Antimicrobial Resistance: An Emerging Global Challenge Waiting for Urgent Actions

Antimicrobial resistance (AMR) is defined as the resistance of microorganisms to an antimicrobial agent to which they were at first sensitive. AMR occurs when microorganisms such as bacteria, viruses, parasites or fungi become resistant to antimicrobial treatments to which they were previously susceptible. 1 Due to drug resistance, antibiotics and other antimicrobial medications lose their effectiveness, making infections harder or impossible to treat. This raises the likelihood of disease transmission, severe illness, disability and death. 2 AMR is driven by the overuse and misuse of antibiotics in human medicine and agriculture, promoting the survival of resistant bacteria. In addition, the excessive use of antimicrobials in agriculture and pollution from various sectors contribute to the problem. 3 The unrestricted use of antimicrobials in livestock feed has significantly contributed to the rise of AMR. 4 The widespread presence of antimicrobial-resistant bacteria has reached alarming levels globally, posing a serious threat to public health as a silent pandemic that requires immediate action. 5 The emergence of resistance to even one antibiotic can pose serious problems. Such resistance can lead to infections that require more aggressive treatments with serious side effects, prolonging patient recovery. Many crucial medical procedures, such as organ transplants and cancer therapy, depend on effective antibiotics. If these drugs lose their effectiveness, there could be dire consequences, including untreatable infections and a significant threat to public health. 6 India's dense population, high disease burden and varied healthcare practices make it particularly vulnerable. Such a crisis jeopardises medical advancements, challenges healthcare delivery and could hinder progress towards achieving Sustainable Development Goals. 7 Antimicrobial Resistance Challenges and Mortality AMR leads to treatment failures, resulting in prolonged illness, disability and death. AMR strains healthcare systems by prolonging hospital stays, increasing the need for more expensive treatments and limiting the effectiveness of routine surgeries and medical procedures. 8 Annually, approximately 4. 95 million deaths worldwide are linked to AMR. The World Bank projects that by 2050, AMR could lead to an extra US1 trillion in healthcare expenses and annual GDP losses ranging from US1 trillion to US3. 4 trillion by 2030. Recent estimates indicate that in 2019, approximately 1. 27 million deaths worldwide were directly linked to drug-resistant infections. If current trends continue, projections suggest that by 2050, the annual death toll from such infections could reach up to 10 million. 1, 9-11 India faces a particularly daunting challenge due to high population density, inadequate sanitation infrastructure and overuse of antimicrobial drugs. In 2019, India reported an estimated 297, 000 deaths linked to AMR and 1, 042, 500 deaths associated with AMR. 12 India is expected to experience around two million deaths attributable to AMR by 2050. 10 In India, five pathogens pose significant concerns due to AMR: Escherichia coli (152, 700 deaths), Klebsiella pneumoniae (123, 200 deaths), Staphylococcus aureus (111, 400 deaths), Acinetobacter baumannii (103, 500 deaths) and Mycobacterium tuberculosis (98, 600 deaths). 12 Methicillin-resistant S. aureus is linked to a significant number of deaths due to antimicrobial-resistant infections worldwide. 4, 5 Factor Contributing to Antimicrobial Resistance AMR is an inevitable part of evolution observed in all organisms, as they develop genetic mutations to survive the lethal effects of selection pressure. 4 AMR occurs naturally as pathogens undergo genetic changes over time, to evade being targeted by antibiotics/antimicrobial. However, human activities, particularly the excessive and inappropriate use of antimicrobials in treating, preventing or managing infections in humans, animals and plants, accelerate its emergence and spread. 2 Resistant strains have emerged in various bacteria, such as S. aureus, Enterococcus species, Pseudomonas aeruginosa, Acinetobacter species, E. coli, K. pneumoniae and Neisseria gonorrhoeae and M. tuberculosis which leads to multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis (XDR-TB). 13 Antimicrobial Resistance and Climate Change On a global scale, AMR and climate change stand out as major health emergencies and are interconnected public health priorities. 14 Climate change can alter disease patterns, influencing the prevalence and spread of infectious diseases, potentially exacerbating the problem of AMR. Considerable evidence suggests that higher temperatures are linked to increased rates of bacterial infections. 15 Rising temperatures are closely connected to AMR because they lead to higher rates of bacterial growth and horizontal gene transfer. 14 The link between temperature and population density is applied to common pathogens such as E. coli, K. pneumoniae and S. aureus. Rising antibiotic resistance was linked to higher average minimum temperatures, which are increasing due to climate change and its impact on evolution, paradigm shift and response to antibacterial agents. Climate change has a direct and indirect impact on human health and affects factors such as water quality, food security, ecosystems and the distribution of disease-carrying vectors. These changes result in higher risks of waterborne, foodborne and vector-borne diseases, as well as potential negative impacts on mental health. Global Action to Combat Antimicrobial Resistance AMR is a complex issue with significant implications for individuals and healthcare systems. 13 In response to the challenge of AMR, nations worldwide embraced the Global Action Plan (GAP) on AMR at the 2015 World Health Assembly. They pledged to create and execute comprehensive national action plans (NAP) that encompass multiple sectors, adopting a One Health approach to combat AMR. 2 Subsequently, collaboration with the World Health Organization (WHO), Food and Agriculture Organization and World Organisation for Animal Health, adopted the GAP on AMR in 2015. 13 In 2015, the WHO initiated the Global AMR and Use Surveillance System (GLASS) to track AMR in common bacteria and fungi, as well as antimicrobial consumption in humans. The system provides vital data to guide national and global responses to AMR. 16 In April 2017, India's Ministry of Health and Family Welfare released the NAP for AMR, aiming to raise awareness, improve surveillance, strengthen infection control, promote research and development, encourage investment and foster collaboration. Based on the NAP, several states have started developing their own State Action Plans. 13 The existing NAP is thorough and in harmony with the WHO's GAP for AMR. It encompasses all five major objectives outlined in the GAP and introduces an extra goal to enhance India's leadership in addressing AMR. In addition, the plan aims to address various facets of AMR in both human and non-human sectors, including agriculture, fisheries, animal husbandry and the environment, utilising a 'One Health approach'. 11 Some recommendations on all addressing AMR across one health sector are listed in Box 1. Box 1: Recommendations for addressing antimicrobial resistance across One Health sectorsThe general physician is a majority of share in healthcare providers in India. There is a need for more simplified and evidence-based guidance for general physicians. The research and public community need to generate more evidence on these areas to step up advocacy. 17 The surveillance systems need to be geared up to support the evidence-informed discourse on AMR and prevention. 18 In low- and middle-income countries such as India, where discussions on strengthening primary healthcare are ongoing, the One Health needs to be integrated and operationalised, as has been indicated in a review article in this issue of the journal. 17, 19 The attention on adult vaccination is likely to address the issue of AMR. 20 There are some early discussions on the National One Health Mission in India, which should categorically and clearly focus and attention on public health actions to tackle AMR. 21 It clearly is time for some concrete actions.