Antimicrobial Resistance (AMR) and Multidrug Resistance (MDR): Overview of Current Approaches, Consortia and Intellectual Property Issues

The supply of new diagnostics and treatments is insufficient to keep up with the increase in antimicrobial resistance (AMR) and multidrug resistance (MDR) as older medicines are used more widely and microbes develop resistance to them. At the same time, significant quantities of antibiotics are used on patients and animals that do not need them, while others who do need them lack access. Effective responses to AMR/MDR require effort by both the public and private sectors to develop and disseminate new diagnostics, vaccines and treatments on a global scale, as well as to adapt them to local needs. This calls for good governance to identify priorities, raise awareness and ensure effective stewardship at global, regional and national levels to minimize the development of resistance. Failure to act appropriately in one country will adversely impact all countries as resistance travels fast. Based on a review of recent literature, this WIPO Global Challenges Report includes a broad overview of current approaches and consortia designed to meet the challenge of research and development (R&D) investment for new treatments. It also examines patent applications by both the public and the private sectors as an indicator of innovative activity. This report finds that there is a need to address the unique market challenges and specific uncertainties associated with the development of new diagnostics and treatments, where current approaches are not optimal. An effective global framework that achieves the necessary political support while ensuring effective local implementation is crucial. There is an opportunity to complement this work by formulating mechanisms that drive innovation for results to incentivize success, while feeding expertise and experience into stewardship and access efforts. Intellectual property (IP) could be used in a constructive manner as one element in any reward or prize system for AMR/MDR R&D – both in terms of providing an incentive and governance

Professional Learning in healthcare settings in resource-limited environments: What are the tensions for professionals’ knowing and learning about antimicrobial resistance?

This article examines tensions that professionals in healthcare settings in low-to-middle income countries (LMICs) face in the evolving field around surveillance of antimicrobial resistance (AMR). Few public health problems are of greater global importance today than AMR, that poses a threat to our ability to treat infections. In this context, the microbiology laboratory occupies a prominent place and the knowledge field of microbiology is expanding. In this study, we interviewed twenty-three (n = 23) professionals with expertise on AMR and public health systems to synthesise knowledge on strengthening AMR surveillance in LMICs. By drawing on a practice approach [Schatzki, T. R. 2001. “Practice Ttheory.” In The Practice Turn in Contemporary Theory (1–14), edited by T. R. Schatzki, K. Knorr-Cetima, and E. von Savigny. New York: Routledge.] combined with socio-cultural and cultural-historical theories (CHAT) [Engeström, Y. 1987. Learning by Expanding: An Activity-Theoretical Approach to Developmental Research. Helsinki: Orienta-Konsultit] the analysis reveals seven tensions between elements of the systems and discusses how such tensions serve to frame implications for implementing a capacity strengthening programme. The analysis shows that the novelty of the AMR as well as being a multi-disease and multisectoral by nature challenges existing forms of professional practice in healthcare settings. It also suggests that AMR requires to be dealt with through inter-professional and inter-sectoral approaches, while maintaining a focus across the local, national, and global systems, which is essential for initiatives that are set to address challenges to global health

AMR policy dialogue : driving innovative solutions for antimicrobial discovery

Antimicrobial resistance (AMR) is a global strategic priority and sits within the UK Government’s National Risk Register. By 2050, AMR is predicted to cause 10 million deaths, more than cancer. In 2019 alone, there were an estimated 4.95 million deaths associated with bacterial AMR. Although global pharmaceutical research and development (R&D) spend continues to increase year on year, research into antimicrobial drug discovery is not currently an attractive commercial investment. This has had two major consequences: an ongoing decline of human capital for R&D in this field, and a decline over the longer term in availability of therapeutically effective antibiotics and other antimicrobial agents. Concerted and coordinated efforts are needed to translate high-level policy commitments into strategic actions for long-term funding and support for the R&D of new antimicrobials

AMR - An R Package for Working with Antimicrobial Resistance Data

Antimicrobial resistance is an increasing threat to global health. Evidence for this trend is generated in microbiological laboratories through testing microorganisms for resistance against antimicrobial agents. International standards and guidelines are in place for this process as well as for reporting data on (inter-)national levels. However, there is a gap in the availability of standardized and reproducible tools for working with laboratory data to produce the required reports. It is known that extensive efforts in data cleaning and validation are required when working with data from laboratory information systems. Furthermore, the global spread and relevance of antimicrobial resistance demands to incorporate international reference data in the analysis process.In this paper, we introduce the AMR package for R that aims at closing this gap by providing tools to simplify antimicrobial resistance data cleaning and analysis, while incorporating international guidelines and scientifically reliable reference data. The AMR package enables standardized and reproducible antimicrobial resistance analyses, including the application of evidence-based rules, determination of first isolates, translation of various codes for microorganisms and antimicrobial agents, determination of (multi-drug) resistant microorganisms, and calculation of antimicrobial resistance, prevalence and future trends. The AMR package works independently of any laboratory information system and provides several functions to integrate into international workflows (e.g. WHONET software provided by the World Health Organization)

Global transmission of extended-spectrum cephalosporin resistance in Escherichia coli driven by epidemic plasmids

Background Extended-spectrum cephalosporins (ESCs) are third and fourth generation cephalosporin antimicrobials used in humans and animals to treat infections due to multidrug-resistant (MDR) bacteria. Resistance to ESCs (ESC-R) in Enterobacterales is predominantly due to the production of extended-spectrum β-lactamases (ESBLs) and plasmid-mediated AmpC β-lactamases (AmpCs). The dynamics of ESBLs and AmpCs are changing across countries and host species, the result of global transmission of ESC-R genes. Plasmids are known to play a key role in this dissemination, but the relative importance of different types of plasmids is not fully understood. Methods In this study, Escherichia coli with the major ESC-R genes blaCTX-M-1, blaCTX-M-15, blaCTX-M-14 (ESBLs) and blaCMY-2 (AmpC), were selected from diverse host species and other sources across Canada, France and Germany, collected between 2003 and 2017. To examine in detail the vehicles of transmission of the ESC-R genes, long- and short-read sequences were generated to obtain complete contiguous chromosome and plasmid sequences (n = 192 ESC-R E. coli). The types, gene composition and genetic relatedness of these plasmids were investigated, along with association with isolate year, source and geographical origin, and put in context with publicly available plasmid sequences. Findings We identified five epidemic resistance plasmid subtypes with distinct genetic properties that are associated with the global dissemination of ESC-R genes across multiple E. coli lineages and host species. The IncI1 pST3 blaCTX-M-1 plasmid subtype was found in more diverse sources than the other main plasmid subtypes, whereas IncI1 pST12 blaCMY-2 was more frequent in Canadian and German human and chicken isolates. Clonal expansion also contributed to the dissemination of the IncI1 pST12 blaCMY-2 plasmid in ST131 and ST117 E. coli harbouring this plasmid. The IncI1 pST2 blaCMY-2 subtype was predominant in isolates from humans in France, while the IncF F31:A4:B1 blaCTX-M-15 and F2:A-:B- blaCTX-M-14 plasmid subtypes were frequent in human and cattle isolates across multiple countries. Beyond their epidemic nature with respect to ESC-R genes, in our collection almost all IncI1 pST3 blaCTX-M-1 and IncF F31:A4:B1 blaCTX-M-15 epidemic plasmids also carried multiple antimicrobial resistance (AMR) genes conferring resistance to other antimicrobial classes. Finally, we found genetic signatures in the regions surrounding specific ESC-R genes, identifying the predominant mechanisms of ESC-R gene movement, and using publicly available databases, we identified these epidemic plasmids from widespread bacterial species, host species, countries and continents. Interpretation We provide evidence that epidemic resistance plasmid subtypes contribute to the global dissemination of ESC-R genes, and in addition, some of these epidemic plasmids confer resistance to multiple other antimicrobial classes. The success of these plasmids suggests that they may have a fitness advantage over other plasmid types and subtypes. Identification and understanding of the vehicles of AMR transmission are crucial to develop and target strategies and interventions to reduce the spread of AMR

Emerging antibiotic resistance: a modern-day horseman of the apocalypse

Background: Antimicrobial resistance (AMR) has emerged as a global public health crisis, posing a significant threat to the effectiveness of antimicrobial agents. Mexico, faces a daunting challenge in tackling the rising prevalence of AMR. The misuse and overuse of antimicrobial drugs, inadequate infection control practices, and a lack of awareness among healthcare providers and the general public have all contributed to the rapid spread of resistant pathogens in the country. We aimed to determine the prevalence of antimicrobial resistance in patients hospitalized from January 2018 to December 2019 Methods: In this study, we analyzed blood, urine, wound, expectoration, and secretion cultures from January 2018 to December 2019 to assess antimicrobial resistance in our unit. We collected patient data, evaluated isolates using EUCAST and CLSI breakpoint tables, and excluded intrinsically resistant antibiotics. A circus plot graph was created to compare resistance profiles between the two years. SPSS version 25 and R Studio software were used for statistical analysis and visualization. Results: AMR increased across diverse organisms (2018-2019), notable rises in A. xylosoxidans (cefuroxime, ciprofloxacin), A. baumannii (piperacillin/tazobactam, ceftazidime), E. coli (ampicillin/sulbactam), K. pneumoniae (ceftazidime), P. aeruginosa (cefuroxime) were observed. Enterococcus faecalis displayed lowest resistance to nitrofurantoin/tobramycin, but highest to fosfomycin. Escherichia coli showed significant resistance to aztreonam, ampicillin/sulbactam, trimethoprim/sulfamethoxazole. Pseudomonas aeruginosa exhibited concerning levels of resistance to ceftriaxone, ampicillin/sulbactam, ceftazidime. Conclusions: AMR in our unit raise concerns for empiric therapy and infection control. Emerging resistance in key pathogens demands enhanced surveillance, rapid response, and robust infection control strategies, including meticulous hygiene, disinfection, antimicrobial stewardship, and resistance monitoring. Continuous optimization is crucial to combat this escalating public health threat in Mexico

Understanding media publics and the antimicrobial resistance crisis

Antimicrobial resistance (AMR) imperils health for people across the world. This enormous challenge is being met with the rationalisation of prescription, dispensing and consumption of antimicrobials in clinical settings and in the everyday lives of members of the general population. Individuals need to be reached outside clinical settings to prepare them for the necessary changes to the pharmaceutical management of infections; efforts that depend on media and communications and, therefore, how the AMR message is mediated, received and applied. In 2016, the UK Review on Antimicrobial Resistance called on governments to support intense, worldwide media activity to promote public awareness and to further efforts to rationalise the use of antimicrobial pharmaceuticals. In this article, we consider this communications challenge in light of contemporary currents of thought on media publics, including: the tendency of health communications to cast experts and lay individuals in opposition; the blaming of individuals who appear to ‘resist’ expert advice; the challenges presented by negative stories of AMR and their circulation in public life, and; the problems of public trust tied to the construction and mediation of expert knowledge on the effective management of AMR

A One Health approach to antimicrobial resistance surveillance: is there a business case for it?

Antimicrobial resistance is a global problem of complex epidemiology, suited to a broad, integrated One Health approach. Resistant organisms exist in humans, animals, food and the environment, and the main driver of this resistance is antimicrobial usage. A One Health conceptual framework for surveillance is presented to include all of these aspects. Global and European (regional and national) surveillance systems are described, highlighting shortcomings compared with the framework. Policy decisions rely on economic and scientific evidence, so the business case for a fully integrated system is presented. The costs of integrated surveillance are offset by the costs of unchecked resistance and the benefits arising from interventions and outcomes. Current estimates focus on costs and benefits of human health outcomes. A One Health assessment includes wider societal costs of lost labour, changes in health-seeking behaviour, impacts on animal health and welfare, higher costs of animal-origin food production, and reduced consumer confidence in safety and international trade of such food. Benefits of surveillance may take years to realise and are dependent on effective and accepted interventions. Benefits, including the less tangible, such as improved synergies and efficiencies in service delivery and more timely and accurate risk identification, should also be recognised. By including these less tangible benefits to society, animal welfare, ecosystem health and resilience, together with the savings and efficiencies through shared resources and social capital-building, a stronger business case for a One Health approach to surveillance can be made

Strengthening strategic management approaches to address antimicrobial resistance in global human health: a scoping review

Introduction The development and implementation of national strategic plans is a critical component towards successfully addressing antimicrobial resistance (AMR). This study aimed to review the scope and analytical depth of situation analyses conducted to address AMR in human health to inform the development and implementation of national strategic plans. Methods A systematic search of the literature was conducted to identify all studies since 2000, that have employed a situation analysis to address AMR. The included studies are analysed against frameworks for strategic analysis, primarily the PESTELI (Political, Economic, Sociological, Technological, Ecological, Legislative, Industry) framework, to understand the depth, scope and utility of current published approaches. Results 10 studies were included in the final review ranging from single country (6) to regional-level multicountry studies (4). 8 studies carried out documentary review, and 3 of these also included stakeholder interviews. 2 studies were based on expert opinion with no data collection. No study employed the PESTELI framework. Most studies (9) included analysis of the political domain and 1 study included 6 domains of the framework. Technological and industry analyses is a notable gap. Facilitators and inhibitors within the political and legislative domains were the most frequently reported. No facilitators were reported in the economic or industry domains but featured inhibiting factors including: lack of ring-fenced funding for surveillance, perverse financial incentives, cost-shifting to patients; joint-stock drug company ownership complicating regulations. Conclusion The PESTELI framework provides further opportunities to combat AMR using a systematic, strategic management approach, rather than a retrospective view. Future analysis of existing quantitative data with interviews of key strategic and operational stakeholders is needed to provide critical insights about where implementation efforts should be focussed, and also how to build contingency at the strategic level for agile responses to macro-level environmental influences