Improving equitable access for effective antibacterials: an ecosystem approach.

BACKGROUND: Antibiotics are indispensable to modern healthcare, yet their equitable access remains a pressing global challenge. Factors contributing to inequities include insufficient evidence for optimal clinical use, limited registration, pricing for Reserve antibiotics, and supply chain challenges. These issues disproportionately affect low- and middle-income countries (LMICs), exacerbating antimicrobial resistance (AMR) burdens. OBJECTIVES: This paper explores the multifaceted dimensions of inequitable antibiotic access and proposes a comprehensive framework to address the crisis. SOURCES: Published articles, grey literature analysis, and the authors' own expertise contributed to this article. CONTENT: While much attention has been paid to push and pull incentives for antibiotic development, these interventions are inadequate to reach sustainable and equitable access to antibiotics. Improving equitable antibiotic access requires an ecosystem approach, involving multiple stakeholders and including public-private partnerships. The paper advocates for initiatives spanning research and development (R&D), regulatory pathways, procurement strategies, and financing mechanisms and suggests concrete interventions in each of these areas. The specific interventions and mix of public and private actors may vary according to antibiotic, market, and health system context, but must be designed to meet public health needs while also supporting a market that will sustain quality-assured production and delivery of antibiotics. IMPLICATIONS: Addressing the challenge of equitable antibiotic access requires coordinated efforts across sectors and regions. By embracing an ecosystem approach centred on public health priorities, stakeholders can pave the way for a sustainable supply of antibiotics, and equitable access, safeguarding the future of global healthcare amidst the growing threat of AMR.

Ensuring progress on sustainable access to effective antibiotics at the 2024 UN General Assembly: a target-based approach.

Rising antimicrobial resistance (AMR) is a global health crisis for countries of all economic levels, alongside the broader challenge of access to antibiotics. As a result, development goals for child survival, healthy ageing, poverty reduction, and food security are at risk. Preserving antimicrobial effectiveness, a global public good, requires political will, targets, accountability frameworks, and funding. The upcoming second high-level meeting on AMR at the UN General Assembly (UNGA) in September, 2024, is evidence of political interest in addressing the problem of AMR, but action on targets, accountability, and funding, absent from the 2016 UNGA resolution, is needed. We propose ambitious yet achievable global targets for 2030 (relative to a prepandemic 2019 baseline): a 10% reduction in mortality from AMR; a 20% reduction in inappropriate human antibiotic use; and a 30% reduction in inappropriate animal antibiotic use. Given national variation in current levels of antibiotic use, these goals (termed the 10-20-30 by 2030) should be met within a framework of universal access to effective antibiotics. The WHO Access, Watch, Reserve (AWARE) system can be used to define, monitor, and evaluate appropriate levels of antibiotic use and access. Some countries should increase access to narrow-spectrum, safe, and affordable (Access) antibiotics, whereas others should discourage the inappropriate use of broader-spectrum (Watch) and last-resort (Reserve) antibiotics; AWARE targets should use a risk-based, burden-adjusted approach. Improved infection prevention and control, access to clean water and sanitation, and vaccination coverage can offset the selection effects of increased antibiotic use in low-income settings. To ensure accountability and global scientific guidance and consensus, we call for the establishment of the Independent Panel on Antimicrobial Access and Resistance and the support of leaders from low-income and middle-income countries.

Knowledge, awareness and practices of healthcare workers regarding antimicrobial use, resistance and stewardship in Zambia: a multi-facility cross-sectional study.

Background: Antimicrobial resistance (AMR) poses a threat to public health globally. Despite its consequences, there is little information about the knowledge, awareness, and practices towards AMR among healthcare workers (HCWs). Therefore, this study assessed the knowledge, awareness and practices regarding antimicrobial use (AMU), AMR and antimicrobial stewardship (AMS) among HCWs who are involved in the implementation of AMS activities across eight hospitals in Zambia. Methods: A cross-sectional study was conducted among 64 HCWs from October to December 2023 using a semi-structured questionnaire. Data were analysed using IBM SPSS version 25.0. Results: Of the 64 HCWs, 59.4% were females, 60.9% were aged between 25 and 34 years, 37.5% were nurses, 18.7% were pharmacists, 17.2% were medical doctors and only one was a microbiologist. Overall, 75% of the HCWs had good knowledge, 84% were highly aware and 84% had good practices regarding AMU, AMR and AMS. Most of the HCWs (90.6%) responded that they had a multidisciplinary AMS team at their hospitals and were implementing the use of the WHO AWaRe classification of antibiotics. Conclusion: This study found good knowledge levels, high awareness and good practices regarding AMU, AMR and AMS among HCWs who were involved in the implementation of AMS activities in hospitals in Zambia. Additionally, most hospitals have been conducting AMS training and implementing the use of the WHO AWaRe classification of antibiotics. However, there is still a need to address some identified gaps in AMU and AMR through the strengthening of AMS activities in hospitals.

Antimicrobial resistance and the great divide: inequity in priorities and agendas between the Global North and the Global South threatens global mitigation of antimicrobial resistance.

To limit the catastrophic effects of the increasing bacterial resistance to antimicrobials on health, food, environmental, and geopolitical security, and ensure that no country or region is left behind, a coordinated global approach is required. In this Viewpoint, we argue that the diverging resource availabilities, needs, and priorities of the Global North and the Global South in terms of the actions required to mitigate the antimicrobial resistance pandemic are a direct threat to success. We argue that evidence suggests a need to prioritise and support infection prevention interventions (ie, clean water and safe sanitation, increased vaccine coverage, and enhanced infection prevention measures for food production in the Global South contrary to the focus on research and development of new antibiotics in the Global North) and to recalibrate global funding resources to address this need. We call on global leaders to redress the current response, which threatens mitigation of the antimicrobial resistance pandemic.

Mitigating antimicrobial resistance (AMR) using implementation research: a development funder's approach.

Despite the escalating burden of antimicrobial resistance (AMR), the global response has not sufficiently matched the scale and scope of the issue, especially in low- and middle-income countries (LMICs). While many countries have adopted national action plans to combat AMR, their implementation has lagged due to resource constraints, dysfunctional multisectoral coordination mechanisms and, importantly, an under-recognized lack of technical capacity to adapt evidence-based AMR mitigation interventions to local contexts. AMR interventions should be tailored, context-specific, cost-effective and sustainable. The implementation and subsequent scale-up of these interventions require multidisciplinary intervention-implementation research (IIR). IIR involves both quantitative and qualitative approaches, occurs across a three-phase continuum (proof of concept, proof of implementation and informing scale-up), and across four context domains (inner setting, outer setting, stakeholders and the implementation process). We describe the theoretical underpinnings of implementation research (IR), its various components, and how to construct different IR strategies to facilitate sustainable uptake of AMR interventions. Additionally, we provide real-world examples of AMR strategies and interventions to demonstrate these principles in practice. IR provides a practical framework to implement evidence-based and sustainable AMR mitigation interventions.

Phenotypic and genotypic antibiotic susceptibility profiles of Gram-negative bacteria isolated from bloodstream infections at a referral hospital, Lusaka, Zambia.

Bloodstream infections (BSI) caused by antimicrobial-resistant (AMR) Gram-negative bacteria (GNB) are a significant cause of morbidity and mortality. Third-generation cephalosporins (3GCs) have been used as empiric treatment for BSI and other invasive infections for years; however, their overuse could promote the emergence of extended-spectrum beta-lactamases (ESBLs). Thus, this study aimed to determine the epidemiological, clinical and microbiological features and the effects of antimicrobial resistance on the outcomes of BSIs at a referral hospital in Lusaka, Zambia. This was a six-month prospective facility-based study undertaken at a referral hospital in Lusaka, Zambia. As part of the routine diagnosis and patient care, blood samples for bacteriological culture were collected from patients presenting with fever and processed for pathogen identification and antimicrobial susceptibility testing using the VITEK 2 Compact instrument. ESBLs and plasmid-mediated quinolone resistance (PMQR) associated genes were determined using the polymerase chain reaction method. Patient information was collected using a structured data collection sheet and entered in CSpro 7.6. Data were analysed in WHOnet and STATA version 14. A total of 88 GNB were isolated, of which 76% were Enterobacterales, 14% Acinetobacter baumannii and 8% Pseudomonas aeruginosa. Resistance to third and fourth-generation cephalosporins was 75% and 32%, respectively. Noteworthy was the high prevalence (68%) of inappropriate empirical treatment, carbapenem resistance (7%), multi-drug resistance (83%) and ESBL-producers (76%). In comparison to E. coli as a causative agent of BSI, the odds of death were significantly higher among patients infected with Acinetobacter baumannii (OR = 3.8). The odds of death were also higher in patients that received 3GCs as empiric treatment than in those that received 4GCs or other (none cephalosporin) treatment options. Structured surveillance, yearly antibiogram updates, improved infection control and a well functional antimicrobial stewardship (AMS) program, are of utmost importance in improving appropriate antimicrobial treatment selection and favourable patient outcomes.

An analysis of existing national action plans for antimicrobial resistance-gaps and opportunities in strategies optimising antibiotic use in human populations.

At the 2015 World Health Assembly, UN member states adopted a resolution that committed to the development of national action plans (NAPs) for antimicrobial resistance (AMR). The political determination to commit to NAPs and the availability of robust governance structures to assure sustainable translation of the identified NAP objectives from policy to practice remain major barriers to progress. Inter-country variability in economic and political resilience and resource constraints could be fundamental barriers to progressing AMR NAPs. Although there have been regional and global analyses of NAPs from a One Health and policy perspective, a global assessment of the NAP objectives targeting antimicrobial use in human populations is needed. In this Health Policy, we report a systematic evidence synthesis of existing NAPs that are aimed at tackling AMR in human populations. We find marked gaps and variability in maturity of NAP development and operationalisation across the domains of: (1) policy and strategic planning; (2) medicines management and prescribing systems; (3) technology for optimised antimicrobial prescribing; (4) context, culture, and behaviours; (5) operational delivery and monitoring; and (6) patient and public engagement and involvement. The gaps identified in these domains highlight opportunities to facilitate sustainable delivery and operationalisation of NAPs. The findings from this analysis can be used at country, regional, and global levels to identify AMR-related priorities that are relevant to infrastructure needs and contexts.

Introducing the global antimicrobial stewardship partnership hub (GASPH): creating conditions for successful global partnership collaboration.

In 2015, 196 countries formally committed to a Global Action Plan to address antimicrobial resistance (AMR). However, translating policy into practice is not happening at pace and the recent Global Research on AntiMicrobial resistance (GRAM) Project report confirms the burden of AMR is increasing. Despite progress in establishing surveillance data and investment in new antimicrobials, education and training including use of behavioural science approaches to change practice is lagging. To contribute to addressing this, we have invited organizations to join us as founding members of the Global Antimicrobial Stewardship Partnership Hub (GASPH) (https://global-asp-hub.com/). We will work together to share education resources and foster collaboration to meet the needs of learners and of partner organizations working on tackling AMR. Membership is open to all-professional societies, academic institutes, nongovernmental organizations/civil society, philanthropists and commercial partners interested in supporting a multi-stakeholder global antimicrobial stewardship (AMS) education platform and network.

National action plan on antimicrobial resistance: An evaluation of implementation in the World Health Organization Africa region.

In line with global instruments, within the last five years, two-thirds of all countries in the WHO Africa Region (WHO AFR) have developed a National Action Plan (NAP) on Antimicrobial Resistance (AMR). We sought to evaluate progress made across the countries implementing NAP for effective response to AMR. A semi-structured survey tool was administered to obtain information from national focal persons on the implementation of strategic elements of NAP on AMR. This was followed by a Lessons Learnt Workshop in June 2019 at Douala, Cameroon, where focal persons made presentations on the country's progress. Later, a desktop review of the LLW report and other key documents was conducted. Countries in WHO AFR that have set up a national surveillance system and are enrolled into the WHO global antimicrobial resistance surveillance system have progressively increased to 30 (of 47 countries), of which 15 are already submitting surveillance data. Of the 20 countries at the Lessons Learnt Workshop, 14 have infection prevention and control (IPC) policies and functional healthcare facility IPC programs, 15 participate in the commemoration of the annual world hand hygiene days. Although almost all countries surveyed have national standard treatment guidelines, only five have incorporated the WHO AWaRe classification into the national essential medicines list. Fourteen of 20 countries have established an active/functional national secretariat/coordinating center for AMR. Discernible progress is being made on the implementation of NAP in WHO AFR region. Gaps identified in the strategic elements of action plans need to be filled for effective AMR control.

Antibiotic resistance: calling time on the 'silent pandemic'.

It is time to stop referring to the antibiotic resistance pandemic as 'silent'. Continuing to use such a term denies the reality that antibiotic-resistant bacterial infections, driven by misuse and abuse of antibiotics by humans against microbial ecosystems that we should be living in symbiosis with, is wrong. Both our terminology and who the real 'enemy' is in relation to antibiotic resistance demands serious reconsideration.

Equitable Access to Antibiotics: A Core Element and Shared Global Responsibility for Pandemic Preparedness and Response.

Securing equitable antibiotic access as an essential component for health system resilience and pandemic preparedness requires a systems perspective. This article discusses key components that need to be coordinated and paired with adequate financing and resources to ensure antibiotic effectiveness as a global public good, which should be central while discussing a new global agreement.

Navigating sociocultural disparities in relation to infection and antibiotic resistance-the need for an intersectional approach.

One of the key drivers of antibiotic resistance (ABR) and drug-resistant bacterial infections is the misuse and overuse of antibiotics in human populations. Infection management and antibiotic decision-making are multifactorial, complex processes influenced by context and involving many actors. Social constructs including race, ethnicity, gender identity and cultural and religious practices as well as migration status and geography influence health. Infection and ABR are also affected by these external drivers in individuals and populations leading to stratified health outcomes. These drivers compromise the capacity and resources of healthcare services already over-burdened with drug-resistant infections. In this review we consider the current evidence and call for a need to broaden the study of culture and power dynamics in healthcare through investigation of relative power, hierarchies and sociocultural constructs including structures, race, caste, social class and gender identity as predictors of health-providing and health-seeking behaviours. This approach will facilitate a more sustainable means of addressing the threat of ABR and identify vulnerable groups ensuring greater inclusivity in decision-making. At an individual level, investigating how social constructs and gender hierarchies impact clinical team interactions, communication and decision-making in infection management and the role of the patient and carers will support better engagement to optimize behaviours. How people of different race, class and gender identity seek, experience and provide healthcare for bacterial infections and use antibiotics needs to be better understood in order to facilitate inclusivity of marginalized groups in decision-making and policy.

Optimising antimicrobial use in humans - review of current evidence and an interdisciplinary consensus on key priorities for research.

Addressing the silent pandemic of antimicrobial resistance (AMR) is a focus of the 2021 G7 meeting. A major driver of AMR and poor clinical outcomes is suboptimal antimicrobial use. Current research in AMR is inequitably focused on new drug development. To achieve antimicrobial security we need to balance AMR research efforts between development of new agents and strategies to preserve the efficacy and maximise effectiveness of existing agents. Combining a review of current evidence and multistage engagement with diverse international stakeholders (including those in healthcare, public health, research, patient advocacy and policy) we identified research priorities for optimising antimicrobial use in humans across four broad themes: policy and strategic planning; medicines management and prescribing systems; technology to optimise prescribing; and context, culture and behaviours. Sustainable progress depends on: developing economic and contextually appropriate interventions; facilitating better use of data and prescribing systems across healthcare settings; supporting appropriate and scalable technological innovation. Implementing this strategy for AMR research on the optimisation of antimicrobial use in humans could contribute to equitable global health security.

Resetting the agenda for antibiotic resistance through a health systems perspective.

Although the individual and societal consequences of antibiotic resistance spiral upwards, coordinated action has not kept pace on a global scale. The COVID-19 pandemic has highlighted the need for resilient health systems and has resulted in an unprecedented rate of collaboration in scientific, medical, social, and political dimensions. The pandemic has also created a renewed awareness of the importance of infectious diseases and is a substantial entry point for reigniting the momentum towards containing the silent pandemic of antibiotic resistance. In this Viewpoint, we discuss the limitations in the current narrative on antibiotic resistance and how it could be improved, including concerted efforts to close essential data gaps. We discuss the need for capacity building and coordination at the national and global levels to strengthen the understanding of the importance of sustainable access to effective antibiotics for all health systems that could generate tangible links to current processes for global health and development.

Multidisciplinary and multisectoral coalitions as catalysts for action against antimicrobial resistance: Implementation experiences at national and regional levels.

The multi-faceted complexities of antimicrobial resistance (AMR) require consistent action, a multidisciplinary approach, and long-term political commitment. Building coalitions can amplify stakeholder efforts to carry out effective AMR prevention and control strategies. We have developed and implemented an approach to help local stakeholders kick-start the coalition-building process. The five-step process is to (1) mobilise support, (2) understand the local situation, (3) develop an action plan, (4) implement the plan, and (5) monitor and evaluate. We first piloted the approach in Zambia in 2004, then used the lessons learned to expand it for use in Ethiopia and Namibia and to the regional level through the Ecumenical Pharmaceutical Network [EPN]. Call-to-action declarations and workshops helped promote a shared vision, resulting in the development of national AMR action plans, revision of university curricula to incorporate relevant topics, infection control activities, engagement with journalists from various mass media outlets, and strengthening of drug quality assurance systems. Our experience with the coalition-building approach in Ethiopia, Namibia, Zambia, and with the EPN shows that coalitions can form in a variety of ways with many different stakeholders, including government, academia, and faith-based organisations, to organise actions to preserve the effectiveness of existing antimicrobials and contain AMR.