key: cord-0935049-ridpevml
authors: Veepanattu, P.; Singh, S.; Mendelson, M.; Nampoothiri, V.; Edathadatil, F.; Surendran, S.; Bonaconsa, C.; Mbamalu, O.; Ahuja, S.; Birgand, G.; Tarrant, C.; Sevdalis, N.; Castro-Sánchez, E.; Ahmad, R.; Holmes, A.; Charani, E.
title: Building resilient and responsive research collaborations to tackle antimicrobial resistance – lessons learnt from India, South Africa and UK
date: 2020-08-27
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.08.057
sha: 9c5055d7217dcf7d281695508ae5f1d60207fee8
doc_id: 935049
cord_uid: ridpevml

Research, collaboration and knowledge exchange are critical to global efforts to tackle antimicrobial resistance (AMR). Different healthcare economies are faced with different challenges in implementing effective strategies to address AMR. Building effective capacity for research to inform AMR related strategies and policies AMR is recognised as an important contributor to success. Interdisciplinary, inter-sector, as well as inter-country collaboration is needed to span AMR efforts from the global to local. Developing reciprocal, long-term, partnerships between collaborators in high-income and low- and middle-income countries (LMICs) needs to be built on principles of capacity building. Using case-studies spanning local to international research collaborations to co-design, implement and evaluate strategies to tackle AMR, we evaluate and build upon the ESSENCE criteria for capacity building in LMICs. The first case-study describes the local co-design and implementation of antimicrobial stewardship in the state of Kerala in India. The second case-study describes an international research collaboration investigating AMR across surgical pathways in India, UK and South Africa. We describe the steps undertaken to develop robust, agile, and flexible antimicrobial stewardship research and implementation teams. Notably, investing in capacity building ensured that the programmes described in these case-studies were sustained through the current severe acute respiratory syndrome corona virus pandemic. Describing the strategies adopted by a local and an international collaboration to tackle AMR, we provide a model for capacity building in LMICs that can support sustainable and agile antimicrobial stewardship programmes.

Antimicrobial resistance (AMR) leading to a decrease in effectiveness of antibiotics is a major global health threat [1] . The 2014 'Review on Antimicrobial Resistance', Chaired by Jim O'Neill, estimated that 10 million deaths could be attributed to AMR by 2050, with the majority of these deaths predicted to be in low-and middle-income countries (LMICs) [2] . Healthcare-associated infections (HCAI) caused by drug resistant pathogens are associated with increased morbidity and mortality, length of hospital stay, and cost [1, 2] .

They also contribute to increased emotional and mental burden on patients [3] . Inconsistent infection prevention and control (IPC) practices and suboptimal antibiotic use remain key areas of concern across high-income countries (HICs) and LMICs [4] . In addition to being integral to AMR containment, IPC is a universal component of all health systems affecting the health and safety of both people who seek the healthcare services and those who provide them. This has implications for antimicrobial stewardship (AMS) at various levels. At the macro level, initiatives tackling AMR, including national action plans, have yet to fully exploit strategic approaches necessary for building the critical capacity and contingency for responsive and sustainable policies and interventions that can be transferred to multiple contexts [5] . At the meso level, hospital based AMS programmes are not consistently implemented, or well-integrated with IPC [6] . This is despite the fact that these programmes are proven to be effective in improving the quality and safety of patient care through increased infection cure rates, reduced treatment failures, and J o u r n a l P r e -p r o o f increased frequency of appropriate prescribing for treatment and prophylaxis [7] . Reasons for this inconsistency vary according to the resources available for AMS programmes and the prevailing context in the implementation setting, to mention a few. The current ongoing severe acute respiratory syndrome corona virus (SARS-CoV-2) pandemic (causing coronavirus disease-2019; COVID-19) has exposed the gaps in current IPC strategies, highlighting the need for robust investment and capacity building in IPC as well strategies to tackle AMR. The pandemic may potentiate the long-term threat of AMR [8] . As part of efforts to control for suspected underlying bacterial infections in patients with COVID-19 infection, treating physicians may prescribe antibiotics more often, thereby unintentionally exposing the patient to selective pressure and AMR.

International partnerships in research and collaboration are critical to the global efforts to tackle AMR.

Sustained efforts on the strategies for IPC and AMS are essential at local hospital staff and management, country and international levels, spanning from policy to implementation [4, 9] . The SARS-CoV-2 pandemic has changed the research landscape and the ability of delivering international research programmes. For example since the emergence of the pandemic the majority of the United Kingdom (UK) Department of International Development (DFID) in-country staff have had to leave their posts to return to the UK, severely impeding the operational delivery of projects in partner countries [10] . The UK government's decision to merge DFID with the Foreign Office also poses threats to long-term funding and opportunity for international collaborations. This is in a time when greater global partnership and collaboration in health was gaining speed. At the 68 th World Health Assembly held at Geneva in 2015, a Global Action Plan on AMR was adopted, in response to recognition of the need to address AMR across a One Health agenda.

Later that year, AMR was included as a threat to the UN sustainable development goals (SDGs) [11] .

Although omitted from specific SDG targets, AMR is mentioned in paragraph 26 which highlights AMR the problem of unattended diseases affecting developing countries [12, 13] . Though not explicitly mentioned, several of the SDGs are directly linked to AMR, including good health and wellbeing (SDG3), clean water J o u r n a l P r e -p r o o f and sanitation (SDG6), industry, innovation and infrastructure (SDG 9), and reduced inequalities (SDG 10).

Building research capacity -key to operationalising strategies and interventions to tackle AMR across different countries -feeds into SDGs nine and ten.

In many LMICs, additional challenges especially at the organisational level, including the lack of robust healthcare infrastructure (e.g. staff workforce, access to clinical microbiology laboratory facilities and mechanisms for disease surveillance) impede the research, implementation and evaluation of effective strategies to tackle AMR [6, 9, 14, 15] . Governments completely or partially control activities that promote, restore, and maintain health; in most cases, governments are the primary funders and the providers of health services. In countries where non-governmental organisations do operate, inadequate local capacity building can lead to a lack of synergy between local and international programmes. This then puts the sustainability of such programmes at risk e.g. when external funding dries up or when faced with external threats such as pandemics. Health strategies in LMICs focus on promoting population level public health through social and community mobilisation, and provision of treatment through hospitals and clinics in the public sector. Due to more constrained health budgets, LMICs are expected to provide essential rather than comprehensive health services [16] . This restricts the National governments to primarily assessing the evolving trends and emerging threats of infectious diseases [17] , with limited resources to further operationalise and sustain AMS programmes. While large regional AMR Surveillance networks have been established in Europe (EARSNet), Latin America (Red Latinoamericana de Vigilancia de la Resistencia a los Antimicrobianos, ReLAVRA) and Central Asia and Eastern Europe (CAESAR), capacity for AMR surveillance in low-income countries is relatively limited and fragmented; this is despite evidence that AMR in lowincome regions is increasing [18] . Research is often hampered by inadequate investments by the government and external funders, in relation to required human resource skills and expertise, equipment, and surveillance and feedback strategies to inform practice. Coordination between researchers and the J o u r n a l P r e -p r o o f policymakers remains inefficient and this can translate into inadequate evidence generation, synthesis and translation and application to practice [19, 20] . Significant patient load, high patient-provider ratios, and lack of sustained training in antimicrobial stewardship and pharmacotherapy can hinder sustainable and long-term improvement in care [21] . Furthermore, the research rarely engages with patients and carers whose perspective is often missing [22] .

There are valuable lessons, however, to be learnt from innovation and resilience of healthcare systems in LMICs which have been able to implement successful change in tackling AMR, in spite of the challenges that they face. This is particularly true for some challenges which remain universal. For example the challenges of access to and correct use of diagnostic laboratories, which though is of particular concern in LMICs remains suboptimal in all settings. Geographical logistics can limit provision of laboratory services in both high and low resource settings [23] . Where there is access to diagnostic laboratories, unnecessary testing as well as antibiotic prescribing in the absence of any microbiology tests results remain high [24, 25] . Solutions to overcome these challenges have been reported in LMICs, an example being in Vietnam where an internationally funded and established research collaboration has been successful in delivering a sustainable AMS programme that included enhancing laboratory capacity [26] . This is an example of how collective efforts in AMR supported by greater international collaboration at the policy, research synthesis and translation and implementation level can lead to sustainable improvements. In the face of diminishing resources, capacity building, supported by funding, should be an integral part of AMR containment and mitigation efforts.

Building capacity for AMR research, and AMS development, and its strategic implementation and adoption, requires a One World agenda and approach. Incorporating interdisciplinary, inter-sectoral, as well as inter-country collaboration is critical. Key to spanning AMR efforts from the global to local is the Case-study 2 demonstrates the added value of funding bodies assigning supporting greater international collaborations in AMR by investing in developing the local workforce.

The state of Kerala geographically situated in the Southern India, was the first in the country to implement a state-wide strategy for addressing AMR through AMS. The AMS programme in Kerala is an example of an effective capacity building programme for tackling AMR, demonstrating the influence of collaborative Effective training was provided at hospital and state level to all medical graduates. Additionally, at the participating private and public hospitals, a train-the-trainer model was created to assure the transfer of knowledge and skills. In the champion lead hospital, an effective monitoring and evaluation programme included embedding mechanisms to ensure effective tools for monitoring outcomes comprising an antibiogram app, feedback forms for antibiotic prescribing, and pharmacist-driven reviews of prescribing practices [29] . Long-term sustainability for the AMS programme was achieved through recruiting competent human resources including trained clinical pharmacists in the stewardship programme. Whilst this approach has proven successful in Kerala, it is important to recognise that the health system in India is diverse and there may be other successful AMS models in place.

The ASPIRES (Antibiotic use across Surgical Pathways -Investigating, Redesigning and Evaluating Systems) (https://www.imperial.ac.uk/arc/aspires/) collaboration is an example of an externally funded partnership that was developed through smaller studies that included student exchange programmes.

The collaboration aims to improve clinical outcomes by optimising antibiotic usage along surgical pathways, working across South Africa, UK and India [30] . The research study was co-designed with surgical, IPC and AMS leads in each setting (Figure 1 ). The multi-disciplinary research team includes pharmacy, nursing and implementation science expertise. To ensure success, the leadership approach was structured to provide mentorship and support to researchers across the three countries. An initial intense phase of face-to-face training was undertaken in each setting, involving two months' of training for local teams by experienced researchers. This was followed on with regular check-in meetings (via video link) to monitor both the development and progress of the researchers as well as the project. The mentorship mix included cross-disciplinary teams (doctors, implementation scientists, social scientists, nurses and pharmacist) to provide broad range of expertise. The more senior researchers also gained skills in global J o u r n a l P r e -p r o o f health research, operationalisation and leadership which allowed for the different cadres of researchers to assess and provide feedback on the skills of their colleagues. The learning from the research was shared through a co-developed virtual learning platform (Massive Open Online Course: https://www.futurelearn.com/courses/social-science-for-tackling-antimicrobial-resistance). This model has proven to be effective and resilient to the unexpected shocks to the process, including lack of access to specific sites by some researchers due to visa restrictions and the unintended consequence of the SARS-CoV-2 pandemic on travel restrictions. Investing in equal proportionate funds from the research in each setting has enabled sustained research presence in South Africa and India facilitating data gathering as well as developing long-standing professional relationships. Furthermore, international training workshops were supplemented with virtual workshops where all researchers could participate in the implementation process in each setting. The emphasis on enabling and encouraging collaborations between early career researchers across the three sites ensured South-South and North-South knowledge transfer in research methodologies and skills to strengthen the overall capacity for AMR research. These newly gained skills also supported local AMS programmes and experiential learning. This international collaboration has not been without its logistical issues, in terms of travel and language barriers; these have been overcome through greater use of technology and the invaluable input of local teams. Investing in capacity building assured sustained delivery of the programme through the current SARS-CoV-2 pandemic, including the imposed travel restrictions, allowing flexibility to realign the research to meet immediate needs in each setting. Furthermore, the historic close collaborations between the principal investigator and country leads played a key role in the delivering this work.

In building collaborations to address AMR, organizations need to ensure that the strengthening of research capacity remains an explicit objective, from consultations with the funders to implementation of Actively seeking to build national and international collaborations that transcend traditional academic and clinical boundaries, and which recognise that little can be achieved by working in silos, will support mentorship of cadres of multi-professional researchers, adept at communicating across disciplines.

Strong, self-sustaining, peer group support for early career researchers that facilitate learning in an environment characterised by openness and mutual respect is essential to developing resilient systems for research that can work in healthcare environments at increasing threat of disruptions, e.g. pandemics.

In the efforts to establish AMS research and learning, it is crucial to account for multiple disciplines, and provide opportunity and mentorship both within and outside of disciplines. The case studies presented incorporate key infrastructure developments in laboratory surveillance capacities and requisite training to enhance resource personnel competence for IPC activities and AMR research, in conjunction with knowledge sharing through regional expertise networks and multinational collaborations. Our comprehensive approach of implementing, evaluating and building upon the ESSENCE criteria for capacity building for research in the context of AMR can provide a sustainable, resilient platform for research and patient-centred care in low resource settings. Ethical approval was not required for this research.

We declare no conflict of interest.

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