Do Infectious Diseases After Kidney Retransplantation Differ From Those After First Kidney Transplantation?

Background: Infectious diseases (IDs) are highly relevant after solid organ transplantation in terms of morbidity and mortality, being among the most common causes of death. Patients undergoing kidney retransplantation (re-K-Tx) have been already receiving immunosuppressive therapy over a prolonged period, potentially facilitating subsequent infections. Comparing ID events after re-K-Tx and first kidney transplantation (f-K-Tx) can delineate patterns and risks of ID events associated with prolonged immunosuppression. Methods: We included adult patients with records on f-K-Tx and re-K-Tx in the Swiss Transplant Cohort Study. We analyzed ID events after f-K-Tx and re-K-Tx within the same patients and compared infection rates, causative pathogens, and infection sites. Recurrent time-to-event analyses were performed for comparison of infection rates. Results: A total of 59 patients with a median age of 47 years (range, 18-73) were included. Overall, 312 ID events in 52 patients occurred. In multivariable recurrent event modeling, the rate of ID events was significantly lower after re-K-Tx (hazard ratio, 0.70; P = .02). More bacterial (68.9% vs 60.4%) and fungal (4.0% vs 1.1%) infections were observed after f-K-Tx but fewer viral infections (27.0% vs 38.5%) as compared with re-K-Tx (P = .11). After f-K-Tx, urinary and gastrointestinal tract infections were more frequent; after re-K-Tx, respiratory tract and surgical site infections were more frequent (P < .001). Conclusions: ID events were less frequent after re-K-Tx. Affected sites differed significantly after f-K-Tx vs re-K-Tx.

Adverse Outcomes of Patients with Non-Ventilator-Associated Hospital-Acquired Pneumonia (nvHAP)-A Single Centre Cohort Study.

Non-ventilator associated hospital-acquired pneumonia (nvHAP) is a common nosocomial infection, but little is known about the outcomes of patients with nvHAP and the risk factors for adverse outcomes. In this retrospective study conducted in a Swiss tertiary care centre, adverse outcomes like in-hospital mortality, intensive care unit (ICU) admission, and mechanical ventilation, both all-cause and nvHAP-associated, were investigated. Of 244 patients with nvHAP, 72 (30%) died, 35 (14%) deaths were attributed to nvHAP. While 36 (15%) patients acquired nvHAP on the ICU, another 173 patients were eligible for ICU-transferral, and 76 (43.9%) needed ICU-admission. Of all patients hospitalized on the ICU 58 (51.8%) needed intubation due to nvHAP. Multivariable logistic regression analysis identified lower body mass index (OR per unit increase: 0.90, 95%CI: 0.82-0.98) and lower haemoglobin on admission (OR per unit in g/l increase: 0.98, 95%CI: 0.97-1.00) as patient specific factors independently associated with nvHAP-associated mortality. Given the frequency of nvHAP adverse outcomes, hospitals should evaluate increasing nvHAP prevention efforts, especially for patients at high risk for nvHAP mortality. To what extent pneumonia prevention interventions do lower nvHAP mortality in these patients is still to be evaluated.

Systematic scoping review of automated systems for the surveillance of healthcare-associated bloodstream infections related to intravascular catheters.

INTRODUCTION: Intravascular catheters are crucial devices in medical practice that increase the risk of healthcare-associated infections (HAIs), and related health-economic adverse outcomes. This scoping review aims to provide a comprehensive overview of published automated algorithms for surveillance of catheter-related bloodstream infections (CRBSI) and central line-associated bloodstream infections (CLABSI). METHODS: We performed a scoping review based on a systematic search of the literature in PubMed and EMBASE from 1 January 2000 to 31 December 2021. Studies were included if they evaluated predictive performance of automated surveillance algorithms for CLABSI/CRBSI detection and used manually collected surveillance data as reference. We assessed the design of the automated systems, including the definitions used to develop algorithms (CLABSI versus CRBSI), the datasets and denominators used, and the algorithms evaluated in each of the studies. RESULTS: We screened 586 studies based on title and abstract, and 99 were assessed based on full text. Nine studies were included in the scoping review. Most studies were monocentric (n = 5), and they identified CLABSI (n = 7) as an outcome. The majority of the studies used administrative and microbiological data (n = 9) and five studies included the presence of a vascular central line in their automated system. Six studies explained the denominator they selected, five of which chose central line-days. The most common rules and steps used in the algorithms were categorized as hospital-acquired rules, infection rules (infection versus contamination), deduplication, episode grouping, secondary BSI rules (secondary versus primary BSI), and catheter-associated rules. CONCLUSION: The automated surveillance systems that we identified were heterogeneous in terms of definitions, datasets and denominators used, with a combination of rules in each algorithm. Further guidelines and studies are needed to develop and implement algorithms to detect CLABSI/CRBSI, with standardized definitions, appropriate data sources and suitable denominators.

Cross-protective HCoV immunity reduces symptom development during SARS-CoV-2 infection.

Numerous clinical parameters link to severe coronavirus disease 2019, but factors that prevent symptomatic disease remain unknown. We investigated the impact of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and endemic human coronavirus (HCoV) antibody responses on symptoms in a longitudinal children cohort (n = 2,917) and a cross-sectional cohort including children and adults (n = 882), all first exposed to SARS-CoV-2 (March 2020 to March 2021) in Switzerland. Saliva (n = 4,993) and plasma (n = 7,486) antibody reactivity to the four HCoVs (subunit S1 [S1]) and SARS-CoV-2 (S1, receptor binding domain, subunit S2 [S2], nucleocapsid protein) was determined along with neutralizing activity against SARS-CoV-2 Wuhan, Alpha, Delta, and Omicron (BA.2) in a subset of individuals. Inferred recent SARS-CoV-2 infection was associated with a strong correlation between mucosal and systemic SARS-CoV-2 anti-spike responses. Individuals with pre-existing HCoV-S1 reactivity exhibited significantly higher antibody responses to SARS-CoV-2 in both plasma (IgG regression coefficients = 0.20, 95% CI = [0.09, 0.32], P < 0.001) and saliva (IgG regression coefficient = 0.60, 95% CI = [0.088, 1.11], P = 0.025). Saliva neutralization activity was modest but surprisingly broad, retaining activity against Wuhan (median NT50 = 32.0, 1Q-3Q = [16.4, 50.2]), Alpha (median NT50 = 34.9, 1Q-3Q = [26.0, 46.6]), and Delta (median NT50 = 28.0, 1Q-3Q = [19.9, 41.7]). In line with a rapid mucosal defense triggered by cross-reactive HCoV immunity, asymptomatic individuals presented with higher pre-existing HCoV-S1 activity in plasma (IgG HKU1, odds ratio [OR] = 0.53, 95% CI = [0.29,0.97], P = 0.038) and saliva (total HCoV, OR = 0.55, 95% CI = [0.33, 0.91], P = 0.019) and higher SARS-CoV-2 reactivity in saliva (IgG S2 fold change = 1.26, 95% CI = [1.03, 1.54], P = 0.030). By investigating the systemic and mucosal immune responses to SARS-CoV-2 and HCoVs in a population without prior exposure to SARS-CoV-2 or vaccination, we identified specific antibody reactivities associated with lack of symptom development.IMPORTANCEKnowledge of the interplay between human coronavirus (HCoV) immunity and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is critical to understanding the coexistence of current endemic coronaviruses and to building knowledge potential future zoonotic coronavirus transmissions. This study, which retrospectively analyzed a large cohort of individuals first exposed to SARS-CoV-2 in Switzerland in 2020-2021, revealed several key findings. Pre-existing HCoV immunity, particularly mucosal antibody responses, played a significant role in improving SARS-CoV-2 immune response upon infection and reducing symptoms development. Mucosal neutralizing activity against SARS-CoV-2, although low in magnitude, retained activity against SARS-CoV-2 variants underlining the importance of maintaining local mucosal immunity to SARS-CoV-2. While the cross-protective effect of HCoV immunity was not sufficient to block infection by SARS-CoV-2, the present study revealed a remarkable impact on limiting symptomatic disease. These findings support the feasibility of generating pan-protective coronavirus vaccines by inducing potent mucosal immune responses.

Bacterial contamination of air and surfaces during dental procedures-An experimental pilot study using Staphylococcus aureus.

OBJECTIVE: The oral cavity contains numerous microorganisms, including antimicrobial-resistant bacteria. These microorganisms can be transmitted via respiratory particles from patients to healthcare providers and vice versa during dental care. We evaluated the spread of Staphylococcus aureus during standardized dental procedures using different scaling devices and rinsing solutions. METHODS: During systematic therapy for dental biofilm removal (guided biofilm therapy), using an airflow or ultrasound device to a model simulation head. Staphylococcus aureus suspension was injected into the mouth of the model to mimic saliva. Different suction devices (conventional saliva ejector or a prototype) and rising solutions (water or chlorhexidine) were used. To assess contamination with S. aureus, an air-sampling device was placed near the oral cavity and samples of surface areas were collected. RESULTS: S. aureus was only detected by air sampling when the conventional saliva ejector with airflow was used. No growth was observed during treatments with the ultrasonic piezo instrument or the prototype suction device. Notably, a rinsing solution of chlorhexidine digluconate decreased the bacterial load compared to water. Surface contamination was rarely detected (1 of 120 samples). CONCLUSIONS: Although our findings indicate potential airborne bacterial transmission during routine prophylactic procedures, specific treatment options during biofilm removal appear to reduce air contamination. These options include ultrasonic piezo devices or the prototype suction device. The use of chlorhexidine reduced the CFU counts of S. aureus detected by air sampling. Surface contamination during dental procedures was a rare occurrence.

Surgical site infections after kidney transplantation are independently associated with graft loss.

Surgical site infections (SSIs) are common health care-associated infections. SSIs after kidney transplantation (K-Tx) can endanger patient and allograft survival. Multicenter studies on this early posttransplant complication are scarce. We analyzed consecutive adult K-Tx recipients enrolled in the Swiss Transplant Cohort Study who received a K-Tx between May 2008 and September 2020. All data were prospectively collected with the exception of the categorization of SSI which was performed retrospectively according to the Centers for Disease Control and Prevention criteria. A total of 58 out of 3059 (1.9%) K-Tx recipients were affected by SSIs. Deep incisional (15, 25.9%) and organ/space infections (34, 58.6%) predominated. In the majority of SSIs (52, 89.6%), bacteria were detected, most frequently Escherichia coli (15, 28.9%), Enterococcus spp. (14, 26.9%), and coagulase-negative staphylococci (13, 25.0%). A BMI ≥25 kg/m2 (multivariable OR 2.16, 95% CI 1.07-4.34, P = .023) and delayed graft function (multivariable OR 2.88, 95% CI 1.56-5.34, P = .001) were independent risk factors for SSI. In Cox proportional hazard models, SSI was independently associated with graft loss (multivariable HR 3.75, 95% CI 1.35-10.38, P = .011). In conclusion, SSI was a rare complication after K-Tx. BMI ≥25 kg/m2 and delayed graft function were independent risk factors. SSIs were independently associated with graft loss.

Treatment effect of remdesivir on the mortality of hospitalised COVID-19 patients in Switzerland across different patient groups: a tree-based model analysis.

AIMS OF THE STUDY: Remdesivir has shown benefits against COVID-19. However, it remains unclear whether, to what extent, and among whom remdesivir can reduce COVID-19-related mortality. We explored whether the treatment response to remdesivir differed by patient characteristics. METHODS: We analysed data collected from a hospital surveillance study conducted in 21 referral hospitals in Switzerland between 2020 and 2022. We applied model-based recursive partitioning to group patients by the association between treatment levels and mortality. We included either treatment (levels: none, remdesivir within 7 days of symptom onset, remdesivir after 7 days, or another treatment), age and sex, or treatment only as regression variables. Candidate partitioning variables included a range of risk factors and comorbidities (and age and sex unless included in regression). We repeated the analyses using local centring to correct the results for the propensity to receive treatment. RESULTS: Overall (n = 21,790 patients), remdesivir within 7 days was associated with increased mortality (adjusted hazard ratios 1.28-1.54 versus no treatment). The CURB-65 score caused the most instability in the regression parameters of the model. When adjusted for age and sex, patients receiving remdesivir within 7 days of onset had higher mortality than those not treated in all identified eight patient groups. When age and sex were included as partitioning variables instead, the number of groups increased to 19-20; in five to six of those branches, mortality was lower among patients who received early remdesivir. Factors determining the groups where remdesivir was potentially beneficial included the presence of oncological comorbidities, male sex, and high age. CONCLUSIONS: Some subgroups of patients, such as individuals with oncological comorbidities or elderly males, may benefit from remdesivir.

Predictive performance of automated surveillance algorithms for intravascular catheter bloodstream infections: a systematic review and meta-analysis.

BACKGROUND: Intravascular catheter infections are associated with adverse clinical outcomes. However, a significant proportion of these infections are preventable. Evaluations of the performance of automated surveillance systems for adequate monitoring of central-line associated bloodstream infection (CLABSI) or catheter-related bloodstream infection (CRBSI) are limited. OBJECTIVES: We evaluated the predictive performance of automated algorithms for CLABSI/CRBSI detection, and investigated which parameters included in automated algorithms provide the greatest accuracy for CLABSI/CRBSI detection. METHODS: We performed a meta-analysis based on a systematic search of published studies in PubMed and EMBASE from 1 January 2000 to 31 December 2021. We included studies that evaluated predictive performance of automated surveillance algorithms for CLABSI/CRBSI detection and used manually collected surveillance data as reference. We estimated the pooled sensitivity and specificity of algorithms for accuracy and performed a univariable meta-regression of the different parameters used across algorithms. RESULTS: The search identified five full text studies and 32 different algorithms or study populations were included in the meta-analysis. All studies analysed central venous catheters and identified CLABSI or CRBSI as an outcome. Pooled sensitivity and specificity of automated surveillance algorithm were 0.88 [95%CI 0.84-0.91] and 0.86 [95%CI 0.79-0.92] with significant heterogeneity (I2 = 91.9, p < 0.001 and I2 = 99.2, p < 0.001, respectively). In meta-regression, algorithms that include results of microbiological cultures from specific specimens (respiratory, urine and wound) to exclude non-CRBSI had higher specificity estimates (0.92, 95%CI 0.88-0.96) than algorithms that include results of microbiological cultures from any other body sites (0.88, 95% CI 0.81-0.95). The addition of clinical signs as a predictor did not improve performance of these algorithms with similar specificity estimates (0.92, 95%CI 0.88-0.96). CONCLUSIONS: Performance of automated algorithms for detection of intravascular catheter infections in comparison to manual surveillance seems encouraging. The development of automated algorithms should consider the inclusion of results of microbiological cultures from specific specimens to exclude non-CRBSI, while the inclusion of clinical data may not have an added-value. Trail Registration Prospectively registered with International prospective register of systematic reviews (PROSPERO ID CRD42022299641; January 21, 2022). https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022299641.

Parallel dynamics in the yield of universal SARS-CoV-2 admission screening and population incidence.

The majority of SARS-CoV-2 transmissions originates from either asymptomatic or presymptomatic individuals. To prevent unnoticed introduction of SARS-CoV-2, many hospitals have implemented universal admission screening during the COVID-19 pandemic. The present study aimed to investigate associations between results of an universal SARS-CoV-2 admission screening and public SARS-CoV-2 incidence. Over a study period of 44 weeks, all patients admitted to a large tertiary care hospital were tested for SARS-CoV-2 by polymerase chain reaction. SARS-CoV-2 positive patients were retrospectively categorized as symptomatic or asymptomatic at admission. Cantonal data were used to calculate weekly incidence rates per 100,000 inhabitants. We used regression models for count data to assess the association of the weekly cantonal incidence rate and the proportion of positive SARS-CoV-2 tests in the canton with (a) the proportion of SARS-CoV-2 positive individuals and (b) the proportion of asymptomatic SARS-CoV-2 infected individuals identified in universal admission screening, respectively. In a 44-week period, a total of 21,508 admission screenings were performed. SARS-CoV-2 PCR was positive in 643 (3.0%) individuals. In 97 (15.0%) individuals, the positive PCR reflected residual viral replication after recent COVID-19, 469 (72.9%) individuals had COVID-19 symptoms and 77 (12.0%) SARS-CoV-2 positive individuals were asymptomatic. Cantonal incidence correlated with the proportion of SARS-CoV-2 positive individuals [rate ratio (RR): 2.03 per 100 point increase of weekly incidence rate, 95%CI 1.92-2.14] and the proportion of asymptomatic SARS-CoV-2 positive individuals (RR: 2.40 per 100 point increase of weekly incidence rate, 95%CI 2.03-2.82). The highest correlation between dynamics in cantonal incidence and results of admission screening was observed at a lag time of one week. Similarly, the proportion of positive SARS-CoV-2 tests in the canton of Zurich correlated with the proportion of SARS-CoV-2 positive individuals (RR: 2.86 per log increase in the proportion of positive SARS-CoV-2 tests in the canton, 95%CI 2.56-3.19) and the proportion of asymptomatic SARS-CoV-2 positive individuals (RR: 6.50 per log increase in the proportion of positive SARS-CoV-2 tests in the canton, 95%CI 3.93-10.75) in admission screening. Around 0.36% of admission screenings were positive in asymptomatic patients. Admission screening results paralleled changes in population incidence with a brief lag.

Hospital Outcomes of Community-Acquired SARS-CoV-2 Omicron Variant Infection Compared With Influenza Infection in Switzerland.

Importance: With the ongoing COVID-19 pandemic, it is crucial to assess the current burden of disease of community-acquired SARS-CoV-2 Omicron variant in hospitalized patients to tailor appropriate public health policies. Comparisons with better-known seasonal influenza infections may facilitate such decisions. Objective: To compare the in-hospital outcomes of patients hospitalized with the SARS-CoV-2 Omicron variant with patients with influenza. Design, Setting, and Participants: This cohort study was based on a national COVID-19 and influenza registry. Hospitalized patients aged 18 years and older with community-acquired SARS-CoV-2 Omicron variant infection who were admitted between January 15 and March 15, 2022 (when B.1.1.529 Omicron predominance was >95%), and hospitalized patients with influenza A or B infection from January 1, 2018, to March 15, 2022, where included. Patients without a study outcome by August 30, 2022, were censored. The study was conducted at 15 hospitals in Switzerland. Exposures: Community-acquired SARS-CoV-2 Omicron variant vs community-acquired seasonal influenza A or B. Main Outcomes and Measures: Primary and secondary outcomes were defined as in-hospital mortality and admission to the intensive care unit (ICU) for patients with the SARS-CoV-2 Omicron variant or influenza. Cox regression (cause-specific and Fine-Gray subdistribution hazard models) was used to account for time-dependency and competing events, with inverse probability weighting to adjust for confounders with right-censoring at day 30. Results: Of 5212 patients included from 15 hospitals, 3066 (58.8%) had SARS-CoV-2 Omicron variant infection in 14 centers and 2146 patients (41.2%) had influenza A or B in 14 centers. Of patients with the SARS-CoV-2 Omicron variant, 1485 (48.4%) were female, while 1113 patients with influenza (51.9%) were female (P = .02). Patients with the SARS-CoV-2 Omicron variant were younger (median [IQR] age, 71 [53-82] years) than those with influenza (median [IQR] age, 74 [59-83] years; P < .001). Overall, 214 patients with the SARS-CoV-2 Omicron variant (7.0%) died during hospitalization vs 95 patients with influenza (4.4%; P < .001). The final adjusted subdistribution hazard ratio (sdHR) for in-hospital death for SARS-CoV-2 Omicron variant vs influenza was 1.54 (95% CI, 1.18-2.01; P = .002). Overall, 250 patients with the SARS-CoV-2 Omicron variant (8.6%) vs 169 patients with influenza (8.3%) were admitted to the ICU (P = .79). After adjustment, the SARS-CoV-2 Omicron variant was not significantly associated with increased ICU admission vs influenza (sdHR, 1.08; 95% CI, 0.88-1.32; P = .50). Conclusions and Relevance: The data from this prospective, multicenter cohort study suggest a significantly increased risk of in-hospital mortality for patients with the SARS-CoV-2 Omicron variant vs those with influenza, while ICU admission rates were similar.

Nosocomial COVID-19 Incidence and Secondary Attack Rates among Patients of Tertiary Care Center, Zurich, Switzerland.

Of 1,118 patients with COVID-19 at a university hospital in Switzerland during October 2020-June 2021, we found 83 (7.4%) had probable or definite healthcare-associated COVID-19. After in-hospital exposure, we estimated secondary attack rate at 23.3%. Transmission was associated with longer contact times and with lower cycle threshold values among index patients.

Epidemiology and outcomes of bone and joint infections in solid organ transplant recipients.

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.

Documentation of adherence to infection prevention best practice in patient records: a mixed-methods investigation.

BACKGROUND: Healthcare-associated infections remain a preventable cause of patient harm in healthcare. Full documentation of adherence to evidence-based best practices for each patient can support monitoring and promotion of infection prevention measures. Thus, we reviewed the extent, nature, and determinants of the documentation of infection prevention (IP) standards in patients with HAI. METHODS: We reviewed electronic patient records (EMRs) of patients included in four annual point-prevalence studies 2013-2016 who developed a device- or procedure-related HAI (surgical site infection (SSI), catheter-associated urinary tract infection (CAUTI), ventilator-associated infection (VAP), catheter-related bloodstream infection (CRBSI)). We examined the documentation quality of mandatory preventive measures published as institutional IP standards. Additionally, we undertook semi-structured interviews with healthcare providers and a two-step inductive (grounded theory) and deductive (Theory of Planned Behaviour) content analysis. RESULTS: Of overall 2972 surveyed patients, 249 (8.4%) patients developed 272 healthcare-associated infections. Of these, 116 patients met the inclusion criteria, classified as patients with SSI, CAUTI, VAP, CRBSI in 78 (67%), 21 (18%), 10 (9%), 7 (6%), cases, respectively. We found documentation of IP measures in EMRs in 432/1308 (33%) cases. Documentation of execution existed in the study patients' EMRs for SSI, CAUTI, VAP, CRBSI, and overall, in 261/931 (28%), 27/104 (26%), 46/122 (38%), 26/151 (17%), and 360/1308 (28%) cases, respectively, and documentation of non-execution in 67/931 (7%), 2/104 (2%), 0/122 (0%), 3/151 (2%), and 72/1308 (6%) cases, respectively. Healthcare provider attitudes, subjective norms, and perceived behavioural control indicated reluctance to document IP standards. CONCLUSIONS: EMRs rarely included conclusive data about adherence to IP standards. Documentation had to be established indirectly through data captured for other reasons. Mandatory institutional documentation protocols or technically automated documentation may be necessary to address such shortcomings in patient safety documentation.

Modifiable and nonmodifiable risk factors for non-ventilator-associated hospital-acquired pneumonia identified in a retrospective cohort study.

OBJECTIVES: Hospital-acquired pneumonia in nonventilated patients (nvHAP) belongs to the most common healthcare-associated infections. This study aimed to investigate risk factors for nvHAP in patients outside the intensive care unit, focusing on modifiable risk factors. METHODS: All inpatients admitted to an academic teaching hospital in Switzerland between 2017 and 2018 were included. nvHAP was defined according to European Centre for Disease Prevention and Control criteria. Patient days during and after ICU stay were excluded. Candidate risk factors-both constant and time varying-were included in uni- and multivariable Cox proportional hazards models. The decay ratio and the characteristic time of influence of hazard ratios (HRs) was estimated by adopting a linear decay in the Cox model. RESULTS: A total of 66 001 hospitalizations with 314 (0.48%) nvHAP and 471 401 patient days were included. Median age was 57 years (interquartile range: 38 to 71 years) and 32 253 (48.9%) patients were male. Among nonmodifiable risk factors, age (adjusted HR (aHR) 2.66 for age ≥60 years, 95% CI 1.59 to 4.45) and male sex (aHR 1.71, 95% CI 1.34 to 2.18) were independently associated with nvHAP. Time-varying exposures showing strongest independent association with nvHAP were tube feeding (aHR 3.24, 95% CI 2.17 to 4.83), impaired consciousness (aHR 2.32, 95% CI 1.63 to 3.31), and severely impaired activity and mobility (aHR 2.06, 95% CI 1.50 to 2.84). The association with nvHAP decayed within 7.1 to 13.2 days after these exposures ended. DISCUSSION: The risk for nvHAP varies with time, depending on the patient's medical condition and medical interventions. Several risk factors for nvHAP represent potential targets for specific prevention measures.

Genomic Surveillance of Vancomycin-Resistant Enterococcus faecium Reveals Spread of a Linear Plasmid Conferring a Nutrient Utilization Advantage.

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. IMPORTANCE Sequencing 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.

Distribution of Aspergillus Species and Prevalence of Azole Resistance in Respiratory Samples From Swiss Tertiary Care Hospitals.

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.

Hospital outcomes of community-acquired COVID-19 versus influenza: Insights from the Swiss hospital-based surveillance of influenza and COVID-19.

BackgroundSince 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.AimThis study compares in-hospital outcomes for patients with community-acquired COVID-19 and patients with community-acquired influenza in Switzerland.MethodsThis 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.ResultsIn 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 < 0.001). The patients with COVID-19 were younger (median 67 years; interquartile range (IQR): 54-78) than the patients with influenza (median 74 years; IQR: 61-84) (p < 0.001). A larger percentage of patients with COVID-19 (12.8%) than patients with influenza (4.4%) died in hospital (p < 0.001). The final adjusted subdistribution hazard ratio for mortality was 3.01 (95% CI: 2.22-4.09; p < 0.001) for COVID-19 compared with influenza and 2.44 (95% CI: 2.00-3.00, p < 0.001) for ICU admission.ConclusionCommunity-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.

Evolution of COVID-19 mortality over time: results from the Swiss hospital surveillance system (CH-SUR).

BACKGROUND: When the periods of time during and after the first wave of the ongoing SARS-CoV-2/COVID-19 pandemic in Europe are compared, 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. METHODS: We investigated the trends in COVID-19-related mortality (in-hospital and in-intermediate/intensive-care) over time in Switzerland, from February 2020 to June 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. RESULTS: Our analysis included 16,984 patients recorded in CH-SUR, with 2201 reported deaths due to COVID-19 (13.0%). We found that overall in-hospital mortality was lower during the second wave of COVID-19 than in the first wave (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.63- 0.78; p <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 with the first wave (HR 1.25, 95% CI 1.05-1.49; p = 0.029), with significant changes in the course of hospitalisation between the first and the second wave. CONCLUSION: We 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.

Trends of the Epidemiology of Candidemia in Switzerland: A 15-Year FUNGINOS Survey.

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.

Reduced Relative Sensitivity of the Elecsys SARS-CoV-2 Antigen Assay in Saliva Compared to Nasopharyngeal Swabs.

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.