at risk for ARDS onset and seemed to benefit from COVID-19 vaccination (RR: 0.51, 95% CI [0.20; 0.90]). COVID-19 vaccination showed to reduce the risk of ARDS occurrence in hospitalized COVID-19 patients, with a particularly strong effect in patients under 60 years old and those with more severe ARDS.

Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial.

BACKGROUND: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection. METHODS: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5-7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013-000577-77). FINDINGS: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI -7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29). INTERPRETATION: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy. FUNDING: Deutsche Forschungsgemeinschaft. TRANSLATIONS: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section.

The protective effect of tumor necrosis factor-alpha inhibitors in COVID-19 in patients with inflammatory rheumatic diseases compared to the general population-A comparison of two German registries.

Objectives: To investigate, whether inflammatory rheumatic diseases (IRD) inpatients are at higher risk to develop a severe course of SARS-CoV-2 infections compared to the general population, data from the German COVID-19 registry for IRD patients and data from the Lean European Survey on SARS-CoV-2 (LEOSS) infected patients covering inpatients from the general population with SARS-CoV-2 infections were compared. Methods: 4310 (LEOSS registry) and 1139 cases (IRD registry) were collected in general. Data were matched for age and gender. From both registries, 732 matched inpatients (LEOSS registry: n = 366 and IRD registry: n = 366) were included for analyses in total. Results: Regarding the COVID-19 associated lethality, no significant difference between both registries was observed. Age > 65°years, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, spondyloarthritis and the use of rituximab were associated with more severe courses of COVID-19. Female gender and the use of tumor necrosis factor-alpha inhibitors (TNF-I) were associated with a better outcome of COVID-19. Conclusion: Inflammatory rheumatic diseases (IRD) patients have the same risk factors for severe COVID-19 regarding comorbidities compared to the general population without any immune-mediated disease or immunomodulation. The use of rituximab was associated with an increased risk for severe COVID-19. On the other hand, the use of TNF-I was associated with less severe COVID-19 compared to the general population, which might indicate a protective effect of TNF-I against severe COVID-19 disease.