MRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as BNT162b2 (Comirnaty^®), have proven to be highly immunogenic and efficient but also show marked reactogenicity, leading to adverse effects (AEs). Here, we analyzed whether the severity of AEs predicts the antibody response against the SARS-CoV-2 spike protein. Healthcare workers without prior SARS-CoV-2 infection, who received a prime-boost vaccination with BNT162b2, completed a standardized electronic questionnaire on the duration and severity of AEs. Serum specimens were collected two to four weeks after the boost vaccination and tested with the COVID-19 ELISA IgG (Vircell-IgG), the LIAISON^® SARS-CoV-2 S1/S2 IgG CLIA (DiaSorin-IgG) and the iFlash-2019-nCoV NAb surrogate neutralization assay (Yhlo-NAb). A penalized linear regression model fitted by machine learning was used to correlate AEs with antibody levels. Eighty subjects were enrolled in the study. Systemic, but not local, AEs occurred more frequently after the boost vaccination. Elevated SARS-CoV-2 IgG antibody levels were measured in 92.5% of subjects with Vircell-IgG and in all subjects with DiaSorin-IgG and Yhlo-NAb. Gender, age and BMI showed no association with the antibody levels or with the AEs. The linear regression model identified headache, malaise and nausea as AEs with the greatest variable importance for higher antibody levels (Vircell-IgG and DiaSorin-IgG). However, the model performance for predicting antibody levels from AEs was very low for Vircell-IgG (squared correlation coefficient r² = 0.04) and DiaSorin-IgG (r² = 0.06). AEs did not predict the surrogate neutralization (Yhlo-NAb) results. In conclusion, AEs correlate only weakly with the SARS-CoV-2 spike protein antibody levels after COVID-19 vaccination with BNT162b2 mRNA.

Adequate and timely antibiotic therapy is crucial for the treatment of sepsis. Innovative systems, like the Q-linea ASTar, have been developed to perform rapid antimicrobial susceptibility testing (AST) directly from positive blood cultures (BCs). We conducted a prospective study to evaluate ASTar under real-life conditions with a focus on time-to-result and impact on antimicrobial therapy. Over 2 months, all positive BCs that showed Gram-negative rods upon microscopy were tested with the ASTar and our standard procedure (VITEK 2 from short-term culture). Additionally, we included multidrug-resistant Gram-negative bacteria from our archive. Both methods were compared to broth microdilution. In total, 78 bacterial strains (51 prospective and 27 archived) were tested. ASTar covered 94% of the species encountered. The categorical and essential agreement was 95.6% and 90.7%, respectively. ASTar caused 2.4% minor, 2.0% major, and 2.4% very major errors. The categorical agreement was similar to standard procedure. The average time between BC sampling and the availability of the antibiogram for the attending physician was 28 h 49 min for ASTar and 44 h 18 min for standard procedure. ASTar correctly identified all patients who required an escalation of antimicrobial therapy and 75% of those who were eligible for de-escalation. In conclusion, ASTar provided reliable AST results and significantly shortened the time to obtain an antibiogram. However, the percentage of patients that will profit from ASTar in a low-resistance setting is limited, and it is currently unclear if a change of therapy 29 h after BC sampling will have a significant impact on the patient’s prognosis.

The sensitivity of blood cultures (BCs) is limited, especially when antimicrobial therapy already has been administered or when non-culturable pathogens are causing the disease. Metagenomic next-generation sequencing of cell-free DNA from plasma has the potential to compensate for the disadvantages of BC diagnostics. We conducted a retrospective study in patients with suspected infections over a period of 3 months. Cell-free DNA from plasma was analysed by metagenomic next-generation sequencing (Illumina NextSeq, 25 million reads per sample, read length 75 base pairs) and sequences were analysed with DISQVER®, a CE-IVDD-labelled software algorithm and curated database. The data were compared with findings obtained with simultaneously taken BC and other microbiological results (±7 days). DISQVER® analysis was performed on 190 samples from 147 patients (124 adult and 23 paediatric). The median time-to-result including transport was 2 days (interquartile range, 2-3; range, 2-8). DISQVER® detected 158 pathogens (103 bacteria, 49 viruses, 4 fungi, and 1 parasite) in 80 plasma samples (positivity rate 42.1%). The median number of pathogens per positive sample was one (interquartile range, 1-2; range, 1-10). The most common bacteria were Enterobacterales (30.1%; 31/103), anaerobic bacteria (18.4%; 19/103), and Enterococcus spp. (15.5%; 16/103); the most frequent viruses were Epstein-Barr virus (28.6%; 14/49), human herpesvirus 6B (18.4%; 9/49), and human cytomegalovirus (18.4%; 9/49). Mycobacterium avium, Legionella pneumophila, Tropheryma whipplei, Rhizomucor pusillus, and Leishmania infantum were detected in one sample each. Simultaneous BC were positive in only 10.2% (18/176) of the samples, but were mostly (68.2%; 120/176) collected under antibiotic therapy. DISQVER® analysis resulted in 24 treatment changes in 20 patients (13.6%; 20/147; 9 start/escalation, 10 stop/de-escalation, 2 catheter replacements, and 3 other). DISQVER® significantly increased the detection rate of pathogens, led to the diagnosis of serious infections that otherwise would have been missed, and possibly improved the treatment of more than 10% of patients.

At the start of the SARS-CoV-2 pandemic, healthcare workers had an increased risk of acquiring coronavirus disease (COVID)-19. As tertiary care hospitals are critical for the treatment of severely ill patients, the University Hospital Erlangen offered BNT162b2 mRNA vaccination against COVID-19 to all employees when the vaccine became available in Germany. Here, we performed a survey to assess the age- and sex-dependent reactogenicity and safety of BNT162b2 in a real-life setting with a special emphasis on the rate of vaccine-related incapacity to work amongst the employees. All vaccinated employees were invited to participate in the survey and received access to an electronic questionnaire between 31 March and 14 June 2021, which allowed them to report local and systemic adverse effects after the first or second vaccine dose. A total of 2372 employees completed the survey. After both the first and second dose, women had a higher risk than men for vaccine-related systemic side effects (odds ratio (OR) 1.48 (1.24–1.77) and 1.49 (1.23–1.81), respectively) and for inability to work (OR 1.63 (1.14–2.34) and 1.85 (1.52–2.25), respectively). Compared to employees ≥ 56 years of age, younger vaccinated participants had a higher risk of systemic reactions after the first (OR 1.35 (1.07–1.70)) and second vaccination (OR 2.08 (1.64–2.63)) and were more often unable to work after dose 2 (OR 2.20 (1.67–2.88)). We also recorded four anaphylactic reactions and received two reports of severe adverse effects indicative of vaccine complications. After the first and second vaccination, 7.9% and 34.7% of the survey participants, respectively, were temporarily unable to work, which added up to 1700 days of sick leave in this cohort. These real-life data extend previous results on the reactogenicity and safety of BNT162b2. Loss of working time due to vaccine-related adverse effects was substantial, but was outweighed by the potential benefit of prevented cases of COVID-19.

Previously, we demonstrated that the majority of vancomycin-resistant Enterococcus faecium (VREfm) strains from in-patients of the University Hospital Erlangen, Germany, belonged to only three clonal lineages, namely ST117/CT71 vanB and two novel ST1299 vanA lineages classified as CT3109 and CT1903. The goal of the current study was (i) to investigate whether VREfm is also detectable in wastewater of the city of Erlangen, (ii) to identify their molecular features, and (iii) to clarify whether VREfm could arise from the community of the city of Erlangen or can be (directly) connected to nosocomial infections in the hospital setting. From April to May 2023, a total of 244 VREfm strains from raw wastewater of the city of Erlangen were analyzed by core genome multilocus sequence typing (cgMLST). Moreover, 20 of them were further investigated for single nucleotide polymorphisms (SNPs). The molecular characterization of the wastewater VREfm strains revealed a high prevalence (27.9%) of the recently identified clonal lineage ST1299/CT3109 vanA, which is mainly characterized by the presence of the tetracycline-resistance determinant tet(M ) and the virulence genes pilA and prpA . The SNPs analysis revealed the presence of two major clusters, namely cluster I (≤65 SNPs), which included well-known hospital-adapted vanB clonal lineages such as ST117/CT71 and ST80/CT1065 and cluster II (≤70 SNPs), which were mainly characterized by the lineage ST1299/CT3109 vanA . Based on the concomitant resistance to vancomycin and tetracycline, we propose that ST1299/CT3109 vanA primarily originated and spread outside of hospital settings. IMPORTANCE: This study provides a detailed genomic analysis of vancomycin-resistant Enterococcus faecium (VREfm) strains isolated from municipal wastewater with a particular focus on clonal lineages, antimicrobial resistance, and the presence of virulence genes. The high wastewater prevalence of the recently identified clonal lineage ST1299/CT3109 vanA , which has been previously detected in hospitals, suggests an enormous potential for future spread in Germany.

Background: Malaria occurred endemically in Germany until the twentieth century. Climate change and globalization are known to promote the spreading of malaria. Erlangen is a city with just under 120,000 inhabitants located in the Nürnberg metropolitan region, Federal State of Bavaria, Southern Germany. Historical findings, current climate data, microbiological data (local and state level) and vector surveillance data are used to estimate the risk of re-emergence and autochthonous transmission of malaria in the area of Erlangen. Methods: Historical data was obtained by searching literature. Climatic data were retrieved from the German Climate Data Centre. Data on reported (supra-)regional infections were obtained from the Robert-Koch Institute. Cases of malaria diagnosed at the Institute of Clinical Microbiology, Immunology and Hygiene (University Hospital Erlangen) complement this data. The citizen science project “Mückenatlas” (Mosquito Atlas), the German mosquito database (CULBASE) and the company Biogents AG provided mosquito surveillance data. Results: Malaria was highly endemic in Erlangen in the nineteenth century, with 18% of hospitalized patients suffering from this disease in 1860, but disappeared during the first half of the twentieth century. After the end of World War II, autochthonous ‘malaria tertiana’ (tertian malaria) occurred in neighbouring Nürnberg, demonstrating the regional malaria potential. In recent decades, the average monthly temperature increased by 1.6 °C. In Erlangen and the surrounding area, three potential vectors of tertian malaria parasites are prevalent (Anopheles messeae, Anopheles maculipennis sensu stricto, and Anopheles plumbeus). In addition, Anopheles daciae, which has unknown potential of Plasmodium transmission, and Anopheles claviger sensu lato have been detected. In recent years, malaria diagnosed in Erlangen mainly resulted from travelling to Africa. Plasmodium vivax accounted for only a small proportion of these cases (2010–2023: n = 5, 17%). Conclusion: Future autochthonous transmission of malaria parasites in Erlangen is possible, although re-establishment of a natural transmission cycle is currently unlikely. In order to avoid unexpected autochthonous malaria, surveillance and prevention measures should be considered. Patients with fever after visiting endemic areas need to be analysed for Plasmodium infection.