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Bone and joint infection (BJI) epidemiology and outcomes in solid organ transplant recipients (SOTr) remain largely unknown. We aim to describe BJI in a multi-center cohort of SOTr (Swiss Transplant Cohort Study). All consecutive SOTr with BJI (01.05.2008-31.12.2019) were included. A nested case-control study to identify risk factors for BJI was performed. Among 4482 patients, 61 SOTr with 82 BJI were included, at an incidence of 1.4% (95% CI 1.1-1.7), higher in heart and kidney-pancreas SOTr (Gray's test p .01). Although BJI were predominately late events (median of 18.5 months post-SOT), most infections occurred during the first year post-transplant in thoracic SOTr. Diabetic foot osteomyelitis was the most frequent infection (38/82, 46.3%), followed by non-vertebral osteomyelitis (26/82, 31.7%). Pathogens included Gram-positive cocci (70/131, 53.4%), Gram-negative bacilli (34/131, 26.0%), and fungi (9/131, 6.9%). BJI predictors included male gender (OR 2.94, 95% CI 1.26-6.89) and diabetes (OR 2.97, 95% CI 1.34-6.56). Treatment failure was observed in 25.9% (21/81) patients and 1-year mortality post-BJI diagnosis was 14.8% (9/61). BJI remain a rare event in SOTr, associated with subtle clinical presentations, high morbidity and relapses, requiring additional studies in the future.

Background With the increasing dimensions of the international cardiac surgery-associated Mycobacterium chimaera outbreak the hypothesis of a point source arose. Objectives To review the published evidence of clonality among cardiac surgery-associated M. chimaera isolates evaluated by whole-genome sequencing (WGS) and to perform an integrative genomic analysis of available genome data. Data sources We searched PubMed and EMBASE for studies applying WGS on cardiac surgery-associated M. chimaera isolates. Study eligibility criteria We included studies that applied WGS on more than a single M. chimaera isolate. Methods Two authors independently extracted data from included studies. Available genome data from published studies were subjected to a joint analysis. Results Of 121 identified articles, nine studies were included. M. chimaera isolates from LivaNova heater–cooler devices (HCDs) had a high level of genetic similarity, but were genetically distant from isolates from HCDs produced by other manufacturers. With the exception of a single (11.1%) study, the remaining eight (89.9%) studies reported a high level of genetic proximity between the majority of M. chimaera isolates derived from cardiac surgery-associated patients and LivaNova HCDs. In-depth analysis revealed involvement of three distinct M. chimaera subgroups in the outbreak (1.1, 1.8, 2.1), with 1.1 suggested as causative of the outbreak. Samples taken at the LivaNova production site supported contamination with strains of subgroups 1.1 and 1.8. In the combined analysis of 526 publicly available WGS data sets, nearly all isolates from cardiac surgery-associated patients contained strain 1.1 (50/52, 96.2%), and at least one of the outbreak strains was found in almost all LivaNova HCDs (241/257, 93.8%), with strain 1.1 in particular present in 198/257 (77.0%). Conclusions HCD contamination during production seems plausible as the predominant point source for the global M. chimaera outbreak. Although HCDs can be contaminated with mixed populations, M. chimaera strains of the subgroup 1.1 caused most infections.

Item does not contain fulltext BACKGROUND: Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease. METHODS: We included 24 M chimaera isolates from 21 cardiac surgery-related patients in Switzerland, Germany, the Netherlands, and the UK, 218 M chimaera isolates from various types of HCUs in hospitals, from LivaNova (formerly Sorin; London, UK) and Maquet (Rastatt, Germany) brand HCU production sites, and unrelated environmental sources and patients, as well as eight Mycobacterium intracellulare isolates. Isolates were analysed by next-generation whole-genome sequencing using Illumina and Pacific Biosciences technologies, and compared with published M chimaera genomes. FINDINGS: Phylogenetic analysis based on whole-genome sequencing of 250 isolates revealed two major M chimaera groups. Cardiac surgery-related patient isolates were all classified into group 1, in which all, except one, formed a distinct subgroup. This subgroup also comprised isolates from 11 cardiac surgery-related patients reported from the USA, most isolates from LivaNova HCUs, and one from their production site. Isolates from other HCUs and unrelated patients were more widely distributed in the phylogenetic tree. INTERPRETATION: HCU contamination with M chimaera at the LivaNova factory seems a likely source for cardiothoracic surgery-related severe M chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the UK, the USA, and Australia. Protective measures and heightened clinician awareness are essential to guarantee patient safety. FUNDING: Partly funded by the EU Horizon 2020 programme, its FP7 programme, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance.

We assessed infection prevention in Swiss hospitals via a national survey focusing on infection prevention practices prior to a large national infection prevention initiative. Of the 59 hospitals that responded (77%), 98% had infection prevention teams and 40% very good or excellent leadership support. However, a minority of hospitals used recommended infection prevention practices and surveillance systems regularly.

Background Since the onset of the COVID-19 pandemic, the disease has frequently been compared with seasonal influenza, but this comparison is based on little empirical data. Aim This study compares in-hospital outcomes for patients with community-acquired COVID-19 and patients with community-acquired influenza in Switzerland. Methods This retrospective multi-centre cohort study includes patients > 18 years admitted for COVID-19 or influenza A/B infection determined by RT-PCR. Primary and secondary outcomes were in-hospital mortality and intensive care unit (ICU) admission for patients with COVID-19 or influenza. We used Cox regression (cause-specific and Fine-Gray subdistribution hazard models) to account for time-dependency and competing events with inverse probability weighting to adjust for confounders. Results In 2020, 2,843 patients with COVID-19 from 14 centres were included. Between 2018 and 2020, 1,381 patients with influenza from seven centres were included; 1,722 (61%) of the patients with COVID-19 and 666 (48%) of the patients with influenza were male (p Conclusion Community-acquired COVID-19 was associated with worse outcomes compared with community-acquired influenza, as the hazards of ICU admission and in-hospital death were about two-fold to three-fold higher.

BackgroundWhen comparing the periods of time during and after the first wave of the ongoing SARS-CoV-2/COVID-19 pandemic in Europe, the associated COVID-19 mortality seems to have decreased substantially. Various factors could explain this trend, including changes in demographic characteristics of infected persons, and the improvement of case management. To date, no study has been performed to investigate the evolution of COVID-19 in-hospital mortality in Switzerland, while also accounting for risk factors.MethodsWe investigated the trends in COVID-19 related mortality (in-hospital and in-intermediate/intensive-care) over time in Switzerland, from February 2020 to May 2021, comparing in particular the first and the second wave. We used data from the COVID-19 Hospital-based Surveillance (CH-SUR) database. We performed survival analyses adjusting for well-known risk factors of COVID-19 mortality (age, sex and comorbidities) and accounting for competing risk.ResultsOur analysis included 16,030 episodes recorded in CH-SUR, with 2,320 reported deaths due to COVID-19 (13.0% of included episodes). We found that overall in-hospital mortality was lower during the second wave of COVID-19 compared to the first wave (HR 0.71, 95% CI 0.69 – 0.72, p-value < 0.001), a decrease apparently not explained by changes in demographic characteristics of patients. In contrast, mortality in intermediate and intensive care significantly increased in the second wave compared to the first wave (HR 1.48, 95% CI 1.42 – 1.55, p-value < 0.001), with significant changes in the course of hospitalisation between the first and the second wave.ConclusionWe found that, in Switzerland, COVID-19 mortality decreased among hospitalised persons, whereas it increased among patients admitted to intermediate or intensive care, when comparing the second wave to the first wave. We put our findings in perspective with changes over time in case management, treatment strategy, hospital burden and non-pharmaceutical interventions. Further analyses of the potential effect of virus variants and of vaccination on mortality would be crucial to have a complete overview of COVID-19 mortality trends throughout the different phases of the pandemic.

Among 400 Aspergillus species from respiratory samples in Switzerland, Aspergillus fumigatus was the most frequent species. Non-fumigatus Aspergillus spp were more prevalent among solid organ transplant recipients and after azole exposure. Azole resistance was detected in 4 A fumigatus isolates, 3 of them with the “environmental” mutation TR34/L98H in the cyp51A gene.

Background The increasing incidence of candidemia and emergence of drug-resistant Candida species are major concerns worldwide. Long-term surveillance studies are needed. Methods The Fungal Infection Network of Switzerland (FUNGINOS) conducted a 15-year (2004–2018), nationwide, epidemiological study of candidemia. Hospital-based incidence of candidemia, Candida species distribution, antifungal susceptibility, and consumption were stratified in 3 periods (2004–2008, 2009–2013, 2014–2018). Population-based incidence over the period 2009–2018 derived from the Swiss Antibiotic Resistance Surveillance System (ANRESIS). Results A total of 2273 Candida blood isolates were studied. Population and hospital-based annual incidence of candidemia increased from 2.96 to 4.20/100 000 inhabitants (P = .022) and 0.86 to 0.99/10 000 patient-days (P = .124), respectively. The proportion of Candida albicans decreased significantly from 60% to 53% (P = .0023), whereas Candida glabrata increased from 18% to 27% (P < .0001). Other non-albicans Candida species remained stable. Candida glabrata bloodstream infections occurred predominantly in the age group 18–40 and above 65 years. A higher proportional increase of C glabrata was recorded in wards (18% to 29%, P < .0001) versus intensive care units (19% to 24%, P = .22). According to Clinical and Laboratory Standards Institute, nonsusceptibility to fluconazole in C albicans was observed in 1% of isolates, and anidulafungin and micafungin nonsusceptibility was observed in 2% of C albicans and C glabrata. Fluconazole consumption, the most frequently used antifungal, remained stable, whereas use of mold-active triazoles and echinocandins increased significantly in the last decade (P < .0001). Conclusions Over the 15-year period, the incidence of candidemia increased. A species shift toward C glabrata was recently observed, concurring with increased consumption of mold-active triazoles., The incidence of candidemia increased in Switzerland from 2004 to 2018. A species shift toward C glabrata was observed after 2013, now accounting for one fourth of all candidemia, concurring with increased consumption of mold-active triazoles.

Early identification and isolation of SARS-CoV-2-infected individuals is central to contain the COVID-19 pandemic. Nasopharyngeal swabs (NPS) serve as a specimen for detection by RT-PCR and rapid antigen screening tests. Saliva has been confirmed as a reliable alternative specimen for RT-PCR and has been shown to be valuable for diagnosing children and in repetitive mass testing due to its non-invasive collection. Combining the advantages of saliva with those of antigen tests would be highly attractive to further increase test capacities. Here, we evaluated the performance of the Elecsys SARS-CoV-2 Antigen assay (Roche) in RT-PCR-positive paired NPS and saliva samples (N = 87) and unpaired NPS (N = 100) with confirmed SARS-CoV-2 infection (Roche cobas SARS-CoV-2 IVD test). We observed a high positive percent agreement (PPA) of the antigen assay with RT-PCR in NPS, reaching 87.2% across the entire cohort, whereas the overall PPA for saliva was insufficient (40.2%). At Ct values ≤ 28, PPA were 100% and 91.2% for NPS and saliva, respectively. At lower viral loads, the sensitivity loss of the antigen assay in saliva was striking. At Ct values ≤ 35, the PPA for NPS remained satisfactory (91.5%), whereas the PPA for saliva dropped to 46.6%. In conclusion, saliva cannot be recommended as a reliable alternative to NPS for testing with the Elecsys Anti-SARS-CoV-2 Antigen assay. As saliva is successfully used broadly in combination with RT-PCR testing, it is critical to create awareness that suitability for RT-PCR cannot be translated to implementation in antigen assays without thorough evaluation of each individual test system.

Background Understaffing has been previously reported as a risk factor for central line-associated bloodstream infections (CLABSI). No previous study addressed the question whether fluctuations in staffing have an impact on CLABSI incidence. We analyzed prospectively collected CLABSI surveillance data and data on employee turnover of health care workers (HCW) to address this research question. Methods In January 2016, a semiautomatic surveillance system for CLABSI was implemented at the University Hospital Zurich, a 940 bed tertiary care hospital in Switzerland. Monthly incidence rates (CLABSI/1000 catheter days) were calculated and correlations with human resources management-derived data on employee turnover of HCWs (defined as number of leaving HCWs per month divided by the number of employed HCWs) investigated. Results Over a period of 24 months, we detected on the hospital level a positive correlation of CLABSI incidence rates and turnover of nursing personnel (Spearman rank correlation, r = 0.467, P = 0.022). In more detailed analyses on the professional training of nursing personnel, a correlation of CLABSI incidence rates and licensed practical nurses (Spearman rank correlation, r = 0.26, P = 0.038) or registered nurses (r = 0.471, P = 0.021) was found. Physician turnover did not correlate with CLABSI incidence (Spearman rank correlation, r = −0.058, P = 0.787). Conclusions Prospectively determined CLABSI incidence correlated positively with the degree of turnover of nurses overall and nurses with advanced training, but not with the turnover of physicians. Efforts to maintain continuity in nursing staff might be helpful for sustained reduction in CLABSI rates.

Background Before kidney transplantation, donors and recipients are routinely screened for viral pathogens using specific tests. Little is known about unrecognized viruses of the urinary tract that potentially result in transmission. Using an open metagenomic approach, we aimed to comprehensively assess virus transmission in living-donor kidney transplantation. Methods Living kidney donors and their corresponding recipients were enrolled at the time of transplantation. Follow-up study visits for recipients were scheduled 4–6 weeks and 1 year thereafter. At each visit, plasma and urine samples were collected and transplant recipients were evaluated for signs of infection or other transplant-related complications. For metagenomic analysis, samples were enriched for viruses, amplified by anchored random polymerase chain reaction (PCR), and sequenced using high-throughput metagenomic sequencing. Viruses detected by sequencing were confirmed using real-time PCR. Results We analyzed a total of 30 living kidney donor and recipient pairs, with a follow-up of at least 1 year. In addition to viruses commonly detected during routine post-transplant virus monitoring, metagenomic sequencing detected JC polyomavirus (JCPyV) in the urine of 7 donors and their corresponding recipients. Phylogenetic analysis confirmed infection with the donor strain in 6 cases, suggesting transmission from the transplant donor to the recipient, despite recipient seropositivity for JCPyV at the time of transplantation. Conclusions Metagenomic sequencing identified frequent transmission of JCPyV from kidney transplant donors to recipients. Considering the high incidence rate, future studies within larger cohorts are needed to define the relevance of JCPyV infection and the donor’s virome for transplant outcomes., Kidney transplantation is inevitably associated with the transmission of viral and microbial pathogens. Using metagenomic virome sequencing, we revealed JC polyomavirus (JCPyV) transmission in 20% of cases, despite seropositivity. The relevance of JCPyV infection in kidney transplantation demands further attention.

Healthcare-associated outbreaks of vancomycin-resistant Enterococcus faecium (VREfm) are a worldwide problem with increasing prevalence. The genomic plasticity of this hospital-adapted pathogen contributes to its efficient spread despite infection control measures. Here, we aimed to identify the genomic and phenotypic determinants of healthcare-associated transmission of VREfm. We assessed the VREfm transmission networks at the tertiary-care University Hospital of Zurich (USZ) between October 2014 and February 2018 and investigated microevolutionary dynamics of this pathogen. We performed whole-genome sequencing for the 69 VREfm isolates collected during this timeframe and assessed the population structure and variability of the vancomycin resistance transposon. Phylogenomic analysis allowed us to reconstruct transmission networks and to unveil external or indirect transmission networks, not detectable by traditional surveillance. Notably, it unveiled a persistent clone, sampled 31 times over a 29-month period. Exploring the evolutionary dynamics of this clone and characterizing the phenotypic consequences revealed the spread of a variant with decreased daptomycin susceptibility and the acquired ability to utilize N-acetyl-galactosamine (GalNAc), one of the primary constituents of the human gut mucins. This nutrient utilization advantage was conferred by a novel plasmid, termed pELF_USZ, which exhibited a linear topology. This plasmid, which was harbored by two distinct clones, was transferable by conjugation. Overall, this work provides an example of the potential of the integration of epidemiological, functional genomic and evolutionary perspectives to understand adaptation strategies contributing to the successful spread of VREfm.Significance statementSequencing microbial pathogens causing outbreaks has become a common practice to characterize transmission networks. In addition to the signal provided by vertical evolution, bacterial genomes harbor mobile genetic elements, shared horizontally between clones. While macroevolutionary studies have revealed an important role of plasmids and genes encoding carbohydrate utilization systems in the adaptation of Enterococcus faecium to the hospital environment, mechanisms of dissemination and the specific function of many of these genetic determinants remain to be elucidated. Here, we characterize a plasmid providing a nutrient utilization advantage and show evidence for its clonal and horizontal spread at a local scale. Further studies integrating epidemiological, functional genomics and evolutionary perspectives will be critical to identify changes shaping the success of this pathogen.

BackgroundRT-PCR of nasopharyngeal swabs (NPS) is the acknowledged gold standard for the detection of SARS-CoV-2 infection. Rising demands for repetitive screens and mass-testing necessitate, however, the development of additional test strategies. Saliva may serve as an alternative to NPS as its collection is simple, non-invasive and amenable for mass- and home-testing but rigorous validation of saliva particularly in children is missing.MethodsWe conducted a large-scale head-to-head comparison of SARS-CoV-2 detection by RT-PCR in saliva and nasopharyngeal swab (NPS) of 1270 adults and children reporting to outpatient test centers and an emergency unit for an initial SARS-CoV-2 screen. The saliva collection strategy developed utilizes common, low-cost plastic tubes, does not create biohazard waste at collection and was tailored for self-collection and suitability for children.ResultsIn total, 273 individuals were tested SARS-CoV-2 positive in either NPS or saliva. SARS-CoV-2 RT-PCR results in the two specimens showed a high agreement (Overall Percent Agreement = 97.8%). Despite lower viral loads in saliva of both adults and children, detection of SARS-CoV-2 in saliva compared well to NPS (Positive Percent Agreement = 92.5%). Importantly, in children, SARS-CoV-2 infections were more often detected in saliva than NPS (Positive Predictive Value = 84.8%), underlining that NPS sampling in children can be challenging.ConclusionsThe comprehensive parallel analysis reported here establishes saliva as a generally reliable specimen for the detection of SARS-CoV-2 with particular advantages for testing children that is readily applicable to increase and facilitate repetitive and mass-testing in adults and children.Article Summary Main PointsComparison with nasopharyngeal swabs in a large test center-based study confirms that saliva is a reliable and convenient material for the detection of SARS-CoV-2 by RT-PCR in adults and increases detection efficacy in children.

The rapid spread of the coronavirus disease 2019 pandemic urged immense testing capacities as one cornerstone of infection control. Many institutions opened outpatient SARS-CoV-2 test centers to allow large number of tests in comparatively short time frames. With increasing positive test rates, concerns for a possible airborne or droplet contamination of specimens leading to false-positive results were raised. In our experimental series performed in a dedicated SARS-CoV-2 test center, 40 open collection tubes placed for defined time periods in proximity to individuals were found to be SARS-CoV-2 negative. These findings argue against false-positive SARS-CoV-2 results due to droplet or airborne contamination.

BACKGROUND SARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world with several million victims in 213 countries. Switzerland was severely hit by the virus, with 43,000 confirmed cases as of 1 September 2020. AIM In cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19, in addition to their mandatory reporting system. METHODS Patients hospitalised for more than 24 hours with a positive polymerase chain-reaction test, from 20 Swiss hospitals, are included. Data were collected in a customised case report form based on World Health Organisation recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms was more than 5 days after the patient’s admission date. RESULTS As of 1 September 2020, 3645 patients were included. Most patients were male (2168, 59.5%), and aged between 50 and 89 years (2778, 76.2%), with a median age of 68 (interquartile range 54–79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported, with hypertension (1481, 61.7%), cardiovascular diseases (948, 39.5%) and diabetes (660, 27.5%) being the most frequent in adults; respiratory diseases and asthma (4, 21.1%), haematological and oncological diseases (3, 15.8%) were the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly respiratory diseases (2470, 93.2% in adults; 16, 55.2% in children), and renal (681, 25.7%) and cardiac (631, 23.8%) complications for adults. The second and third most frequent complications in children affected the digestive system and the liver (7, 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989, 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. A total of 527 (14.5%) deaths were registered, all among adults. CONCLUSION The surveillance system has been successfully initiated and provides a robust set of data for Switzerland by including about 80% (compared with official statistics) of SARS-CoV-2/COVID-19 hospitalised patients, with similar age and comorbidity distributions. It adds detailed information on the epidemiology, risk factors and clinical course of these cases and, therefore, is a valuable addition to the existing mandatory reporting.

Daily chlorhexidine bathing has been associated with a reduction in central line-associated bloodstream infections (CLABSI). In the setting of an already established CLABSI surveillance system and an implemented CLABSI prevention bundle, we analysed the effect of daily chlorhexidine bathing in ICU patients on CLABSI incidence and its causative pathogens.This was a before-and-after study in intensive care units (ICUs) at a tertiary-care centre in Switzerland. Prospective surveillance of CLABSIs and their aetiologies was established. The intervention consisted of daily chlorhexidine bathing of ICU patients with a central venous catheter. A baseline period of 19 months was followed by an intervention period of 9 months.A total of 5008 patients were included. In the baseline period a mean CLABSI rate of 2.45/1000 catheter days (95% confidence interval (CI) 1.93-3.07) was observed, followed by 1.00/1000 catheter days (95% CI 0.55-1.67; P0.001) in the intervention period. Introduction of chlorhexidine bathing was independently associated with a reduced risk of CLABSI (adjusted odds ratio 0.47, 95% CI 0.26-0.84, P=0.011). We did not observe a significant change in aetiology except for an increase of Serratia marcescens in the intervention period.Introduction of daily chlorhexidine bathing resulted in a decline in CLABSI incidence on ICUs. Starting from a baseline CLABSI rate that can be considered standard in a high-income setting and several measures for CLABSI prevention implemented, chlorhexidine bathing proved helpful for a further reduction.

BackgroundSARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world causing several million victims in 213 countries. Switzerland was severely hit by the virus, with 43’000 confirmed cases as of September 1st, 2020.AimIn cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19 in addition to their mandatory reporting system.MethodsPatients hospitalised for more than 24 hours with a positive PCR test, from 20 Swiss hospitals, are included. Data collection follows a custom Case Report Form based on WHO recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms started more than 5 days after the patient’s admission date.ResultsAs of September 1st, 2020, 3645 patients were included. Most patients were male (2168 - 59.5%),and aged between 50 and 89 years (2778 - 76.2%), with a median age of 68 (IQR 54-79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported: hypertension (1481 - 61.7%), cardiovascular diseases (948 - 39.5%), and diabetes (660 - 27.5%) being the most frequent in adults; respiratory diseases and asthma (4 −21.1%), haematological and oncological diseases (3 – 15.8%) being the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly for respiratory diseases (2470 - 93.2% in adults, 16 – 55.2% in children), renal (681 – 25.7%) and cardiac (631 – 23.8%) complication for adults. The second and third most frequent complications in children affected the digestive system and the liver (7 - 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989 - 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. 527 (14.5%) deaths were registered, all among adults.ConclusionThe surveillance system has been successfully initiated and provides a very representative set of data for Switzerland. We therefore consider it to be a valuable addition to the existing mandatory reporting, providing more precise information on the epidemiology, risk factors, and clinical course of these cases.

BackgroundSuper-spreaders are individuals infecting disproportionately large numbers of contacts. They probably play a crucial role in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe a super-spreading event within a team working in an open-space office and investigate factors potentially having facilitated SARS-CoV-2 transmission.MethodsIn this retrospective cohort study, semi-structured telephone interviews with all team members were carried out to identify symptoms, contacts, and adherence to basic hygiene measures. During site visits, we gathered information about workplace and seating arrangements. The secondary attack rate in office and households was calculated. Potential respiratory viral co-infections were assessed by multiplex PCR. SARS-CoV-2 whole-genome sequencing was performed using a tiled-amplicon sequencing approach.ResultsOf 13 team members, 11 fell ill with Coronavirus disease 2019 (COVID-19). Due to the sequence of events and full genome sequence data, one person was considered the index case for this outbreak, directly infecting 67 to 83% of the teammates. All team members reported repetitive close contacts among themselves during joint computer work, team meetings and a “Happy Birthday” serenade. Two individuals shared nuts and dates. The arrangement of the office and meeting rooms precluded sufficient adherence to physical distancing. The index case and a further individual were diagnosed with an adenovirus serotype 4 co-infection.ConclusionWe identified several environmental and behavioral factors that probably have facilitated the transmission of SARS-CoV-2. The relevance of the adenovirus co-infection remains unclear and merits further investigation.

SUMMARY Objective The international outbreak of cardiac-surgery-associated Mycobacterium chimaera infections was traced back to infectious aerosols originating from contaminated water reservoirs of heater-cooler devices (HCDs). In general, non-tuberculous mycobacteria (NTM) frequently colonize water systems and can contaminate medical devices. Data on detection of NTM other than M. chimaera in samples gathered from HCDs are scarce. The present study summarizes prospective mycobacterial surveillance of five HCDs over more than 4 years. Methods Five LivaNova 3T (London, UK) HCDs, acquired factory-new in 2014, were followed prospectively. Until mid-April 2014, the HCDs were maintained according to the manufacturer's recommendations, and subsequently, they were maintained according to an intensified in-house protocol including exhaust air evacuation. Mycobacterial surveillance cultures consisted of monthly water samples gathered from patient and cardioplegia circuits, as well as airflow samples. Results Of 441 water samples, 170 (38.6%) revealed NTM growth. The most frequently detected NTM were M. chimaera [N=120 (67.4%)], Mycobacterium gordonae [N=35 (19.7 %)] and Mycobacterium paragordonae [N=17 (9.6%)]. Growth of NTM, M. chimaera and M. paragordonae was significantly more common in water samples derived from the patient circuit than the cardioplegia circuit of the HCD. Three (2.0%) of 150 air samples grew NTM. Conclusion Growth of NTM in HCD water samples was common. Diverse NTM species were detected, with M. chimaera being the most common. The majority of air samples remained negative. The relevance of NTM other than M. chimaera contaminating HCDs is poorly defined, but a recent report on an HCD-associated outbreak with Mycobacterium abscessus confirmed a potential threat.

AIMS OPF THE STUDY Healthy adults have had the option to receive prescriptionless vaccination against influenza in pharmacies of several Swiss cantons since the 2015/16 influenza season. We aimed to assess in a cost-benefit analysis the resulting net benefits for the Swiss economy and public health, and the benefits that could be expected if an extension of the current vaccination recommendations was implemented. METHODS The proportion of influenza vaccines administered in pharmacies was calculated from data provided by pharmacies entering information in phS-net.ch, data from vaccines covered by insurance companies, and vaccine supply data. The economic and public health impact was estimated in a cost-benefit analysis based on published data. RESULTS In the 2016/17 and 2017/18 influenza seasons, 7306 of a total of 1.07 million (0.7%) and 15,617 of a total of 1.15 million (1.4%) influenza vaccine doses, respectively, were administered in pharmacies in Switzerland. The net cost savings for the economy due to vaccination in pharmacies in the 2016/17 and 2017/18 seasons were CHF 66,633 and CHF 143,021, respectively. In the 2017/18 season, this resulted –in a net saving per 100,000 inhabitants of CHF 1918, 94.4 cases of illness, 17.6 visits to primary care physicians, 0.328 hospitalisations, 1.1 hospitalisation days, 0.019 deaths prevented, and 0.353 life-years gained. Influenza vaccination proved to be cost-effective provided that a vaccine efficacy of 59% is exceeded. Extrapolations for the healthy, working-age population revealed that a vaccination coverage rate of 50% and a vaccine efficacy of 70% could save the Swiss economy CHF 18.4 million annually. CONCLUSIONS The service allowing citizens to receive influenza vaccination in Swiss pharmacies is sparsely used. Since influenza vaccination is cost-beneficial as soon as vaccine efficacy surpasses a critical threshold, an extension of the vaccine recommendation for healthy, working-age adults should be considered from an economic point of view.

In the general population, Mycoplasma spp. and Ureaplasma spp. are considered as pathogens with low virulence. Asymptomatic urogenital colonization with genital mycoplasmas is common. M. pneumoniae infections most frequently present as tracheobronchitis. In immunosuppressed individuals, a broad spectrum of invasive diseases has been attributed to these pathogens. After kidney transplantation and hematopoietic stem cell transplantation, Mycoplasma spp. and Ureaplasma spp. have been detected as causative pathogens in urogenital infections. Surgical site infections following solid organ transplantation are rarely caused by Mycoplasma spp. and Ureaplasma spp.. Recently, an association between hyperammonemia syndrome and genital mycoplasmas has been described after lung, kidney, and hematopoietic stem cell transplantation. Hyperammonemia syndrome, characterized by a combination of progressive elevations in plasma ammonium levels and worsening neurological symptoms, is a rare but potentially fatal disorder. Routine cultural approaches are poorly sensitive, and nucleic acid amplification tests should be applied for diagnosis. Commonly used broad-spectrum antibiotics are frequently not active against these cell wall-lacking bacteria. Mycoplasma spp. or Ureaplasma spp. should be considered as etiologic agents if routine diagnostics do not identify relevant pathogens or if response to empiric antibiotic therapy is insufficient.

Using prospectively collected surveillance data at a tertiary care hospital in Central Europe, we investigated seasonal differences in central line-associated bloodstream infection incidence. Central line-associated bloodstream infection incidence rates were highest during the third quarter over an observation period of 24 months. Investigating influence of meteorological parameters identified a significant correlation with precipitation (r = 0.460, P = .023).

Background Aspergillus spp. of section Usti (A. ustus) represent a rare cause of invasive aspergillosis (IA). This multicenter study describes the epidemiology and outcome of A. ustus infections. Methods Patients with A. ustus isolated from any clinical specimen were retrospectively identified in 22 hospitals from 8 countries. When available, isolates were sent for species identification (BenA/CaM sequencing) and antifungal susceptibility testing. Additional cases were identified by review of the literature. Cases were classified as proven/probable IA or no infection, according to standard international criteria. Results Clinical report forms were obtained for 90 patients, of whom 27 had proven/probable IA. An additional 45 cases were identified from literature review for a total of 72 cases of proven/probable IA. Hematopoietic cell and solid-organ transplant recipients accounted for 47% and 33% cases, respectively. Only 8% patients were neutropenic at time of diagnosis. Ongoing antimold prophylaxis was present in 47% of cases. Pulmonary IA represented 67% of cases. Primary or secondary extrapulmonary sites of infection were observed in 46% of cases, with skin being affected in 28% of cases. Multiple antifungal drugs were used (consecutively or in combination) in 67% of cases. The 24-week mortality rate was 58%. A. calidoustus was the most frequent causal agent. Minimal inhibitory concentrations encompassing 90% isolates (MIC90) were 1, 8, >16, and 4 µg/mL for amphotericin B, voriconazole, posaconazole, and isavuconazole, respectively. Conclusions Aspergillus ustus IA mainly occurred in nonneutropenic transplant patients and was frequently associated with extrapulmonary sites of infection. Mortality rate was high and optimal antifungal therapy remains to be defined.

Objectives Conducting manual surveillance of non-ventilator-associated hospital-acquired pneumonia (nvHAP) using ECDC (European Centre for Disease Prevention and Control) surveillance criteria is very resource intensive. We developed and validated a semi-automated surveillance system for nvHAP, and describe nvHAP incidence and aetiology at our hospital. Methods We applied an automated classification algorithm mirroring ECDC definition criteria to distinguish patients ‘not at risk' from patients ‘at risk' for suffering from nvHAP. ‘At risk'-patients were manually screened for nvHAP. For validation, we applied the reference standard of full manual evaluation to three validation samples comprising 2091 patients. Results Among the 39 519 University Hospital Zurich inpatient discharges in 2017, the algorithm identified 2454 ‘at-risk' patients, reducing the number of medical records to be manually screened by 93.8%. From this subset, nvHAP was identified in 251 patients (0.64%, 95%CI: 0.57–0.73). Sensitivity, negative predictive value, and accuracy of semi-automated surveillance versus full manual surveillance were lowest in the validation sample consisting of patients with HAP according to the International Classification of Diseases (ICD-10) discharge diagnostic codes, with 97.5% (CI: 93.7–99.3%), 99.2% (CI: 97.9–99.8%), and 99.4% (CI: 98.4–99.8%), respectively. The overall incidence rate of nvHAP was 0.83/1000 patient days (95%CI: 0.73–0.94), with highest rates in haematology/oncology, cardiac and thoracic surgery, and internal medicine including subspecialties. Conclusions The semi-automated surveillance demonstrated a very high sensitivity, negative predictive value, and accuracy. This approach significantly reduces manual surveillance workload, thus making continuous nvHAP surveillance feasible as a pivotal element for successful prevention efforts.

Infections caused by carbapenemase-producing, multidrug-resistant (MDR), or extensively drug-resistant (XDR) Gram-negative bacteria constitute a major therapeutic challenge. Whether combination antibiotic therapy is superior to monotherapy remains unknown. In this systematic review and meta-analysis OVID MEDLINE, EMBASE, PubMed, The Cochrane Library, and Scopus databases were searched for randomized controlled trials (RCTs) and observational studies published by December 2016 comparing mono- with combination antibiotic therapy for infections with carbapenemase-producing, MDR, or XDR Gram-negative bacteria. Mortality and clinical cure rates served as primary and secondary outcome measures, respectively. Of 8847 initially identified studies, 53 studies – covering pneumonia (n = 10 studies), blood stream (n = 15), osteoarticular (n = 1), and mixed infections (n = 27) - were included. 41% (n = 1848) of patients underwent monotherapy, and 59% (n = 2666) combination therapy. In case series/cohort studies (n = 45) mortality was lower with combination- vs. monotherapy (RR 0.83, CI 0.73–0.93, p = 0.002, I2 = 24%). Subgroup analysis revealed lower mortality with combination therapy with at least two in-vitro active antibiotics, in blood stream infections, and carbapenemase-producing Enterobacteriaceae. No mortality difference was seen in case-control studies (n = 6) and RCTs (n = 2). Cure rates did not differ regardless of study type. The two included RCTs had a high and unknown risk of bias, respectively. 16.7% (1/6) of case-control studies and 37.8% (17/45) of cases series/cohort studies were of good quality, whereas quality was poor in the remaining studies. In conclusion, combination antimicrobial therapy of multidrug-resistant Gram-negative bacteria appears to be superior to monotherapy with regard to mortality.