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A warning in 2002 on the doors of a department at St. Mary’s Hospital, London, where penicillin was first discovered, ominously claimed that the post-antibiotic era is already here. The warning has become more intense with the realization that effective antibiotics are already or soon will not be effective anymore (Davies et al. 2013). Each year 5 million deaths are associated globally with antimicrobial resistance (AMR), which is more than the burden from HIV, TB and malaria combined, and yet there is a lack of urgent public attention especially in regions where antibiotic use remains largely unchecked. This rise has been dubbed as the “silent pandemic”.
Like many other chemical pollutants, AMR has spread from health facilities and penetrated multiple environmental riches like soil, water bodies and even clouds (Rossi et al., 2023). With the help of nucleic acid integrating units called plasmids, integrons and transposons, genetic elements of AMR existing in one species of bacteria are being transmitted to other species even in the absence of specific antibiotics. The quantity can be huge. For example, 20,800 copies of antibiotic resistance (AR) genes can be found per ml of cloud water (Rossi et al., 2022). Although air-borne transport of AR genes is a natural phenomenon with little known implications, the widespread use of antibiotics in agriculture, livestock, poultry and medicine has contributed to the proliferation of these resistant strains and their dissemination over short and long ranges. Within the human body, antibiotic resistant bacteria can persist for up to 9 years causing disease and also acting as a reservoir for the spread of infection to other people (Aguilar-Bullet et al., 2023).
In tandem with other similar global initiatives the Govt. of India launched the National Programme on AMR Containment in 2013 coordinated by the National Centre for Disease Control (NCDC), New Delhi with a lab network of 50 medical colleges, and laboratories in 27 states and 6 Union Territories. The results contributed to the Global AMR Surveillance System (GLASS) with annual submission of country data. A parallel resistance surveillance network with emphasis on research, overseen by ICMR also compiled drug resistance data on 6 pathogenic bacterial groups.
Having 2 reporting systems, in my opinion, has complicated the issue concerning synergies, guidelines, and regulations. While both systems do annual reporting, there is little evidence of analysis of long-term trajectories of AMR patterns in the different geographical areas in India where different diseases and antibiotic prescription patterns may prevail. Secondly, the data collected by both agencies is collected almost entirely from tertiary care health settings bypassing community-level settings. Very little of this data however gets to citizens whose understanding of this phenomenon of AMR and its dangers, is minimal. They remain prey to equally ill-informed medical and informal practitioners doling out irrational prescriptions (Ofori-Asenso et al., 2016). Lastly, the transformation of this vast collection of data to changes at the policy level viz. regulation, medical education, guidelines remain largely a black box despite ICMR’s all-India guidelines on therapy. Overall, as per the 2022 ICMR Annual Report (Antimicrobial Resistance Research and Surveillance Network, AMRSN, 2022), fluoroquinolones show very poor levels of susceptibility (90-95% resistance) in Salmonella, Aeromonas and diarrheagenic E. coli, all diarrhoeal pathogens. Fungi specifically from the Candida species will also require future monitoring due to declining susceptibility to fluconazole (AMRSN, 2022). And finally, the need for local, specific measures to mitigate regional AMR patterns remains unfulfilled.
While community surveillance of new zoonotic viral pathogens is currently on the upswing and being fine-tuned through wastewater sampling (especially in the labs of the western world), wastewater AMR surveillance, even there, is undertaken by very few laboratories and methods remain ill-standardized with no clear definition of a comparative data dashboard. Community/wastewater surveillance (WWS) of AMR in India is in its nascent stages. For instance, in a preliminary effort to gather an AMR snapshot in wastewater through the use of signature drugs in specific locations in Mumbai, high levels of antibiotic-resistant genes were observed for the various classes of antibiotics viz. cephalosporins, fluoroquinolones, methicillin and tetracyclines (unpublished data from The Foundation for Medical Research, Mumbai). However, WWS may not automatically translate to clinical resistance. Detection of AMR genes is profoundly influenced by climate, chemical pollutants, overall waste microbiome and presence of elements of horizontal gene transfer (Van Hamelsveld et al., 2023). Undoubtedly this may impinge life forms downstream where wastewater is released and be of public health significance in the long term through entering of marine, land, and food chains. The analysis of samples collected from inlet, outlet, and sludge components of sewage treatment plans would be a valuable guide for better sewage management and offsetting AMR dispersal.
Observations in environmental wastewater (e.g., sewage treatment plant) could serve as a comparator to the geographically stratified data published by ICMR and NCDC, provided the genes can be traced to known key pathogens through bioinformatic programmes. However, cleaner still, wastewater from hospitals with varying practices and levels of waste treatment would be a revealing index for good wastewater treatment just as would be the outlet samples of wastewater plants, which will serve as a good comparator with clinical surveillance data.
Of great significance is community education on AMR and its implications to engender behaviour change. Doctors will also need to be reeducated on emerging paradigms with concurrent updating of medical education.
AMR is a natural phenomenon, which can never be completely eliminated. But it can be dampened to a great extent through measures like periodic cycling of antibiotics that slow high degrees of resistance (Raymond et al., 2002), adjunct use of phytomedicine with complex active compounds (Gupta and Birdi., 2017), revisiting the use of phages/viruses that naturally destroy bacteria and can be particularly effective when antibiotics fail (Bayat et al., 2024). Lastly, there is the time-honored avenue of infectious disease prevention through infection control measures like vaccines and better water management and sanitation practices (Glover et al., 2024). All of these measures must be invested in and rigorously implemented.
Dame Sally Davies, a co-founder of Investor Action on AMR opines that “policy from governments only takes you so far… Investors and consumers have so much power.” Investor groups in the West do put pressure on companies and food retailers but has yielded no action despite several resolutions.
Robust evidence generated by a trained workforce with reliable data to spur critical behavioural and regulatory changes remains the cornerstone of future interventions. Undoubtedly, technological challenges also need to be eased through innovation and reduction in costs. But without data and understanding of AMR, we may well be doomed. Imagine a world where antibiotics don’t work.
Dr. Nerges Mistry is a Director and Trustee of The Foundation for Medical Research, Mumbai and The Foundation for Research in Community Health, Pune. A microbiologist and immunologist by training from the University of Mumbai and The University of Birmingham, U.K, Dr. Mistry’s work encompasses infectious diseases with a recent focus on AMR stewardship, TB transmission, infection control and nutritional approaches to engender better outcomes for patients. She has been involved in studying TB patient pathways with reference to private sector engagements in Mumbai and Patna.
Dr. Nerges Mistry and her team recently developed a mask-based aerosol capture method for COVID-19 to understand viral transmission and are currently engaged in
(i) Designing cost-effective measures of pooled sampling for community screening
(ii) Use of Sars COVID genomics to explore virus pathogenesis
(iii) Wastewater surveillance for COVID-19 & AMR
Dr. Mistry has over 112 publications in peer-reviewed journals and has been a principal investigator of over 40 major projects. She serves as an Expert on the Global Coalition Against Tuberculosis (GCAT) and is an Advisor to the TB PPM Learning Network and also a member of the National Technical Expert Group on Diagnosis of TB under NTEP.
India Health Fund is registered as Confluence for Health Action and Transformation Foundation (CHATF), a Section 8
charitable company incorporated in India, supported by the Tata Trusts.
