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The emergence of bloodstream infections (BSI) caused by vancomycin-resistant Enterococci (VRE) has caused concern.Nonetheless, it remains unclear whether these types are associated with an excess risk of severe outcomes whencompared with infections caused by vancomycin-susceptible Enterococci (VSE). This cohort study includedhospitalized patients in Denmark with Enterococcus faecium-positive blood cultures collected between 2010 and 2019identified in the Danish Microbiology Database. We estimated 30-day hazard ratio (HR) of death or discharge amongVRE compared to VSE patients adjusted for age, sex, and comorbidity. The cohort included 6071 patients withE. faecium BSI (335 VRE, 5736 VSE) among whom VRE increased (2010–13, 2.6%; 2014–16, 6.3%; 2017–19; 9.4%).Mortality (HR 1.08, 95%CI 0.90–1.29; 126 VRE, 37.6%; 2223 VSE, 37.0%) or discharge (HR 0.89, 95%CI 0.75–1.06; 126VRE, 37.6%; 2386 VSE, 41.6%) was not different between VRE and VSE except in 2014 (HR 1.87, 95% CI 1.18–2.96).There was no interaction between time from admission to BSI (1–2, 3–14, and >14 days) and HR of death (P = 0.14) ordischarge (P = 0.45) after VRE compared to VSE, despite longer time for VRE patients (17 vs. 10 days for VSE, P <0.0001). In conclusion, VRE BSI was not associated with excess morbidity and mortality. The excess mortality in 2014only may be attributed to improved diagnostic- and patient-management practices after 2014, reducing time toappropriate antibiotic therapy. The high level of mortality after E. faecium BSI warrants further study., The emergence of bloodstream infections (BSI) caused by vancomycin-resistant Enterococci (VRE) has caused concern. Nonetheless, it remains unclear whether these types are associated with an excess risk of severe outcomes when compared with infections caused by vancomycin-susceptible Enterococci (VSE). This cohort study included hospitalized patients in Denmark with Enterococcus faecium-positive blood cultures collected between 2010 and 2019 identified in the Danish Microbiology Database. We estimated 30-day hazard ratio (HR) of death or discharge among VRE compared to VSE patients adjusted for age, sex, and comorbidity. The cohort included 6071 patients with E. faecium BSI (335 VRE, 5736 VSE) among whom VRE increased (2010–13, 2.6%; 2014–16, 6.3%; 2017–19; 9.4%). Mortality (HR 1.08, 95%CI 0.90–1.29; 126 VRE, 37.6%; 2223 VSE, 37.0%) or discharge (HR 0.89, 95%CI 0.75–1.06; 126 VRE, 37.6%; 2386 VSE, 41.6%) was not different between VRE and VSE except in 2014 (HR 1.87, 95% CI 1.18–2.96). There was no interaction between time from admission to BSI (1–2, 3–14, and >14 days) and HR of death (P = 0.14) or discharge (P = 0.45) after VRE compared to VSE, despite longer time for VRE patients (17 vs. 10 days for VSE, P < 0.0001). In conclusion, VRE BSI was not associated with excess morbidity and mortality. The excess mortality in 2014 only may be attributed to improved diagnostic- and patient-management practices after 2014, reducing time to appropriate antibiotic therapy. The high level of mortality after E. faecium BSI warrants further study.

Staphylococcus aureus (S. aureus) represents a major clinical challenge due to its explicit capacity to select mutations that increase antibiotic resistance and immune evasion. However, the molecular mechanisms are poorly defined, especially for adaptive immunity. Cancer immunotherapy targeting programmed cell death protein 1 (PD-1) enhances T-cell activity and is emerging for the treatment of certain viral infections, while its potential against bacterial infections remains elusive. We show that an S. aureus clpP mutant, selected during clinical antibiotic therapy, inhibits T-cell activity by directly interacting with PD-1 on human T cells. Specificity of the interaction was confirmed using recombinant PD-1, as well as PD-1 overexpressing and knock out cells. Moreover, the PD-1-binding S. aureus inhibited intracellular calcium mobilization, T-cell proliferation, CD25 expression, and IL-2 secretion, while the key effects were alleviated by antibody-mediated PD-1 blockade using an engineered IgG1-based anti-PD-1 antibody. Our results suggest that clpP mutant S. aureus directly targets PD-1 to evade immune activation and that therapeutic targeting of PD-1 may be used against certain staphylococcal infections. IMPORTANCE Therapies that target and aid the host immune defense to repel cancer cells or invading pathogens are rapidly emerging. Antibiotic resistance is among the largest threats to human health globally. Staphylococcus aureus (S. aureus) is the most common bacterial infection, and it poses a challenge to the healthcare system due to its significant ability to develop resistance toward current available therapies. In long-term infections, S. aureus further adapt to avoid clearance by the host immune defense. In this study, we discover a new interaction that allows S. aureus to avoid elimination by the immune system, which likely supports its persistence in the host.

Background Staphylococcus aureus may worsen already established atopic dermatitis (AD), but its primary role in the aetiopathogenesis and severity of AD is unclear. Objectives To compare the prevalence of S. aureus colonization in early infancy in children who developed AD during the first 2 years of life with children who did not. Methods In this prospective birth cohort study, which included 450 infants, we analysed bacterial swabs collected from cheek skin at 0 and 2 months of age. The development of AD, and its severity, was diagnosed by a physician and monitored prospectively for 2 years. Information on parental atopy, filaggrin gene mutation status and use of antibiotics and emollients was included in the analyses. Results At birth, the occurrence of S. aureus colonization was similar in infants who developed subsequent AD and those who did not. At 2 months of age, S. aureus colonization was more common in children who later developed AD (adjusted hazard ratio 1.97, 95% confidence interval 1.21–3.19; P = 0.006). No association was found between S. aureus colonization and AD severity or age at onset. Conclusions It remains unknown whether colonization with S. aureus may directly increase the risk of AD, or whether it should be considered as secondary to skin barrier impairment or a skewed immune activity, but according to our findings, S. aureus colonization is more commonly increased at 2 months of age in children who later developed AD., Background Staphylococcus aureus may worsen already established atopic dermatitis (AD), but its primary role in the aetiopathogenesis and severity of AD is unclear. Objectives To compare the prevalence of S. aureus colonization in early infancy in children who developed AD during the first 2 years of life with children who did not. Methods In this prospective birth cohort study, which included 450 infants, we analysed bacterial swabs collected from cheek skin at 0 and 2 months of age. The development of AD, and its severity, was diagnosed by a physician and monitored prospectively for 2 years. Information on parental atopy, filaggrin gene mutation status and use of antibiotics and emollients was included in the analyses. Results At birth, the occurrence of S. aureus colonization was similar in infants who developed subsequent AD and those who did not. At 2 months of age, S. aureus colonization was more common in children who later developed AD (adjusted hazard ratio 1.97, 95% confidence interval 1.21-3.19; P = 0.006). No association was found between S. aureus colonization and AD severity or age at onset. Conclusions It remains unknown whether colonization with S. aureus may directly increase the risk of AD, or whether it should be considered as secondary to skin barrier impairment or a skewed immune activity, but according to our findings, S. aureus colonization is more commonly increased at 2 months of age in children who later developed AD.

A B S T R A C T Multinational surveillance programmes for methicillin-resistant Staphylococcus aureus (MRSA) are dependent on national structures for data collection. This study aimed to capture the diversity of national MRSA surveillance programmes and to propose a framework for harmonisation of MRSA surveillance. The International Society of Antimicrobial Chemotherapy (ISAC) MRSA Working Group conducted a structured survey on MRSA surveillance programmes and organised a webinar to discuss the programmes' strengths and challenges as well as guidelines for harmonisation. Completed surveys represented 24 MRSA surveil-lance programmes in 16 countries. Several countries reported separate epidemiological and microbiolog-ical surveillance. Informing clinicians and national policy-makers were the most common purposes of surveillance. Surveillance of bloodstream infections (BSIs) was present in all programmes. Other invasive infections were often included. Three countries reported active surveillance of MRSA carriage. Method-ology and reporting of antimicrobial susceptibility, virulence factors, molecular genotyping and epidemi-ological metadata varied greatly. Current MRSA surveillance programmes rely upon heterogeneous data collection systems, which hampers international epidemiological monitoring and research. To harmonise MRSA surveillance, we suggest improving the integration of microbiological and epidemiological data, im-plementation of central biobanks for MRSA isolate collection, and inclusion of a representative sample of skin and soft-tissue infection cases in addition to all BSI cases.Crown Copyright (c) 2022 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Spread of livestock-associated methicillin resistant Staphylococcus aureus (LA-MRSA) to farmworkers has been recognized as a risk when working in LA-MRSA positive stables, due to LA-MRSA being present on airborne dust particles. Based on this, airborne spread of LA-MRSA through stable vents is a concern that is addressed in this study. The aim of the investigation was to quantify the airborne spread of LA-MRSA from a MRSA positive swine farm. In order to achieve this, a method for sampling large volumes of air was applied. The results were compared to meteorological data and bacteriological investigation of samples from the air inside the swine barn, soil outside the farm, and nasal samples from the individuals participating in the sampling process. MRSA was detected up to 300 m (the maximal measuring distance) from the swine farm in the air but only at low levels at distances above 50 meters (0.085 CFU/m3 at a distance of 50 m in the wind plume). MRSA was detected in sock samples obtained at the soil surfaces up to 400 m (the maximal measuring distance) from the farm building. The proportion of MRSA positive soil samples decreased from ~80 to 30% with increasing distance from the farm. A total of 25 human nasal samples were sampled after the farm visits after the participants had stayed in the surroundings of the farm for an average of 10.5 h. When leaving the farm, only two of the samples (8%) were LA-MRSA-positive both obtained from one individual who was the one who had sampled the ventilation shafts. In conclusion, airborne spread of MRSA from swine farms does not seem to be an important route for human contamination for individuals staying a whole working day outside a swine farm.

Since the late 1990s, changes in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) were recognized with the emergence of community-associated MRSA (CA-MRSA). CA-MRSA belonging to clonal complex 152 (CC152), carrying the small staphylococcal cassette chromosome mec (SCCmec) type V and encoding the Panton-Valentine leukocidin (PVL), has been observed in Europe. The aim of this study was to investigate its origin, evolution, and dissemination. Whole-genome sequencing was performed on a global collection of 149 CC152 isolates spanning 20 years (93 methicillin-susceptible S. aureus [MSSA] and 56 MRSA isolates). Core genome phylogeny, Bayesian inference, in silico resistance analyses, and genomic characterization were applied. Phylogenetic analysis revealed two major distinct clades, one dominated by MSSA and the other populated only by MRSA. The MSSA isolates were predominately from sub-Saharan Africa, whereas MRSA was almost exclusively from Europe. The European MRSA isolates all harbored an SCCmec type V (5C2&5) element, whereas other SCCmec elements were sporadically detected in MRSA from the otherwise MSSA-dominated clade, including SCCmec types IV (2B), V (5C2), and XIII (9A). In total, 93% of the studied CC152 isolates were PVL positive. Bayesian coalescent inference suggests an emergence of the European CC152-MRSA in the 1990s, while the CC152 lineage dates back to the 1970s. The CA-MRSA CC152 clone mimics the European CC80 CA-MRSA lineage by its emergence from a PVL-positive MSSA ancestor from North Africa or Europe. The CC152 lineage has acquired SCCmec several times, but acquisition of SCCmec type V (5C2&5) seems associated with expansion of MRSA CC152 in Europe. IMPORTANCE Understanding the evolution of CA-MRSA is important in light of the increasing importance of this reservoir in the dissemination of MRSA. Here, we highlight the story of the CA-MRSA CC152 lineage using whole-genome sequencing on an international collection of CC1