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  1. Harbarth S, Tuan Soh S, Horner C, Wilcox MH
    J Hosp Infect, 2014 Aug;87(4):194-202.
    PMID: 24996517 DOI: 10.1016/j.jhin.2014.04.012
    Given the breadth and depth of antiseptic use, it is surprising how few large-scale studies have been undertaken into the consequences of their use, particularly in clinical practice. Depending on your point of view, this may either reflect an assurance that reduced susceptibility to antiseptics, and notably whether this confers cross-resistance to systemically administered antimicrobial agents, is not an issue of concern, or relative ignorance about the potential threat.
  2. Léger A, Lambraki I, Graells T, Cousins M, Henriksson PJG, Harbarth S, et al.
    J Antimicrob Chemother, 2021 01 01;76(1):1-21.
    PMID: 33057678 DOI: 10.1093/jac/dkaa394
    The global threat of antimicrobial resistance (AMR) requires coordinated actions by and across different sectors. Increasing attention at the global and national levels has led to different strategies to tackle the challenge. The diversity of possible actions to address AMR is currently not well understood from a One Health perspective. AMR-Intervene, an interdisciplinary social-ecological framework, describes interventions to tackle AMR in terms of six components: (i) core information about the publication; (ii) social system; (iii) bio-ecological system; (iv) triggers and goals; (v) implementation and governance; and (vi) assessment. AMR-Intervene provides a broadly applicable framework, which can inform the design, implementation, assessment and reporting of interventions to tackle AMR and, in turn, enable faster uptake of successful interventions to build societal resilience to AMR.
  3. Léger A, Lambraki I, Graells T, Cousins M, Henriksson PJG, Harbarth S, et al.
    BMC Infect Dis, 2021 Aug 26;21(1):873.
    PMID: 34445962 DOI: 10.1186/s12879-021-06483-z
    BACKGROUND: Antimicrobial resistance (AMR) is among the most pressing One Health issues. While interventions and policies with various targets and goals have been implemented, evidence about factors underpinning success and failure of interventions in different sectors is lacking. The objective of this study is to identify characteristics of AMR interventions that increase their capacity to impact AMR. This study focuses on AMR interventions targeting E. coli.

    METHODS: We used the AMR-Intervene framework to extract descriptions of the social and ecological systems of interventions to determine factors contributing to their success.

    RESULTS: We identified 52 scientific publications referring to 42 unique E. coli AMR interventions. We mainly identified interventions implemented in high-income countries (36/42), at the national level (16/42), targeting primarily one sector of society (37/42) that was mainly the human sector (25/42). Interventions were primarily funded by governments (38/42). Most intervention targeted a low leverage point in the AMR system, (36/42), and aimed to change the epidemiology of AMR (14/42). Among all included publications, 55% (29/52) described at least one success factor or obstacle (29/52) and 19% (10/52) identified at least one success factor and one obstacle. Most reported success factors related to communication between the actors and stakeholders and the role of media, and stressed the importance of collaboration between disciplines and external partners. Described obstacles covered data quality, access to data and statistical analyses, and the validity of the results.

    CONCLUSIONS: Overall, we identified a lack of diversity regarding interventions. In addition, most published E. coli interventions were poorly described with limited evidence of the factors that contributed to the intervention success or failure. Design and reporting guidelines would help to improve reporting quality and provide a valuable tool for improving the science of AMR interventions.

  4. Lambraki IA, Chadag MV, Cousins M, Graells T, Léger A, Henriksson PJG, et al.
    Front Microbiol, 2022;13:992507.
    PMID: 36687632 DOI: 10.3389/fmicb.2022.992507
    BACKGROUND: With AMU projected to increase, South East Asia (SEA) is at high risk of experiencing disproportionate health, social, and economic burdens due to antimicrobial resistance (AMR). Our objective was to identify factors influencing AMR in SEA's food system and places for intervention by integrating the perspectives of experts from the region to inform policy and management decisions.

    MATERIALS AND METHODS: We conducted two 6.5 h workshops and two 90-min interviews involving 18 AMR and other disciplinary experts from human, animal, and environment sectors who brainstormed the factors influencing AMR and identified leverage points (places) for intervention. Transcripts and workshop materials were coded for factors and their connections and transcribed into a causal loop diagram (CLD). Thematic analysis described AMR dynamics in SEA's food system and leverage points for intervention. The CLD and themes were confirmed via participant feedback.

    RESULTS: Participants constructed a CLD of AMR in the SEA food system that contained 98 factors interlinked by 362 connections. CLD factors reflected eight sub-areas of the SEA food system (e.g., government). Seven themes [e.g., antimicrobial and pesticide use and AMR spread (n = 40 quotes)], six "overarching factors" that impact the entire AMR system [e.g., the drive to survive (n = 12 quotes)], and 10 places for intervention that target CLD factors (n = 5) and overarching factors (n = 2) emerged from workshop discussions.

    CONCLUSION: The participant derived CLD of factors influencing AMR in the SEA food system demonstrates that AMR is a product of numerous interlinked actions taken across the One Health spectrum and that finding solutions is no simple task. Developing the model enabled the identification of potentially promising leverage points across human, animal, and environment sectors that, if comprehensively targeted using multi-pronged interventions, could evoke system wide changes that mitigate AMR. Even targeting some leverage points for intervention, such as increasing investments in research and capacity building, and setting and enforcing regulations to control antimicrobial supply, demand, and use could, in turn, shift mindsets that lead to changes in more difficult to alter leverage points, such as redefining the profit-driven intent that drives system behavior in ways that transform AMU and sustainably mitigate AMR.

  5. Wernli D, Søgaard Jørgensen P, Parmley EJ, Majowicz SE, Lambraki I, Carson CA, et al.
    Lancet Planet Health, 2023 Jul;7(7):e630-e637.
    PMID: 37438004 DOI: 10.1016/S2542-5196(23)00128-6
    Social-ecological systems conceptualise how social human systems and ecological natural systems are intertwined. In this Personal View, we define the scope and applicability of social-ecological resilience to antimicrobial resistance. Resilience to antimicrobial resistance corresponds to the capacity to maintain the societal benefits of antimicrobial use and One Health systems' performance in the face of the evolutionary behaviour of microorganisms in response to antimicrobial use. Social-ecological resilience provides an appropriate framework to make sense of the disruptive impacts resulting from the emergence and spread of antimicrobial resistance; capture the diversity of strategies needed to tackle antimicrobial resistance and to live with it; understand the conditions that underpin the success or failure of interventions; and appreciate the need for adaptive and coevolutionary governance. Overall, resilience thinking is essential to improve understanding of how human societies dynamically can cope with, adapt, and transform to the growing global challenge of antimicrobial resistance.
  6. Lambraki IA, Majowicz SE, Parmley EJ, Wernli D, Léger A, Graells T, et al.
    JMIR Res Protoc, 2021 Jun 10;10(6):e24378.
    PMID: 34110296 DOI: 10.2196/24378
    BACKGROUND: Antimicrobial resistance (AMR) is an escalating global crisis with serious health, social, and economic consequences. Building social-ecological system resilience to reduce AMR and mitigate its impacts is critical.

    OBJECTIVE: The aim of this study is to compare and assess interventions that address AMR across the One Health spectrum and determine what actions will help to build social and ecological capacity and readiness to sustainably tackle AMR.

    METHODS: We will apply social-ecological resilience theory to AMR in an explicit One Health context using mixed methods and identify interventions that address AMR and its key pressure antimicrobial use (AMU) identified in the scientific literature and in the gray literature using a web-based survey. Intervention impacts and the factors that challenge or contribute to the success of interventions will be determined, triangulated against expert opinions in participatory workshops and complemented using quantitative time series analyses. We will then identify indicators using regression modeling, which can predict national and regional AMU or AMR dynamics across animal and human health. Together, these analyses will help to quantify the causal loop diagrams (CLDs) of AMR in the European and Southeast Asian food system contexts that are developed by diverse stakeholders in participatory workshops. Then, using these CLDs, the long-term impacts of selected interventions on AMR will be explored under alternate future scenarios via simulation modeling and participatory workshops. A publicly available learning platform housing information about interventions on AMR from a One Health perspective will be developed to help decision makers identify promising interventions for application in their jurisdictions.

    RESULTS: To date, 669 interventions have been identified in the scientific literature, 891 participants received a survey invitation, and 4 expert feedback and 4 model-building workshops have been conducted. Time series analysis, regression modeling of national and regional indicators of AMR dynamics, and scenario modeling activities are anticipated to be completed by spring 2022. Ethical approval has been obtained from the University of Waterloo's Office of Research Ethics (ethics numbers 40519 and 41781).

    CONCLUSIONS: This paper provides an example of how to study complex problems such as AMR, which require the integration of knowledge across sectors and disciplines to find sustainable solutions. We anticipate that our study will contribute to a better understanding of what actions to take and in what contexts to ensure long-term success in mitigating AMR and its impact and provide useful tools (eg, CLDs, simulation models, and public databases of compiled interventions) to guide management and policy decisions.

    INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24378.

  7. Grant R, Benamouzig D, Catton H, Cheng VC, Dhingra N, Laxminarayan R, et al.
    Lancet Infect Dis, 2023 Oct;23(10):1108-1110.
    PMID: 37572686 DOI: 10.1016/S1473-3099(23)00485-1
  8. Macedo-Viñas M, Conly J, Francois P, Aschbacher R, Blanc DS, Coombs G, et al.
    J Glob Antimicrob Resist, 2014 Mar;2(1):43-47.
    PMID: 27873637 DOI: 10.1016/j.jgar.2013.08.003
    The antibiotic susceptibility and molecular epidemiology of Panton-Valentine leukocidin (PVL)-positive meticillin-resistant Staphylococcus aureus (MRSA) isolates reported from 17 countries in the Americas, Europe and, Australia-Asia were analysed. Among a total of 3236 non-duplicate isolates, the lowest susceptibility was observed to erythromycin in all regions. Susceptibility to ciprofloxacin showed large variation (25%, 75% and 84% in the Americas, Europe and Australia-Asia, respectively). Two vancomycin-intermediate PVL-positive MRSA isolates were reported, one from Hong Kong and the other from The Netherlands. Resistance to trimethoprim/sulfamethoxazole and linezolid was <1%. Among 1798 MRSA isolates from 13 countries that were tested for the requested 10 non-β-lactam antibiotics, 49.4% were multisusceptible. However, multiresistant isolates (resistant to at least three classes of non-β-lactam antibiotics) were reported from all regions. Sequence type 30 (ST30) was reported worldwide, whereas ST80 and ST93 were exclusive to Europe and Australia, respectively. USA300 and related clones (ST8) are progressively replacing the ST80 clone in several European countries. Eight major clusters were discriminated by multilocus variable-number tandem repeat assay (MLVA), showing a certain geographic specificity. PVL-positive MRSA isolates frequently remain multisusceptible to non-β-lactam agents, but multiresistance is already prevalent in all regions. Surveillance of MRSA susceptibility patterns should be monitored to provide clinicians with the most current information regarding changes in resistance patterns.
  9. Wernli D, Jørgensen PS, Parmley EJ, Troell M, Majowicz S, Harbarth S, et al.
    Lancet Infect Dis, 2020 Dec;20(12):e307-e311.
    PMID: 32853549 DOI: 10.1016/S1473-3099(20)30392-3
    Improving evidence for action is crucial to tackle antimicrobial resistance. The number of interventions for antimicrobial resistance is increasing but current research has major limitations in terms of efforts, methods, scope, quality, and reporting. Moving the agenda forwards requires an improved understanding of the diversity of interventions, their feasibility and cost-benefit, the implementation factors that shape and underpin their effectiveness, and the ways in which individual interventions might interact synergistically or antagonistically to influence actions against antimicrobial resistance in different contexts. Within the efforts to strengthen the global governance of antimicrobial resistance, we advocate for the creation of an international One Health platform for online learning. The platform will synthesise the evidence for actions on antimicrobial resistance into a fully accessible database; generate new scientific insights into the design, implementation, evaluation, and reporting of the broad range of interventions relevant to addressing antimicrobial resistance; and ultimately contribute to the goal of building societal resilience to this central challenge of the 21st century.
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