Fourier-transform infrared spectroscopy for typing of vancomycin-resistant Enterococcus faecium: performance analysis and outbreak investigation.

Vancomycin-resistant Enterococci, mainly Enterococcus faecium (VREfm), are causing nosocomial infections and outbreaks. Bacterial typing methods are used to assist in outbreak investigations. Most of them, especially genotypic methods like multi-locus sequence typing (MLST), whole genome sequencing (WGS), or pulsed-field gel electrophoresis, are quite expensive and time-consuming. Fourier-transform infrared (FT-IR) spectroscopy assesses the biochemical composition of bacteria, such as carboxyl groups in polysaccharides. It is an affordable technique and has a faster turnaround time. Thus, the aim of this study was to evaluate FT-IR spectroscopy for VREfm outbreak investigations. Basic performance requirements like reproducibility and the effects of incubation time were assessed in distinct sample sets. After determining a FT-IR spectroscopy cut-off range, the clustering agreement between FT-IR and WGS within a retrospective (n: 92 isolates) and a prospective outbreak (n: 15 isolates) was investigated. For WGS an average nucleotide identity (ANI) cut-off score of 0.999 was used. Basic performance analysis showed reproducible results. Moreover, FT-IR spectroscopy readouts showed a high agreement with WGS-ANI analysis in clinical outbreak investigations (V-measure 0.772 for the retrospective and 1.000 for the prospective outbreak). FT-IR spectroscopy had a higher discriminatory power than MLST in the outbreak investigations. After determining cut-off values to achieve optimal resolution, FT-IR spectroscopy is a promising technique to assist in outbreak investigation as an affordable, easy-to-use tool with a turnaround time of less than one day. IMPORTANCE Vancomycin-resistant Enterococci, mainly Enterococcus faecium (VREfm), are a frequent cause of nosocomial outbreaks. Several bacterial typing methods are used to track transmissions and investigate outbreaks, whereby genome-based techniques are used as a gold standard. Current methods are either expensive, time-consuming, or both. Additionally, often, specifically trained staff needs to be available. This study provides insight into the use of Fourier-transform infrared (FT-IR) spectroscopy, an affordable, easy-to-use tool with a short turnaround time as a typing method for VREfm. By assessing clinical samples, this work demonstrates promising results for species discrimination and reproducibility. FT-IR spectrosopy shows a high level of agreement in the analysis of VREfm outbreaks in comparison with whole genome sequencing-based methods.

Comparing Prevalence of Sarcopenia Using Twelve Sarcopenia Definitions in a Large Multinational European Population of Community-Dwelling Older Adults.

OBJECTIVES: Multinational prevalence data on sarcopenia among generally healthy older adults is limited. The aim of the study was to assess prevalence of sarcopenia in the DO-HEALTH European trial based on twelve current sarcopenia definitions. SETTING AND PARTICIPANTS: This is an analysis of the DO-HEALTH study including 1495 of 2157 community-dwelling participants age 70+ years from Germany, France, Portugal, and Switzerland with complete measurements of the sarcopenia toolbox including muscle mass by DXA, grip strength, and gait speed. MEASUREMENTS: The twelve sarcopenia definitions applied were Asian Working Group on Sarcopenia (AWGS1), AWGS2, Baumgartner, Delmonico, European Working Group on Sarcopenia in Older People (EWGSOP1), EWGSOP2, EWGSOP2-lower extremities, Foundation for the National Institutes of Health (FNIH1), FNIH2, International Working Group on Sarcopenia in Older People (IWGS), Morley, and Sarcopenia Definitions and Outcomes Consortium (SDOC). RESULTS: Mean age was 74.9 years (SD 4.4); 63.3% were women. Sarcopenia prevalence ranged between 0.7% using the EWGSOP2 or AWGS2 definition, up to 16.8% using the Delmonico definition. Overall, most sarcopenia definitions, including Delmonico (16.8%), Baumgartner (12.8%), FNIH1(10.5%), IWGS (3.6%), EWGSOP1 (3.4%), SDOC (2.0%), Morley (1.3%), and AWGS1 (1.1%) tended to be higher than the prevalence based on EWGSOP2 (0.7%). In contrast, the definitions AWGS2 (0.7%), EWGSOP2-LE (1.1%), FNIH2 (1.0%) - all based on muscle mass and muscle strength - showed similar lower prevalence as EWGSOP2 (0.7%). Moreover, most sarcopenia definitions did not overlap on identifying sarcopenia on an individual participant-level. CONCLUSION: In this multinational European trial of community-dwelling older adults we found major discordances of sarcopenia prevalence both on a population- and on a participant- level between various sarcopenia definitions. Our findings suggest that the concept of sarcopenia may need to be rethought to reliably and validly identify people with impaired muscle health.

Effects of Vitamin D, Omega-3 Fatty Acids and a Home Exercise Program on Prevention of Pre-Frailty in Older Adults: The DO-HEALTH Randomized Clinical Trial.

BACKGROUND: The benefits of supplemental vitamin D3, marine omega-3 fatty acids, and a simple home exercise program (SHEP) on frailty prevention in generally healthy community-dwelling older adults are unclear. OBJECTIVE: To test the effect of vitamin D3, omega-3s, and a SHEP, alone or in combination on incident pre-frailty and frailty in robust older adults over a follow-up of 36 months. METHODS: DO-HEALTH is a multi-center, double-blind, placebo-controlled, 2x2x2 factorial randomized clinical trial among generally healthy European adults aged 70 years or older, who had no major health events in the 5 years prior to enrollment, sufficient mobility and intact cognitive function. As a secondary outcome of the DO-HEALTH trial, among the subset of participants who were robust at baseline, we tested the individual and combined benefits of supplemental 2,000 IU/day of vitamin D3, 1 g/day of marine omega-3s, and a SHEP on the odds of being pre-frail and frail over 3 years of follow-up. RESULTS: At baseline, 1,137 out of 2,157 participants were robust (mean age 74.3 years, 56.5% women, mean gait speed 1.18 m/s). Over a median follow-up time of 2.9 years, 696 (61.2%) became pre-frail and 29 (2.6%) frail. Odds ratios for becoming pre-frail were not significantly lower for vitamin D3, or omega 3-s, or SHEP, individually, compared to control (placebo for the supplements and control exercise). However, the three treatments combined showed significantly decreased odds (OR 0.61 [95% CI 0.38-0.98; p=0.04) of becoming pre-frail compared to control. None of the individual treatments or their combination significantly reduced the odds of becoming frail. CONCLUSION: Robust, generally healthy and active older adults without major comorbidities, may benefit from a combination of high-dose, supplemental vitamin D3, marine omega-3s, and SHEP with regard to the risk of becoming pre-frail over 3 years.

Iron Deficiency and Incident Infections among Community-Dwelling Adults Age 70 Years and Older: Results from the DO-HEALTH Study.

OBJECTIVES: To assess if baseline iron deficiency, with or without anemia, is associated with incident infections over 3 years among community-dwelling older adults. DESIGN: Prospective secondary analysis of DO-HEALTH, a 3-year randomized, double-blind controlled trial. SETTING AND PARTICIPANTS: 2157 community-dwelling adults age 70+ from 5 European countries with good cognitive function and mobility and no major health events in the 5 years prior to enrollment Measurements: Incident infections, their severity and type were recorded every 3 months throughout the 3-year follow-up. Iron deficiency was defined as soluble transferrin receptor (sTfR) levels > 28.1 nmol/l and anemia as hemoglobin levels < 120 g/l for women and 130 g/l for men. We applied negative binomial mixed effects regression models with random effects for countries, and controlling for treatment allocation, age, sex, body mass index, polypharmacy, number of comorbidities, smoking status, living situation, alcohol intake, frailty status, and physical activity levels. A pre-defined stratified analysis was performed to explore if the associations between iron deficiency and infections were consistent by baseline anemia status. RESULTS: In total, 2141 participants were included in the analyses (mean age 74.9 years, 61.5% of women, 26.8% with iron deficiency). Across all participants, baseline iron deficiency was not associated with incident overall infections, but was associated with a 63% greater rate of incident severe infections requiring hospitalization (incidence rate ratio [IRR] 1.63, 95% Confidence Interval [CI] 1.11-2.41, p=0.01). This association was more pronounced among the 2000 participants who did not have anemia at baseline (IRR=1.80, 95% CI 1.20-2.69, p=0.005). CONCLUSION: Based on this prospective study among generally healthy European community-dwelling older adults, iron deficiency was not associated with the incidence rate of overall infections but may increase the incidence of severe infections. Intervention studies are needed to prove the causality of this observation.

Surgical site infections after simultaneous pancreas kidney and pancreas transplantation in the Swiss Transplant Cohort Study.

BACKGROUND: Among hospital-acquired infections, surgical site infections (SSIs) are frequent. SSI in the early post-transplant course poses a relevant threat to transplant recipients. AIM: To determine incidence, risk factors for SSI and its association with post-transplant outcomes and pancreas transplant (P-Tx) recipients. METHODS: Adult simultaneous kidney-pancreas transplantation (SPK-T) and P-Tx recipients with a follow-up of at least 90 days were identified in the Swiss Transplant Cohort Study (STCS) dataset. Except for the categorization of SSIs according to Centers for Disease Control and Prevention (CDC) criteria, all other data were prospectively collected. Risk factors for SSI were investigated with logistic regression. A Weibull accelerated failure-time model was applied to address the impact of SSI on length of stay, correcting for transplant-related complications and delayed graft function. FINDINGS: Of 130 transplant recipients, 108 SPK-Tx and 22 P-Tx, 18 (14%) individuals developed SSI within the first 90 days after transplantation. Deep incisional (seven, 38.9%) and organ/space infections (eight, 44.4%) predominated. In the majority of SSIs (11, 61.1%; two SSIs with simultaneous identification of fungal pathogens) bacteria were detected with Enterococcus spp. being most frequent. The median duration of hospitalization after transplantation was significantly longer in recipients with SSI (median: 26 days; interquartile range (IQR): 19-44) than in patients without SSI (median: 17 days; IQR: 12-25; P = 0.002). In multivariate analysis, SSI was significantly associated with increased length of stay and prolonged the duration of hospitalization by 36% (95% confidence interval: 4-79). CONCLUSION: SSI after SPK-Tx and P-Tx occurred at a frequency of 14%. Among pathogens, Enterococcus spp. predominated. SSI was independently associated with a longer hospitalization after transplantation.

Matching Clostridioides difficile strains obtained from shoe soles of healthcare workers epidemiologically linked to patients and confirmed by whole-genome sequencing.

BACKGROUND: The source of transmission of Clostridioides difficile in healthcare institutions is frequently unknown. The aim of this prospective cohort study was to assess the association between strains cultured from patients and shoe soles of healthcare workers (HCWs), as already shown in the operating theatre, but not on general hospital wards in an acute-care institution. METHODS: We conducted a study at a university tertiary care centre in Switzerland. From October 2019 to July 2020, shoe soles of HCWs were cultured for C. difficile twice per shift while taking care of a patient infected with toxigenic C. difficile. Additional risk factors were assessed by interviewing involved HCWs. Patients' faecal samples were processed by routine microbiological methods. Similarity of the HCWs' and patients' strains was determined by whole-genome sequencing (WGS). RESULTS: A total of 103 HCWs exposed to 42 hospitalized patients participated in the study, providing 206 samples. Contamination of shoe soles with C. difficile was detected in 37 samples (17.8%) of HCWs taking care of patients infected with C. difficile. Overall, transmission was suspected by epidemiological link and matching strains demonstrated by WGS in 74%. CONCLUSIONS: HCWs' shoe soles were positive in 17.8% with C. difficile strains linked epidemiologically and confirmed by WGS to infected patients suggesting potential transmission by HCWs' shoe soles. This pilot study provides sufficient evidence to further evaluate this potential mode of healthcare-associated transmission of C. difficile by a larger clinical trial.

Prevalence of Physical Frailty: Results from the DO-HEALTH Study.

BACKGROUND: Frailty is a geriatric syndrome associated with multiple negative health outcomes. However, its prevalence varies by population and instrument used. We investigated frailty and pre-frailty prevalence by 5 instruments in community-dwelling older adults enrolled to a randomized-controlled trial in 5 European countries. METHODS: Cross-sectional baseline analysis in 2,144 DO-HEALTH participants recruited from Switzerland, Austria, France, Germany, and Portugal with complete data for frailty. Frailty status was assessed by the Physical Frailty Phenotype [PFP], SOF-Frailty Index [SOF-FI], FRAIL-Scale, SHARE-Frailty Instrument [SHARE-FI], and a modified SHARE-FI, and compared by country, age, and gender. Logistic regression was used to determine relevant factors associated with frailty and pre-frailty. RESULTS: Mean age was 74.9 (±4.4) years, 61.6% were women. Based on the PFP, overall frailty and pre-frailty prevalence was 3.0% and 43.0%. By country, frailty prevalence was highest in Portugal (13.7%) and lowest in Austria (0%), and pre-frailty prevalence was highest in Portugal (57.3%) and lowest in Germany (37.1%). By instrument and overall, frailty and pre-frailty prevalence was highest based on SHARE-FI (7.0% / 43.7%) and lowest based on SOF-FI (1.0% / 25.9%). Frailty associated factors were residing in Coimbra (Portugal) [OR 12.0, CI 5.30-27.21], age above 75 years [OR 2.0, CI 1.17-3.45], and female gender [OR 2.8, CI 1.48-5.44]. The same three factors predicted pre-frailty. CONCLUSIONS: Among relatively healthy adults age 70 and older enroled to DO-HEALTH, prevalence of frailty and pre-frailty differed significantly by instrument, country, gender, and age. Among instruments, the highest prevalence of frailty and pre-frailty was documented by the SHARE-FI and the lowest by the SOF-FI.

Does high adherence to contact precautions lead to low in-hospital transmission of multi-drug-resistant micro-organisms in the endemic setting?

BACKGROUND: Conflicting results have been published on the impact of contact precautions (CPs) on reduction of transmission of multi-drug-resistant micro-organisms (MDROs) in the endemic setting. Ambiguous definitions coupled with low adherence partly explain these differences. AIM: We prospectively monitored the level of adherence to CPs and aimed to relate it to in-hospital transmission of MDROs. METHODS: Between January 2016 and March 2018, all patients under CPs underwent continuous monitoring of adherence to CPs by routine on-site visits on days 0, 3 and 7 after initiating CPs using a standardized checklist. The protocol included 10 interventions that were routinely checked such as CP sign at the door as well as wearing of gowns and gloves upon entry to the patient room. Patients requiring CPs were defined as colonized or infected with MDROs (meticillin-resistant Staphylococcus aureus (MRSA), non-Escherichia coli extended-spectrum beta lactamase (ESBL) Enterobacterales, vancomycin-resistant enterococci (VRE) and carbapenem-resistant Gram-negative micro-organisms (CRGN)) as well as patients infected with respiratory viruses, norovirus, scabies and hypervirulent strains of Clostridioides difficile. FINDINGS: Overall, data from 13,756 CP records from 1378 visits of 812 patients were analysed. Adherence varied between 93% and 100% for each intervention, except for "separate space for contaminated material" with an adherence of 5.3-6.1%. The incidence of in-hospital transmission during the study period was extremely low for MRSA, VRE, non-E.coli ESBL Enterobacterales and CRGN with 0.00-0.064 cases/1000 patient days. CONCLUSION: High adherence coupled with continuous monitoring of CPs correlated with a very low in-hospital transmission rate. These results indicate that CPs are highly effective if routine monitoring of adherence is implemented.

Unexpected Mycoplasma hominis infection in two renal transplant recipients traced back to the same donor by whole-genome sequencing.

Mycoplasma hominis is a common colonizer of the lower genitourinary tract. Although its clinical relevance for causing urogenital infections in immunocompetent individuals is controversial, this bacterium has been involved in severe invasive infections in allograft recipients. In this report, we describe two cases of M. hominis infection in two young renal transplant recipients within the first month post-transplant. Although at first no epidemiological link between the two cases had been suspected, whole-genome sequencing (WGS) analysis showed that both isolates were identical, highly suggestive of an origin with the common organ donor.

Successful management of a Clostridioides difficile ribotype 027 outbreak with a lean intervention bundle.

BACKGROUND: In a 2015 point-prevalence study, Clostridioides difficile 027, a hypervirulent ribotype, was absent from healthcare institutions in Switzerland. In late 2016, we detected an outbreak of C. difficile infection (CDI) with ribotype 027 occurring across several hospitals in the same hospital network. METHODS: The first cases of CDI due to ribotype 027 triggered an outbreak investigation, including whole genome sequencing (WGS) to identify outbreak strains. FINDINGS: Twenty-eight patients with CDI caused by ribotype 027 between December 2016 and December 2017 were identified, out of which 20 were caused by a single clone. Commonalities among these patients were hospitalization in the same room or on the same ward, receiving care from the same healthcare workers, and shared toilet areas. In addition to the epidemiological links suggesting possible transmission pathways between cases, WGS confirmed the clonality of this C. difficile 027 outbreak. The outbreak was contained by isolation precautions, raising awareness among healthcare workers, harmonizing diagnostic algorithms, and switching to a sporicidal agent for environmental disinfection. Of note, neither default gowning and gloving nor hand washing with water and soap were implemented. CONCLUSION: This C. difficile 027 outbreak was recognized belatedly due to lack of screening for this ribotype in some hospitals, and was contained by a swift response with simple infection prevention measures and adapting the laboratory approach. In order to have a better understanding of C. difficile epidemiology, diagnostic approaches should be standardized, CDI declared notifiable, and longitudinal data on prevalent ribotypes collected in countries where this is not established.

Digital microbiology.

BACKGROUND: Digitalization and artificial intelligence have an important impact on the way microbiology laboratories will work in the near future. Opportunities and challenges lie ahead to digitalize the microbiological workflows. Making efficient use of big data, machine learning, and artificial intelligence in clinical microbiology requires a profound understanding of data handling aspects. OBJECTIVE: This review article summarizes the most important concepts of digital microbiology. The article gives microbiologists, clinicians and data scientists a viewpoint and practical examples along the diagnostic process. SOURCES: We used peer-reviewed literature identified by a PubMed search for digitalization, machine learning, artificial intelligence and microbiology. CONTENT: We describe the opportunities and challenges of digitalization in microbiological diagnostic processes with various examples. We also provide in this context key aspects of data structure and interoperability, as well as legal aspects. Finally, we outline the way for applications in a modern microbiology laboratory. IMPLICATIONS: We predict that digitalization and the usage of machine learning will have a profound impact on the daily routine of laboratory staff. Along the analytical process, the most important steps should be identified, where digital technologies can be applied and provide a benefit. The education of all staff involved should be adapted to prepare for the advances in digital microbiology.

Emendation of the Genus Auritidibacter Yassin et al. 2011 and Auritidibacter ignavus Yassin et al. 2011 based on features observed from Canadian and Swiss clinical isolates and whole-genome sequencing analysis.

Auritidibacter ignavus is a Gram-stain-positive bacillus derived from otorrhea. Four strains derived from ear discharges in Canada and Switzerland, with features consistent with but distinguishable from Auritidibacter ignavus IMMIB L-1656T (accession number FN554542) by 16S rRNA gene sequencing (97.5 % similarity), were thought to represent a novel species of the genus Auritidibacter. Auritidibacter ignavus DSM 45359T (=IMMIB L-1656T) was acquired to compare with Canadian and Swiss strains by whole-genome sequencing (WGS). Unexpectedly, those isolates were observed to be consistent with A. ignavus DSM 45359T by WGS (ANIb scores >98 %), MALDI-TOF (Bruker), cellular fatty acid analysis and biochemically (some differences were observed). A nearly full 16S rRNA gene sequence could not be readily prepared from A. ignavus DSM 45359T, even after multiple attempts. A 16S rRNA gene chimeric consensus sequence created from the genome assembly of A. ignavus DSM 45359T had only 97.5 % similarity to that of A. ignavus IMMIB L-1656T, implying that 16S rRNA sequence accession number FN554542 could not be replicated. We concluded that our isolates of members of the genus Auritidibacter were consistent with A. ignavus DSM 45359T, did not represent a novel species, and that the sequence corresponding to FN554542 was not reproducible. By WGS, A. ignavus DSM 45359T had genome of 2.53×106 bp with a DNA G+C content of 59.34%, while genomes of Canadian and Swiss isolates ranged from 2.47 to 2.59×106 bp with DNA G+C contents of 59.3-59.52 %. A. ignavus NML 100628 (=NCTC 14178=LMG 30897) did not demonstrate a rodcoccus cycle. Emendation of Auritidibacter ignavus was proposed based on these results.

Antibiotic-resistant pathogens in different patient settings and identification of surveillance gaps in Switzerland - a systematic review.

The prevalence of antimicrobial resistance (AMR) varies significantly among different patient populations. We aimed to summarise AMR prevalence data from screening studies in different patient settings in Switzerland and to identify surveillance gaps. We performed a systematic review, searching Pubmed, MEDLINE, Embase (01/2000-05/2017) and conference proceedings for Swiss studies reporting on carbapenemase-producing Enterobacteriaceae (CPE), extended-spectrum beta-lactamases (ESBL), mobilised colistin-resistance, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) within different patient settings. We identified 2345 references and included 46 studies. For acute care patients, most screening data come from admission screenings, whereas AMR prevalence among hospitalised patients is largely unknown. Universal admission screenings showed ESBL-prevalences of 5-8% and MRSA-prevalences of 2-5%. For targeted screening, ESBL-prevalence ranged from 14-21%; MRSA-prevalence from 1-4%. For refugees, high ESBL (9-24%) and MRSA (16-24%) carriage rates were reported; returning travellers were frequently (68-80%) colonised with ESBL. Screening data for other pathogens, long-term care facility (LTCF) residents and pediatric populations were scarce. This review confirms high ESBL- and MRSA-carriage rates for risk populations in Switzerland. Emerging pathogens (CPE and VRE) and certain populations (inpatients, LTCF residents and children) are understudied. We encourage epidemiologists and public health authorities to consider these findings in the planning of future surveillance studies.

Influence of fall environment and fall direction on risk of injury among pre-frail and frail adults.

In this prospective study, half of all falls resulted in injury. Pre-frail adults sustained more injuries, while more frail adults had injuries requiring hospitalization or fractures. Pre-frail adults fell more often when in movement compared with frail adults who fell more often when standing and in indoor public spaces. PURPOSE: To assess prospectively how fall environment and direction are related to injury among pre-frail and frail adults. METHODS: We included 200 community-dwelling adults with a prior fall (pre-frail, mean age 77 years) and 173 adults with acute hip fracture (frail, mean age 84 years; 77% community-dwelling). Falls were prospectively recorded using standardized protocols in monthly intervals, including date, time, fall direction and environment, and injury. We used logistic regression to assess the odds of injury adjusting for age, body mass index (BMI), and gender. RESULTS: We recorded 513 falls and 331 fall-related injuries (64.5%) among the 373 participants. While the fall rate was similar between groups, pre-frail adults had more injuries (71% among pre-frail vs. 56% among frail, p = 0.0004) but a lower incidence of major injuries (9% among pre-frail vs. 27% among frail, p = 0.003). Pre-frail adults fell more often while in movement (84% among pre-frail vs. 55% among frail, p < 0.0001), and frail adults fell more often while standing (26% vs. 15% respectively, p = 0.01). The odds of injury among frail adults was increased 3.3-fold when falling sideways (OR = 3.29, 95% CI = 1.68-6.45) and 2.4-fold when falling in an indoor public space (OR = 2.35, 95% CI = 1.00-5.53), and was reduced when falling at home (OR = 0.55, 95% CI = 0.31-0.98). The odds of injury among pre-frail adults was not influenced by environment and was 53% lower when falling backwards (OR = 0.47, 95% CI = 0.26-0.82). CONCLUSION: While pre-frail adults sustain more fall-related injuries, frail adults were more likely to sustain major injuries, especially when falling sideways or outside their home.

Complete Genome Assembly of an Auritidibacter ignavus Isolate Obtained from an Ear Infection in Switzerland and a Comparison to Global Isolates.

We present the whole-genome sequence of an isolate of Auritidibacter ignavus, associated with ear infections. This complete assembly was compared to genomes of four global isolates, which revealed a high diversity within the species.