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Fostering Research Into Antimicrobial Resistance in India

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Fostering Research Into Antimicrobial Resistance in India ANTIMICROBIAL RESISTANCE IN SOUTH EAST ASIA Fostering research into antimicrobial resistance BMJ: first published as 10.1136/bmj.j3535 on 6 September 2017. Downloaded from in India Bhabatosh Das and colleagues discuss research and development of new antimicrobials and rapid diagnostics, which are crucial for tackling antimicrobial resistance in India ndia is among the world’s largest Box 1: Examples of the impact of antimicrobial resistance research and interventions consumers of antibiotics.1 The efficacy globally of several antibiotics is threatened by the emergence of resistant microbial • In 2011, the Chinese Ministry of Health implemented a campaign for rational use of pathogens. Multiple factors, such antibiotics in healthcare, accompanied by supervision audits and inspections. Over a year, Ias a high burden of disease, poor public superfluous prescription of antimicrobials was reduced by 10-12% for patients in hospital 45 health infrastructure, rising incomes, and and for outpatients, as were drug sales for antimicrobials. unregulated sales of cheap antibiotics, • The Swedish Strategic Programme against Antibiotic Resistance (STRAMA) led to a decrease have amplified the crisis of antimicrobial in antibiotic use for outpatients from 15.7 to 12.6 daily doses per 1000 inhabitants and from resistance (AMR) in India.2 536 to 410 prescriptions per 1000 inhabitants per year from 1995 to 2004.6 The decrease The Global Action Plan on AMR was most evident for macrolides (65%) emphasises the need to increase • The effect of WHO essential medicines policies was studied in 55 countries. These policies knowledge through surveillance and were linked to reductions in antibiotic use of ≥20% in upper respiratory tract infections. 3 research. Box 1 provides examples of A national strategy to contain antibiotic resistance was associated with a 30% reduction in global research into AMR and its impact. the use of antibiotics in acute diarrhoeal illness7 Most research into AMR is carried out • An antimicrobial stewardship programme (2009-2014) in 47 South African hospitals led to a in developed countries. This includes reduction in mean antibiotic defined daily doses per 100 patient days from 101.4 to 83.048 research into the biology of resistant pathogens,11 12 mechanisms of AMR,13-15 • In the US, infections with carbapenem resistant Enterobacteriaceae declined after the natural sources of AMR,16 17 development Antimicrobial Resistance Monitoring and Research Programme was started. In addition, 9 of new antimicrobials from uncultured there were no further reports of outbreaks caused by colistin resistant Acinetobacter spp bacteria,18 expanding the chemical • In the Netherlands, a decrease of CTX-M-1-1-like ESBL genes (from 44% to 25%) in livestock http://www.bmj.com/ diversity of existing antimicrobials,19 was seen during 2010-14, possibly linked to considerable (>60%) reduction in antibiotic use resensitising resistant pathogens against in livestock10 available antibiotics,20 and development of non-antibiotic agents as substitutes.21 Table 1 outlines the scope of research into Methods and adopted the Parasuraman gap model of AMR and the importance of the different We searched PubMed for studies, reports, service quality to assess our knowledge of areas of research. and policy documents on AMR in India AMR.31 We developed this article based on Little such research is being conducted using the search terms “antimicrobial these findings and our experience. We did on 29 September 2021 by guest. Protected copyright. in India, reflecting the situation of AMR resistance, India,” “Antibiotics, India”, and not evaluate the quality and robustness of research in South East Asia in general. A “Antibiotic resistant pathogens, India.” We identified publications. key strategy of the National Action Plan identified 5530 publications up to August on AMR (NAP-AMR), launched by the 2016. Articles referring to helminths, mos- Insufficient research to guide action government of India in 2017, is to promote quitoes, scorpion, steroids, and other unre- AMR research in India has largely focused investment for research. lated topics were excluded. AMR research on the epidemiology —that is, understand- We provide an overview of research into in animals, agriculture, and aquaculture ing the incidence and burden of resist- AMR in India, describing gaps and possible were also not considered. A total of 4872 ant pathogens in clinical and community obstacles. We propose strategies to advance articles, including original research, review settings. Research into the mechanism of research and to convert research evidence articles, case reports, comments, and edito- AMR is the second most common type. into policies and actions at a local and rials, on AMR in India were considered for This includes the effectiveness of routinely national level. this analysis. used antimicrobials, genesis of resistant We also reviewed patents filed in India pathogens, and acquisition of AMR traits. for antimicrobial drug discovery, herbal The remaining publications focused on KEY MESSAGES antimicrobial preparations, diagnostic the development of interventions to tackle tools for antimicrobial susceptibility, and AMR. Over 170 different organisations • Antimicrobial resistance research in India is focused on burden and pat- alternatives to antimicrobials. We relied on across India have contributed to AMR terns of resistance, yet nationwide information from the United States Patent and research. surveillance is lacking Trademark Office; the Office of the Controller Indian investigators have filed a General of Patents, Designs, and Trademarks; total of 93 relevant patents. Most were More research is needed to discover • the Indian Patents and Trademarks Office; filed by private pharmaceutical or new antibiotics and develop rapid and the public database “lens.org.” biopharmaceutical companies, followed diagnostic tests Two authors (BD and SC) extracted by academic research organisations and Investment in research and national • information from relevant publications and individual inventors. Most patents are surveillance of resistant pathogens all authors analysed the findings according for new formulations and new antibiotic must be prioritised to the type of research domain. We modified compounds from natural sources. The the bmj | BMJ 358:Suppl1 63 ANTIMICROBIAL RESISTANCE IN SOUTH EasT ASIA Table 1 | Potential effect of research into antimicrobial resistance (AMR) Category of research Types of studies included Role of this research Potential effect BMJ: first published as 10.1136/bmj.j3535 on 6 September 2017. Downloaded from Epidemiology Disease burden studies for various micro- To understand the trend in To guide actions locally, regionally, and nationally organisms in the community or hospitals Incidence emergence of AMR To guide clinical decisions and appropriate use of antimicrobials studies, reports of new resistance strains through data gathering and real time data sharing throughout national public health systems Clinical AMR related to healthcare set-up, treatment To understand the effectiveness of To help to develop strategies to combat AMR regimen, drug evaluation, evaluation of interventions and trends of AMR diagnostics in health Mechanistic Mechanism of emergence of resistance and To understand factors contributing To provide knowledge of the mechanism of emergence to enhance spread across species and from environment, to emergence and transmission of readiness for emergence of new resistance traits characterisation of resistance traits/strains resistance Intervention New drug development, diagnostics, alternative To rapidly and efficiently diagnose To provide a rapid diagnostic assay to guide clinical decision making antimicrobial treatment, assay development, resistant traits and pathogens, To develop alternative treatment and drugs to deal with the evaluation of antibiotic properties of herbal and develop medications to treat emergence of multidrug resistance preparations infections Policy Policies and priorities and opinion articles, health To monitor impact of policies and To devise health systems improvisations, set up governance systems research to improve effectiveness of programmes and guide further arrangements, develop target product profile for new interventions, stewardship programmes, regulatory research interventions recommend modification of the regulatory process for drugs, diagnostics, and devices for AMR Review Review of literature on AMR To provide update of knowledge and - comparison of research into AMR Council of Scientific and Industrial Overall, we note that insufficient on new antimicrobial formulations, Research, Indian Institutes of Technology, research has been carried out into characterisation of antimicrobial properties the Defence Research and Development new interventions and alternatives to of known synthetic or natural products, Organisation, and universities are among antimicrobial treatment. Most research and development of nanoparticle based the top patent applicants. (70% of 1744 studies) has concentrated antimicrobial agents. Most studies are Discovery and deployment of antibiotics - Meticillin (β-lactam) Ampicillin (β-lactam) Nalidixic acid (quinolone) Trimethoprim (pyrimidine) Fusidic acid (tetracyclic triterpenoid) Fosfomycin (phosphoenolpyruvate) http://www.bmj.com/ Actinomycin D (peptide) Lincomycin (lincosamide) - - - - Gramicidin (peptide) Erythromycin (macrolide) Gentamicin (aminoglycoside) Linezolid (oxazolidinone) Neomycin
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