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Abstract An outbreak of OXA-23-producing carbapenem-resistant Acinetobacter baumannii amongst ICU-patients with COVID-19 likely occurred by transmission through inanimate surfaces, potentially facilitated by a contaminated positioning pillow shared between patients. Subsequent rapid spread may have been caused by exposure to respiratory secretions contaminating healthcare worker’s gloves and gowns during prone positioning.

Abstract The implementation of isolation precautions for patients with suspected Coronavirus Disease 2019 (COVID-19) and pending test results is resource intensive. Due to the limited availability of single-bed rooms at our institution, we isolated patients with suspected COVID-19 together with patients without suspected COVID-19 on-site in multiple-bed rooms until SARS-CoV-2-test results were available. We evaluated the likelihood of SARS-CoV-2 transmission to individuals sharing the room with patients isolated on-site. This observational study was performed at the University Hospital Basel, Switzerland, from 03/20 − 11/20. Secondary attack rates were compared between patients hospitalized in multiple-bed rooms and exposed to individuals subjected to on-site isolation precautions (on-site isolation group), and patients exposed to individuals initially not identified as having COVID-19, and not placed under isolation precautions until the diagnosis was suspected (control group). Transmission events were confirmed by whole-genome sequencing. Among 1,218 patients with suspected COVID-19, 67 (5.5%) tested positive for SARS-CoV-2. Of these, 21 were isolated on-site potentially exposing 27 patients sharing the same room. Median contact time was 12 h (interquartile range 7–18 h). SARS-CoV-2 transmission was identified in none of the patients in the on-site isolation group vs. 10/63 (15.9%) in the control group (p = 0.03). Isolation on-site of suspected COVID-19-patients in multiple-bed rooms avoided single-room occupancy and subsequent in-hospital relocation for many patients without confirmed SARS-CoV-2-infection. The absence of secondary transmission among the exposed patients in the on-site isolation group allows for assessment of the risk/benefit ratio of this strategy given the limitation of a small sample size.

Abstract Background Few methicillin-resistant Staphylococcus aureus (MRSA) from the early years of its global emergence have been sequenced. Knowledge about evolutionary factors promoting the success of specific MRSA multi-locus sequence types (MLSTs) remains scarce. We aimed to characterize a legacy MRSA collection isolated from 1965 to 1987 and compare it against publicly available international and local genomes. Methods We accessed 451 historic (1965–1987) MRSA isolates stored in the Culture Collection of Switzerland, mostly collected from the Zurich region. We determined phenotypic antimicrobial resistance (AMR) and performed whole genome sequencing (WGS) using Illumina short-read sequencing on all isolates and long-read sequencing on a selection with Oxford Nanopore Technology. For context, we included 103 publicly available international assemblies from 1960 to 1992 and sequenced 1207 modern Swiss MRSA isolates from 2007 to 2022. We analyzed the core genome (cg)MLST and predicted SCCmec cassette types, AMR, and virulence genes. Results Among the 451 historic Swiss MRSA isolates, we found 17 sequence types (STs) of which 11 have been previously described. Two STs were novel combinations of known loci and six isolates carried previously unsubmitted MLST alleles, representing five new STs (ST7843, ST7844, ST7837, ST7839, and ST7842). Most isolates (83% 376/451) represented ST247-MRSA-I isolated in the 1960s, followed by ST7844 (6% 25/451), a novel single locus variant (SLV) of ST239. Analysis by cgMLST indicated that isolates belonging to ST7844-MRSA-III cluster within the diversity of ST239-MRSA-III. Early MRSA were predominantly from clonal complex (CC)8. From 1980 to the end of the twentieth century, we observed that CC22 and CC5 as well as CC8 were present, both locally and internationally. Conclusions The combined analysis of 1761 historic and contemporary MRSA isolates across more than 50 years uncovered novel STs and allowed us a glimpse into the lineage flux between Swiss-German and international MRSA across time.

This study aimed to determine cefazolin target attainment in patients with invasive Staphylococcus aureus (S. aureus) infections and to develop a population pharmacokinetic (PK) model. Adult patients with invasive S. aureus infections treated with cefazolin bolus infusions were included. Unbound and total trough and mid-dose cefazolin concentrations were measured, and strain-specific MICs were determined. The primary outcome was the proportion of patients attaining 100% fT>MIC at all time points evaluated. A population PK model was developed, using non-linear mixed-effects modelling. Overall, 51 patients were included, with a total of 226 unbound and total cefazolin concentrations measured (mean: 4.4 per patient). The median daily dosage in patients with an estimated glomerular filtration rate of >60 mL/min/m2 was 8 g. The median age was 74 years (interquartile range (IQR) 57–82) and 26% were female. A history of chronic kidney disease and acute kidney injury were present in 10/51 (19.6%) and 6/51 (11.7%), respectively. Achievement of 100% fT>MIC occurred in 86% of the patients and decreased to 45% when a target of 100% fT>4xMIC was evaluated. The mean unbound cefazolin fraction was 27.0% (standard deviation (SD) 13.4). Measured and estimated mean cefazolin trough concentrations differed significantly [13.1 mg/L (SD 23.5) vs. 7.4 mg/L (SD 7.9), p < 0.001]. In the population PK model, elevated estimated creatinine clearance and bolus instead of continuous application were covariates for target non-attainment. In conclusion, cefazolin target achievement was high, and the measurement of the unbound cefazolin concentration may be favored. The Monte Carlo simulations indicated that target attainment was significantly improved with continuous infusion.

STUDY AIMS: During the COVID-19 pandemic, there was increasing pressure to be vaccinated to prevent further spread of the virus and improve outcomes. At the same time, part of the population expressed reluctance to vaccination, for various reasons. Only a few studies have compared the perceptions of vaccinated and non-vaccinated patients being treated in hospitals for COVID-19. Our aim was to investigate the association between vaccination status and perceived healthcare-associated discrimination in patients with COVID-19 receiving hospital treatment. METHODS: Adult patients presenting to the emergency department or hospitalised for inpatient care due to or with COVID-19 from 1 June to 31 December 2021 in two Swiss hospitals were eligible. The primary endpoint was patients’ perceived healthcare-associated discrimination, measured with the Discrimination in Medical Settings (DMS) scale. Secondary endpoints included different aspects of perceived quality of care and symptoms of psychological distress measured with the Hospital Anxiety and Depression Scale. RESULTS: Non-vaccinated patients (n = 113) had significantly higher DMS scores compared to vaccinated patients (n = 80) (mean: 9.54 points [SD: 4.84] vs 7.79 points [SD: 1.85]; adjusted difference: 1.18 [95% CI: 0.04–2.33 points]) and 21 of 80 vaccinated patients felt discriminated against vs 54 of 113 non-vaccinated patients (adjusted OR: 2.09 [95% CI: 1.10–3.99 ]). Non-vaccinated patients reported lower scores regarding respectful treatment by the nursing team (mean: 8.39 points [SD: 2.39] vs 9.30 points [SD: 1.09]; adjusted difference: –0.6 [95% CI: -1.18 – –0.02 points]). CONCLUSION: We found an association between vaccination status and perceived healthcare-associated discrimination. Healthcare workers should act in a professional manner regardless of a patient’s vaccination status; in doing so, they might prevent the creation of negative perceptions in patients.

Abstract Background Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, often caused by uropathogenic Escherichia coli. Multiple bacterial virulence factors or patient characteristics have been linked separately to progressive, more invasive infections. In this study, we aim to identify pathogen- and patient-specific factors that drive the progression to urosepsis by jointly analysing bacterial and host characteristics. Methods We analysed 1076 E. coli strains isolated from 825 clinical cases with UTI and/or bacteraemia by whole-genome sequencing (Illumina). Sequence types (STs) were determined via srst2 and capsule loci via fastKaptive. We compared the isolates from urine and blood to confirm clonality. Furthermore, we performed a bacterial genome-wide association study (bGWAS) (pyseer) using bacteraemia as the primary clinical outcome. Clinical data were collected by an electronic patient chart review. We concurrently analysed the association of the most significant bGWAS hit and important patient characteristics with the clinical endpoint bacteraemia using a generalised linear model (GLM). Finally, we designed qPCR primers and probes to detect papGII-positive E. coli strains and prospectively screened E. coli from urine samples (n = 1657) at two healthcare centres. Results Our patient cohort had a median age of 75.3 years (range: 18.00–103.1) and was predominantly female (574/825, 69.6%). The bacterial phylogroups B2 (60.6%; 500/825) and D (16.6%; 137/825), which are associated with extraintestinal infections, represent the majority of the strains in our collection, many of which encode a polysaccharide capsule (63.4%; 525/825). The most frequently observed STs were ST131 (12.7%; 105/825), ST69 (11.0%; 91/825), and ST73 (10.2%; 84/825). Of interest, in 12.3% (13/106) of cases, the E. coli pairs in urine and blood were only distantly related. In line with previous bGWAS studies, we identified the gene papGII (p-value

Abstract Background The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) detects microorganisms with high accuracy in positive blood cultures (BC) – a key step in the management of patients with suspected bacteraemia. We aimed to compare the time to optimal antimicrobial therapy (OAT) for the BF-FA-BCIP vs. standard culture-based identification. Methods In this retrospective single-centre study with a before-after design, 386 positive BC cases with identification by BF-FA-BCIP were compared to 414 controls with culture-based identification. The primary endpoint was the time from BC sampling to OAT. Secondary endpoints were time to effective therapy, length of stay, (re-)admission to ICU, in-hospital and 30-day mortality. Outcomes were assessed using Cox proportional hazard models and logistic regressions. Results Baseline characteristics of included adult inpatients were comparable. Main sources of bacteraemia were urinary tract and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7%, for cases and controls, respectively). Median (95%CI) time to OAT was 25.5 (21.0–31.2) hours with BF-FA-BCIP compared to 45.7 (37.7–51.4) hours with culture-based identification. We observed no significant difference for secondary outcomes. Conclusions Rapid microorganism identification by BF-FA-BCIP was associated with a median 20-h earlier initiation of OAT in patients with positive BC. No impact on length of stay and mortality was noted. Trial registration Clinicaltrials.gov, NCT04156633, registered on November 5, 2019.

Abstract Background We sought to decipher transmission pathways in healthcare-associated infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within our hospital by epidemiological work-up and complementary whole genome sequencing (WGS). We report the findings of the four largest epidemiologic clusters of SARS-CoV-2 transmission occurring during the second wave of the pandemic from 11/2020 to 12/2020. Methods At the University Hospital Basel, Switzerland, systematic outbreak investigation is initiated at detection of any nosocomial case of SARS-CoV-2 infection, as confirmed by polymerase chain reaction, occurring more than five days after admission. Clusters of nosocomial infections, defined as the detection of at least two positive patients and/or healthcare workers (HCWs) within one week with an epidemiological link, were further investigated by WGS on respective strains. Results The four epidemiologic clusters included 40 patients and 60 HCWs. Sequencing data was available for 70% of all involved cases (28 patients and 42 HCWs), confirmed epidemiologically suspected in house transmission in 33 cases (47.1% of sequenced cases) and excluded transmission in the remaining 37 cases (52.9%). Among cases with identical strains, epidemiologic work-up suggested transmission mainly through a ward-based exposure (24/33, 72.7%), more commonly affecting HCWs (16/24, 66.7%) than patients (8/24, 33.3%), followed by transmission between patients (6/33, 18.2%), and among HCWs and patients (3/33, 9.1%, respectively two HCWs and one patient). Conclusions Phylogenetic analyses revealed important insights into transmission pathways supporting less than 50% of epidemiologically suspected SARS-CoV-2 transmissions. The remainder of cases most likely reflect community-acquired infection randomly detected by outbreak investigation. Notably, most transmissions occurred between HCWs, possibly indicating lower perception of the risk of infection during contacts among HCWs.

Abstract Core body temperature (CBT) is a key vital sign and fever is an important indicator of disease. In the past decade, there has been growing interest for vital sign monitoring technology that may be embedded in wearable devices, and the COVID-19 pandemic has highlighted the need for remote patient monitoring systems. While wrist-worn sensors allow continuous assessment of heart rate and oxygen saturation, reliable measurement of CBT at the wrist remains challenging. In this study, CBT was measured continuously in a free-living setting using a novel technology worn at the wrist and compared to reference core body temperature measurements, i.e., CBT values acquired with an ingestible temperature-sensing pill. Fifty individuals who received the COVID-19 booster vaccination were included. The datasets of 33 individuals were used to develop the CBT prediction algorithm, and the algorithm was then validated on the datasets of 17 participants. Mean observation time was 26.4 h and CBT > 38.0 °C occurred in 66% of the participants. CBT predicted by the wrist-worn sensor showed good correlation to the reference CBT (r = 0.72). Bland–Altman statistics showed an average bias of 0.11 °C of CBT predicted by the wrist-worn device compared to reference CBT, and limits of agreement were − 0.67 to + 0.93 °C, which is comparable to the bias and limits of agreement of commonly used tympanic membrane thermometers. The small size of the components needed for this technology would allow its integration into a variety of wearable monitoring systems assessing other vital signs and at the same time allowing maximal freedom of movement to the user.

Objective Discussing sensitive topics (eg, medical uncertainty, social issues, non-adherence) during ward rounds is challenging and may negatively impact patient satisfaction with the healthcare they are receiving. In the previous multicentre randomised BEDSIDE-OUTSIDE trial focusing on communication during ward rounds, we investigated the interplay between sensitive topics and low reported satisfaction with care.Design Pre-planned secondary analysis of a randomised controlled trial. For this analysis data of the original trial was pooled across intervention groups.Setting Three Swiss teaching hospitals.Participants Adult patients hospitalised for medical care.Interventions We analysed predefined sensitive health topics and specific elements of communication from audiotapes recorded during ward rounds, for both patients dealing with and without sensitive topics.Primary and secondary outcome measures The primary endpoint was overall patient satisfaction with care; measured on a Visual Analogue Scale from 0 to 100. Secondary endpoints included duration of ward rounds and further satisfaction outcomes.Results Of the 919 included patients, 474 had at least one sensitive topic including medical uncertainty (n=251), psychiatric comorbidities (n=161), tumour diagnosis (n=137) and social issues (n=125). Compared with patients without sensitive topics, patients with sensitive topics reported lower satisfaction with care (mean (SD), 87.7 (±14.6) vs 90.2 (±12.1), adjusted difference −2.5 (95% CI −4.28 to −0.72), p=0.006. Among patients with sensitive topics, risk factors for low satisfaction included several parameters concerning patient–physician interaction such as disagreements during ward rounds (mean (SD), 14/212 (6.6%) vs 41/254 (16.1%), adjusted OR 2.78 (95% CI 1.47 to 5.27), p=0.002).Conclusions A large proportion of medical inpatients must deal with sensitive health topics. This is associated with lower satisfaction with care, particularly if the patient perceives the interaction with doctors during ward rounds as unsatisfactory. Educating physicians on specific communication techniques may help improve care for these patients.Trial registration number NCT03210987.

AIMS: There is a lack of national and international publicly available long-term survival outcome data from individual healthcare providers in medical oncology. In this study, the overall survival at a medium-sized medical oncology service at Olten Cantonal Hospital was evaluated and compared as a local benchmark report with national data from the Swiss Cancer Registries. Furthermore, adherence to treatment guidelines was investigated as an additional quality indicator. METHODS: The 1- and 5-year overall survival of all patients with breast cancer, testicular cancer, colon cancer, non-small-cell lung cancer, Hodgkin lymphoma, and diffuse large B-cell lymphoma in Switzerland from 2008 to 2017 with at least one outpatient visit at the in-house medical oncology service at Olten Cantonal Hospital was analysed and compared with the specific overall population-based outcome data provided by the National Agency for Cancer Registration (NACR), which were set as a national benchmark. Until 2020, no data from the Canton of Solothurn, to which Olten belongs, were reported to the NACR. Further, adherence to internationally recognized clinical guidelines for stage-specific treatment was assessed. RESULTS: Until September 8, 2020, data on 842 patients with a median follow-up period of 70 months were collected and analysed. The 1- and 5-year overall survival for colon and non-small cell cancer, Hodgkin lymphoma, and diffuse large B-cell lymphoma and the 5-year overall survival for testicular cancer in the Olten cohort did not significantly differ from the NACR data. The 1-year overall survival for testicular cancer was not comparable statistically. The 5-year overall survival for breast cancer (unadjusted for stage) was significantly higher in the NACR collective (84.5%) than in the Olten collective (79.7%) but not for the individual breast cancer stages. The Olten collective included approximately 2.5 times as many patients with stage 4 breast cancer (17.5%) as the NACR collective (6.9%). Approximately 92.4% of the patients in the curative setting and 85.8% of the patients in the palliative setting received first-line treatment according to guidelines. CONCLUSIONS: The statistically comparable local 1- and 5-year overall survival of the analysed malignancies, with adjustment for stage for the 5-year overall survival for breast cancer, is in line with the national benchmark. Adherence to treatment guidelines is high.

BackgroundBlood cultures (BC) are critical for the diagnosis of bloodstream infections, pathogen identification, and resistance testing. Guidelines recommend a blood volume of 8-10 mL per bottle as lower volumes result in decreased sensitivity. We aimed to evaluate factors for non-adherence to recommended volumes and assess the effects on diagnostic performance.MethodsFrom February to April 2020, we measured collected blood volumes by weighing all BC containers from inpatient samples at the University Hospital Basel. Information on BC volumes was merged with clinical and microbiological data, as well as nursing staff schedules. We analyzed factors associated with (i) BC sampling volume, (ii) reaching recommended volumes (≥8 mL), (iii) BC positivity, and (iv) time to positivity using linear and generalized linear mixed effect models.ResultsWe evaluated a total of 4'118 BC bottles collected from 686 patients. A total of 1'495 (36.3%) of all bottles contained the recommended filling volume of ≥8 mL. Using a central venous and arterial catheter for drawing blood resulted in an increase of filling volume by 0.26 mL (95% CI 0.10, 0.41) and 0.50 mL (95% CI 0.31, 0.69) compared to peripheral venipuncture, respectively. Each additional nursing staff working at the time of blood drawing was associated with 6% higher odds of achieving the recommended filling volume. We found no significant correlation between the filling volume and the positivity rate.ConclusionOur results indicate critical pre-analytical quality markers linked to BC collection procedures to reach recommended collection volumes. No significant impact on the positivity rate was found.

Abstract Background Klebsiella spp. are opportunistic pathogens which can cause severe infections, are often multi-drug resistant and are a common cause of hospital-acquired infections. Multiple new Klebsiella species have recently been described, yet their clinical impact and antibiotic resistance profiles are largely unknown. We aimed to explore Klebsiella group- and species-specific clinical impact, antimicrobial resistance (AMR) and virulence. Methods We analysed whole-genome sequence data of a diverse selection of Klebsiella spp. isolates and identified resistance and virulence factors. Using the genomes of 3594 Klebsiella isolates, we predicted the masses of 56 ribosomal subunit proteins and identified species-specific marker masses. We then re-analysed over 22,000 Matrix-Assisted Laser Desorption Ionization - Time Of Flight (MALDI-TOF) mass spectra routinely acquired at eight healthcare institutions in four countries looking for these species-specific markers. Analyses of clinical and microbiological endpoints from a subset of 957 patients with infections from Klebsiella species were performed using generalized linear mixed-effects models. Results Our comparative genomic analysis shows group- and species-specific trends in accessory genome composition. With the identified species-specific marker masses, eight Klebsiella species can be distinguished using MALDI-TOF MS. We identified K. pneumoniae (71.2%; n = 12,523), K. quasipneumoniae (3.3%; n = 575), K. variicola (9.8%; n = 1717), “K. quasivariicola” (0.3%; n = 52), K. oxytoca (8.2%; n = 1445), K. michiganensis (4.8%; n = 836), K. grimontii (2.4%; n = 425) and K. huaxensis (0.1%; n = 12). Isolates belonging to the K. oxytoca group, which includes the species K. oxytoca, K. michiganensis and K. grimontii, were less often resistant to 4th-generation cephalosporins than isolates of the K. pneumoniae group, which includes the species K. pneumoniae, K. quasipneumoniae, K. variicola and “K. quasivariicola” (odds ratio = 0.17, p < 0.001, 95% confidence interval [0.09,0.28]). Within the K. pneumoniae group, isolates identified as K. pneumoniae were more often resistant to 4th-generation cephalosporins than K. variicola isolates (odds ratio = 2.61, p = 0.003, 95% confidence interval [1.38,5.06]). K. oxytoca group isolates were found to be more likely associated with invasive infection to primary sterile sites than K. pneumoniae group isolates (odds ratio = 2.39, p = 0.0044, 95% confidence interval [1.05,5.53]). Conclusions Currently misdiagnosed Klebsiella spp. can be distinguished using a ribosomal marker-based approach for MALDI-TOF MS. Klebsiella groups and species differed in AMR profiles, and in their association with invasive infection, highlighting the importance for species identification to enable effective treatment options.

BackgroundThromboinflammation may influence disease outcome in COVID-19. We aimed to evaluate complement and endothelial cell activation in patients with confirmed COVID-19 compared to controls with clinically suspected but excluded SARS-CoV-2 infection.MethodsIn a prospective, observational, single-center study, patients presenting with clinically suspected COVID-19 were recruited in the emergency department. Blood samples on presentation were obtained for analysis of C5a, sC5b-9, E-selectin, Galectin-3, ICAM-1 and VCAM-1.Results153 cases and 166 controls (suffering mainly from non-SARS-CoV-2 respiratory viral infections, non-infectious inflammatory conditions and bacterial pneumonia) were included. Hospital admission occurred in 62% and 45% of cases and controls, respectively. C5a and VCAM-1 concentrations were significantly elevated and E-selectin concentrations decreased in COVID-19 out- and inpatients compared to the respective controls. However, relative differences in outpatients vs. inpatients in most biomarkers were comparable between cases and controls. Elevated concentrations of C5a, Galectin-3, ICAM-1 and VCAM-1 on presentation were associated with the composite outcome of ICU- admission or 30-day mortality in COVID-19 and controls, yet more pronounced in COVID-19. C5a and sC5b-9 concentrations were significantly higher in COVID-19 males vs. females, which was not observed in the control group.ConclusionsOur data indicate an activation of the complement cascade and endothelium in COVID-19 beyond a nonspecific inflammatory trigger as observed in controls (i.e., “over”-activation).

Abstract The proportion of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive and the potential benefit of systematic screening during the SARS-CoV-2-pandemic is controversial. We investigated the proportion of asymptomatic inpatients who were identified by systematic screening for SARS-CoV-2 upon hospital admission. Our analysis revealed that systematic screening of asymptomatic inpatients detects a low total number of SARS-CoV-2 infections (0.1%), questioning the cost–benefit ratio of this intervention. Even when the population-wide prevalence was low, the proportion of asymptomatic carriers remained stable, supporting the need for universal infection prevention and control strategies to avoid onward transmission by undetected SARS-CoV-2-carriers during the pandemic.

Abstract Background Urinary tract infection (UTI) is diagnosed combining urinary symptoms with demonstration of urine culture growth above a given threshold. Our aim was to compare the diagnostic accuracy of Urine Flow Cytometry (UFC) with urine test strip in predicting bacterial growth and in identifying contaminated urine samples, and to derive an algorithm to identify relevant bacterial growth for clinical use. Methods Species identification and colony-forming unit (CFU/ml) quantification from bacterial cultures were matched to corresponding cellular (leucocytes/epithelial cells) and bacteria counts per μl. Results comprise samples analysed between 2013 and 2015 for which urine culture (reference standard) and UFC and urine test strip data (index tests, Sysmex UX-2000) were available. Results 47,572 urine samples of 26,256 patients were analysed. Bacteria counts used to predict bacterial growth of ≥105 CFU/ml showed an accuracy with an area under the receiver operating characteristic curve of > 93% compared to 82% using leukocyte counts. The relevant bacteriuria rule-out cut-off of 50 bacteria/μl reached a negative predictive value of 98, 91 and 89% and the rule-in cut-off of 250 bacteria/μl identified relevant bacteriuria with an overall positive predictive value of 67, 72 and 73% for microbiologically defined bacteriuria thresholds of 105, 104 or 103 CFU/ml, respectively. Measured epithelial cell counts by UFC could not identify contaminated urine. Conclusions Prediction of a relevant bacterial growth by bacteria counts was most accurate and was a better predictor than leucocyte counts independently of the source of the urine and the medical specialty ordering the test (medical, surgical or others).

Abstract Objectives SARS-CoV-2 may cause acute lung injury, and secondary infections are thus relevant complications in patients with COVID-19 pneumonia. However, detailed information on community- and hospital-acquired infections among patients with COVID-19 pneumonia is scarce. Methods We identified 220 SARS-CoV-2-positive patients hospitalized at the University Hospital Basel, Switzerland (between 25 February and 31 May 2020). We excluded patients who declined the general consent (n = 12), patients without clinical evidence of pneumonia (n = 29), and patients hospitalized for

AIMS OF THE STUDY: In the global COVID-19 pandemic, female sex is associated with comparable infection rates but better outcome. However, most studies lacked appropriate controls. We investigated whether these sex disparity findings are specific to patients with COVID-19 or generalizable to patients presenting to the emergency room (ER) with similar symptoms but no COVID-19. METHODS: In this prospective cohort study, consecutive patients presenting with symptoms suggestive of COVID-19 were recruited at the ER of the University Hospital Basel, Switzerland from March to June 2020. Patients were categorized as SARS-CoV-2 positive (cases) or negative (controls) based on nasopharyngeal PCR swab tests. The final clinical diagnosis was determined for all patients. The primary outcome was a composite of intensive care admission, rehospitalization for respiratory distress and all-cause death within 30 days. We used Kaplan–Meier curves and Cox proportional hazards models to explore associations between sex and outcomes. RESULTS: Among 1,081 consecutive ER patients, 191 (18%) tested positive for SARS-CoV-2, with an even sex distribution (17.9% female vs. 17.5% male, p = 0.855). In COVID-19 patients, female sex was associated with lower risk of hospitalization (51% vs. 66%, p = 0.034), lower necessity of haemodynamic support (8% vs. 20%, p = 0.029), lower rates of intubation (10% vs. 21%, p = 0.037) and the primary outcome (18% vs. 31%, p = 0.045; age-adjusted HR 0.536, 95%CI 0.290–0.989, p = 0.046) compared with male sex. Sex disparities were most prominent in patients ≥55 years (HR for composite primary outcome in women 0.415, 95%CI 0.201–0.855, p = 0.017). In contrast to the COVID-19 patients, no sex-specific differences in outcomes were observed in the unselected overall control group (age-adjusted HR 0.844, 95%CI 0.560–1.273, p = 0.419) or in a subgroup of controls with upper respiratory tract infections or pneumonia (age-adjusted HR 0.840, 95%CI 0.418–1.688, p = 0.624). CONCLUSION: In this unselected, consecutive cohort study at a tertiary hospital in Switzerland, female sex is associated with better outcome in patients presenting to the ER with COVID-19. These sex disparities seem to be at least partly specific to COVID-19, as they were not observed in comparable controls.

BACKGROUND: We recently compared the effects of bedside and outside the room ward rounds on patients’ knowledge about their medical care. Here, we report preferences of medical and nursing staff members regarding outside versus bedside ward rounds. METHODS: Within this ancillary project of a large multicentre randomised controlled trial, we prospectively conducted a survey of medical and nursing staff members participating in the weekly consultant ward rounds in the internal medicine division of three Swiss teaching hospitals between July 2017 and October 2019. Participants were asked about their preferences on outside versus bedside ward rounds. The primary endpoint was satisfaction of healthcare workers with the ward round measured with a visual analogue scale from 0 to 100. RESULTS: Between July 2017 and October 2019, 919 patients were included in the trial, and we received 891 survey responses (nurses 15.6%, residents 26.8%, attending physicians 29.6%, consultants 7.8% and chief physicians 20.2%. In the overall analysis, mean (± standard deviation) satisfaction of healthcare workers was higher with outside the room than bedside ward rounds (78.03 ± 16.96 versus 68.25 ± 21.10 respectively; age-, gender- and centre-adjusted difference of –10.46, 95% confidence interval [CI] –12.73 to –8.19; p

BackgroundInflammatory biomarkers are associated with severity of coronavirus disease 2019 (COVID-19). However, direct comparisons of their utility in COVID-19 versus other respiratory infections are largely missing.ObjectiveWe aimed to investigate the prognostic utility of various inflammatory biomarkers in COVID-19 compared to patients with other respiratory infections.Materials and methodsPatients presenting to the emergency department with symptoms suggestive of COVID-19 were prospectively enrolled. Levels of Interleukin-6 (IL-6), c-reactive protein (CRP), procalcitonin, ferritin, and leukocytes were compared between COVID-19, other viral respiratory infections, and bacterial pneumonia. Primary outcome was the need for hospitalisation, secondary outcome was the composite of intensive care unit (ICU) admission or death at 30 days.ResultsAmong 514 patients with confirmed respiratory infections, 191 (37%) were diagnosed with COVID-19, 227 (44%) with another viral respiratory infection (viral controls), and 96 (19%) with bacterial pneumonia (bacterial controls). All inflammatory biomarkers differed significantly between diagnoses and were numerically higher in hospitalized patients, regardless of diagnoses. Discriminative accuracy for hospitalisation was highest for IL-6 and CRP in all three diagnoses (in COVID-19, area under the curve (AUC) for IL-6 0.899 [95%CI 0.850-0.948]; AUC for CRP 0.922 [95%CI 0.879-0.964]). Similarly, IL-6 and CRP ranged among the strongest predictors for ICU admission or death at 30 days in COVID-19 (AUC for IL-6 0.794 [95%CI 0.694-0.894]; AUC for CRP 0.807 [95%CI 0.721-0.893]) and both controls. Predictive values of inflammatory biomarkers were generally higher in COVID-19 than in controls.ConclusionIn patients with COVID-19 and other respiratory infections, inflammatory biomarkers harbour strong prognostic information, particularly IL-6 and CRP. Their routine use may support early management decisions.

Although initial immunophenotypical studies on peripheral blood and bronchoalveolar lavage samples have provided a glimpse into the immunopathology of COVID-19, analyses of pulmonary draining lymph nodes are currently scarce. 22 lethal COVID-19 cases and 28 controls were enrolled in this study. Pulmonary draining lymph nodes (mediastinal, tracheal, peribronchial) were collected at autopsy. Control lymph nodes were selected from a range of histomorphological sequelae [unremarkable histology, infectious mononucleosis, follicular hyperplasia, non-SARS related HLH, extrafollicular plasmablast activation, non-SARS related diffuse alveolar damage (DAD), pneumonia]. Samples were mounted on a tissue microarray and underwent immunohistochemical staining for a selection of immunological markers and in-situ hybridization for Epstein Barr Virus (EBV) and SARS-CoV-2. Gene expression profiling was performed using the HTG EdgeSeq Immune Response Panel. Characteristic patterns of a dysregulated immune response were detected in COVID-19: 1. An accumulation of extrafollicular plasmablasts with a relative paucity or depletion of germinal centers. 2. Evidence of T-cell dysregulation demonstrated by immunohistochemical paucity of FOXP3+, Tbet+ and LEF1+ positive T-cells and a downregulation of key genes responsible for T-cell crosstalk, maturation and migration as well as a reactivation of herpes viruses in 6 COVID-19 lymph nodes (EBV, HSV). 3. Macrophage activation by a M2-polarized, CD163+ phenotype and increased incidence of hemophagocytic activity. 4. Microvascular dysfunction, evidenced by an upregulation of hemostatic (CD36, PROCR, VWF) and proangiogenic (FLT1, TEK) genes and an increase of fibrin microthrombi and CD105+ microvessels. Taken together, these findings imply widespread dysregulation of both innate and adoptive pathways with concordant microvascular dysfunction in severe COVID-19.

AIMS OF THE STUDY: There is increasing interest in better understanding of long COVID, a condition characterised by long-term sequelae — appearing or persisting after the typical convalescence period — of coronavirus disease 2019 (COVID-19). Herein, we describe long-term outcomes regarding residual symptoms and psychological distress in hospitalised patients 1 year after COVID-19. METHODS: This prospective cohort study included consecutive adult patients hospitalised for confirmed COVID-19 in two Swiss tertiary-care hospitals between March and June 2020. The primary endpoint was evidence of long COVID 1 year after discharge, defined as ≥1 persisting or new symptom related to COVID-19, from a predefined list of symptoms. Secondary endpoints included psychological distress and symptoms of post-traumatic stress disorder (PTSD). RESULTS: Among 90 patients included in the study, 63 (70%) had symptoms of long COVID 1 year after hospitalisation, particularly fatigue (46%), concentration difficulties (31%), shortness of breath (21%) and post-exertion malaise (20%). Three predictors, namely duration of hospitalisation (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.00–1.22; p = 0.041), severity of illness (OR 1.19, 95% CI 1.04–1.37; p = 0.013), and self-perceived overall health status 30 days after hospitalisation (OR 0.97, 95% CI 0.94–1.00; p = 0.027) were associated with long COVID. Regarding secondary endpoints, 16 (18%) experienced psychological distress and 3 (3.3%) patients had symptoms of PTSD. CONCLUSION: A high proportion of COVID-19 patients report symptoms of long COVID 1 year after hospitalisation, which negatively affects their quality of life. The most important risk factors were severe initial presentation of COVID-19 with long hospital stays.

AimsAlthough the exact factors promoting disease progression in COVID-19 are not fully elucidated, unregulated activation of the complement system (CS) seems to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by SARS-CoV-2. In particular, the lectin pathway (LP) has been implicated in previous autopsy studies. The primary purpose of our study is to investigate the role of the CS in hospitalized COVID-19 patients with varying degrees of disease severity.MethodsIn a single-center prospective observational study, 154 hospitalized patients with PCR-confirmed SARS-CoV-2 infection were included. Serum samples on admission to the COVID-19 ward were collected for analysis of CS pathway activities and concentrations of LP proteins [mannose-binding lectin (MBL) and ficolin-3 (FCN-3)] & C1 esterase inhibitor (C1IHN). The primary outcome was mechanical ventilation or in-hospital death.ResultsThe patients were predominately male and had multiple comorbidities. ICU admission was required in 16% of the patients and death (3%) or mechanical ventilation occurred in 23 patients (15%). There was no significant difference in LP activity, MBL and FCN-3 concentrations according to different peak disease severities. The median alternative pathway (AP) activity was significantly lower (65%, IQR 50-94) in patients with death/invasive ventilation compared to patients without (87%, IQR 68-102, p=0.026). An optimal threshold of

OBJECTIVES Patients with severe COVID-19 may be at risk of longer term sequelae. Long-term clinical, immunological, pulmonary and radiological outcomes of patients treated with anti-inflammatory drugs are lacking. METHODS In this single-centre prospective cohort study, we assessed 90-day clinical, immunological, pulmonary and radiological outcomes of hospitalised patients with severe COVID-19 treated with tocilizumab from March 2020 to May 2020. Criteria for tocilizumab administration were oxygen saturation 30/min, C-reactive protein levels >75 mg/l, extensive area of ground-glass opacities or progression on computed tomography (CT). Descriptive analyses were performed using StataIC 16. RESULTS Between March 2020 and May 2020, 50 (27%) of 186 hospitalised patients had severe COVID-19 and were treated with tocilizumab. Of these, 52% were hospitalised on the intensive care unit (ICU) and 12% died. Eleven (22%) patients developed at least one microbiologically confirmed super-infection, of which 91% occurred on ICU. Median duration of hospitalisation was 15 days (interquartile range [IQR] 10–24) with 24 days (IQR 14–32) in ICU patients and 10 days (IQR 7–15) in non-ICU patients. At day 90, 41 of 44 survivors (93%) were outpatients. No long-term adverse events or late-onset infections were identified after acute hospital care. High SARS-CoV-2 antibody titres were found in all but one patient, who was pretreated with rituximab. Pulmonary function tests showed no obstructive patterns, but restrictive patterns in two (5.7%) and impaired diffusion capacities for carbon monoxide in 11 (31%) of 35 patients, which predominated in prior ICU patients. Twenty-one of 35 (60%) CT-scans at day 90 showed residual abnormalities, with similar distributions between prior ICU and non-ICU patients. CONCLUSIONS In this cohort of severe COVID-19 patients, no tocilizumab-related long-term adverse events or late-onset infections were identified. Although chest CT abnormalities were highly prevalent at day 90, the majority of patients showed normal lung function. Trial registration ClinicalTrials.gov NCT04351503

AIMS The aim of this study was to analyse the demographics, risk factors and in-hospital mortality rates of patients admitted with coronavirus disease 2019 (COVID-19) to a tertiary care hospital in Switzerland. METHODS In this single-centre retrospective cohort study at the University Hospital Basel, we included all patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection hospitalised from 27 February 2020 to 10 May 2021. Patients’ characteristics were extracted from the electronic medical record system. The primary outcome of this study was temporal trends of COVID-19-related in-hospital mortality. Secondary outcomes were COVID-19-related mortality in patients hospitalised on the intensive care unit (ICU), admission to ICU, renal replacement therapy and length of hospital stay, as well as a descriptive analysis of risk factors for in-hospital mortality. RESULTS During the study period we included 943 hospitalisations of 930 patients. The median age was 65 years (interquartile range [IQR] 53–76) and 63% were men. The numbers of elderly patients, patients with multiple comorbidities and need for renal replacement therapy decreased from the first and second to the third wave. The median length of stay and need for ICU admission were similar in all waves. Throughout the study period 88 patients (9.3%) died during the hospital stay. Crude in-hospital mortality was similar over the course of the first two waves (9.5% and 10.2%, respectively), whereas it decreased in the third wave (5.4%). Overall mortality in patients without comorbidities was low at 1.6%, but it increased in patients with any comorbidity to 12.6%. Predictors of all-cause mortality over the whole period were age (adjusted odds ratio [aOR] per 10-year increase 1.81, 95% confidence interval [CI] 1.45–2.26; p

Abstract Background Infective endocarditis (IE) caused by gram-negative bacilli is rare. However, the incidence of this severe infection is rising because of the increasing number of persons at risk, such as patients with immunosuppression or with cardiac implantable devices and prosthetic valves. The diagnosis of IE is often difficult, particularly when microorganisms such as Pseudomonas aeruginosa, which rarely cause this infection, are involved. One of the mainstays for the diagnosis of IE are persistently positive blood cultures with the same bacteria, while polymicrobial bacteremia usually points to another cause, e.g. an abscess. The antimicrobial resistance profile of some P. aeruginosa strains may change, falsely suggesting an infection with several strains, thus further increasing the diagnostic difficulties. Case presentation A 66-year old male patient who had a transcatheter aortic valve implantation (TAVI) one year previously developed fever seven days after an elective inguinal hernia repair. During the following four weeks, P. aeruginosa with different antibiotic resistance profiles was repeatedly isolated from blood cultures. Repeated trans-esophageal echocardiograms (TEE) were negative and an infection by different P. aeruginosa strains was suspected. Extensive diagnostic workup for an infectious focus was performed with no results. Finally, an oscillating mass on the aortic valve was detected by TEE five weeks after the initial positive blood cultures. P. aeruginosa endocarditis was confirmed by culture of the surgically removed valve. Whole genome sequencing of the last two P. aeruginosa isolates (valve and blood culture) revealed identical strains, with genome mutations for AmpR, AmpD and OprD. Conclusions The diagnosis of prosthetic valve endocarditis is particularly difficult for several reasons. The modified Duke criteria have a lower sensitivity for patients with prosthetic valve endocarditis and the infection may be caused by “unusual” pathogens such as P. aeruginosa. Patients with repeatedly positive blood cultures should make clinicians suspicious for endocarditis even if imaging studies are negative and if isolated pathogens are “unusual”. Repeatedly positive blood cultures for P. aeruginosa should be considered as “persistent bacteremia” (suspicious for IE) even in the presence of different antibiotic susceptibility patterns, since P. aeruginosa might rapidly activate or deactivate resistance mechanisms depending on antibiotic exposition.

Abstract Background A comprehensive in-hospital patient management with reasonable and economic resource allocation is arguably the major challenge of health-care systems worldwide, especially in elderly, frail, and polymorbid patients. The need for patient management tools to improve the transition process and allocation of health care resources in routine clinical care particularly for the inpatient setting is obvious. To address these issues, a large prospective trial is warranted. Methods The “Integrative Hospital Treatment in Older patients to benchmark and improve Outcome and Length of stay” (In-HospiTOOL) study is an investigator-initiated, multicenter effectiveness trial to compare the effects of a novel in-hospital management tool on length of hospital stay, readmission rate, quality of care, and other clinical outcomes using a time-series model. The study aims to include approximately 35`000 polymorbid medical patients over an 18-month period, divided in an observation, implementation, and intervention phase. Detailed data on treatment and outcome of polymorbid medical patients during the in-hospital stay and after 30 days will be gathered to investigate differences in resource use, inter-professional collaborations and to establish representative benchmarking data to promote measurement and display of quality of care data across seven Swiss hospitals. The trial will inform whether the “In-HospiTOOL” optimizes inter-professional collaboration and thereby reduces length of hospital stay without harming subjective and objective patient-oriented outcome markers. Discussion Many of the current quality-mirroring tools do not reflect the real need and use of resources, especially in polymorbid and elderly patients. In addition, a validated tool for optimization of patient transition and discharge processes is still missing. The proposed multicenter effectiveness trial has potential to improve interprofessional collaboration and optimizes resource allocation from hospital admission to discharge. The results will enable inter-hospital comparison of transition processes and accomplish a benchmarking for inpatient care quality.

Abstract Background The clinical course of Campylobacter infection varies in symptoms and severity depending on host factors, virulence of the pathogen and initiated therapy. The type VI secretion system (T6SS) has been identified as a novel virulence factor, which mediates contact-dependent injection of enzymes and toxins into competing bacteria or host cells and facilitates the colonisation of a host organism. We aimed to compare the clinical course of Campylobacter infection caused by strains with and without the T6SS and identify possible associations between this putative virulence factor and the clinical manifestations of disease. Methods From April 2015 to January 2017, patients with detection of Campylobacter spp. were identified at the University Hospital of Basel and the University Children’s Hospital of Basel and included in this case-control study. Presence of the T6SS gene cluster was assayed by PCR targeting the hcp gene, confirmed with whole genome sequencing. Pertinent clinical data was collected by medical record review. Differences in disease- and host-characteristics between T6SS-positive (case) and –negative (control) were compared in a uni- and multi-variable analysis. Hospital admission, antibiotic therapy, admission to intensive care unit, development of bacteraemia and in-hospital mortality were considered as clinical endpoints. Results We identified 138 cases of Campylobacter jejuni infections and 18 cases of Campylobacter coli infections from a paediatric and adult population. Analyses were focused on adult patients with C. jejuni (n = 119) of which 16.8% were T6SS-positive. Comparisons between T6SS-positive and -negative C. jejuni isolates did not reveal significant differences regarding clinical manifestations or course of disease. All clinical endpoints showed a similar distribution in both groups. A higher score in the Charlson Comorbidity Index was associated with T6SS-positive C. jejuni isolates (p

AIM OF THE STUDY Teaching is one of the three pillars of medical-academic activity, alongside patient care and research. The aim of our study was to assess current teaching practice in the medical departments of the University Hospital Basel, Switzerland, in order to organise a faculty development programme tailored to local needs. METHODS We performed a cross-sectional online survey among the teaching faculty and the residents. For both groups, we assessed their estimation of the general importance and perceived frequency of various teaching formats in everyday practice. Additionally, we asked the senior physicians to evaluate their teaching competencies and the residents to state their opinion on factors promoting a positive learning experience. RESULTS Twenty-eight of 34 senior physicians (82%) and 48 of 90 residents (53%) participated in the study. Both groups broadly agreed on the importance of various teaching formats for the professional development of physicians, placing particular importance on bedside teaching, providing feedback, teaching during case discussions, and observation and modeling. However, the residents perceived that they obtained less teaching, feedback and support than the senior physicians perceived they were giving. Overall, teaching during case discussions represented the format most often applied, and it was also the one in which the senior physicians felt most competent. Residents claimed “time” to be the most important factor promoting a positive learning experience, followed by a positive attitude und the personal characteristics of the supervisor. CONCLUSION Our study shows that, despite being an integral part of everyday work at a university clinic, many aspects of current teaching practice allow discussion on possibilities of adaptations and improvement. Evaluation of current teaching practice provides the basis for designing a faculty development programme tailored to specific needs.

The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2nd, although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T ('Basel cluster'), including 157 identical sequences at the root of the 'Basel cluster', some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503.

BackgroundDue to the dramatic measures accompanying isolation and the general uncertainty and fear associated with COVID-19, patients and relatives may be at high risk for adverse psychological outcomes. Until now there has been limited research focusing on the prevalence of psychological distress and associated factors in COVID-19 patients and their relatives. The objective of our study was to assess psychological distress in COVID-19 patients and their relatives 30 days after hospital discharge.MethodsIn this prospective observational cohort study at two Swiss tertiary-care hospitals we included consecutive adult patients hospitalized between March and June 2020 for a proven COVID-19 and their relatives. Psychological distress was defined as symptoms of anxiety and/or depression measured with the Hospital Anxiety and Depression Scale (HADS), i.e., a score of ≥8 on the depression and/or anxiety subscale. We further evaluated symptoms of post-traumatic stress disorder (PTSD), defined as a score of ≥1.5 on the Impact of Event Scale-Revised (IES-R).ResultsAmong 126 included patients, 24 (19.1%) had psychological distress and 10 (8.7%) had symptoms of PTSD 30 days after hospital discharge. In multivariate logistic regression analyses three factors were independently associated with psychological distress in patients: resilience (OR 0.82; 95%CI 0.71 to 0.94; p = 0.005), high levels of perceived stress (OR 1.21; 95%CI 1.06 to 1.38; p = 0.006) and low frequency of contact with relatives (OR 7.67; 95%CI 1.42 to 41.58; p = 0.018). The model showed good discrimination, with an area under the receiver-operating characteristic curve (AUC) of 0.92. Among 153 relatives, 35 (22.9%) showed symptoms of psychological distress, and 3 (2%) of PTSD. For relatives, resilience was negatively associated (OR 0.85; 95%CI 0.75 to 0.96; p = 0.007), whereas perceived overall burden caused by COVID-19 was positively associated with psychological distress (OR 1.72; 95%CI 1.31 to 2.25; pConclusionA relevant number of COVID-19 patients as well as their relatives exhibited psychological distress 30 days after hospital discharge. These results might aid in development of strategies to prevent psychological distress in COVID-19 patients and their relatives.

(1) Background: Some COVID-19 vaccine recipients show breakthrough infection. It remains unknown, which factors contribute to risks and severe outcomes. Our aim was to identify risk factors for SCoV2 breakthrough infections in fully vaccinated individuals. (2) Methods: We conducted a retrospective case-control study from 28 December 2020 to 25 October 2021. Data of all patients with breakthrough infection was compared to data of all vaccine recipients in the Canton of Basel-City, Switzerland. Further, breakthrough infections by Alpha- and Delta-variants were compared. (3) Results: Only 0.39% (488/126,586) of all vaccine recipients suffered from a breakthrough infection during the observational period, whereof most cases were asymptomatic or mild (97.2%). Breakthrough infections after full vaccination occurred in the median after 78 days (IQR 47-123.5). Factors with lower odds for breakthrough infection were age (OR 0.987) and previous COVID-19 infection prior to vaccination (OR 0.296). Factors with higher odds for breakthrough infection included vaccination with Pfizer/BioNTech instead of Moderna (OR 1.459), chronic disease (OR 2.109), and healthcare workers (OR 1.404). (4) Conclusions: Breakthrough infections are rare and mild but can occur early after vaccination. This implies that booster vaccination might be initiated earlier, especially for risk groups. Due to new variants emerging repeatedly, continuous monitoring of breakthrough infections is crucial.

A dysregulated immune response with hyperinflammation is observed in patients with severe coronavirus disease 2019 (COVID-19). The aim of the present study was to assess the safety and potential benefits of human recombinant C1 esterase inhibitor (conestat alfa), a complement, contact activation and kallikrein-kinin system regulator, in severe COVID-19. Patients with evidence of progressive disease after 24 h including an oxygen saturation

BACKGROUND Physician well-being has an impact on productivity and quality of care. Residency training is a particularly stressful period. OBJECTIVE To assess the well-being of general internal medicine (GIM) residents and its association with personal and work-related factors. METHODS We conducted an anonymous electronic survey among GIM residents from 13 Swiss teaching hospitals. We explored the association between a reduced well-being (≥5 points based on the Physician Well-Being Index [PWBI]) and personal and work-related factors using multivariable mixed-effects logistic regression. RESULTS The response rate was 54% (472/880). Overall, 19% of residents had a reduced well-being, 60% felt burned out (emotional exhaustion), 47% were worried that their work was hardening them emotionally (depersonalisation), and 21% had career choice regret. Age (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.05–1.34), working hours per week (OR 1.04 per hour, 95% CI 1.01–1.07) and

The World Health Organization (WHO) declared the COVID-19 outbreak a “Public Health Emergency of International Concern” on 30 January 2020, after rapid spread from a few initial cases to thousands of cases across China and introductions into several other countries. On 11 March 2020, the WHO classified the outbreak as a pandemic. The first cases in Switzerland, Basel-Stadt, and Basel-Landschaft were confirmed on 25 February, 27 February and 28 February 2020. As of 22 April 2020, there are 28,154 confirmed cases in Switzerland, including 933 and 811 in the Cantons of Basel-Stadt and Basel-Landschaft, respectively. The rapid increase of confirmed cases in March suggests considerable community transmission. We estimated the reproductive number through time for the whole of Switzerland and its cantons for which sufficient data are available. For this estimation, we used publicly available data on the number of confirmed cases and COVID-related deaths through time, as well as additional data directly obtained from the University Hospital of Basel and the Cantonal Office of Public Health, Economics and Health Directorate of Basel-Landschaft. If the reproductive number is below 1, the epidemic is overall under control for that specific location, with the number of new infections per day decreasing through time. If this number is above 1, the epidemic is exponentially increasing in size. We found that the reproductive number in Switzerland was between 1.5 and 2 during the first third of March, and has consistently decreased to around 1. After the announcement of the latest strict measure on 20 March 2020, namely that gatherings of more than five people in public spaces are prohibited, the reproductive number dropped significantly below 1, we estimated the reproductive number to be between 0.6 and 0.8 in the first third of April. Our sensitivity analyses addressed the concern of a decreasing reproductive number being merely an artifact of less intense testing through time. In summary, our results suggest that from the last week of March onwards, the reproductive number was significantly below 1 in Switzerland and thus the epidemic was declining. However, our analyses do not allow us to identify a cause for this decline. From now on, we will provide daily estimates for the reproductive number on our webpage. Important to note in this respect is that estimates of the reproductive number lag about 10 days behind the last date of data collection since confirmation of the diagnosis occurs around 10 days after infection.

INTRODUCTION Code status discussions are useful for understanding patients’ preferences in the case of a cardiac/pulmonary arrest. These discussions can also provide patients with a basis for informed decision-making regarding life-sustaining treatment. We conducted a survey to understand current practices and perceptions of code status discussions in a tertiary-care Swiss hospital. METHODS We performed systematic interviews across different departments of the University Hospital of Basel. We interviewed 258 physicians and 145 patients who were hospitalised between May and July 2018 using a questionnaire designed to assess the use of code status discussions and to gauge patients’ individual experiences and opinions. RESULTS A total of 61.4% of patients did not recall having had a code status discussion during the hospital stay. However, a higher proportion of medical patients compared to surgical patients recalled having had a discussion (43.6 vs 22.4%, p = 0.03). For 9 out of 38 (23.7%) patients who did recall the discussion, there was a lack of agreement between the preference given in the interview regarding resuscitation measures and the documented code status in the medical electronic chart. Furthermore, a majority of physicians (72.4%) recalled defining a do-not-resuscitate (DNR) status for a patient without prior discussion with the patient. Physicians who recalled determining the DNR status without patient consultation reported conflicts with patients and relatives regarding code status at a higher rate compared to physicians who did not define DNR status without consultation (62.4 vs 39.4%, p

Sporopachydermia cereana is a rare yeast found in necrotic cactus tissue, predominantly in the Americas. Infection in humans with clinical data has only been reported in four patients so far, all of whom died, either directly from the pathogen or from other complications of immunosuppression. Treatment of the yeast is complicated by difficulties in identification of the pathogen with conventional diagnostic techniques and by intrinsic resistance to echinocandins. The first patient to survive a disseminated infection with S. cereana is presented herein. The patient had acute myeloid leukemia and was treated successfully with antifungal therapy and subsequently underwent a successful allogeneic hematopoietic stem cell transplantation.

AIMS OF THE STUDY Inappropriate use of antimicrobials is associated with the emergence of antimicrobial resistance and adverse events. Antimicrobial stewardship programmes may both optimise treatment of infections and reduce antimicrobial resistance but are implemented in only a minority of Swiss hospitals. In addition, data on prescribing patterns and quality are scarce. We conducted a repeated point prevalence survey to evaluate the quality of antimicrobial prescribing in a single tertiary care centre. METHODS Antimicrobial use was audited twice (summer 2017 and winter 2018) among all patients admitted to the University Hospital Basel, Switzerland. Data were collected from the electronic health record. Appropriateness of antimicrobial use was evaluated according to previously published rules and local national guidelines. RESULTS We evaluated 1112 patients of whom 378 (34%) received 548 prescriptions in total (30% for prophylaxis). Penicillins with β-lactamase inhibitors were most commonly used (30%), followed by cotrimoxazole (12%) and ceftriaxone (7%). Intravenous administration was chosen in 56% of patients. Prior to antimicrobial therapy, blood cultures were collected in 69% of patients. Overall, 182 (33%) prescriptions were not appropriate; reasons included lack of indication (11%), incorrect dosing (7%), delay in intravenous to oral switch (9%) or non-adherence to local guidelines (15%). A minority of patients received antimicrobials despite documented allergies (2%). Almost 38% of empirical prescriptions were inappropriate, compared with only 19% of prophylactic and 20% of targeted prescriptions. Penicillins with β-lactamase inhibitors and cephalosporins were most commonly involved in inappropriate prescribing (>50%) followed by carbapenems (30%), narrow-spectrum penicillins (17%) and cotrimoxazole (6%), with oral administration being involved less frequently than intravenous administration (15 vs 37%). Infectious diseases consultation and presence of immunosuppression were associated with reduced odds (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.21–0.70 and OR 0.31, 95% CI 0.17–0.54, respectively) of inappropriate prescription in the per-patient multivariable analysis, whereas being admitted to a surgical or intensive care unit was associated with increased odds (OR 1.83 and 5.67) compared with a medical unit. CONCLUSION Almost one third of prescriptions were inappropriate in our tertiary care centre despite local guidelines and an on-demand infectious diseases consultation service. Our results underscore the need for expanding current antimicrobial stewardship efforts, including national initiatives such as stewardship and prescribing guidelines, repeated surveys and identification of areas for improvement including timely intravenous to oral switches in order to reduce the consequences of inappropriate prescribing and of multidrug resistant organisms.

A variety of antiviral treatments for COVID-19 have been investigated, involving many repurposed drugs. Currently, the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8) has been targeted by numerous inhibitors, e.g., remdesivir, the only provisionally approved treatment to-date, although the clinical impact of these interventions remains inconclusive. However, the potential emergence of antiviral resistance poses a threat to the efficacy of any successful therapies on a wide scale. Here, we propose a framework to monitor the emergence of antiviral resistance, and as a proof of concept, we address the interaction between RdRp and remdesivir. We show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare in circulating lineages, and that those mutations, where present, do not destabilise RdRp. In more than 56,000 viral genomes from 105 countries from the first pandemic wave, we found negative selective pressure affecting nsp12 (Tajima’s D = −2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Potential escape mutations included known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations involved globally, in silico structural models found that they were unlikely to be associated with loss of stability in RdRp. No potential escape mutation was found in a local cohort of remdesivir treated patients. Collectively, these findings indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. We anticipate our framework to be the starting point of a larger effort for a global monitoring of drug resistance throughout the COVID-19 pandemic.

The recent crisis of refugees seeking asylum in European countries challenges public health on many levels. Most refugees currently arrive from Syria, Afghanistan, or Eritrea. Data about multidrug resistant bacteria (MDR) prevalence are not present for these countries. However, when entering the European heath care systems, data about colonisation rates regarding highly resistant bacterial pathogens are important.We performed a cross-sectional screening in four Swiss refugee centres to determine the colonization rates for MRSA and ESBL- and carbapenemase-producing Enterobacteriaceae. We used pharyngeal, nasal, and inguinal swabs for MRSA and rectal swabs and urine for ESBL and carbapenemase screening using standard microbiological procedures. Whole genome sequencing (WGS) was used to determine the relatedness of MRSA isolates with high resolution due to a suspected outbreak.41/261(15.7%) refugees were colonized with MRSA. No differences regarding the country of origin were observed. However, in a single centre significantly more were colonized, which was confirmed to be a recent local outbreak. 57/241 (23.7%) refugees were colonized with ESBL with significantly higher colonisation in persons originating from the Middle East (35.1%, p

[This corrects the article DOI: 10.1371/journal.pone.0170251.].

Polypharmacy and inappropriate medication prescriptions are associated with increased morbidity and mortality. Most interventions proposed to improve appropriate prescribing are time and resource intensive and therefore hardly applicable in daily clinical practice.To test the efficacy of an easy-to-use checklist aimed at supporting the therapeutic reasoning of physicians in order to reduce inappropriate prescribing and polypharmacy.We assessed the efficacy and safety of a 5-point checklist to be used by all physicians on the internal medicine wards of a Swiss hospital by comparing outcomes in 450 consecutive patients aged ≥65 years hospitalized after the introduction of the checklist, and in 450 consecutive patients ≥65 years hospitalized before the introduction of the checklist. The main measures were the proportion of patients with prescription of potentially inappropriate medications (PIMs) at discharge, according to STOPP criteria, and the number of prescribed medications at discharge, before and after the introduction of the checklist. Secondary outcomes were the prevalence of polypharmacy (≥ 5 drugs) and hyperpolypharmacy (≥ 10 drugs), and the prevalence of potentially inappropriate prescribing omissions (PPOs) according to START criteria.At admission 59% of the 900 patients were taking > 5 drugs, 13% ≥ 10 drugs, 37% had ≥ 1 PIM and 25% ≥ 1 PPO. The introduction of the checklist was associated with a significant reduction by 22% of the risk of being prescribed ≥ 1 PIM at discharge (adjusted risk ratios [RR] 0.78; 95% CI: 0.68-0.94), but not with a reduction of at least 20% of the number of drugs prescribed at discharge, nor with a reduction of the risk of PPOs at discharge.The introduction of an easy-to-use 5-point checklist aimed at supporting therapeutic reasoning of physicians on internal medicine wards significantly reduced the risk of prescriptions of inappropriate medications at discharge.

Certain bacteria dispersed by health-care workers can cause hospital infections. Asymptomatic health-care workers colonized rectally, vaginally, or on the skin with group A streptococci have caused outbreaks of surgical site infection by airborne dispersal. Outbreaks have been associated with skin colonization or viral upper respiratory tract infection in a phenomenon of airborne dispersal of Staphylococcus aureus called the "cloud" phenomenon. This review summarizes the data supporting the existence of cloud health-care workers.

BACKGROUND: Although most experts recommend empirical antibiotic treatment, covering also atypical bacteria, for patients admitted to an intensive care unit (ICU), the data are not clear for patients admitted to a general ward. European guidelines recommend starting empirical treatment with a beta-lactam antibiotic with or without a macrolide, but the with/without is not clarified. We investigated whether the use of antibiotic coverage for atypical pathogens was guided by clinical parameters. METHODS: We retrospectively analysed 300 patients hospitalised with community-acquired pneumonia. Four parameters for possible atypical pneumonia (age III the proportion receiving coverage for atypical bacteria was even smaller than in patients with less severe pneumonia (OR 0.77; 95% CI 0.60–0.99, p = 0.03), but no difference was found for PSI >IV compared with PSI ≤IV (OR = 1.03; 95% CI 0.61–1.74, p = 0.9). The other clinical parameters had no effect on antibiotic coverage: ICU admission (OR =1.39; 95% CI 0.87–2.4, p = 0.15); pO2>8 kPa or O2-Saturation >90% (OR 1.36; 95% CI 0.85–2.17, p = 0.19); abdominal symptoms (OR 1.06; 95% CI 0.51–2.25, p = 0.88); sodium

BACKGROUND: The urinary pneumococcal antigen (PnAG) test is widely used in the setting of community acquired pneumonia (CAP). Data regarding the impact of the test on antibiotic prescriptions are lacking. METHOD: The study population consisted of patients with suspicion of CAP in whom PnAG testing was performed. From November 2007 until August 2008, all patients in whom pneumococcal antigen testing (Binax Now®, PnAG) was performed were evaluated. In a second period, from September 2008 until March 2009, we stopped PnAG testing in our institution. We compared the microbiological verification procedures, antibiotic prescription and the final diagnosis of CAP of the first period (n = 139) against the second period (n = 147). RESULTS: Only 139/188 patients in whom PnAG was performed had CAP. Of these, 22 (15%) were PnAG positive. In 11/22 patients, the diagnosis of pneumococcal pneumonia was additionally confirmed by positive blood and/or sputum culture. In only 6 of the remaining 11 patients, antibiotic treatment was changed as a consequence of the positive PnAG test. In cases of blood culture positive and in sputum positive pneumococcal pneumonia, only 8/13 (61%) and 3/15 (20%) were PnAG positive, respectively. The costs of the PnAG test were 188 × 42 CHF (in total 7,896 CHF) and no cost savings were observed. Neither with empiric nor with consequently prescribed antibiotic treatment was a difference found between the PnAG and control period. CONCLUSION: In our patient population, the routine Binax Now® PnAG testing did not lead to cost savings or narrowing of antibiotic prescriptions. Thus, PnAG testing should be limited to cases of diagnostic uncertainty where blood or sputum cultures are negative or not available.