Antimicrobial resistance poses a growing threat to public health and the provision of health care. Its surveillance should provide up-to-date and relevant information to monitor the appropriateness of therapy guidelines, antibiotic formulary, antibiotic stewardship programmes, public health interventions, infection control policies, and antimicrobial development. In Europe, although the European Antimicrobial Resistance Surveillance Network provides annual reports on monitored resistant bacteria, national surveillance efforts are still fragmented and heterogeneous, and have substantial structural problems and issues with laboratory data. Most incidence and prevalence data cannot be linked with relevant epidemiological, clinical, or outcome data. Genetic typing, to establish whether trends of antimicrobial resistance are caused by spread of resistant strains or by transfer of resistance determinants among different strains and species, is not routinely done. Furthermore, laboratory-based surveillance using only clinical samples is not likely to be useful as an early warning system for emerging pathogens and resistance mechanisms. Insufficient coordination of surveillance systems of human antimicrobial resistance with animal surveillance systems is even more concerning. Because results from food surveillance are considered commercially sensitive, they are rarely released publicly by regulators. Inaccurate or incomplete surveillance data delay a translational approach to the threat of antimicrobial resistance and inhibit the identification of relevant target microorganisms and populations for research and the revitalisation of dormant drug-discovery programmes. High-quality, comprehensive, and real-time surveillance data are essential to reduce the burden of antimicrobial resistance. Improvement of national antimicrobial resistance surveillance systems and better alignment between human and veterinary surveillance systems in Europe must become a scientific and political priority, coordinated with international stakeholders within a global approach to reduce the burden of antimicrobial resistance.

Characterization of AMR genes in livestock is applied heterogeneously among countries. Most antibiotics of human interest are included in animal surveillance, although results are difficult to compare as a result of lack of representativeness of animal samples. We suggest that EU/EEA countries provide better uniform AMR monitoring and reporting in livestock and link them better to surveillance systems in humans. Reducing the delay between data collection and publication is also important to allow prompt identification of new resistance patterns.

Insulin and dexamethasone were encapsulated in poly(lactic-co-glycolic acid) (PLGA) microspheres to induce adipogenesis for potential applications in soft tissue reconstruction. Release kinetics and bioactivity of the drugs were examined. Surface morphology and diameter of the PLGA microspheres was evaluated using scanning electron microscopy. The release of insulin was determined using ELISA whereas the release of dexamethasone was evaluated spectrophotometrically. The activity of the drugs was assessed by releasing the drugs in the presence of human adipose-derived stem cells. The ability of the cells cultured with microspheres to differentiate into adipocytes was evaluated using Oil Red O stains. Cells treated with the dexamethasone and insulin microspheres demonstrated a significant increase in lipid inclusions compared with control groups. Insulin and dexamethasone microspheres can reproduce the adipogenic effect exerted by differentiation medium, and may represent a clinically relevant method of stimulating adipogenesis in tissue engineering therapies.

Publicly available information about the methods and indicators of the surveillance system is frequently lacking. Despite the efforts of European Centre for Disease Control and Prevention (ECDC) and other organizations, wide heterogeneity in procedures and indicators still exists.

Objectives: In 2017 the WHO published a global priority list of 12 antibiotic-resistant bacteria (ARB) in urgent need of new antibiotics. We aimed to identify and assess publicly accessible mandatory surveillance systems and outbreaks reporting for these pathogens in the 28 European Union and four European Free Trade Association member states. Methods: Compulsory reporting was mapped by reviewing national documents without applying language restrictions and through expert consultation. Information on surveillance targets, indicators, metrics and dissemination modalities was extracted and a qualitative assessment was performed for open access systems only. Results: Twenty-one countries (66%) had a mandate to survey at least one among the 12 WHO priority pathogens; 15 provided access to surveillance frameworks. These systems covered most frequently carbapenem-resistant Enterobacteriales (12; 38%), methicillin-resistant Staphylococcus aureus (12; 38%), and vancomycin-resistant enterococci (8; 25%). None of the European countries required reporting of resistance in Salmonella, Campylobacter, Helicobacter pylori and Neisseria gonorrhoeae. High heterogeneity was observed in data collection, reporting and dissemination among countries with clinical outcomes and risk factors being reported in less than half (22% and 25%). Only six countries (19%) implemented mandatory surveillance of outbreaks due to at least one WHO priority pathogen. Conclusions: Our review shows that despite the increasing burden of ARB on the European population, very few countries implemented mandatory surveillance and outbreak reporting of the WHO priority pathogens. International efforts are needed to define the effectiveness of implementing mandatory reporting of these pathogens and to assess their role in reducing the spread of ARB in health-care and community settings.

The coagulase-negative species Staphylococcus lugdunensis is an emerging cause of serious and potentially life-threatening infections, such as infective endocarditis. The pathogenesis of these infections is characterized by the ability of S. lugdunensis to form biofilms on either biotic or abiotic surfaces. To elucidate the genetic basis of biofilm formation in S. lugdunensis, we performed transposon (Tn917) mutagenesis. One mutant had a significantly reduced biofilm-forming capacity and carried a Tn917 insertion within the competence gene comEB. Site-directed mutagenesis and subsequent complementation with a functional copy of comEB verified the importance of comEB in biofilm formation. In several bacterial species, natural competence stimulates DNA release via lysis-dependent or -independent mechanisms. Extracellular DNA (eDNA) has been demonstrated to be an important structural component of many bacterial biofilms. Therefore, we quantified the eDNA in the biofilms and found diminished eDNA amounts in the comEB mutant biofilm. High-resolution images and three-dimensional data obtained via confocal laser scanning microscopy (CSLM) visualized the impact of the comEB mutation on biofilm integrity. The comEB mutant did not show reduced expression of autolysin genes, decreased autolytic activities, or increased cell viability, suggesting a cell lysis-independent mechanism of DNA release. Furthermore, reduced amounts of eDNA in the comEB mutant biofilms did not result from elevated levels or activity of the S. lugdunensis thermonuclease NucI. In conclusion, we defined here, for the first time, a role for the competence gene comEB in staphylococcal biofilm formation. Our findings indicate that comEB stimulates biofilm formation via a lysis-independent mechanism of DNA release.

Background: The increasing burden of candidemia and the emergence of resistance, especially among non-Candida albicans strains, represent a new threat for public health. We aimed to assess the status of surveillance and to identify publicly accessible resistance data in Candida spp blood isolates from surveillance systems and epidemiological studies in 28 European and 4 European Free Trade Association member states. Methods: A systematic review of national and international surveillance networks, from 2015 to 2020, and peer-reviewed epidemiological surveillance studies, from 2005 to 2020, lasting for at least 12 consecutive months and with at least two centers involved, was completed to assess reporting of resistance to amphotericin B, azoles, and echinocandins in C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and C. auris. Results: Only 5 (Austria, Italy, Norway, Spain, and United Kingdom) of 32 countries provided resistance data for Candida spp blood isolates. Among 322 surveillance studies identified, 19 were included from Belgium, Denmark, Iceland, Italy, Portugal, Spain, Sweden, Switzerland, and United Kingdom. C. albicans and C. glabrata were the most monitored species, followed by C. parapsilosis and C. tropicalis. C. krusei was not included in any national surveillance system; 13 studies assessed resistance. No surveillance system or study reported resistance for C. auris. Fluconazole, voriconazole, caspofungin, and amphotericin B resistance in C. albicans, C. glabrata, and C. parapsilosis were the most common drug–species combination monitored. Quality of surveillance data was poor, with only two surveillance systems reporting microbiological methods and clinical data. High heterogeneity was observed in modalities of reporting, data collection, and definitions. Conclusion: Surveillance of antifungal resistance in Candida spp blood-isolates is fragmented and heterogeneous, delaying the application of a translational approach to the threat of antifungal resistance and the identification of proper targets for antifungal stewardship activities. International efforts are needed to implement antifungal resistance surveillance programs in order to adequately monitor antifungal resistance.

Objective Interest in application programming interfaces (APIs) is increasing as key stakeholders look for technical solutions to interoperability challenges. We explored three thematic areas to assess the current state of API use for data access and exchange in health care: (1) API use cases and standards; (2) challenges and facilitators for read and write capabilities; and (3) outlook for development of write capabilities. Methods We employed four methods: (1) literature review; (2) expert interviews with 13 API stakeholders; (3) review of electronic health record (EHR) app galleries; and (4) a technical expert panel. We used an eight-dimension sociotechnical model to organize our findings. Results The API ecosystem is complicated and cuts across five of the eight sociotechnical model dimensions: (1) app marketplaces support a range of use cases, the majority of which target providers' needs, with far fewer supporting patient access to data; (2) current focus on read APIs with limited use of write APIs; (3) where standards are used, they are largely Fast Healthcare Interoperability Resources (FHIR); (4) FHIR-based APIs support exchange of electronic health information within the common clinical data set; and (5) validating external data and data sources for clinical decision making creates challenges to provider workflows. Conclusion While the use of APIs in health care is increasing rapidly, it is still in the pilot stages. We identified five key issues with implications for the continued advancement of API use: (1) a robust normative FHIR standard; (2) expansion of the common clinical data set to other data elements; (3) enhanced support for write implementation; (4) data provenance rules; and (5) data governance rules. Thus, while APIs are being touted as a solution to interoperability challenges, they remain an emerging technology that is only one piece of a multipronged approach to data access and use.