Research is the most important need to improve the quality of healthcare in any country. This can be verified by measuring the number of peer-reviewed articles published in the country. The search term “antibiotic resistance, India” in PubMed with restriction to “human” studies for the past 10 years yielded a result of 2,633 research articles. More importantly, there is an increasing trend of publications since 2009, suggesting that more research programmes are being undertaken to understand antimicrobial resistance in India. This is the outcome of several programmes started by the government of India since 2009. India recently signed up to become a part of Global Antimicrobial Research and Development Hub. Global genome analysis-based research from India in the past 10 years produced 58 peer-reviewed papers, of which the majority were on Mycobacterium tuberculosis.
However, at the same time, the United States of America and China have published 8,209 and 4,467 research articles, suggesting that there are more research activities in those countries than in India. Furthermore, whole-genome sequencing-based research was dominated by the USA, with 1,715 research articles, followed by 170 from China. Whole genomic analysis of AMR pathogens is the need of the hour and India’s doctors and researchers must focus on increasing the amount of the research conducted, for better clinical outcomes. The use of the latest technological advances has not fully reached translational research in India and this needs urgent attention. In order to combat antimicrobial resistance, it is imperative to understand the molecular mechanisms associated with the emergence of resistance. The key strategy which must help in improving research in AMR is the National Action Plan on AMR (NAP-AMR) launched in 2017 by the government of India.
Focus on natural resources
The majority of research on AMR in India focused on epidemiology, rather than the molecular basis of AMR traits. Considering the fact that there are 170 research organizations working in this field, the research output is very minimal. It can also be noted that 70% of AMR research for new compounds or formulations focused on natural resources and 93 relevant patents were filed. These patents were filed primarily by private pharmaceutical or biopharmaceutical companies. Very few were filed by academic research organizations. The majority of academic patents were from Indian Institutes of Technology, the Defense Research and Development Organisation, Council of Scientific and Industrial Research and other universities. These products or formulations were studied in vitro or via small animal studies, but none has progressed to clinical evaluation, suggesting that there is a lack of translation to clinical practice. One important reason for such lack of progress could be the need for high investments for conducting clinical evaluations. There are also poor clinician-scientist collaboration, as can be seen in authorship data for these publications. These barriers can be reduced by better collaborative research programmes.
Healthcare in India is dominated by private hospitals. They must play a crucial role by taking research outputs such as patents to their logical conclusions. The Indian Council of Medical Research launched the Antimicrobial Resistance Surveillance and Research Network (AMRSN) in 2013 to understand the epidemiology of antimicrobial resistance in six pathogenic bacterial and fungal species (such as Klebsiella pneumoniae, Escherichia coli, Salmonella enterica serovar typhi, Staphylococcus aureus, and enterococci and candida species). This network includes 12 public and 8 private agencies, but lack of infrastructure and gaps in coordination has restricted outcomes. The NAP-AMR calls for private investments into AMR research. In the past 10 years, major pharmaceutical companies in India have increased their research and development expenditure 40-fold, but not into new antimicrobial drugs. All the pharmaceutical companies are focused on chemical modifications of existing antimicrobial compounds rather than attempting to leverage the 93 patents or to discover new therapeutic agents. In the past 6 decades, more than 80 beta-lactam derivatives have been introduced, but no new classes of antibiotics.
Needed: Multipronged approach
The other important aspect is a public campaign against the unnecessary use of antimicrobials. There have been several successful attempts that can be studied, and better ways yet can be implemented in India. The Chinese Ministry of Health implemented a campaign regarding the rational use of antibiotics, which resulted in a 10-12% reduction in the prescription of antimicrobials. The antimicrobial stewardship programme from 2009-2014 in 47 hospitals in South Africa showed a considerable reduction in antibiotic doses. In the US, infections with carbapenem-resistant Enterobacteriaceae declined after Antimicrobial Resistance Monitoring and Research Programme was started. These examples suggest that outreach programmes can also make an enormous influence on AMR and can significantly change the paradigm of clinical utility. In India, such programmes must be made mandatory at all primary healthcare centers to bring awareness and a reduction in drug resistance.
In order to tackle AMR, we need a multi-pronged approach targeted at improving research, drug discovery and hospitals, including awareness campaigns. One other important aspect that needs urgent attention has been flagged by the World Health Organization’s (WHO) recently published AMR surveillance data from 169 member countries. The report highlighted a lack of national surveillance data on resistant pathogens in India and 14 other member countries. In these countries, systematic, nationwide surveillance of AMR pathogens in clinical settings, animals, and the environment is inadequate or lacking. A national repository of AMR pathogens in India, therefore, will really boost research and clinical efforts.