AMR seminar 4.3.23.pptx

ANTI-MICROBIAL RESISTANCE: CURRENT SCENARIO, FUTURE CHALLENGES AND MITIGATING STRATEGIES IN INDIAN CONTEXT

1. ANTI-MICROBIAL RESISTANCE: CURRENT SCENARIO, FUTURE CHALLENGES AND MITIGATING STRATEGIES IN INDIAN CONTEXT Presenter- Dr. Yukti Bhandari, Senior Resident Moderator- Dr. Vivek Sagar, Associate Professor Department of Community Medicine and School of Public Health, PGIMER, Chandigarh

2. Contents What is AMR? Current Global Scenario Indian Scenario Various challenges faced Mitigation strategies in place in India Discussion on new innovations

3. What is AMR? Antimicrobial Resistance (AMR) occurs when bacteria, viruses, fungi and parasites change over time and no longer respond to medicines making infections harder to treat and increasing the risk of disease spread, severe illness and death.  Antimicrobial Resistance. Fac t Sheet. World Health Organisation.

4. The direct consequences of infection with resistant microorganisms can be severe, including longer illnesses and prolonged stays in hospital increased mortality loss of protection for patients undergoing operations and other medical procedures increased costs Global Action Plan on Antimicrobial Resistance, World Health Organization

5. How does AMR Develop?

6. Spread of AMR

7. Detection of AMR Phenotypic methods Genotypic methods Relates only to the concentration of an antimicrobial that inhibits bacterial growth in vitro. Provides the opportunity for accelerated cultures, and may even be performed directly on the clinical specimens . They provide no indication of the mechanisms of resistance which may disseminate to other bacterial species. These methods help assess the genetic makeup, identify antimicrobial resistance genes and understand the mechanism of resistance. Time taken – 36-72 hours Time taken – 30 minutes - 8 hours For eg. broth microdilution, disk diffusion, gradient tests, agar dilution and breakpoint tests etc. For eg. Whole Genome Sequencing (WGS), Nucleic acid amplification test, Polymerase Chain Reaction (PCR), Fluorescent in-situ hybridisation (FISH) etc. Vasala A, Hytönen VP, Laitinen OH. Modern tools for rapid diagnostics of antimicrobial resistance. Frontiers in Cellular and Infection Microbiology. 2020 Jul 15;10:308.

8. Global Scenario WHO has declared AMR as one of the top 10 global public health threats facing humanity. Misuse and overuse of antimicrobials are the main drivers in the development of drug-resistant pathogens. AMR has become a major threat to the treatment of not only common bacterial infections, but also to the treatment of - Fungal infections like Candida Parasitic diseases like malaria Viral diseases like HIV Important public health threats like Tuberculosis Anti-microbial resistance, WHO Fact Sheet

9. Global Antimicrobial Resistance and Use Surveillance System (GLASS) Launched by the World Health Organization (WHO) in 2015 to support the strengthening of the antimicrobial resistance (AMR) evidence base, the Global Antimicrobial Resistance and Use Surveillance System (GLASS) is the first system that enables harmonized global reporting of official national AMR and antimicrobial consumption (AMC) data.

10. GLASS enrolment map as on 30 April 2021 Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report, 2022

11. AMR and Sustainable Development Goals In 2020, two new AMR indicators were included in the monitoring framework of the SDGs linked to the health target 3.d (“strengthen the capacity of all countries, in particular developing countries, for early warning, risk reduction and management of national and global health risks”). These indicators monitor proportion of bloodstream infections (BSIs) due to: Escherichia coli resistant to 3rd generation cephalosporins Methicillin-resistant Staphylococcus aureus (MRSA)

12. ResistanceMap : Antibiotic resistance. Sourced from GLASS 2019.

13. All-age rate of deaths attributable to and associated with bacterial antimicrobial resistance by GBD region 2019 Murray CJ, Ikuta KS, Sharara F, Swetschinski L, Aguilar GR, Gray A et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet. 2022 Feb 12;399(10325):629-55. 1·27 million deaths 47,600 DALYs

14. Global Action Plan on Anti-Microbial Resistance In May 2015, World Health Assembly adopted a global action plan on antimicrobial resistance, which outlines five objectives:

15. Indian Scenario Antibiotic % Resistance (with 95% C.I.) Aminopenicillins 87% (83-90%) Fluroquinolones 86% (85-87%) Cephalosporins 3rd Gen 83% (82-84%) Amoxicillin-clavulanate 60% (51-69%) Carbapenems 41% (38-44%) Piperacillin-tazobactam 28% (26-30%) Aminoglycosides 17% (15-19%) Data from GLASS. ResistanceMap . https:// resistancemap.onehealthtrust.org / AntibioticResistance.php AMR in Human Beings: Resistance of E. coli to Antimicrobials in India More than 70% isolates of Klebsiella pneumoniae and Acinetobacter baumannii  and 50% of Pseudomonas aeruginosa were also resistant to fluoroquinolones and third generation cephalosporins.

16. Indian Scenario AMR in Animals and Food: 48% of Gram-negative bacilli detected in cow and buffalo milk were extended-spectrum β- lactamases (ESBL) producers (West Bengal) and 47.5 per cent were resistant to oxytetracycline (Gujarat). Vibrio cholera and V. parahaemolyticus, isolated from the retail markets of shrimps, shellfish and crabs in Kerala were 100 per cent resistant to ampicillin, while resistance to ceftazidime ranged from 67 to 96 per cent. In the poultry industry, presence of ESBL producers vary from 9.4% in Odisha to 33.5% in Madhya Pradesh to 87% in Punjab. Salmonella species in broilers varied from 3.3% in Uttar Pradesh to 23.7% in Bihar with 100% isolates being resistant to ciprofloxacin, gentamicin and tetracycline in Bihar and West Bengal. Taneja N, Sharma M. Antimicrobial resistance in the environment: The Indian scenario. Indian J Med Res. 2019 Feb;149(2):119-128. doi : 10.4103/ijmr.IJMR_331_18. PMID: 31219076; PMCID: PMC6563737.

17. Indian Scenario AMR in the Environment The groundwater and surface water that are used for drinking and recreational purposes have been reported with 17% of E. coli, resistant to third generation cephalosporin, in central India, 7% in Kashmir, 50% in Sikkim and 100% in Hyderabad. The rate of isolation of E. coli resistant to third generation cephalosporin at water treatment plants was 25, 70 and 95% when the inlet to the plant was domestic water alone, domestic waste along with hospital effluent and hospital effluent alone, respectively. Taneja N, Sharma M. Antimicrobial resistance in the environment: The Indian scenario. Indian J Med Res. 2019 Feb;149(2):119-128. doi : 10.4103/ijmr.IJMR_331_18. PMID: 31219076; PMCID: PMC6563737.

18. Development of AMR related policies in India

19. Timeline and Development of AMR in India

20. Timeline and Development of AMR in India

21. National Programme on AMR Containment (2012-2017) Objectives of this programme were:  Establish a laboratory-based AMR surveillance system in the country to generate quality data on antimicrobial resistance Carry out surveillance of antimicrobial usage in different health care settings Strengthen infection control practices and promote rational use of antimicrobials through Antimicrobial stewardship activities Generate awareness amongst health care providers and community on antimicrobial resistance and rational use of antimicrobials. National Centre for Disease Control, 2012

22. National Health Policy 2017 The problem of anti-microbial resistance calls for a - Rapid standardization of guidelines regarding antibiotic use Limiting the use of antibiotics as Over-the-Counter medication Banning or restricting the use of antibiotics as growth promoters in animal livestock. Pharmacovigilance including prescription audit inclusive of antibiotic usage, in the hospital and community, is a must in order to enforce change in existing practices. The policy also includes AMR as one of areas where the private sector could play an active role in through use of the corporate social responsibility platform.

23. National Action Plan on Antimicrobial Resistance (NAP-AMR) 2017 – 2021 The following are the specific objectives of the NAP-AMR: Define the strategic priorities , key actions, outputs, responsibilities, and indicative timeline and budget to slow the emergence of AMR in India and strengthen the organizational & management structures to ensure intra- & inter-sectoral coordination with a One Health approach ; Combat AMR in India through better understanding and awareness of AMR, strengthened surveillance , prevention of emergence and spread of resistant bacteria through infection prevention and control, optimised use of antibiotics in all sectors, and enhanced investments for AMR activities, research and innovations; Enable monitoring and evaluation (M&E) of the NAP-AMR implementation based on the M&E framework.

24. STATE ACTION PLAN FOR CONTAINMENT OF ANTIMICROBIAL RESISTANCE

25. National Programme on Antimicrobial Resistance Containment This guidance document defines standards for antimicrobial susceptibility testing, data collection and reporting processes for sites participating in the AMRSN co-ordinated by the NCDC. It provides guidelines to ensure consistent AST procedures and systematic AMR surveillance data reporting from sites across the network.

26. India's Antimicrobial Resistance Surveillance & Research Initiative India’s Antimicrobial Resistance Surveillance & Research Initiative https:// iamrsn.icmr.org.in / index.php /about

27. Annual Report, Anti-microbial Resistance Research and Surveillance Network, 2021

28. Antimicrobial Resistance Research & Surveillance Network Under AMRSN, there are nodal centres (NCs) for each pathogenic group in four tertiary care hospitals from the country. Enterobacterales causing sepsis (PGIMER, Chandigarh) Fungal pathogens (PGIMER, Chandigarh) Gram-positives: staphylococci and enterococci, (JIPMER, Puducherry) Typhoidal Salmonella (AIIMS New Delhi) Diarrhoeagenic bacterial organisms (CMC Vellore) Streptococcus pneumoniae (CMC Vellore) Gram-negative non-fermenters (CMC Vellore) Annual Report, Anti-microbial Resistance Research and Surveillance Network, 2021

29. NARS-NET Under the National Programme on AMR Containment, National AMR Surveillance Network has been established which is a network of state medical college laboratories from across the country for generating AMR surveillance data through a sentinel surveillance system. MoHFW identified NCDC in July 2017 as the National coordinating centre for AMR surveillance.

30. Challenges in AMR Surveillance Network in India Walia K, Madhumathi J, Veeraraghavan B, Chakrabarti A, Kapil A, Ray P, Singh H, Sistla S, Ohri VC. Establishing Antimicrobial Resistance Surveillance & Research Network in India: Journey so far. Indian J Med Res. 2019 Feb;149(2):164-179. doi : 10.4103/ijmr.IJMR_226_18. PMID: 31219080; PMCID: PMC6563732.

31. Antimicrobial prescribing facts: The 30% Rule Antimicrobial Stewardship Program Guidelines. ICMR

32. Antimicrobial Stewardship Coordinated interventions designed to improve and measure the appropriate use of antimicrobial agents by promoting the selection of the optimal antimicrobial drug regimen including dosing, duration of therapy, and route of administration. Antimicrobial Stewardship Program Guidelines. ICMR

33. Components of Antimicrobial Stewardship Program Antimicrobial Stewardship Program Guidelines. ICMR

34. Antimicrobial Stewardship in Community Settings Antimicrobial stewardship in community settings is required to help out health care practitioners which are often compelled to treat empirically and to prevent use of unregulated drugs approved in the community and to prevent self medication and antibiotics on over the counter. The core elements of AMSP in primary care OPDs and community settings includes: Accountability for optimizing antibiotic prescription Use of evidence based diagnostic criteria and treatment recommendation Self-evaluate antibiotic prescribing practices Use effective communication strategy to educate patients. Antimicrobial Stewardship Program Guidelines. ICMR

35. Standard Operating Procedures from ICMR External Quality Assessment Scheme (EQAS) Bacteriology Mycology Veterinary practices Rational Prescribing guidelines Hospital Infection Control guidelines

36. Factors behind acceleration of AMR in India Huge burden of infectious diseases Poor sanitation, poor implementation of infection control practices Close animal-human interface Lack of infectious disease specialists Lack of diagnostics Absence/non-adherence to standard treatment guidelines Irrational self-administration or prescription Drugs available without prescription Poor quality of drugs Advancing Antimicrobial Stewardship. ICMR

37. AMR in HIV HIV Drug Resistance Report 2021

38. AMR in Malaria Drug Resistance in the Malaria-Endemic World. CDC. 2018

39. AMR in Tuberculosis Global Tuberculosis Report, 2022. WHO.

40. AMR in Tuberculosis The first national anti-tuberculosis drug resistance survey (NDRS) revealed that 28% of TB patients were resistant to any drugs (22% among new and 36.82% among previously treated). MDR-TB was 6.19% among all TB patients with 2.84% among new and 11.60% (CI 10.21–13.15%) among previously treated TB patients. I n 2021, 48,232 MDR/RR-TB patients were diagnosed. 8,455 Pre-XDR-TB, 376 XDR-TB and 13,724 H mono/poly patients were diagnosed.

41. Mitigation Strategies Uchil RR, Kohli GS, Katekhaye VM, Swami OC. Strategies to combat antimicrobial resistance. J Clin Diagn Res. 2014 Jul;8(7):ME01-4.

42. Role of Surveillance in AMR Cornerstone for assessing the spread of AMR. Inform local, national and global strategies. Inform infection prevention and control responses. Monitor the impact of local, national and global strategies. WHO. Initiatives. GLASS. WHO. Initiatives. GLASS

43. WHO AWaRe Tool The AWaRe Classification of antibiotics was developed in 2017 by the WHO Expert Committee on Selection and Use of Essential Medicines as a tool to support antibiotic stewardship efforts at local, national and global levels. Antibiotics are classified into three groups, Access, Watch and Reserve, taking into account the impact of different antibiotics and antibiotic classes on antimicrobial resistance, to emphasize the importance of their appropriate use.  It is a useful tool for monitoring antibiotic consumption, defining targets and monitoring the effects of stewardship policies that aim to optimize antibiotic use and curb antimicrobial resistance. 2021 AWaRe Classification. https:// www.who.int /publications/ i /item/2021-aware-classification

44. 2021 AWaRe Classification Tool

45. Steps of rational antimicrobial use Making a clinical diagnosis Limiting empiric antimicrobial therapy Know your bugs Choose appropriate antimicrobial De-escalation/Modification Identify clinical situations where antimicrobial use needs to be stopped Reduce duration of therapy Optimize pharmacodynamics and pharmacokinetics

46. Strategies to improve Antimicrobial Use Front-end strategies: Antimicrobials are made available through an approval process (formulary restriction and preauthorization) Shows immediate reduction in use and expenditure of restricted antibiotics Back-end strategies: Antimicrobials are reviewed after antimicrobial therapy has been initiated (prospective audit and feedback) Timely de-escalation of antibiotics Reduction in inappropriate use Principles of Antimicrobial Prescribing. CMC Vellore & WHO

47. Strategies to improve Antimicrobial Use Advantages Disadvantages Pre-authorization Reduces empiric initiation of inappropriate Antimicrobials Encourages early and frequent review of culture data Reduces costs May delay therapy Loss of prescriber autonomy Impacts only restricted agents Prospective Audit & Feedback Visibility of the stewardship is increased More data is available and hence uptake is better Educative and collaborative effort which could address de-escalation and duration of therapy Prescriber autonomy is maintained Labor intensive Compliance voluntary and prescriber reluctance to change if patient better Principles of Antimicrobial Prescribing. CMC Vellore & WHO

48. Antimicrobial Stewardship in PGIMER Shafiq N, Kumar MP, Kumar G, Rohilla R,Saha S, Gautam V, Agarwal R, Ray P, Singh G, Muralidharan J,Arora P. Antimicrobial Stewardship Program of PostgraduateInstitute of Medical Education and Research, Chandigarh:Running Fast to catch the Missed Bus. J Postgrad Med EduRes 2017;51(3):123-127

49. Infection Prevention and Control Guidelines

50. Way forward

51. Priority 1 - Stepping up leadership for the AMR response WHO Strategic Priorities on AMR. 2022

52. Priority 2 – Driving public health impact in every country to address AMR National AMR action plans in 148 countries Practical guidance and tools to member countries Annual World Antimicrobial Awareness Week (18-24 November) – the theme for 2022 was “Preventing Antimicrobial Resistance Together”. WHO Strategic Priorities on AMR. 2022

53. Strategic Priorities Priority 3 – Research and Development for better access to quality AMR prevention and care Development of priority bacterial and fungal pathogen lists List of Critically Important Antimicrobials for Human Medicine Priority 4 – Monitoring AMR burden and global AMR response GLASS Tripartite AMR Country Self Assessment Survey ( TrACCS ) WHO Strategic Priorities on AMR. 2022

54. Antimicrobial Resistance: A complex multi-factorial problem requiring orchestrated interdisciplinary response. From the Australian Academy of Science Report. 2017

55. One Health Consortium The Department of Biotechnology under the Ministry of Science and Technology, has launched the country’s first One Health consortium. This Consortium consists of 27 organisations from human, veterinary and related environmental fields. It envisages carrying out surveillance of important bacterial, viral and parasitic infections of zoonotic and transboundary pathogens in India. It also looks into the use of existing diagnostic tests and the development of additional methodologies for the surveillance and understanding the spread of emerging diseases. There exists a need to make mitigation of AMR as one of the priorities of the One Health Consortium. Press Information Bureau, Ministry of Science and Technology, GoI , Dec 2021

56. TrACCS Country Report 2022 - India Tracking AMR Country Self Assessment Survey ( TrACSS ) 2022 Country Report

57. Innovations Kumar M, Sarma DK, Shubham S, Kumawat M, Verma V, Nina PB, Jp D, Kumar S, Singh B, Tiwari RR. Futuristic non-antibiotic therapies to combat antibiotic resistance: A review. Frontiers in microbiology. 2021 Jan 26;12:609459.

58. Application of Synthetic Antimicrobials in AMR

59. Artificial Intelligence in AMR Development of synthetic antimicrobial peptides using AI A class of small host defense peptides, found in all classes of biological species. AI guided discovery and development of new antibiotics Discovery of new and structurally different antibiotics from the ones already known using AI. Assisting in appropriate antibiotic prescription Appropriate therapy selection, dose, and correct administration route Prediction of antibiotic resistance ML techniques to predict early AMR or the probability of a microbial agent becoming resistant Prediction of severity of infection Machine/deep learning tools for infectious pathology recognition and appropriate management Rabaan AA, Alhumaid S, Mutair AA, Garout M, Abulhamayel Y, Halwani MA et al. Application of Artificial Intelligence in Combating High Antimicrobial Resistance Rates. Antibiotics (Basel). 2022 Jun 8;11(6):784.

60. Future directions for India Taneja N, Sharma M. Antimicrobial resistance in the environment: The Indian scenario. Indian J Med Res. 2019 Feb;149(2):119-128. doi : 10.4103/ijmr.IJMR_331_18. PMID: 31219076; PMCID: PMC6563737.

61. Future directions for India Taneja N, Sharma M. Antimicrobial resistance in the environment: The Indian scenario. Indian J Med Res. 2019 Feb;149(2):119-128. doi : 10.4103/ijmr.IJMR_331_18. PMID: 31219076; PMCID: PMC6563737.

62. AMR and GoI Initiatives ICMR has initiated antibiotic stewardship program (AMSP) on a pilot project basis in 20 tertiary care hospitals across India to control misuse and overuse of antibiotics in hospital wards and ICUs. DCGI has banned 40 fixed dose combinations (FDCs) which were found inappropriate. ICMR worked in collaboration with Indian Council of Agriculture Research, Department of Animal Husbandry, Dairy and Fisheries and the DCGI to ban use of Colistin as growth promoter in animal feed in poultry. Various IEC activities like public conclave, poster and quiz competitions have been conducted by National Centre for Disease Control (NCDC) in schools, colleges and Health melas to create awareness about AMR, its containment & prevention and judicial use of antibiotics among the common public. To raise awareness among the community and the health care providers, communication material includes posters, videos and radio jingles has been developed with emphasis on prevention of irrational use of antibiotics during viral-illnesses and also on infection prevention through hand hygiene to prevent spread of infections. Press Information Bureau. MOHFW. GoI . 5 Aug 2022

63. AMR and PGIMER WHO-AGISAR Monitoring the Antimicrobial Resistance Profile of Bacterial Food-borne Pathogens in Humans, Food Animals and Retail Meat in India. 2017-21 ICMR-AIIMS-CDC India Collaborative Project: Capacity Building and Strengthening of Hospital Infection Control to detect and prevent antimicrobial resistance in India 2019 PHFI Project: Antimicrobial resistance and zoonotic transmission in enteric bacteria at human and animal interface in an intensive food production geographic area Nodal centre for surveillance of Enterbacterales causing sepsis & fungal pathogens.

64. THANK YOU