Apr 9

The Silent Pandemic: AMR in Low and Middle-Income Countries

Introduction  

For decades, the world has benefited hugely from the power of antimicrobials- drugs that combat infections caused by microorganisms. Among these, antibiotics specifically target bacteria and have been transformative, turning once-deadly illnesses into treatable conditions. However, this success story is increasingly threatened by the rise of antimicrobial resistance (AMR), in which microbes adapt and become less susceptible or entirely resistant to the drugs designed to destroy them. This is not a localised issue but a global threat to public health, recognised by leading international organisations, including the World Health Assembly and the United Nations General Assembly.

The potential consequences of the increase in AMR are dire. A sobering projection from a 2016 United Kingdom report estimates that AMR could cause a staggering 10 million deaths per year by 2050, exceeding the current mortality rate of cancer. Furthermore, the economic toll is projected to be devastating, with a 100 trillion USD global economic impact if effective measures are not implemented now. Even in a high income country, with access to advanced healthcare, like the United States, the scale of the problem is significant. Here, there are over 2.8 million AMR infections annually, leading to approximately 35,900 deaths.

A primary driver of this escalating crisis is the overuse and misuse of antimicrobials in both human and animal health. When antibiotics are used unnecessarily or incorrectly, susceptible bacteria will be eliminated, but resistant strains are more likely to survive and multiply, contributing to the spread of resistance. In response to this growing threat, antimicrobial stewardship (AMS) programs have emerged as vital interventions. These programs are composed of a range of strategies aimed at optimising the use of antimicrobials, ensuring they are prescribed only when needed, at the correct dose, for the appropriate duration, and the most suitable agent for the target. Effective AMS not only improves patient outcomes by ensuring appropriate treatment but also plays a vital role in reducing the development and spread of AMR.  Closely related will be a reduction in healthcare-associated infections, leading to significant savings in healthcare costs.  

The Imperative of Antimicrobial Stewardship in LMICs

While AMR is a global challenge, its concern is disproportionately higher in low- and middle-income countries (LMICs). Several factors contribute to this increased vulnerability, including higher rates of infectious diseases, limited access to diagnostic tools, and often less regulated access to antibiotics. Data from the early implementation of the Global AMR Surveillance System (GLASS) in 2017-2018 provide a harsh demonstration of this disparity. For instance, in Malawi, over 75% of Klebsiella pneumoniae and Escherichia coli blood culture isolates showed resistance to ceftriaxone, a commonly used antibiotic. Similarly, concerning levels of resistance to important antibiotics like cefepime and even carbapenems have been reported in India and other LMICs such as Egypt, Nepal, Nigeria, and Pakistan. This situation contrasts sharply with high-income countries like the United Kingdom, which reported significantly lower resistance rates for the same bacterial species. Furthermore, a 2016 review of data from South and Southeast Asia highlighted the significant local incidence of AMR, with many countries in these regions estimating that over 40% of Acinetobacter baumannii isolates were resistant to carbapenems, a class of last-resort antibiotics.

Given these alarmingly high rates of AMR and the potentially devastating consequences for already strained healthcare systems, antimicrobial stewardship (AMS) programs are essential for optimising antibiotic use, slowing the emergence of resistance, and ultimately improving patient outcomes in LMICs. These programs aim to instil a culture of responsible antibiotic use among healthcare professionals and the public, safeguarding the effectiveness of these life-saving medicines for future generations.

While the implementation of AMS programmes is crucial globally, LMICs face unique challenges that must be addressed to ensure their success. These can include:
  • Limited financial and human resources: Healthcare systems in LMICs generally operate with significantly fewer resources in comparison to high-income countries. In 2016, LMICs spent an average of 5.42% of their GDP on healthcare ($234 per person), in stark contrast to the 12.59% ($5,179 per person) spent by high-income countries. This scarcity of resources can directly impact the availability of trained staff, essential diagnostic tools, and the necessary infrastructure to support comprehensive AMS programs.


  • Over-the-counter antimicrobial prescribing: In many LMICs, antibiotics are readily available for purchase without an official prescription, often over the counter. This easy access contributes significantly to the inappropriate use of antibiotics, as individuals may self-medicate for viral infections or use incorrect dosages and durations, accelerating the development of resistance. Addressing this issue through stricter regulations and public awareness campaigns is vital to limiting AMR in LMICs.


  • Inadequate water sanitation and hygiene: Poor water sanitation and hygiene practices are prevalent in many LMICs, contributing significantly to the high number of infectious diseases, particularly diarrhoeal illnesses. This higher incidence of infections often leads to increased antimicrobial use, further driving resistance. Studies suggest that universal access to improved sanitation could potentially decrease antimicrobial prescribing for diarrhoeal illnesses by a significant margin.
  • Communication barriers: Countries with a high degree of linguistic diversity may face additional hurdles in the communication of AMS guidelines, educational materials, and public health messages. Communication in different languages and cultural contexts is essential for successful AMS implementation.


  • Limited data on antimicrobial use and resistance: Comprehensive and reliable data on antibiotic consumption and resistance patterns may be scarce or incomplete in many LMICs. This lack of data makes it challenging to accurately assess the local AMR situation, identify specific targets for AMS interventions, and effectively monitor the impact of these programs. A 2019 study in central Thailand reported that only 49% of 45 surveyed hospitals had access to antimicrobial consumption data, highlighting this challenge.


Despite these considerable challenges, the World Health Organisation (WHO) recognises the urgent need for the implementation and strengthening of AMS programs in these resource-limited settings. To address this need, the WHO has developed the comprehensive “Antimicrobial Stewardship Programmes in Health-Care Facilities in Low- and Middle-Income Countries: A WHO Practical Toolkit". This invaluable resource offers valuable, stepwise guidance for establishing effective AMS programs at both national and healthcare facility levels, specifically tailored to the unique constraints and opportunities present in LMICs. The toolkit emphasises an adaptable approach, encouraging countries and healthcare facilities to start with achievable interventions and gradually increase their AMS efforts.

The WHO toolkit outlines the importance of establishing core elements as a foundation to support robust AMS programs at both national (state/regional) and healthcare facility levels. These core elements provide a framework for building comprehensive and sustainable AMS initiatives.

1. National (State/Regional) Core Elements focus on creating a supportive environment and infrastructure for AMS implementation across the country:

  • Establishment of a governance structure: This includes forming a national AMS technical working group (TWG) linked to the national AMR steering committee to provide strategic leadership and coordination.


  • Development and implementation of a national AMS strategy and plan: This strategy should include national indicators to monitor progress


  • Regulation and guidelines: This involves integrating the WHO's AWaRe (Access, Watch, Reserve) classification of antibiotics into the national Essential Medicines List (EML) and developing up-to-date clinical guidelines that incorporate AMS principles and the AWaRe classification.


  • Awareness, education, and training: Implementing nationwide campaigns to improve public awareness of AMR and providing pre- and in-service training for healthcare professionals on optimised antibiotic prescribing.


  • Supporting technologies and data: Facilitating access to relevant diagnostic tests and building the capacity for data collection and analysis related to antimicrobial consumption and resistance.


  • Monitoring and evaluation: Establishing systems to monitor the implementation of the national AMS strategy and evaluate its impact.



2. Healthcare Facility Core Elements focus on the practical implementation of AMS within individual hospitals and clinics:

  • Establishment of an AMS committee and/or team: This multidisciplinary group should include physicians, pharmacists, microbiologists (if available), and nurses to oversee and implement AMS programs. In resource-limited settings, AMS champions can lead these efforts.

  • Conducting a facility AMS situational analysis (SWOT analysis): This helps to understand the local context, identify existing strengths and weaknesses, and pinpoint opportunities and threats to successful AMS outcomes.

  • Prioritisation and implementation of healthcare facility core elements: Based on the situational analysis, facilities should prioritise and implement core elements such as developing local antibiotic guidelines (including for surgical prophylaxis and common infections), establishing surveillance of antibiotic use and resistance, and providing regular feedback to prescribers.

  • Implementation of AMS interventions: Starting with the most obvious interventions and gradually introducing more advanced strategies such as audit and feedback, pre-authorisation of specific antibiotics, and prospective review of antibiotic prescriptions.

  • Regular monitoring and evaluation of AMS interventions: Tracking the main indicators related to antibiotic use, resistance rates, and patient outcomes to assess the impact of AMS efforts and make the necessary adjustments.

  • Offering basic and continued educational resources and training: Providing ongoing learning opportunities for healthcare professionals on optimised antibiotic prescribing and AMS principles.

  • Clearly defined collaboration between AMS and Infection Prevention and Control (IPC) programs. Recognising the relationship between these two vital areas in combating AMR and healthcare-associated infections.

    The success of AMS in general hinges on a collaborative approach, actively involving healthcare professionals at all levels, building on existing infrastructure, and fostering workable changes in antibiotic prescribing practices. The WHO toolkit strongly emphasises a stepwise implementation of AMS interventions, encouraging facilities to start small and keep it simple and doable. Undertaking a situational analysis or SWOT analysis is highlighted as an initial step to thoroughly understand the local context and identify existing strengths, weaknesses, opportunities, and potential threats to successful AMS implementation within a specific healthcare facility.


Key practical strategies and components for building effective Antimicrobial Stewardship Programs (ASPs) in LMICs, as outlined in the WHO toolkit and other sources, include:

  • Establish an ASP Committee: This multidisciplinary team is the cornerstone of an effective ASP, ideally including an infectious disease physician, clinical pharmacist, clinical microbiologist (if available), and nurses. Even in the absence of all these specialists, antimicrobial stewardship champions – passionate individuals from various healthcare professions – can drive the efforts, with access to expert advice when needed. The ASP committee can function as a standalone body or be integrated into an existing structure like the infection prevention committee, ensuring AMS is a regular agenda item.

  • Conduct a Situational Analysis (SWOT): Before launching any interventions, a thorough understanding of the local situation is essential. Conducting a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis helps identify what is already in place regarding antibiotic use and resistance data, existing AMS activities, and available resources, as well as potential barriers to implementing the ASP. This analysis aids in the prioritisation of AMS interventions.

  • Develop Local Antibiotic Guidelines: Guidelines tailored to the local situation, based on national or international recommendations and, vitally, local antibiotic susceptibility data. These are all essential for guiding appropriate antibiotic prescribing. These guidelines should cover the treatment of common infections and surgical prophylaxis. Using mobile phone-based applications can be a cost-effective and wide-reaching method to disseminate these guidelines among healthcare providers in LMICs, given the high mobile phone penetration in these regions.

  • Implement Basic AMS Interventions: Start with the most obvious interventions that are relatively easy to implement and can yield noticeable results. These might include education for prescribers on optimal antibiotic use, reviewing indications for antibiotic prescriptions to ensure they are documented and justified, and auditing antibiotic use with feedback to prescribers. Feedback can be provided in real-time during ward rounds or retrospectively through reports. Even simple measures like ensuring clear documentation of the indication, drug, dose, route, and duration of antibiotic prescriptions in medical records can significantly improve antibiotic use.

  • Focus on Education and Training: Continuous education and training for all healthcare professionals involved in antibiotic prescribing, dispensing, and administration are vital for long-term success. This can include interactive workshops, case-based discussions, and utilising readily accessible e-learning resources. Understanding key concepts such as the importance of using recommended first-line antibiotics whenever possible and the potential harm of broad -spectrum therapy is crucial. Medical school education is also a key target for closing knowledge gaps. Active methods of education, such as audit and feedback and antimicrobial restriction, have proven to be particularly effective.

  • Utilise Available Resources: Take full advantage of readily available resources such as the WHO's AWaRe (Access, Watch, Reserve) classification of antibiotics to prioritise the use of narrow-spectrum "Access" antibiotics whenever possible, reserving "Watch" and "Reserve" antibiotics for specific indications. The WHO toolkit itself provides detailed guidance on the structures, interventions, and assessment of AMS programs specifically for LMICs.

The Role of IT in AMS Programs: Information technology will play an increasingly significant role in enhancing the efficiency and effectiveness of AMS programs, even in resource-limited settings where only a basic IT infrastructure exists. This can be separated into basic, intermediate and advanced applications. Basic applications include databases for procurement and dispensing, which can aid in tracking antimicrobial consumption. Intermediate applications include alerts for specific antibiotic use and electronic dissemination of guidelines. Advanced systems include CPOE (computerised physician order entry) with clinical decision support and automated reporting of facility-level data. Developing data collection should be considered in limited resource settings, especially linking AMS with IPC programs.

Monitoring and Evaluation of AMS Interventions: Regularly assessing the impact of AMS interventions is crucial for ensuring their effectiveness and making necessary adjustments. According to WHO there are measurements for
assessing the
effectiveness of AMS programs. These can be categorised as:

  • Structure measures – presence of an AMS team
  • Process measures – adherence to guidelines
  • Outcome measures- antibiotic consumption, resistance rates, patient outcomes

Education and Training in Detail: Again, from the WHO toolkit, education and training are critical for the success of AMS in LMICs. It is important to define AMS competencies for different staff groups and develop a tailored training plan for these groups. There should be pre- and in-service training, integrating AMS with IPC, incorporating or strengthening in curricula and continuing medical education. Face-to-face workshops, while common in LMICs, can be augmented with more active methods like e-learning, which offers flexibility and cost-effectiveness. There should be consideration of digital literacy as well. It has been found that Active teaching methods, such as discussion groups, audit and feedback, and interactive workshops, are generally more effective in changing prescribing behaviour compared to passive methods like lectures and printed materials. The toolkit also emphasises the importance of "train-the-trainer" models to build local capacity for delivering quality AMS education.

Conclusion

Antimicrobial resistance poses a significant and growing threat, disproportionately impacting low- and middle-income countries (LMICs). To combat this, antimicrobial stewardship (AMS) programs are essential for optimising antibiotic use, slowing the emergence of resistance, and ultimately improving patient outcomes in these settings. While the challenges in implementing AMS in LMICs, such as limited resources and diagnostic capabilities, are unique, resources like the WHO practical toolkit offer valuable, stepwise guidance for establishing effective programs at both national and healthcare facility levels. The success of AMS hinges on a collaborative approach, building on existing infrastructure, and actively engaging healthcare professionals to bring about sustainable changes in antibiotic prescribing practices.

Reference

Topics to ponder or to seek further knowledge

Considering the substantial burden of AMR in LMICs and the critical role of well-implemented AMS programs, what innovative, context-specific strategies do you believe could further enhance the effectiveness and sustainability of these efforts in resource-limited settings?

If you found this overview insightful and are keen to delve deeper into the strategies and tools available for implementing AMS in LMICs, consider exploring the WHO toolkit (link) and other related resources to learn more and contribute to this vital area.

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