AMR

– Dr. Suranjana Basak,MD General Medicine, Fortis Hiranandani Hospital, Navi Mumbai

 

Antibiotic resistance is one of the biggest public health challenges of our time. Each year in the U.S., at least 2.8 million people get an antibiotic-resistant infection, and more than 35,000 people die. 

Antibiotic resistance happens when germs like bacteria and fungi develop the ability to defeat the drugs designed to kill them. That means the germs are not killed and continue to grow. 

Infections caused by antibiotic-resistant germs are difficult, and sometimes impossible, to treat. In most cases, antibiotic-resistant infections require extended hospital stays, additional follow-up doctor visits, and costly and toxic alternatives. Antibiotic resistance does not mean the body is becoming resistant to antibiotics; it is that bacteria have become resistant to the antibiotics designed to kill them. 

With 700,000 people losing battle to antimicrobial resistance (AMR) per year and another 10 million projected to die from it by 2050, AMR alone is killing more people than cancer and road traffic accidents combined together1. Economic projections suggest that by 2050, AMR would decrease gross domestic product (GDP) by 2-3.5 per cent with a fall in livestock by 3-8 per cent, costing USD100 trillion to the world2. The global rise of AMR has attracted the attention of World Health Organization (WHO) and several other stakeholders. With WHO announcing AMR as an urgent priority area3 and several world leaders from Europe framing their Action Plans for the containment of AMR4,5. It is obvious that sincere efforts are being directed against this common enemy. India has also framed its National Action Plan (NAP) for AMR6.

 

AMR in India

The One Health concept highlights the importance of inter-dependence of human, animal and environmental parameters for the containment of AMR. The same holds true for India wherein the rates of AMR in all these three sectors have been rising disproportionately in the past decades10. Another issue is the lack of sufficient research and paucity of data that not only hampers the estimation of exact rise and extent of AMR in India but also prevents a nation-wide comparison. Of the 2152 studies published by Indian institutions on AMR, 1,040 (48.3%) were on humans, while only 70 (3.3%) on animals, 90 (4.2%) on environment and 11 (0.5%) on One Health. The rest were based on novel agents, diagnostics, editorials and miscellaneous11.

As per the ‘scoping report on antimicrobial resistance in India (2017)’11, under the aegis of government of India, among the Gram-negative bacteria, more than 70 per cent isolates of Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii and nearly half of all Pseudomonas aeruginosawere resistant to fluoroquinolones and third generation cephalosporins. Although the resistance to drug combination of piperacillin-tazobactum was still <35 per cent for E. coli and P. aeruginosa, the presence of multiple resistance genes including carbapenemases made 65 per cent K. pneumoniae resistant11. Increasing rates of carbapenem resistance to the tune of 71 per cent in A. baumannii led to frequent use of colistin as the last resort antimicrobial11. The resistance to colistin has also emerged in India. Although the rate of colistin resistance was <1 per cent, except for 4.1 per cent reported by Gandra et al12, high mortality of 70 per cent was associated with colistin-resistant K. pneumoniae. Among the Gram-positive organisms, 42.6 per cent of Staphylococcus aureus were methicillin-resistant and 10.5 per cent of Enterococcus faecium were vancomycin-resistant. The rates of resistance among Salmonella Typhi and Shigella species were 28 and 82 per cent, respectively, for ciprofloxacin, 0.6 and 12 per cent for ceftriaxone and 2.3 and 80 per cent for co-trimoxazole. For Vibrio cholerae, resistance rates to tetracycline varied from 17 to 75 per cent in different parts of the country11.

 

Challenges of AMR in India

India has been referred to as ‘the AMR capital of the world’29. While on one hand, emergence of newer multi-drug resistant (MDR) organisms pose newer diagnostic and therapeutic challenges, on the other hand India is still striving to combat old enemies such as tuberculosis, malaria and cholera pathogens, which are becoming more and more drug resistant. Factors such as poverty, illiteracy, overcrowding and malnutrition further compound the situation30. Lack of awareness about infectious diseases in the general masses and inaccessibility to healthcare often preclude them from seeking medical advice31. This, more often than not, leads to self-prescription of antimicrobial agents without any professional knowledge regarding the dose and duration of treatment32. Among those who seek medical advice, many end up receiving broad-spectrum high-end antimicrobials owing to lack of proper diagnostic modalities for identifying the pathogen and its drug susceptibility. Low doctor to patient and nurse to patient ratios along with lack of infection prevention and control (IPC) guidelines favour the spread of MDR organisms in the hospital settings. Easy availability of over-the-counter (OTC) drugs, further contributes to AMR.

The rise in the pharmaceutical sector has caused parallel rise in the amount of waste generated from these companies. With the lack of strict supervisory and legal actions, this waste reaches the water bodies and serves as a continuous source of AMR in the environment. Another important challenge could be the use of antimicrobial agents as pesticides and insecticides in the agriculture industry, although the evidence for the same is currently lacking. India has vast agricultural lands and farmers already face a lot of adversities at the hands of harsh weather, difficult terrain and natural calamities. They fall an easy prey to the lure of protecting their hard-earned field from pests and rodents by using antimicrobial agents without considering the future consequences. This large reservoir of antimicrobial agents forms a favourable niche for the emergence of MDR pathogens who then drift into the water bodies with rains and floods. The paucity of data on the extent of AMR, especially in animals and environment, presents hurdles to framing and implementation of policies on the control of AMR.

Chereau et al, in their evaluation of risk assessment for AMR, have shown that while AMR originating from environmental sources may be contributing a low proportion in developed countries, it poses a moderate to high-risk in developing countries of South East Asia including India due to several co-factors associated with the overall event. The following drivers of AMR in the environment are noteworthy: 

  1. Excess use or misuse of antimicrobial agents
  2. AMR contributed by antimicrobial use in animals
  3. AMR contributed by biocides
  4. Contaminated water as a source of AMR
  5. Hospital effluencts
  6. Agricultural manure and sludge
  7. Livestock discard
  8. Heavy metals

 

Ideas to combat AMR:

The National Health Mission of India started the Swachh Bharat Abhiyan or the Clean India Mission to improve the basic hygiene and sanitation in all spheres of life. As a part of this massive programme, education was imparted through mass media on the health hazards of open defecation. UNICEF data shows that out of one billion openly-defecating people in the world, 60 per cent reside in India. It is further argued that it is a behavioural problem with the Indians as other poverty-struck nations of Africa and South East Asia did not have the problem of open defecation to this an extent10. To deal with such sociocultural issues, innovative ideas along with mass media are needed in India. 

Antimicrobial Stewardship Strategies

AMSP refers to comprehensive strategies designed for rational use of antimicrobial agents (AMAs) by optimal antimicrobial drug, dosing, duration of therapy and route of administration with minimal toxicity. The various AMSP strategies include building capacity for stewardship activities, developing policies and guidelines, establishing systems, educating healthcare workers and introducing useful interventions, specifically customized for the national setting. The core strategies can be in the form of two major approaches, with the most successful programmes generally implementing a combination of both. The front-end or pre-prescription approach to stewardship uses restrictive prescriptive authority which requires approval to use certain restricted antibiotics, except trained clinicians. The back-end or post-prescription approach to stewardship uses prospective review and feedback. Based on the review and feedback, the clinicians are recommended by the AMSP team to modify or discontinue specific antibiotic use.

 

AMSP capacities in Indian healthcare institutions (HCIs) are rudimentary or rather non-existent and this has been well documented in one of the surveys carried out by ICMR in 2013 among 20 tertiary HCIs about AMSP components, implementation and outcome15. It showed that only 40 per cent of HCIs had AMSP written documents, 75 per cent of HCIs had HIC guidelines and 65 per cent had AMAs prescription guidelines. Moreover, only 30 per cent of HCIs had AMSP implementation strategies. Private HCIs showed better performance compared to government HCIs in AMSP that was attributed to the accreditation process. The survey reported the absence of IDs physicians and clinical pharmacists in institutions. This shows a lacuna for AMSP in India and the dire need to implement AMSP as priority.

In March 2017, the National Health Policy 2017 of Ministry of Health and Family Welfare (MoHFW), Government of India, prioritized AMR in India. In response to the call by 71st UN General Assembly for AMR threat in the meeting of global leaders (September 2016), the Government of India launched the National Action Plan on AMR (2017-2021) in April 2017 with support from WHO India office coordinated by MoHFW. The document notified the governance mechanisms by three groups – an intersectoral coordination committee, a technical advisory group and a core working group on AMR.

 

Future strategies for AMR in India-

1. Promoting further research on the drivers of AMR with due importance to components other than antimicrobial use for human health alone
2. Framing of antibiotic stewardship plans for healthcare settings to monitor and ensure judicious use of antimicrobials, including all tiers of healthcare-primary health centres, secondary and tertiary hospitals
3. Strict vigilance and control over sale of antimicrobial agents. Prescription audit to bring down the over the counter (OTC) sale
4. Disciplinary control over the functioning of hospital effluent plants with periodic assessment and reporting of antimicrobial residue in the discharge
5. Regulation of waste water discharges from pharmaceutical companies with regular monitoring of antimicrobial residues in them along with provision of legislative support to punish offenders
6. Framing and implementing rules and regulations for the use of antimicrobial agents in food animals including farmed seafood
7. Improving agricultural practices by ensuring use of environment-friendly manure and fertilizers
8. Educating the masses at the community level regarding AMR and formulating educational bodies/non-governmental organizations for continued dissipation of information.

 

For further details and interest in steps taken by Government of India – Indian Council of Medical Research (ICMR) in AMSP you can download the guidelines here : https://www.icmr.nic.in/sites/default/files/guidelines/AMSP_0.pdf

 

References:

  1. O’Neill J. Tackling drug-resistant infections globally: final report and recommendations. Review on Antimicrobial Resistance. 2016. [accessed on April 15, 2017]. Available from: https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf.
  2. O’Neill J. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. Review on Antimicrobial Resistance. 2014. [accessed on April 15, 2017]. Available from: https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf.
  3. World Health Organization, Regional office for South-East Asia. Jaipur declaration on antimicrobial resistance. 2011. [accessed on April 15, 2017].  http://www.who.int/iris/handle/10665/205397.
  4. Smith E, Lichten CA, Taylor J, MacLure C, Lepetit L, Harte E, et al. Evaluation of the action plan against the rising threats from antimicrobial resistance. Final Report. European Commission. 2016. [accessed on April 15, 2017]. Available from: https://www.ec.europa.eu/health/amr/sites/amr/files/amr_final-report_2016_rand.pdf.
  5. Department of Health, Department for Environment Food and Rural Affairs. UK Five Year Antimicrobial Resistance Strategy 2013 to 2018. Government of UK. 2013. [accessed on April 15, 2017]. Available from: https://www.gov.uk/government/publications/uk-5-year-antimicrobialresistance-strategy-2013-to-2018.
  6. Government of India. National Action Plan on Antimicrobial Resistance (NAP-AMR) 2017 – 2021.2017. [accessed on April 15, 2017]. Available from: http://www.searo.who.int/india/topics/antimicrobial_resistance/nap_amr.pdf.
  7. Dahal R, Upadhyay A, Ewald B. One health in South Asia and its challenges in implementation from stakeholder perspective. Vet Rec. 2017;181:626. [PubMed] [Google Scholar]
  8. World Health Organization, Regional office for South-East Asia. Situational analysis on antimicrobial resistance in the South-East Asia Region. Report. 2016. [accessed on April 15, 2017]. Available from: http://www.searo.who.int/entity/antimicrobial_resistance/situational-analysis-on-amr-sear-2016.pdf?ua=1.
  9. Singer AC, Shaw H, Rhodes V, Hart A. Review of antimicrobial resistance in the environment and its relevance to environmental regulators. Front Microbiol. 2016;7:1728. [PMC free article] [PubMed] [Google Scholar]
  10. Kahn LH. Antimicrobial resistance: A one health perspective. Trans R Soc Trop Med Hyg. 2017;111:255–60. [PubMed] [Google Scholar]
  11. Gandra S, Joshi J, Trett A, Lamkang A, Laxminarayan R. Washington, DC: Center for Disease Dynamics, Economics & Policy; 2017. [accessed on April 15, 2017]. Scoping Report on Antimicrobial Resistance in India. Available from: http://www.dbtindia.nic.in/wp-content/uploads/ScopingreportonAntimicrobialresistanceinIndia.pdf. [Google Scholar]
  12. Gandra S, Mojica N, Klein EY, Ashok A, Nerurkar V, Kumari M, et al. Trends in antibiotic resistance among major bacterial pathogens isolated from blood cultures tested at a large private laboratory network in India, 2008-2014. Int J Infect Dis. 2016;50:75–82. [PMC free article] [PubMed] [Google Scholar]
  13. Government of India. State of Indian Agriculture 2015-16. Ministry of Agriculture & Farmers Welfare Department. 2016. [accessed on April 15, 2017]. Available from: http://agricoop.nic.in/sites/default/files/State_of_Indian_Agriculture%2C2015-16.pdf.
  14. Van Boeckel TP, Brower C, Gilbert M, Grenfell BT, Levin SA, Robinson TP, et al. Global trends in antimicrobial use in food animals. Proc Natl Acad Sci U S A. 2015;112:5649–54. [PMC free article][PubMed] [Google Scholar]
  15. Walia K, Ohri VC, Mathai D, Antimicrobial Stewardship Programme of ICMR. Antimicrobial stewardship programme (AMSP) practices in India. Indian J Med Res2015; 142 : 130-8

 

You may also like...

Leave a Reply

Your email address will not be published.