Anti-Microbial Resistance - The Next Pandemic

The emergence of AMR in microorganisms is a phenomenon driven by the Darwinian selection process, with microbes having developed robust mechanisms to evade elimination by anti-microbial agents.

Sir Alexander Fleming, a Scottish researcher working in the laboratory at St. Mary’s Hospital in London first identified Penicillin in 1928 and revolutionized medicine with the discovery of the world’s first antibiotic. By the time World War II ended in 1945, US companies were making 650 billion units of Penicillin a month! At the same time, Fleming predicted that use of non-lethal doses of the drug to cure infections would make bacteria resistant to Penicillin.

Let us fast-forward to the present - The WHO has now projected that Anti-Microbial Resistance (AMR) in bacteria, viruses and parasites is emerging as one of the greatest challenges to public health and could lead to the emergence of a post-anti-microbial era – where a simple infection could be fatal. Thus AMR, a natural consequence of excessive anti-microbial usage, coupled with sluggish development of novel drugs, and poor anti-microbial stewardship, is today a global, multi-factorial problem with immense complexity. This phenomenon is not only intrinsically linked to human health and behaviour, but also inherently connected with our entire ecosystem including animal health, food production, agriculture and the environment.

A large number of drugs are of microbial origin, produced by environmental fungi or bacteria, and are also available as synthetic modifications, except for sulphonamides and fluoroquinolones which are synthetic. The emergence of AMR in microorganisms is a phenomenon driven by the Darwinian selection process, with microbes having developed robust mechanisms to evade elimination by anti-microbial agents. There is, however, not much evidence to suggest that selection of anti-microbial resistance occurs in the natural environment. It is noteworthy that in a pristine (i.e. free from external anti-microbial selection pressure) ecosystem, anti-microbial resistant and non-resistant species co-exist in a stable balance.

Although the link between human anti-microbial use and emergence of resistance is established, several factors contribute to the complexity of the problem such as bacteria-drug interactions, bacteria-host interactions, mutation rates of bacteria, evolution of anti-microbial resistance clones as well as transmission rates of resistance determinants between microorganisms. The emergence of resistance is likely to be specific to each drug and to each microorganism, as well as the effect of changes in its use. There is also the need for addressing an integrated approach to be adopted across both community and health-care structures.

In the light of the recent pandemic, this looming global crisis takes on even more significance due to the increase in anti-microbial use coupled with the invasive procedures that are associated with the treatment of COVID19 patients, resulting in a heightened risk of emergence as well as spread of AMR. Furthermore, data from around the world, especially Asia, has implicated that more than 70% of patients undergoing Covid-19 treatment receive anti-microbials though only 10% were actually suffering from antibacterial or antifungal infections, further contributing to the AMR crisis!

Use of anti-microbials in clinical medicine has exposed human microbiota to unprecedented high concentrations of drugs, resulting in the development of de novo resistance within an individual during treatment. A better understanding of resistance mechanisms could facilitate novel approaches to diagnostics and therapeutics. It is evident that several complementary, overlapping, collaborative and synergistic approaches with common goals will be essential to ensure and sustain access to effective anti-microbial therapies.

In response to the gravity of the situation, the United Nations adopted a resolution and reaffirmed the WHO Global Action Plan on AMR, which is reflected in the strategic objectives of the National Action Plan (NAP) on AMR set up by the Government of India in 2017, based on national needs and priorities. In addition to the five priorities of the Global Action Plan on AMR, India has a sixth priority dealing with India’s leadership in AMR. The NAP on AMR includes:
 

1. Improving awareness and understanding of AMR through effective communication, education and training
2. Strengthening knowledge and evidence through surveillance
3. Reducing incidence of infection through effective infection prevention and control
4. Optimizing use of anti-microbials in health, animals and food
5. Promoting investment for AMR activities, research & innovation
6. Strengthening India’s leadership in AMR

In this regard, developing effective strategies and interventions in the Indian context, planning effective antibiotic stewardship in India, promoting investments for AMR activities, research and innovation, as well as strengthening India’s commitment on AMR are of paramount importance.

The need for rapid diagnostics to regulate indiscriminate prescription of anti-microbials is vital. The availability of rapid diagnostic tests to distinguish between viral and bacterial infections in primary point of care settings could significantly improve clinical management of undifferentiated fever, thereby helping to optimize anti-microbial prescriptions and limit irrational anti-microbial usage. Collaboration, coordination as well as synergistic interaction between surveillance networks can enable standardized collection and analysis of samples, as well as avoiding redundancy. In this regard, sample collection and analysis with enhanced focus on the AMR profile and the dissemination of results should follow the recommendation of the WHO Global Anti-microbial Resistance Surveillance System (GLASS), which promotes and supports a standardized approach to the collection, analysis and sharing of AMR data at a global level, by encouraging and facilitating the establishment of national AMR surveillance systems that are capable of monitoring AMR trends and harnessing reliable and comparable data.

Anti-microbial stewardship has been recognized as a key component of the fight against AMR. A comprehensive understanding of why anti-microbial prescriptions are often doled out without diagnostic testing could help to restrict the inclinations to use anti-microbials indiscriminately. Understanding and evaluating the relative contribution of different drivers of AMR development could greatly facilitate rapid progression toward a global solution for AMR. With the focus on patient level interventions to eliminate Covid-19, it is important to evaluate its collateral effects on management of anti-microbial resistance. It is a matter of concern that the ongoing pandemic is exacerbating existing challenges to optimal antibiotic stewardship and thereby elevating the threat to patient safety and public health via antibiotic over prescription leading to acceleration of bacterial resistance.

As an important step towards tackling the global AMR menace, the United Nations has decided to observe November 18 to 24th, 2020, as World Anti-microbial Awareness Week [WAAW], with aims to increase awareness of global Anti-microbial Resistance (AMR) and to encourage best practices among general public, health workers and policy makers to contain further emergence and spread of drug resistant infections.

It is now obvious, that along with other global challenges that threaten human existence and the planet, global cooperation is an absolute necessity to reduce the evolution and spread of AMR—the next pandemic in the making.