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Background: International travel has been recognized as a risk factor contributing to the spread of antimicrobial resistance (AMR). However, tools focused on AMR in the context of international travel and designed to guide decision-making are limited. We aimed at developing an evidence-based educational tool targeting both healthcare professionals (HCPs) and international travellers to help prevent the spread of AMR.Methods: A literature review on 12 antimicrobial-resistant bacteria (ARB) listed as critical and high tiers in the WHO Pathogen Priority List covering four key areas was carried out: AMR surveillance data; epidemiological studies reporting ARB prevalence data on carriage in returning travellers; guidance documents reporting indications on screening for ARB in returning travellers and recommendations for ARB prevention for the public. The evidence, catalogued at country-level, provided the content for a series of visualizations that allow assessment of the risk of AMR acquisition through travel.Results: Up to January 2021, the database includes data on: (i) AMR surveillance for 2.018.241 isolates from 86 countries; (ii) ARB prevalence of carriage from 11.679 international travellers and (iii) 15 guidance documents published by major public health agencies. The evidence allowed the development of a consultation scheme for the evaluation of risk factors, prevalence of carriage, proportion and recommendations for screening of AMR. For the public, pre-travel practical measures to minimize the risk of transmission were framed.Conclusions: This easy-to-use, annually updated, freely accessible AMR travel tool (https://epi-net.eu/travel-tool/overview/), is the first of its kind to be developed. For HCPs, it can provide a valuable resource for teaching and a repository that facilitates a stepwise assessment of the risk of AMR spread and strengthen implementation of optimized infection control measures. Similarly, for travellers, the tool has the potential to raise awareness of AMR and outlines preventive measures that reduce the risk of AMR acquisition and spread. [ABSTRACT FROM AUTHOR]

Current anti-inflammatory strategies for the treatment of pulmonary disease in cystic fibrosis (CF) are limited; thus, there is continued interest in identifying additional molecular targets for therapeutic intervention. Given the emerging role of sphingolipids (SLs) in various respiratory disorders, including CF, drugs that selectively target the enzymes associated with SL metabolism are under development. Miglustat, a well-characterized iminosugar-based inhibitor of β-glucosidase 2 (GBA2), has shown promise in CF treatment because it reduces the inflammatory response to infection by P. aeruginosa and restores F508del-CFTR chloride channel activity. This study aimed to probe the molecular basis for the anti-inflammatory activity of miglustat by examining specifically the role of GBA2 following the infection of CF bronchial epithelial cells by P. aeruginosa. We also report the anti-inflammatory activity of another potent inhibitor of GBA2 activity, namely N-(5-adamantane-1-yl-methoxy)pentyl)-deoxynojirimycin (Genz-529648). In CF bronchial cells, inhibition of GBA2 by miglustat or Genz-529648 significantly reduced the induction of IL-8 mRNA levels and protein release following infection by P. aeruginosa. Hence, the present data demonstrate that the anti-inflammatory effects of miglustat and Genz-529648 are likely exerted through inhibition of GBA2. [ABSTRACT FROM AUTHOR]

Current anti-inflammatory strategies for the treatment of pulmonary disease in cystic fibrosis (CF) are limited; thus, there is continued interest in identifying additional molecular targets for therapeutic intervention. Given the emerging role of sphingolipids (SLs) in various respiratory disorders, including CF, drugs that selectively target the enzymes associated with SL metabolism are under development. Miglustat, a well-characterized iminosugar-based inhibitor of β-glucosidase 2 (GBA2), has shown promise in CF treatment because it reduces the inflammatory response to infection by P. aeruginosa and restores F508del-CFTR chloride channel activity. This study aimed to probe the molecular basis for the anti-inflammatory activity of miglustat by examining specifically the role of GBA2 following the infection of CF bronchial epithelial cells by P. aeruginosa. We also report the anti-inflammatory activity of another potent inhibitor of GBA2 activity, namely N-(5-adamantane-1-yl-methoxy)pentyl)-deoxynojirimycin (Genz-529648). In CF bronchial cells, inhibition of GBA2 by miglustat or Genz-529648 significantly reduced the induction of IL-8 mRNA levels and protein release following infection by P. aeruginosa. Hence, the present data demonstrate that the anti-inflammatory effects of miglustat and Genz-529648 are likely exerted through inhibition of GBA2. [ABSTRACT FROM AUTHOR]

Strategic and standardised approaches to analysis and reporting of surveillance data are essential to inform antimicrobial resistance (AMR) mitigation measures, including antibiotic policies. Targeted guidance on linking full-scale AMR and antimicrobial consumption (AMC)/antimicrobial residues (AR) surveillance data from the human, animal, and environmental sectors is currently needed. This paper describes the initiative whereby a multidisciplinary panel of experts (56 from 20 countries-52 high income, 4 upper middle or lower income), representing all three sectors, elaborated proposals for structuring and reporting full-scale AMR and AMC/AR surveillance data across the three sectors. An evidence-supported, modified Delphi approach was adopted to reach consensus among the experts for dissemination frequency, language, and overall structure of reporting; core elements and metrics for AMC/AR data; core elements and metrics for AMR data. The recommendations can support multisectoral national and regional plans on antimicrobials policy to reduce resistance rates applying a One Health approach., Competing Interests: JA received grants/contracts from the Spanish Ministry of Agriculture, Food and Fisheries and EU Horizon 2020. Work of BPG was funded by the German Center for Infection research Clinical Research Unit (DZIF-CRU) at Tübingen. RD participated on Data Safety Monitoring Board of the ASTARTÉ study (for which no payments were received). WG received grants/contracts from the Horizon Europe grant (supported by UKRI) on AMR and pathogen evolution in costal environments and the UK Natural Environment Research Council grants on AMR Knowledge Exchange NE/V019279/1 and AMR evolution NE/W006251/1; WG received consultation fee for EU DG Sante AMR policy evaluation and recommendations. Work of AK was funded in the context of the project One Health EJP, which has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 773830. EP received grants/contracts from the Austrian Ministry of Health for the National Surveillance Network of healthcare-associated infections (ANISS); EP received honorarium for participation as a chair of the Advisory board on AMR and MDRO Pfizer Austria (27.09.22). MB received grants/contracts from Janssen Vaccines, Novartis, CureVac, and Merck; MB received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Takeda (November 2019); MB participated on Data Safety Monitoring Board or Advisory Board of Sanofi, Spherecydes, Pfizer, Merck, Novartis, and Astra-Zeneca. MM received support for attending meetings and/or travel from the Global Antibiotic Research and Development Partnership (12.10.22–13.10.2022). LS received grants or contracts from the JPIAMR network grant 2020; LS received support for attending meetings and/or travel from ESCMID for the attendance of ECCMID 2022. DT is an employee of GlaxoSmithKline and holds shares in GlaxoSmithKline. TVB received consultation fees from Stonehaven Consulting; TVB received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Swedish Veterinary Council. Work of AV was supported by the COMBACTE-MAGNET consortium; AV serves as the ISAC president (International Society of Antimicrobial Chemotherapy) and board member of NVMM (Dutch Microbiology Society). All other authors declare no competing interests., (© 2022 The Authors.)