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Additional treatment options for coronavirus disease (COVID-19) are urgently needed, particularly for populations at high risk of severe disease. This cross-sectional, retrospective study characterized the outcomes of 43 patients with nosocomial severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with and without treatment using monoclonal SARS-CoV-2 spike antibodies (bamlanivimab or casirivimab/imdevimab). Our results indicate that treatment with monoclonal antibodies results in a significant decrease in disease progression and mortality when used for asymptomatic patients with early SARS-CoV-2 infection. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-021-01657-y.

Hintergrund: Betalaktamantibiotika (BLA) sind fur viele bakterielle Infektionen die Therapie der Wahl. Vermeintliche BLA-Allergien werden haufig von

Summary Background Beta-lactam antibiotics (BLA) are the treatment of choice for a large number of bacterial infections. Putative BLA allergies are often reported by patients, but rarely confirmed. Many patients do not receive BLA due to suspected allergy. There is no systematic approach to risk stratification in the case of a history of suspected BLA allergy. Methods Using the available stratification programs and taking current guidelines into account, an algorithm for risk stratification, including recommendations on the use of antibiotics in cases of compellingly indicated BLA despite suspected BLA allergy, was formulated by the authors for their maximum care university hospital. Results The hospital is in great need of recommendations on how to deal with BLA allergies. Patient-reported information in the history forms the basis for classifying the reactions into four risk categories: (1) BLA allergy excluded, (2) benign delayed reaction, (3) immediate reaction, and (4) severe cutaneous and extracutaneous drug reaction. Recommendations strictly depend on this classification and range from use of full-dose BLA or use of BLA under certain conditions (e.g., two-stage dose escalation, non-cross-reactive BLA only) to prohibiting all BLA and the use of alternative non-BLA. In case of suspected immediate or delayed allergic reactions, there is an additional recommendation regarding subsequent allergy testing during a symptom-free interval. Conclusion Triage of patients with suspected BLA is urgently required. While allergy testing, including provocation testing, represents the most reliable solution, this is not feasible in all patients due to the high prevalence of BLA allergies. The risk stratification algorithm developed for the authors’ hospital represents a tool suitable to making a contribution to rational antibiotic therapy.

The prevalence of Parkinson’s disease (PD) is rising, rendering it one of the most common neurodegenerative diseases. Treatment and monitoring of patients require regular specialized in- and outpatient care. Patients with PD are more likely to have a complicated disease course if they become infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Regular in-hospital appointments place these patients at risk of exposure to SARS-CoV-2 due to travel and contact with other patients and staff. However, guidelines for the management of outpatients with PD during times of increased risk of infection are currently lacking. These are urgently needed to conduct risk–benefit evaluations to recommend the best medical treatment. This article discusses best practice approaches based on the current literature, as suggested by the multidisciplinary Network of University Medicine (NUM) in Germany. These include measures such as mask-wearing, hand hygiene, social distancing measures, and appropriate testing strategies in outpatient settings, which can minimize the risk of exposure. Furthermore, the urgency of appointments should be considered. Visits of low urgency may be conducted by general practitioners or via telemedicine consultations, whereas in-person presentation is required in case of moderate and high urgency visits. Classification of urgency should be carried out by skilled medical staff, and telemedicine (telephone or video consultations) may be a useful tool in this situation. The currently approved vaccines against SARS-CoV-2 are safe and effective for patients with PD and play a key role in minimizing infection risk for patients with PD.

Background: Institutional programs such as antibiotic stewardship (ABS) programs offer possibilities to monitor and modify antibiotic usage with the aim of reducing antibiotic resistance. In orthop...

Due to the drastically rising coronavirus disease (COVID-19) incidence since March 2020, social life was shut down across the globe, and most opera houses were closed. As a result, there are limited data on SARS-CoV-2 infections among artists. The Bavarian State Opera has been reopened in September 2020. This study aimed to identify the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among employees in the Bavarian State Opera. In addition, the various hygiene strategies for the work groups within the institution are described. During the study period from September 1, 2020 to July 31, 2021, 10,061 nasopharyngeal swabs were obtained from 1,460 artistic staff members in a rolling system. During the entire study period, 61 individuals tested positive for SARS-CoV-2. None of the patients had a severe disease course. Compared to the seven-day-incidence per 100,000 German inhabitants, the estimated corresponding incidence among employees was lower at 37 weeks and higher or equal at 9 weeks. Among the infected individuals, 58.3% were symptomatic, 23.3% were presymptomatic, and 18.3% were asymptomatic. Forty-five percent of employees reported that they had been infected in their private environment, 41.7% suspected that their colleagues were the main contact, and 13.3% were unsure about the origin of their infection. Twenty-four diseased employees were ballet dancers, eight from the orchestra, seven from the administration, seven from the choir singers, six from the costume department, 10 from technical support, and one guest solo singer. In the 2020/2021 theater season, increased SARS-CoV-2 infections and large disease outbreaks were avoided at the Bavarian State Opera. Hygiene strategies, that existed since the beginning, was specifically designed for various work areas in the opera. Regular, mandatory PCR testing and follow-up of positive cases with the issuance of quarantine were performed. Using this disease management approach, artistic work at and reopening of the Bavarian State Opera was feasible with a well-controlled risk.

Durch die weltweit steigenden Zahlen an „coronavirus disease 2019“(COVID-19)-Infektionen besteht fur samtliche Kliniken die Aufgabe, sich der Herausforderung einer Pandemie zu stellen. Es gilt insbesondere auch fur die Notaufnahmen, sich auf vollstandig veranderte Arbeitsablaufe vorzubereiten und sie umzusetzen. Dies betrifft insbesondere den Bereich Patientenscreening und -selektion (Triage). Auch mit anderen Fachbereichen wie der Hygiene, Infektiologie oder Virologie muss Hand in Hand zusammengearbeitet werden, um vor, wahrend und nach Abschluss der Diagnostik entsprechende Behandlungskonzepte zu realisieren. Daruber hinaus sind Kommunikation und Qualitats- und Risikomanagement nebst den klinischen Bereichen von hoher Relevanz. Dieser Artikel beschreibt an einem Beispiel, wie sich Notaufnahmen hier am Beispiel COVID-19 (coronavirus disease 2019) konkret und praxisnah auf eine Pandemie vorbereiten konnen.

Background Hospital staff are at high risk of infection during the coronavirus disease (COVID-19) pandemic. We analysed the exposure characteristics, efficacy of protective measures, and transmission dynamics in this hospital-wide prospective seroprevalence study. Methods and Findings Overall, 4554 individuals were tested for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies using a chemiluminescent immunoassay. Individual risk factors, use of personal protective equipment (PPE), occupational exposure, previous SARS-CoV-2 infection, and symptoms were assessed using a questionnaire and correlated to anti-SARS-CoV-2 IgG antibody titres and PCR testing results. Odds ratios with corresponding exact 95% confidence intervals were used to evaluate associations between individual factors and seropositivity. Spatio-temporal trajectories of SARS-CoV-2-infected patients and staff mobility within the hospital were visualised to identify local hotspots of virus transmission. The overall seroprevalence of anti-SARS-CoV-2-IgG antibody was 2.4% [95% CI 1.9–2.9]. Patient-facing staff, including those working in COVID-19 areas, had a similar probability of being seropositive as non-patient-facing staff. Prior interaction with SARS-CoV-2-infected co-workers or private contacts and unprotected exposure to COVID-19 patients increased the probability of seropositivity. Loss of smell and taste had the highest positive predictive value for seropositivity. The rate of asymptomatic SARS-CoV-2 infections was 25.9%, and higher anti-SARS-CoV-2 IgG antibody titres were observed in symptomatic individuals. Spatio-temporal hotspots of SARS-CoV-2-positive staff and patients only showed partial overlap. Conclusions Patient-facing work in a healthcare facility during the SARS-CoV-2 pandemic may be safe if adequate PPE and hygiene measures are applied. The high numbers of asymptomatic SARS-CoV-2 infections that escaped detection by symptomatic testing underline the value of cross-sectional seroprevalence studies. Unprotected contact is a major risk factor for infection and argues for the rigorous implementation of hygiene measures.

Objectives To assess the admission prevalence of third-generation cephalosporin-resistant Enterobacterales (3GCREB) and to assess whether risk factors vary by β-lactamase genotype. Methods Adult patients were recruited within 72 h of admission to general wards of six university hospitals in 2014 and 2015. Rectal swabs were screened for 3GCREB and isolates were analysed phenotypically and genotypically. Patients were questioned on potential risk factors. Multivariable analyses were performed to identify risk factors for 3GCREB colonization and for specific β-lactamases. Results Of 8753 patients screened, 828 were 3GCREB positive (9.5%). Eight hundred and thirteen isolates were available for genotyping. CTX-M-15 was the most common ESBL (38.0%), followed by CTX-M-1 (22.5%), CTX-M-14 (8.7%), CTX-M-27 (7.5%) and SHV-ESBL (4.4%). AmpC was found in 11.9%. Interestingly, 18 Escherichia coli isolates were AmpC positive, 12 of which (67%) contained AmpC on a gene of plasmid origin [CMY (n = 10), DHA (n = 2)]. Risk factors for 3GCREB colonization varied by genotype. Recent antibiotic exposure and prior colonization by antibiotic-resistant bacteria were risk factors for all β-lactamases except CTX-M-14 and CTX-M-27. Travel outside Europe was a risk factor for CTX-M-15 and CTX-M-27 [adjusted OR (aOR) 3.49, 95% CI 2.88–4.24 and aOR 2.73, 95% CI 1.68–4.43]. A previous stay in a long-term care facility was associated with CTX-M-14 (aOR 3.01, 95% CI 1.98–4.59). A preceding hospital stay in Germany increased the risk of CTX-M-15 (aOR 1.27, 95% CI 1.14–1.41), while a prior hospital stay in other European countries increased the risk of SHV-ESBL colonization (aOR 3.85, 95% CI 1.67–8.92). Conclusions The detection of different ESBL types is associated with specific risk factor sets that might represent distinct sources of colonization and ESBL-specific dissemination routes.

Wound management is one of the major tasks in emergency departments. The surrounding intact skin but not the wound itself should be disinfected before starting definitive wound treatment. Hair should first be removed by clipping to 1-2 mm above the skin with scissors or clippers as shaving the area with a razor damages the hair follicles and increases the risk of wound infections. Administration of local anesthetics should be performed directly through the exposed edges of the wound. After wound examination, irrigation is performed with Ringer's solution, normal saline or distilled water. The next step is debridement of contaminated and devitalized tissue. There are several wound closure techniques available, including adhesive tapes, staples, tissue adhesives and numerous forms of sutures. Management of specific wounds requires particular strategies. A bleeding control problem frequently occurs with scalp lacerations. Superficial scalp lacerations can be closed by alternative wound closure methods, for example by twisting and fixing hair and the use of tissue adhesives, i.e. hair apposition technique (HAT). For strongly bleeding lacerations of the scalp, the epicranial aponeurosis should be incorporated into the hemostasis. Aftercare varies depending on both the characteristics of the wound and those of the patient and includes adequate analgesia as well as minimizing the risk of infection. Sufficient wound aftercare starts with the treating physician informing the patient about the course of events, potential complications and providing relevant instructions.

Size-dependent protein segregation at the cell-cell contact interface has been suggested to be critical for regulation of lymphocyte function. We investigated the role of ligand dimensions in regulation of mouse NK-cell activation and inhibition. Elongated forms of H60a, a mouse NKG2D ligand, were generated and expressed stably in the RMA cell line. RMA cells expressing the normal size H60a were lysed efficiently by both freshly isolated and IL-2 stimulated C57BL/6 mouse-derived NK cells; however the level of lysis decreased as the H60a ligand size increased. Importantly, H60a elongation did not affect NKG2D binding, as determined by soluble NKG2D tetramer staining, and by examining NK-cell target cell conjugate formation. CHO cells are efficient at activating NK cells from C57BL/6 mice, and expression of a single chain form of H-2K(b), a ligand for the mouse inhibitory receptor Ly49C, strongly inhibited such activation of Ly49C/I positive NK cells. Elongation of H-2K(b) resulted in decreased inhibition of both lysis and IFN-gamma production by NK cells. These results establish that small ligand dimensions are important for both NK-cell activation and inhibition, and suggest that there are shared features between the mechanisms of receptor triggering on different types of lymphocytes.

As part of the multicentre Antibiotic Therapy Optimisation Study (ATHOS), minimum inhibitory concentrations (MICs) were determined for cephalosporins alone and in combination with the β-lactamase inhibitors tazobactam, clavulanic acid and avibactam against third-generation cephalosporin-resistant Escherichia coli, Klebsiella spp. and Enterobacter spp. isolates collected in German hospitals. MIC50/90 values were 0.25–4 mg/L for cefepime/tazobactam, 0.25–2 mg/L for ceftazidime/avibactam, 0.125–0.5 mg/L for ceftaroline/avibactam, 0.5–4 mg/L for cefpodoxime/clavulanic acid and 0.25–1 mg/L for aztreonam/avibactam, depending on the underlying resistance mechanism and organism. Based on in vitro testing, β-lactam antibiotics play an important role in the treatment of infections due to β-lactamase-producing organisms.

Most models regarding the 'clonal' origin of CD8(+) T cell effector and memory subset diversification suggest that during the first contact of a naïve T cell with the priming antigen-presenting cell major decisions for subsequent differentiation are made. Data using novel single-cell T cell tracking technologies demonstrate that a single naïve CD8(+) T cell can give rise to virtually all different subtypes of effector and memory T cells, and direct major determinants of subset diversification to the time period beyond the first cell division. Thereby, some 'stem cell-like' characteristics typical for naïve T cells are probably still maintained within distinct subsets of memory T cells. These observations have direct consequences for clinical applications like adoptive T cell therapy.

Surgical site infections (SSI) following abdominal surgery are frequent and a major cause of postoperative morbidity and prolonged hospital stay. Besides antibiotic prophylaxis, antiseptic skin preparation is an important measure to prevent SSI.Here we prospectively analyzed the effectiveness of antiseptic skin preparation in a cohort of 93 patients undergoing laparotomy, with special emphasis on the umbilical region.The microflora of the umbilicus contained a large number of resident (mostly staphylococci species and corynebacteria) and transient germs (including enterococci species). Following antiseptic skin preparation, bacteria could still be cultured from 24.7% of the patients' umbilici. In case of postoperative SSI, only one of seven SSI was caused by the microorganism that was present in the umbilicus before and after skin preparation.Antiseptic skin preparation fails to completely eradicate the microflora of the umbilical region in one quarter of the patients. However, at least in abdominal surgery, the vast majority of SSI are caused by intra-abdominal contamination rather than the skin microflora.

The susceptibility of certain inbred mouse strains to murine cytomegalovirus (MCMV) is related to their inability to generate a strong natural killer (NK) cell response. We addressed here whether the MCMV susceptibility of the BALB/c strain is due to viral functions that control NK cell activation in a strain-specific manner. MCMV expresses two proteins, gp48 and gp40, that are encoded by the genes m06 and m152, respectively ; they down-regulate major histocompatibility complex (MHC) class I expression at the plasma membrane. Using MCMV deletion mutants and revertants, we found that gp40 but not gp48 controls NK cell activation. Absence of gp40 improved antiviral NK cell control in BALB/c, but not C57BL/6, mice. Down-regulation of H-60, the high-affinity ligand for the NKG2D receptor, was the mechanism by which gp40 modulates NK cell activation. Thus, a single herpesvirus protein has a dual function in inhibiting both the adaptive as well as the innate immune response.

CD8(+) T cells play an essential role in immunity against intracellular pathogens, with cytotoxicity being considered their major effector mechanism. However, we here demonstrate that a major part of central and effector memory CD8(+) T cells expresses CD40L, one key molecule for CD4(+) T-cell-mediated help. CD40L(+) CD8(+) T cells are detectable among human antigen-specific immune responses, including pathogens such as influenza and yellow fever virus. CD40L(+) CD8(+) T cells display potent helper functions in vitro and in vivo, such as activation of antigen-presenting cells, and exhibit a cytokine expression signature similar to CD4(+) T cells and unrelated to cytotoxic CD8(+) T cells. The broad occurrence of CD40L(+) CD8(+) T cells in cellular immunity implicates that helper functions are not only executed by major histocompatibility complex (MHC) class II-restricted CD4(+) helper T cells but are also a common feature of MHC class I-restricted CD8(+) T cell responses. Due to their versatile functional capacities, human CD40L(+) CD8(+) T cells are promising candidate cells for immune therapies, particularly when CD4(+) T-cell help or pathogen-associated molecular pattern signals are limited.

Immunization with purified antigens is a safe and practical vaccination strategy but is generally unable to induce sustained CD8(+) T cell-mediated protection against intracellular pathogens. Most efforts to improve the CD8(+) T cell immunogenicity of these vaccines have focused on co-administration of adjuvant to support cross-presentation and dendritic cell maturation. In addition, it has been shown that CD4(+) T cell help during the priming phase contributes to the generation of protective CD8(+) memory T cells. In this report we demonstrate that the depletion of CD4(+) T cells paradoxically enhances long-lasting CD8-mediated protective immunity upon protein vaccination. Functional and genetic in vivo inactivation experiments attribute this enhancement primarily to MHC class II-restricted CD4(+) regulatory T cells (Treg), which appear to physiologically suppress the differentiation process towards long-living effector memory T cells. Since, in functional terms, this suppression by Treg largely exceeds the positive effects of conventional CD4(+) T cell help, even the absence of all CD4(+) T cells or lack of MHC class II-mediated interactions on priming dendritic cells result in enhanced CD8(+) T cell immunogenicity. These findings have important implications for the improvement of vaccines against intracellular pathogens or tumors, especially in patients with highly active Treg.

In addition to their bridging function between innate and adaptive immunity, dendritic cells (DCs) may also contribute to primary resistance against infection. Here we analyzed the role of DCs during infection with Listeria monocytogenes by performing systemic in vivo depletion of these cells. We showed that CD8alpha(+) DCs were crucial for L. monocytogenes spreading and proliferation in the spleen. Efficient and rapid uptake of L. monocytogenes by CD8alpha(+) DCs required the small GTPase Rac1 and is a general characteristic of this DC subpopulation in filtering particles out of the blood. Thus, CD8alpha(+) DCs appear to play an important role for efficient bacterial entry into the spleen, which is of relevance for subsequent immune responses.

Few regional and seasonal Guillain–Barre syndrome (GBS) clusters have been reported so far. It is unknown whether patients suffering from sporadic GBS differ from GBS clusters with respect to clinical and paraclinical parameters, HLA association and antibody response to glycosphingolipids and Campylobacter jejuni (Cj). We examined 40 consecutive patients with GBS from the greater Munich area in Germany with 14 of those admitted within a period of 3 months in fall 2010 defining a cluster of GBS. Sequencing-based HLA typing of the HLA genes DRB1, DQB1, and DPB1 was performed, and ELISA for anti-glycosphingolipid antibodies was carried out. Clinical and paraclinical findings (Cj seroreactivity, cerebrospinal fluid parameters, and electrophysiology) were obtained and analyzed. GBS cluster patients were characterized by a more severe clinical phenotype with more patients requiring mechanical ventilation and higher frequencies of autoantibodies against sulfatide, GalC and certain ganglioside epitopes (54 %) as compared to sporadic GBS cases (13 %, p = 0.017). Cj seropositivity tended to be higher within GBS cluster patients (69 %) as compared to sporadic cases (46 %, p = 0.155). We noted higher frequencies of HLA class II allele DQB1*05:01 in the cluster cohort (23 %) as compared to sporadic GBS patients (3 %, p = 0.019). Cluster of severe GBS was defined by higher frequencies of autoantibodies against glycosphingolipids. HLA class II allele DQB1*05:01 might contribute to clinical worsening in the cluster patients.