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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.

Switzerland began a national lockdown on March 16, 2020, in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the prevalence of SARS-CoV-2 infection among patients admitted to 4 hospitals in the canton of Zurich, Switzerland, in April 2020. These 4 acute care hospitals screened 2,807 patients, including 2,278 (81.2%) who did not have symptoms of coronavirus disease (COVID-19). Overall, 529 (18.8%) persons had >1 symptom of COVID-19, of whom 60 (11.3%) tested positive for SARS-CoV-2. Eight asymptomatic persons (0.4%) also tested positive for SARS-CoV-2. Our findings indicate that screening on the basis of COVID-19 symptoms, regardless of clinical suspicion, can identify most SARS-CoV-2–positive persons in a low-prevalence setting.

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 health care-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 time frame 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 wider transmission networks undetectable by routine 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 highlights the potential of combining epidemiological, functional genomic, and evolutionary perspectives to unveil adaptation strategies of VREfm., mBio, 132 (2), ISSN:2150-7511, ISSN:2161-2129

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.

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.

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.

Background In intensive care units (ICUs) treating patients with Coronavirus disease 2019 (COVID-19) invasive ventilation poses a high risk for aerosol and droplet formation. Surface contamination of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) or bacteria can result in nosocomial transmission. Methods Two tertiary care COVID-19 intensive care units treating 53 patients for 870 patient days were sampled after terminal cleaning and preparation for regular use to treat non-COVID-19 patients. Results A total of 176 swabs were sampled of defined locations covering both ICUs. No SARS-CoV-2 ribonucleic acid (RNA) was detected. Gram-negative bacterial contamination was mainly linked to sinks and siphons. Skin flora was isolated from most swabbed areas and Enterococcus faecium was detected on two keyboards. Conclusions After basic cleaning with standard disinfection measures no remaining SARS-CoV-2 RNA was detected. Bacterial contamination was low and mainly localised in sinks and siphons.

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.

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.

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.

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.

ObjectivesWe explored patient perceptions regarding physician attire in different clinical contexts and resultant effects on the physician–patient relationship.SettingThe 900-bed University Hospital Zurich, Switzerland.ParticipantsA convenience sample of patients receiving care in dermatology, infectious diseases and neurology ambulatory clinics of the University Hospital Zurich participated in a paper-based survey.Primary and secondary outcome measuresThe survey instrument was randomised and showed photographs of male or female physicians wearing various forms of attire. On the basis of the respondents’ ratings of how the physician’s attire affected perceptions across five domains (knowledgeable, trustworthy, caring, approachable and comfort with the physician), a composite preference score for attire was calculated as the primary outcome. Secondary outcomes included variation in preferences by respondent characteristics and context in which care was provided.ResultsOf 834 patient respondents (140 in dermatology, 422 in infectious diseases and 272 in neurology), 298 (36%) agreed that physician attire was important. When compared with all available choices, the combination of white scrubs with white coat was rated highest while a business suit ranked lowest. Variation in preferences and opinions for attire were noted relative to respondent demographics and the clinical setting in which the survey was administered. For example, compared with younger patients, respondents ≥65 years of age more often reported that physician dress was both important to them and influenced how happy they were with their care (p=0.047 and p=0.001, respectively).ConclusionsOutpatients at a large Swiss University hospital prefer their physicians to be dressed in white scrubs with white coat. Substantial variation among respondents based on demographics, type of physician and clinical setting were observed. Healthcare systems should consider context of care when defining policies related to dress code.

ObjectiveThe preventable proportion of healthcare-associated infections (HAIs) may decrease over time as standards of care improve. We aimed to assess the proportion of HAIs prevented by multifaceted infection control interventions in different economic settings.MethodsIn this systematic review and meta-analysis, we searched OVID Medline, EMBASE, CINAHL, PubMed, and The Cochrane Library for studies published between 2005 and 2016 assessing multifaceted interventions to reduce catheter-associated urinary tract infections (CAUTIs), central-line–associated bloodstream infections (CLABSIs), surgical site infections (SSIs), ventilator-associated pneumonia (VAP), and hospital-acquired pneumonia not associated with mechanical ventilation (HAP) in acute-care or long-term care settings. For studies reporting raw rates, we extracted data and calculated the natural log of the risk ratio and variance to obtain pooled risk ratio estimates.ResultsOf the 5,226 articles identified by our search, 144 studies were included in the final analysis. Pooled incidence rate ratios associated with multifaceted interventions were 0.543 (95% confidence interval [CI], 0.445–0.662) for CAUTI, 0.459 (95% CI, 0.381–0.554) for CLABSI, and 0.553 (95% CI, 0.465–0.657) for VAP. The pooled rate ratio was 0.461 (95% CI, 0.389–0.546) for interventions aiming at SSI reduction, and for VAP reduction initiatives, the pooled rate ratios were 0.611 (95% CI, 0.414–0.900) for before-and-after studies and 0.509 (95% CI, 0.277–0.937) for randomized controlled trials. Reductions in infection rates were independent of the economic status of the study country. The risk of bias was high in 143 of 144 studies (99.3%).ConclusionsPublished evidence suggests a sustained potential for the significant reduction of HAI rates in the range of 35%–55% associated with multifaceted interventions irrespective of a country’s income level.

BackgroundPatients who start combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection show a smaller HIV-1 latent reservoir, less immune activation, and less viral diversity compared to patients who start cART during chronic infection. We conducted a pilot study to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir monotherapy.MethodsEARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial. Patients who started cART ResultsOf the 101 patients randomized, 68 were assigned to simplification to dolutegravir monotherapy and 33 to continuation of cART. At week 48 in the per-protocol population, 67/67 (100%) had virological response in the dolutegravir monotherapy group vs 32/32 (100%) in the cART group (difference, 0.00%; 95% confidence interval, –100%, 4.76%). This showed noninferiority of the dolutegravir monotherapy at the prespecified level.ConclusionIn this pilot study consisting of patients who initiated cART during primary HIV-1 infection and had Clinical Trials RegistrationNCT02551523.

ObjectivePreventing ventilator-associated pneumonia (VAP) is an important goal for intensive care units (ICUs). We aimed to identify the optimal behavior leverage to improve VAP prevention protocol adherence.DesignMixed-method study using adherence measurements to assess 4 VAP prevention measures and qualitative analysis of semi-structured focus group interviews with frontline healthcare practitioners (HCPs).SettingThe 6 ICUs in the 900-bed University Hospital Zurich in Zurich, Switzerland.Patients and participantsAdherence to VAP prevention measures were assessed in patients with a device for invasive ventilation (ie, endotracheal tube, tracheostomy tube). Participants in focus group interviews included a convenience samples of ICU nurses and physicians.ResultsBetween February 2015 and July 2017, we measured adherence to 4 protocols: bed elevation showed adherence at 27% (95% confidence intervals [CI], 23%–31%); oral care at 41% (95% CI, 36%–45%); sedation interruption at 81% (95% CI, 74%–85%); and subglottic suctioning at 88% (95% CI, 83%–92%). Interviews were analyzed first inductively according a grounded theory approach then deductively against the behavior change wheel (BCW) framework. Main behavioral facilitators belonged to the BCW component ‘reflective motivation’ (ie, perceived seriousness of VAP and self-efficacy to prevent VAP). The main barriers belonged to ‘physical capability’ (ie, lack of equipment and staffing and side-effects of prevention measures). Furthermore, 2 primarily technical approaches (ie, ‘restructuring environment’ and ‘enabling HCP’) emerged as means to overcome these barriers.ConclusionsOur findings suggest that technical, rather than education-based, solutions should be promoted to improve VAP prevention. This theory-informed mixed-method approach is an effective means of guiding infection prevention efforts.

Multiplex PCR assays for respiratory viruses are widely used in routine diagnostics, as they are highly sensitive, rapid, and cost effective. However, depending on the assay system, cross-reactivity between viruses that share a high sequence homology as well as detection of rare virus isolates with sequence variations can be problematic. Virus sequence-independent metagenomic high-throughput sequencing allows for accurate detection of all virus species in a given sample, as we demonstrate here for human Enterovirus and Rhinovirus in a lung transplant patient. While early in infection a commercial PCR assay recorded Rhinovirus, high-throughput sequencing correctly identified human Enterovirus C104 as the source of infection, highlighting the potential of the technology and the benefit of applying open assay formats in complex diagnostic situations., Highlights • Commercial test produced ambivalent results regarding Enterovirus/Rhinovirus infection. • To resolve etiology of infection, we performed unbiased metagenomic sequencing. • We detected HEV-C104 and other coinfecting viruses. • We identified sequence variations in HEV-C104 responsible for low sensitivity. • Metagenomics can complement specific routine diagnostics in complex cases.

Background Knowledge of the risk factors of individuals with an asymptomatic sexually transmitted infection (STI) is essential for implementation of targeted STI screening strategies. Methods Between June 2015 and January 2017, an STI screening was offered to all participants in the Zurich Primary human immunodeficiency virus (HIV)-1 Infection study. Patients were tested for gonorrhea, chlamydia, syphilis, and hepatitis C virus (HCV). Results Of 214 participants, 174 (81%) were screened at least once. Most patients were men who have sex with men (MSM) (87.4%). Presenting with a primary HIV infection was associated with higher odds for later risky sexual behavior, as compared with presenting in the chronic phase (odds ratio [OR], 5.58; 95% confidence interval [CI], 3.68-8.8). In total, 79 STIs were detected, reflecting a high period prevalence of 33.3% (58 of 174 patients). Sixty-six percent of patients (52 of 79) were asymptomatic. Most common STIs were chlamydia (50.6%; 40 of 79 patients), gonorrhea (25.3%; 20 of 79), and syphilis (19%; 15 of 79). In a multivariable model, engaging in insertive (OR, 6.48; 95% CI, 1.14-36.76) or both insertive and receptive (4.61; 1.01-20.96) anal intercourse, STI symptoms (3.4; 1.68-6.89), and condomless sex (2.06; 1.14-3.74) were positively correlated with a positive screening result. The hazard of an incident STI increased with the presence of STI symptoms (hazard ratio, 3.03; 95% CI, 1.17-7.84) and any recent drug use (2.63; 1-6.9). Conclusions A trimonthly STI screening including asymptomatic individuals should be considered in this population, particularly in MSM who report sexual risk behavior. Clinical trial registration NCT 00537966.

Mycobacterium chimaera infections following cardiac surgery have been reported from an increasing number of countries. These infections are characterized by a poor prognosis with a case fatality rate around 50% despite treatment. Since the first description in 2013, our understanding has grown steadily. Several outbreak investigations, case series, and experiments with heater-cooler units (HCUs) have been published. This review summarizes the current knowledge.M. chimaera transmission occurs during cardiopulmonary bypass via bioaerosols emitted from contaminated HCU water systems. Manifestations of M. chimaera infection comprise endocarditis, vascular graft infections, surgical site infections, and dissemination. So far, all cases were exposed to a single HCU brand. Samples from the manufacturing site as well as clonality of M. chimaera strains isolated from HCUs and patients suggest a contamination already at time of delivery representing the main source for the outbreak. Nevertheless, HCU contamination in hospitals cannot be excluded.Improved awareness of physicians of M. chimaera infection is crucial to prompt adequate diagnostic workup in patients that have been exposed to HCU presenting with compatible symptoms. For risk mitigation, strict separation between the air volume in contact with HCUs and critical clinical areas such as operating rooms is essential.

Background Lung transplant patients are a vulnerable group of immunosuppressed patients that are prone to frequent respiratory infections. We studied 60 episodes of respiratory symptoms in 71 lung transplant patients. Almost half of these episodes were of unknown infectious etiology despite extensive routine diagnostic testing. Methods We re-analyzed respiratory samples of all episodes with undetermined etiology in order to detect potential viral pathogens missed/not accounted for in routine diagnostics. Respiratory samples were enriched for viruses by filtration and nuclease digestion, whole nucleic acids extracted and randomly amplified before high throughput metagenomic virus sequencing. Viruses were identified by a bioinformatic pipeline and confirmed and quantified using specific real-time PCR. Results In completion of routine diagnostics, we identified and confirmed a viral etiology of infection by our metagenomic approach in four patients (three Rhinovirus A, one Rhinovirus B infection) despite initial negative results in specific multiplex PCR. Notably, the majority of samples were also positive for Torque teno virus (TTV) and Human Herpesvirus 7 (HHV-7). While TTV viral loads increased with immunosuppression in both throat swabs and blood samples, HHV-7 remained at low levels throughout the observation period and was restricted to the respiratory tract. Conclusion This study highlights the potential of metagenomic sequencing for virus diagnostics in cases with previously unknown etiology of infection and in complex diagnostic situations such as in immunocompromised hosts.

An outbreak of invasive Mycobacterium chimaera infections associated with heater-cooler devices (HCDs) has now affected patients in several countries on different continents. Clinical infections are characterized by delayed diagnosis, inadequate treatment response to antimicrobial agents, and poor prognosis. Outbreak investigators found M. chimaera in HCD water circuits and air samples while HCDs were running, suggesting that transmission from the HCD to the surgical site occurs via the airborne route. New HCDs at the manufacturing site were also contaminated with M. chimaera, and recent whole-genome sequencing data suggest a point source. Some guidance on screening for M. chimaera colonization in HCD water and exhaust air is available. In contrast, reliable disinfection procedures are not well described, and it is not yet known whether eradication of M. chimaera from a contaminated HCD can be achieved. Meanwhile, strict separation of the HCD from operating room air is necessary to ensure patient safety, and these efforts may require engineering solutions. While our understanding of the causes and the extent of the M. chimaera outbreak is growing, several aspects of patient management, device handling, and risk mitigation still require clarification.Infect Control Hosp Epidemiol 2016;1–6

Invasive Mycobacterium chimaera infections after open-heart surgery have been reported internationally. These devastating infections result from aerosols generated by contaminated heater-cooler units used with extracorporeal circulation during surgery. Despite intensified cleaning and disinfection, surveillance samples from factory-new units acquired during 2014 grew nontuberculous mycobacteria after a median of 174 days.