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Understanding the transmission dynamics of carbapenem-resistant Enterobacterales (CRE) is critical to addressing the escalating global threat of antimicrobial resistance (AMR). Although hospital transmission of CRE has been extensively studied, information on community transmission is lacking. To identify genomic clusters of CRE from two nearby institutions that may be indicative of community or inter-facility transmission. CRE isolates between January 1st, 2019 and December 31st, 2020 from two tertiary hospitals, detected in the respective routine microbiology laboratories, were collected and characterized by short-read whole-genome sequencing. A total of 272 CRE were collected, with Enterobacter cloacae complex (71/192, 37%) predominant in Heidelberg and Escherichia coli (19/80, 24%) in Mannheim. The most common carbapenem resistance gene, bla OXA-48 , was detected in 38% of CRE from both centres. Several putative transmission clusters were found, including six clusters of E. cloacae complex, five clusters of Klebsiella pneumoniae , four clusters of Citrobacter freundii , and two clusters each of Escherichia coli and K. aerogenes. No clusters involved isolates from both study centres, except for an ST22 C. freundii cluster. Globally circulating clones were identified between the two centres for ST131 E. coli , ST66 E. hormaechei , and ST22 C. freundii. This study found no widespread transmission clusters among isolates from both centres, suggesting a hospital-specific clonal structure. This suggests that CRE clusters involving both institutions may indicate emerging or circulating clones in the community, highlighting the need for intersectoral surveillance and data sharing. [ABSTRACT FROM AUTHOR]

Transmission and outbreaks of carbapenem-resistant Gram-negative bacteria (CRGN) in hospitals are often associated with contamination of the wastewater environment. We performed a prospective observational study to investigate the colonization of the hospital wastewater environment during the first year of occupancy of the surgical intermediate and intensive care units of a newly constructed building at the University Hospital of Heidelberg, Germany. We performed monthly screening of the wastewater system (toilets and sinks) for 12 months, starting 1 month before opening (1st October 2020 to 30th October 2021). Admission and weekly rectal screening of patients for CRGN were also performed in parallel. Bacterial isolates were characterized by whole-genome sequencing. Twenty-seven of 1978 (1.4%) admitted patients were colonized/infected with CRGN. A total of 29 CRGN isolates from 24 patients and 52 isolates were available for sequencing. Within the first month of occupancy, we identified seven patients colonized/infected with CRGN, while none were found in the environmental reservoirs. The first detection of CRGN isolates in the sewage system started five months after the first occupancy. Two previously non-colonized patients were colonized/infected with Pseudomonas aeruginosa strains colonizing the sewage system. The significant identity of plasmids carrying the carbapenemase gene suggests that long-term colonization of the sewage system facilitates the emergence of new carbapenem-resistant clones. Cross-contamination between patients and the hospital environment is bidirectional. Our study demonstrated that contamination of the hospital wastewater environment may lead to persistent colonization and may serve as a reservoir for nosocomial acquisition of CRGN. [ABSTRACT FROM AUTHOR]

Objectives: Vancomycin-resistant Enterococcus faecium (VREfm) has emerged as a pathogen of major concern for public health. Although definitive evidence is lacking, contact precautions have been a crucial element in infection prevention and control (IPC) strategies designed to limit nosocomial VRE transmission. This study investigated the effect of discontinuing contact precautions while enforcing basic hygiene measures, including hand hygiene, environmental cleaning and antiseptic body washing, for patients with VRE in intensive care units (ICUs) on the prevention of nosocomial VRE transmission causing bacteraemia.Methods: Contact precautions were discontinued in January 2018. In total, 96 VREfm isolates from 61 patients with VREfm bacteraemia and/or colonization hospitalized in eight ICUs in a tertiary care hospital in 2016 and 2019 in were characterized by whole-genome sequencing. VRE transmission was investigated using patient movement data and admission screening for reliable identification of nosocomial acquisition.Results: Discontinuation of contact precautions did not increase VREfm transmission events (eight in 2016 vs one in 2019). While the rate of endogenous VREfm was similar in both years (38% vs 31%), the number of non-colonized patients prior to VREfm bacteraemia was 16 (16/29, 55%) in 2019, which was significantly higher than in 2016 (8/32, 25%). The mean incidence density for VREfm bacteraemia was similar for both years (0.26 vs 0.31 per 1000 patient-days in 2016 and 2019, respectively).Conclusion: Discontinuation of contact precautions while enforcing basic hygiene measures did not lead to an increase in nosocomial bloodstream infection rates due to VREfm transmission in a hyperendemic ICU setting. [ABSTRACT FROM AUTHOR]

New Delhi metallo-β-lactamase (blaNDM) acquisition by Gram-negative bacteria is a primary concern due to its broad-host-range distribution. This study investigated two potential in-vivo horizontal gene transfers (HGTs) of blaNDM between Enterobacterales and Pseudomonas aeruginosa, initially indicated by polymerase chain reaction. Whole-genome sequencing showed independent parallel acquisition of two different blaNDM variants (NDM-1 and NDM-5) in P. aeruginosa and Enterobacterales, respectively. The data show that short-read sequencing provides the necessary resolution to confirm or dispute HGT by the comparison of genetic elements surrounding the gene of interest, and thus provide a timely response to potential outbreaks. [ABSTRACT FROM AUTHOR]

Background: Patients with sepsis-induced Acute Respiratory Distress Syndrome (ARDS) are hallmarked by high mortality rates. Early, targeted antibiotic therapy is crucial for patients' survival. The clinical use of a Next Generation Sequencing (NGS)-based approach for pathogen identification may lead to an improved diagnostic performance. Therefore, the objective of this study was to examine changes in the pulmonary-microbiome and resulting influences on patients' outcome in septic ARDS, but also to compare NGS- and culture-based diagnostic methods for pathogen identification.Methods: In total, 30 patients in two groups were enrolled in the study: (1) 15 septic ARDS patients following major abdominal surgery and (2) 15 patients undergoing oesophageal resection serving as controls. In the ARDS group, blood samples were collected at ARDS onset as well as 5 days and 10 days afterwards. At the same timepoints, bronchoalveolar lavages (BAL) were performed to collect epithelial lining fluid for culture-, as well as NGS-based analyses and to evaluate longitudinal changes in the pulmonary microbiome. In the control group, only one BAL and one blood sample were collected.Results: ARDS patients showed a significantly reduced α-diversity (p=0.007**) and an increased dominance (p=0.012*) in their pulmonary-microbiome. The α-diversity-index correlated with the length of stay in the intensive care unit (p-value=0.015) and the need for mechanical ventilation (p-value=0.009). In 42.9% of all ARDS patients, culture-based results were negative, while NGS findings indicated bacterial colonization.Conclusion: Sepsis-induced ARDS is associated with a significant dysbiosis of patients' pulmonary-microbiome, which is closely correlated with the clinical course of the disease.Trial Registration: This prospective, observational pilot study was approved by the Ethics Committee of the Medical Faculty of Heidelberg (trial code no. S-063/2015) and was prospectively registered in the German clinical trials register (DRKS-ID: DRKS00008317 prospectively registered: 28.10.2015). All study patients or their legal representatives signed written informed consent. [ABSTRACT FROM AUTHOR]

Background: Increased occurrence of a particular species of Gram-negative bacteria (GNB), especially when multi-drug-resistant (MDR), in routine screening surveillance in neonatal intensive care units (NICUs) can be evoked by selection pressure.Aim: To evaluate adaptation of the empiric antibiotic regimen for its usefulness as a control measure in suspected outbreaks in the NICU.Methods: In a retrospective outbreak analysis, cases between 1st December 2017 and 31st March 2018 were identified through microbiology and hygiene surveillance records. Furthermore, risk factors for MDR-GNB colonization were collected. Whole-genome sequencing (WGS) was performed on all isolates. Control measure documentations and interviews were employed to define interventions. As well as infection control measures, administration of third-generation cephalosporins was avoided and replaced whenever clinically acceptable as part of the intervention bundle.Findings: In total, nine patients were found to have rectal colonization with third-generation cephalosporin-resistant Enterobacter cloacae in routine screening surveillance in the pre-intervention period. After implementation of an infection control bundle, the incidence declined rapidly. WGS analysis revealed that two MDR E. cloacae were transmitted, and the majority were new cases. The incidence density of MDR-GNB colonization was 7.94/1000 patient-days (PD) before the intervention and 1.68/1000 PD during the altered antibiotic regimen. No infections with MDR-GNB occurred during the study.Conclusions: Altering the antibiotic regimen with regard to selection pressure may be considered as part of an intervention bundle to rapidly control the emergence of MDR-GNB in suspected outbreak situations in the NICU. [ABSTRACT FROM AUTHOR]

Conjugative gene transfer has been considered as one of the driving factors in the transmission and dissemination of multidrug resistance in bacteria. The abundance of antimicrobial resistance genes and bacteria in the gut microbiome may provide the ideal platform for plasmid exchange. Systematic data on in vivo horizontal gene transfer (HGT) and its frequency are scarce. One hundred and ninety-six carbapenem-resistant gram-negative bacilli (CRGNBs) from 179 patients (158 inpatients and 21 outpatients) between January 2016 and April 2017 were analysed retrospectively. Alignment of plasmid content for 32 isolates from 16 patients with multiple CRGNB species was performed from whole-genome sequencing (WGS) data. Sixteen of the 179 patients (8.9%) were colonized and/or infected with more than one CRGNB species; 11/179 (6.1%) were colonized by multiple carbapenem-resistant Enterobacteriaceae (CREs) and 5/179 (2.8%) by carbapenem-resistant non-fermenters (CRNFs) and CREs. WGS suggested interspecies transfer as the predominant mechanism rather than independent acquisition in 8/10 patients (80%, one non-recoverable isolate) with multiple CREs but not in CRNF–CRE combinations; 30/158 inpatients (20%) had underlying haematological malignancies, and they are more likely to exhibit multiple CRGNB strains (OR 3.0, 95%CI 0.98–8.89, p 0.05) and CRE strains (OR 3.9, 95%CI 1.02–14.58, p 0.04) during hospital stay compared to other patient groups. Our data give insight into the occurrence of natural in vivo HGT in a clinical setting. Better understanding of HGT will help optimize containment measures and may guide antibiotic stewardship programmes. [ABSTRACT FROM AUTHOR]

Recently, following import by travel and migration, epidemic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has caused nosocomial outbreaks in Europe, sometimes with a fatal outcome. We describe clinico-epidemiological characteristics of CA-MRSA detected by the European Network for the Surveillance of imported S. aureus (www.staphtrav.eu) from May 2011 to November 2016. Sentinel surveillance at 13 travel clinics enrolling patients with travel-associated skin and soft-tissue infection (SSTI) and analysing lesion and nose swabs at one central laboratory. A total of 564 independent case-patients with SSTI were enrolled and had 374 (67%) S. aureus -positive lesions, of which 14% (51/374) were MRSA. The majority of CA-MRSA isolates from SSTI were Panton–Valentine leucocidin (PVL) -positive (43/51, 84%). The risk of methicillin-resistance in imported S. aureus varied by travel region (p <0.001) and was highest in Latin America (16/57, 28%, 95% CI 17.0–41.5) and lowest in Sub-Saharan Africa (4/121, 3%, 95% CI 0.9–8.3). Major epidemic clones (USA300 / USA300 Latin-American Variant, Bengal Bay, South Pacific) accounted for more than one-third (19/51, 37%) of CA-MRSA imports. CA-MRSA SSTI in returnees was complicated (31/51 multiple lesions, 61%; 22/50 recurrences, 44%), led to health-care contact (22/51 surgical drainage, 43%; 7/50 hospitalization, 14%), was transmissible (13/47 reported similar SSTI in non-travelling contacts, 28%), and associated with S. aureus nasal colonization (28 of 51 CA-MRSA cases, 55%; 24 of 28 colonized with identical spa -type in nose and lesion, 85%). Travel-associated CA-MRSA SSTI is a transmissible condition that leads to medical consultations and colonization of the infected host. [ABSTRACT FROM AUTHOR]

Introduction Le recours systématique à la SSPI au décours d’actes réalisés en ambulatoire (UCAA) est discuté notamment par la HAS. Le court-circuit a pour objectif d’améliorer le confort du patient sans altérer sa sécurité dans le respect de « l’esprit » du décret de 1994. Dans nos 2 établissements, le parcours des patients opérés d’une cataracte (PKE) sous-topique en ambulatoire (avec ou sans sédation de confort) et surveillance anesthésique prévoit la possibilité d’un court-circuit de la SSPI (CCPI). L’objectif de ce travail est d’évaluer la pertinence, la faisabilité et la sécurité du CCPI dans cette indication. Matériel et méthodes Étude observationnelle rétrospective puis prospective, bicentrique. Nous avons analysé les dossiers des patients admis en UCAA sur la période 2012 et 2013 dans un CHU et un CHG proches. Le CCPI a été mis en œuvre depuis 2007 au CHU et octobre 2012 au CHG. Une formalisation avec traçabilité (CCPIFOR) comprenant notamment le score d’Aldret modifié, réalisé avant la sortie de la salle interventionnelle vers l’UCAA et l’apposition de la signature du chirurgien et de l’anesthésiste a été mise en place en février 2013 dans le CHG et en décembre 2013 dans le CHU. Au CHG, notre base de données en SSPI nous a permis d’analyser rétrospectivement les informations concernant la période antérieure au CCPI (janvier 2010 à octobre 2012). Une évaluation prospective du CCPIFOR a été ensuite réalisée. Un questionnaire de satisfaction proposé aux patients comprenait la récupération des moyens physiques à la sortie du bloc opératoire et de l’UCAA et la satisfaction globale. Résultats Sur la période antérieure au CCPI (base de données CHG), n = 845, la durée, médiane (IQR 25-75), du séjour en SSPI était de 35 (26–43) mins et 9 évènements étaient rapportés (5 NVPO, 1 hyperglycémie et 3 attentes brancardages prolongées). Sur la période postérieure au CCPI, n = 483, 4 (0,8 %) patients se sont avérés non éligibles au CCPI : un cas anticipé dès la consultation d’anesthésie, deux cas d’hypertension et un cas d’hypotension artérielle. L’analyse du CCPIFOR (données préliminaires) a inclus 278 patients (123 au CHG et 156 au CHU), (cf Tableau 1 ) (médiane IQR 25-75). Deux cent trente patients ont répondu au questionnaire et un seul n’a pas été satisfait de son séjour. La récupération des moyens physiques à la sortie du bloc opératoire a été jugé insuffisante pour 5 patients, cette appréciation persistait pour 3 d’entre eux à la sortie de l’UCAA. Sept évènements ont été observés : 2 céphalées, 4 hypertensions, 1 NVPO et un retour en SSPI pour malaise. Aucun patient n’a nécessité un lit de recours. Discussion Un court-circuit de la SSPI dans un cadre organisationnel strict impliquant le chirurgien est réalisable et simplifie le parcours du patient sans altérer la sécurité et la qualité de la prise en charge. [ABSTRACT FROM AUTHOR]

Abstract: Critical to the conservation of biodiversity is knowledge of status and trends of species. To that end, monitoring programmes have reported on the state of biodiversity using reference conditions as comparison. Little consensus exists on how reference conditions are defined and how such information is used to index intactness. Most use protected areas or an arbitrary year as reference. This is problematic since protected areas are often spatially biased, while arbitrarily defined reference years are often not sufficiently distant in time. We propose an alternative that relies on empirical estimates of reference conditions. Statistical ranges of reference are estimated and compared with observed occurrence and abundance to index status of individual species. When averaged among species, overall intactness is estimated. We demonstrate the approach using 202-winter mammal tracking sites from the boreal forest of Alberta, Canada. Intactness was estimated at 89 out of 100 with the southern boreal having lowest intactness and greatest human footprint. We suggest empirical predictions of reference conditions be used as baselines for comparing changes in the state of species and biodiversity. Reporting can occur at any spatial (e.g., ecosystem) or hierarchical (e.g., species, guilds, taxonomic group, or overall biodiversity) scale and is easily interpreted (scaled from 0-degraded to 100-intact). When used in a long-term monitoring framework, statistical trends in biodiversity intactness can be estimated, individual status of species assessed, and relevant policy evaluated. [Copyright &y& Elsevier]

• We present a model of apparent competition, parametrized using empirical data, to predict habitat restoration efficacy. • Habitat restoration has the potential to increase caribou densities by up to 2.51-fold. • Increases in caribou density can occur with minimal changes to wolf or moose density. • Incorporating the numerical feedback into simulations of foraging efficiency increased our understanding of the total response. • Simulated predator reductions increased caribou densities by more than twice the total response of restoration, suggesting restoration should be coupled with other direct management actions. Predator-prey dynamics are increasingly being modified by the alteration of natural habitats. Such alteration has led to increased predation rates and local extirpation of woodland caribou (Rangifer tarandus caribou) in western Canada. Linear features such as roads or seismic lines (narrow corridors used for petroleum exploration that are cleared of vegetation) increase predation rates on caribou by increasing wolf (Canis lupus) movement rates and by facilitating access into caribou habitat. Linear feature restoration is therefore hypothesised to help reverse caribou declines. However, with the high financial cost to restore approximately 350,000 km of seismic lines within western Canada's boreal forests, theoretical predictions can clarify the efficacy of such actions. We use a mathematical model based on coupled ordinary differential equations representing predator-prey dynamics to estimate equilibrium densities of caribou, moose (Alces alces) and wolves under various parameter scenarios. Changes in equilibrium density serve as a proxy for the expected effect of linear feature restoration on population densities. Our model captures dynamical feedbacks between caribou and wolf densities, and also includes moose, which are the wolf's primary prey species. With our best estimates of parameter values, caribou density increased 2.51-fold if all linear features were restored and 1.61-fold if only seismic lines were restored. As a comparison, simulated predator reductions increased caribou densities 3.92-fold, nearly twice the total response of linear feature restoration. The effect of restoration was increased if caribou group size was smaller, yet was less pronounced if carrying capacity for ungulates was higher. By varying the parameter values and fixing population densities, our approach allowed us to partition the caribou populations' response from restoration into the contributions of the various mechanisms and feedbacks. In particular, contrasting simulation results where wolf densities are kept fixed with those where they are free to respond to prey allowed us to disentangle the relative importance of wolf functional and numerical response. This novel approach indicates that most of the increase in caribou densities after restoration was due to reduced foraging efficiency of wolves, especially reduced habitat overlap. Overall, our results suggest that restoration could substantially benefit caribou populations, but only if all linear features are restored, which is far from realistic. Linear feature restoration alone may not lead to population recovery, and should therefore be coupled with other direct management actions to successfully recover caribou. [ABSTRACT FROM AUTHOR]