Two zinc ions (purple) at the active site of the NDM 1 enzyme. Image: NoetherIsLikeNoOther/Wikimedia Commons, CC BY-SA 4.0.
Antimicrobial resistance (AMR), brewing unnoticeably for the past couple of decades, has now evolved into a potential public-health emergency on the cusp of threatening our medical fraternity in the near future. India has one of the highest incidences of bacterial infections in the world, including in the form of typhoid, cholera, pneumonia, tuberculosis, etc. AMR happens when fungi, parasites, bacteria, etc. evolve and stop responding to medicines meant to kill them. As such, this phenomenon threatens to wipe out gains made over decades of scientific innovation and medical advances – if it isn’t prevented and managed effectively and on priority.
The microbes’ evolution and mutation can take place at multiple sites and via diverse methods, be it inside the human body, in sewage dumps, from animals to humans via the food chain, and so on. The presence of contaminants like arsenic and other heavy materials could also foster mutation – as could immune pressure in the cells of a human body. The resistant organism can potentially circulate in communities or in a hospital environment, and the resistance thus spread could be primary or acquired, given the pressure exerted by indiscriminate use of drugs. Infections caused by these multi/extreme drug-resistant organisms are often fatal.
In the food chain, apart from the fact that animals get antibiotics via the food they consume, they are often treated with the same antibiotics as used by humans, negating any gaps between the two species. So not only have humans been encroaching on the exclusive preserve of animals via excess urbanisation, deforestation, etc., increased interaction via the food chain has only eased the exchange of microbes between the two species.
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This in turn serves to highlight the importance of the ‘One Health’ concept as far as tackling AMR is concerned. Initiatives like molecular surveillance of humans and animals can help highlight antimicrobial resistance in different geographies as well as between communities and hospitals, and there’s a lot we could learn by way of it. For perspective: bacterial strains with the New Delhi metallo-ß-lactamase (NDM 1) enzyme were first detected in an Indian passenger travelling from Delhi to Sweden.
Finally, we must address the threat posed by effluents from pharmaceutical manufacturing units. Most bulk drug manufacturers often discharge their antibiotic-laden effluents as sewage without treating it properly. This is one of the weakest links in the AMR management chain and needs the attention of policymakers given the sheer volume of effluents involved. There is an urgent need to establish surveillance and appropriate guidelines to mitigate the risk of AMR through the effluent discharge route.
The other challenges here include creating cost effective diagnostics which could provide immediate inputs to the clinician for them to make informed policy decisions. New modes of therapies such as change in microbiota, the new peptide based antibiotics with novel delivery systems which will not be effected by mutations would also have a vital role to play.
India’s national response to the challenges posed by AMR started after the discovery of the NDM 1 strain. A study conducted in 2017 examining the presence of bacteria Streptococcus pneumonia in blood samples of pneumonia-infected children in 11 states revealed how a majority strains of these bacteria had already acquired resistance to first-line antibiotics.
In fact, in 2017, the Government of India had come up with a National Action Plan on AMR with a multi-pronged strategy to tackle the issue, including developing standards for antibiotic residue in such industrial effluents. Four years earlier, the Indian Council of Medical Research (ICMR) had initiated the ‘Antimicrobial Resistance Surveillance and Research Network’ to analyse and publish drug-resistance data from across India, compile data on six pathogenic groups and use it to devise and update relevant treatment guidelines. Such an exercise can also potentially guide the development of new drug candidates and other diagnostics. In January 2020, the Government of India also introduced legislation aimed at limiting harmful antibiotic residues released by pharmaceutical manufacturing plants.
Speaking of prevention, AMR could be tackled by the judicious withdrawal of particular antibiotics. Unfortunately, there are very few new antibiotics which are being discovered given that the existing ones are families of each other and hence there exists a chance of resistance developing as soon as 2 years. This helps explain why companies have been reluctant to invest in new discoveries. Development of new diagnostic tools could be very helpful. However, often times diagnostics can potentially lead to more resistance than antibiotics themselves.
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From a policy perspective, some important changes we could consider to effectively tackle AMR in India are:
1. Detection and prevention of the sale of spurious drugs, particularly i tier 2 and tier 3 cities
2. Making drug packaging tamper-proof while improving the capacity of drug-testing laboratories
3. The occasional measurement of bioavailability at pharmacokinetics and pharmacodynamics, enforcement of antibiotics policies via prescription databases and auditing of pharmacies
4. Monitoring sale of drugs with GST tracking/matching of e-prescriptions
5. Shift from the syndromic approach to treatment of the diagnosis, use of new technologies such as imaging and bioinformatics and geographic information systems
6. Appropriate continuing medical education courses and virtual/in-person training for registered medical practitioners, and behavioural changes in community through holistic communication and advocacy strategies
7. Rationalised treatment of fever, cough, cold and diarrhoea (the three major drivers of AMR)
8. Adherence to the WASH strategy: antibiotic-free animal feed, and antibiotics fed to animals should be different from those consumed by humans (e.g. marked by different colour schemes)
9. Enhanced antibiotic lifetimes and creation of a prescription database, so sub-regional and country-wide policies can be credibly formulated; new antibiotic-discovery policies, such as through the Global Antibiotic Research and Development Partnership
10. Global approach and adoption rather than just local interventions
11. A commission to coordinate activities, plan and effectively implement policy decisions
Each of these interventions could lead to better health outcomes and potentially vast socio-economic benefits as well. Given the lack of India-specific data vis-à-vis AMR-related mortalities, communications and advocacy assume an even more important role. India already carries one of the highest burdens of drug-resistant pathogens worldwide; one estimate suggests AMR will cause nearly 10 million deaths every year by 2050 around the world. So despite our efforts, the scale of the problem needs us to do a lot more.
Nirmal Kumar Ganguly is former director-general, Indian Council of Medical Research.